RESUMO
The pro-inflammatory IFNγ-STAT1 pathway and anti-inflammatory IL10-STAT3 pathway elicit cellular responses primarily utilizing their canonical STATs. However IL10 mediated STAT1 and IFNγ mediated STAT3 activation is also observed, suggesting crosstalk of these functionally opposing signaling pathways can potentially reshape the canonical dynamics both STATs and alter the expression of their target genes. Herein, we measured the dynamics of STATs in response to different doses of IL10 or IFNγ and in their co-stimulation and employed quantitative modeling to understand the regulatory mechanisms controlling signal responses in individual and co-simulation scenarios. Our experiments show, STAT3 in particular, exhibits a bell-shaped dose-response while treated with IFNγ or IL10 and our model quantiatively captured the dose-dependent dynamics of both the STATs in both pathways. The model next predicted and subsequent experiments validated that STAT3 dynamics would robustly remain IL10 specific when subjected to a co-stimulation of both IFNγ and IL10. Genes common to both pathways also exhibited IL10 specific expression during the co-stimulation. The findings thus uncover anovel feature of the IL10-STAT3 signaling axis during pathway crosstalk. Finally, parameter sampling coupled to information theory based analysis showed that bell-shaped signal-response of STAT3 in both pathways is primarily dependent on receptor concentration whereas robustness of IL10-STAT3 signaling axis in co-stimulation results from the negative regulation of the IFNγ pathway.
Assuntos
Interferon gama/farmacologia , Interleucina-10/farmacologia , Transdução de Sinais , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Animais , Calibragem , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos Endogâmicos BALB C , Modelos Biológicos , Fosforilação/efeitos dos fármacos , Reprodutibilidade dos Testes , Fator de Transcrição STAT1/metabolismoRESUMO
Solid tumors elicit suppressive T cell responses which impair antigen-presenting cell (APC) functions. Such immune suppression results in uncontrolled tumor growth and mortality. Addressing APC dysfunction, dendritic cell (DC)-mediated anti-tumor vaccination was extensively investigated in both mice and humans. These studies never achieved full resistance to tumor relapse. Herein, we describe a repetitive RM-1 murine tumor rechallenge model for recurrence in humans. Using this newly developed model, we show that priming with tumor antigen-pulsed, Toll-like receptor (TLR)2 ligand-activated DCs elicits a host-protective anti-tumor immune response in C57BL/6 mice. Upon stimulation with the TLR2 ligand peptidoglycan (PGN), the tumor antigen-pulsed DCs induce complete resistance to repetitive tumor challenges. Intra-tumoral injection of PGN reduces tumor growth. The tumor resistance is accompanied by increased expression of interleukin (IL)-27, T-box transcription factor TBX21 (T-bet), IL-12, tumor necrosis factor (TNF)-α and interferon (IFN)-γ, along with heightened cytotoxic T lymphocyte (CTL) functions. Mice primed four times with PGN-stimulated tumor antigen-pulsed DCs remain entirely resistant to repeat challenges with RM-1 tumor cells, suggesting complete prevention of relapse and recurrence of tumor. Adoptive transfer of T cells from these mice, which were fully protected from RM-1 rechallenge, confers anti-tumor immunity to syngeneic naive recipient mice upon RM-1 challenge. These observations indicate that PGN-activated DCs induce robust host-protective anti-tumor T cells that completely resist tumor growth and recurrence.
Assuntos
Vacinas Anticâncer/imunologia , Células Dendríticas/imunologia , Imunoterapia Adotiva/métodos , Neoplasias da Próstata/imunologia , Linfócitos T Citotóxicos/imunologia , Animais , Antígenos de Neoplasias/imunologia , Antígenos de Neoplasias/metabolismo , Citocinas/metabolismo , Células Dendríticas/transplante , Modelos Animais de Doenças , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Recidiva Local de Neoplasia , Peptidoglicano/metabolismo , Receptor 2 Toll-Like/agonistas , Carga TumoralRESUMO
Global incidence of dengue has drastically increased in the last few years. Despite the global morbidity and mortality associated with dengue infection, mechanisms of immune control and viral pathogenesis are poorly explored. Pancytopenias, along with increased oxidative stress, are salient clinical findings in severe dengue patients. Previously, we demonstrated significant differences of circulating immune complexes (CICs) among severe and non-severe dengue patients. Accordingly, here we sought to determine the contributory role of affinity-purified antibody-bound CICs in dengue severity. To characterize intracellular oxidative stress induced by antibody-bound CICs, 5-(and-6)-chloromethyl-2'-7'-dichlorodihydrofluorescein diacetate (DCFDA) was measured by flow cytometry. At the same time, CICs sensitized healthy red blood cells (RBC) and patients' RBC morphology was determined by scanning electron microscopy and flow cytometry analysis. Erythrophagocytosis and ferritin levels were further determined in severe and non-severe dengue patients. Our results showed that the severe patients had high titres of immunoglobulin (Ig)M-bound CICs (P < 0·0001) in their sera, increased intracellular oxidative stress (P < 0·0001), high ferritin levels (P < 0·0001), altered morphology of RBC and finally enhanced erythrophagocytosis. This study shows for the first time that RBC morphology is altered in severe dengue patients. Taken together, this study suggests that the enhanced IgM-bound CICs could contribute to the increased oxidative stress and act directly on RBC destruction of severe dengue patients, and is an important pathophysiological determinant. Hence, IgM-bound CICs can serve as an important laboratory parameter to monitor dengue infection progression.
Assuntos
Complexo Antígeno-Anticorpo , Eritrócitos , Imunoglobulina M , Estresse Oxidativo/imunologia , Dengue Grave , Adulto , Complexo Antígeno-Anticorpo/sangue , Complexo Antígeno-Anticorpo/imunologia , Eritrócitos/imunologia , Eritrócitos/metabolismo , Eritrócitos/patologia , Humanos , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Masculino , Pessoa de Meia-Idade , Dengue Grave/sangue , Dengue Grave/imunologia , Dengue Grave/patologia , Índice de Gravidade de DoençaRESUMO
Commercial high-resolution optical microscopes are essential for microscopy imaging; however, they are expensive and bulky, which limits their use in point-of-care devices, resource-limited areas, and real-time imaging of a sample in a large apparatus. In this study, we report a novel compact (10 cm × 5 cm × 5 cm, without the light source) lightweight (â¼0.5 kg) submicron-resolution inverted optical microscope at low cost (â¼$ 300). Our technique utilises the proximity of the image sensor to a commercial microscope objective lens for compactness of the microscope. The use of an image sensor with a small pixel size helps to reduce the information loss, which provides high-resolution images. Moreover, our technique offers a freedom to tailor the design of microscope according to the required resolution, cost, and portability for specific applications, which makes it a suitable candidate for affordable point-of-care devices. Images of several micron-to-submicron scale patterns and spherical beads are acquired to observe the resolution and quality of the images obtained using our microscope. In addition, we demonstrate the applications of our microscope in various fields such as recording of high-speed water microdroplet formation inside a microfluidic device, high-resolution live cell imaging inside an incubator, and real-time imaging of crack propagation in a sample under stretching by a material testing system (MTS). Therefore, this portable and inexpensive microscope provides the essential functionalities of a bulky expensive high-performance microscope at a lower cost. LAY DESCRIPTION: Microscope is an essential tool in research allowing for observation of microsized objects and life forms. Contemporary commercial high-resolution microscopes have long optical paths involving series of lenses and filters. Although this configuration precisely corrects for optical distortions and produces clear images, it makes modern microscopes very costly and bulky, restricting their usage to low-funded research laboratories and at remote places. We have developed a simple digital microscope with high-resolution but with much smaller size and lighter in weight at low cost by removing the long optical terrain. Our microscope consists of a commercial microscope objective lens for magnification and semiconductor image sensor with small pixels placed right after the lens, both of which are affordable and easily available. The small pixel size helps to translate the magnified analogue sample image to high-resolution digital image. In our paper, we show that our microscope can view micro and submicron-sized patterns and beads. Moreover, our fist-sized microscope can be placed inside an incubator for real-time imaging of cells or rotated sideways for recording submicron-sized crack generation due stretching of novel materials, both of which could not be accomplished with the 2 feet tall laboratory microscopes.
Assuntos
Desenho de Equipamento , Dispositivos Lab-On-A-Chip , Microscopia de Polarização/instrumentação , Animais , Escherichia coli/ultraestrutura , Fibroblastos/ultraestrutura , Holografia , Lentes , Camundongos , Microscopia de Polarização/métodos , Células NIH 3T3 , Oócitos/ultraestrutura , Peixe-ZebraRESUMO
Leishmania donovani, the causative parasite of Visceral Leishmaniasis (VL), deviously manipulates host monocytes/macrophages to ensure its survival. Although monocytes/macrophages from patients with VL have demonstrated an impaired oxidative burst and antigen presentation, an unanswered yet pertinent question remains as to whether they are deactivated or alternatively activated. The significantly raised plasma levels of IL-4/IL-13 and IL-10 in VL patients suggested a microenvironment conducive for alternative activation of monocytes/macrophages. Accordingly, the classical markers for IL-4-driven monocytes/macrophages [M(IL-4)] were studied namely intramonocytic CD206+ , circulating CCL22 and CCL17, and were unchanged. Furthermore, the mRNA expression of Kruppel-like factor 4 (KLF4), peroxisome proliferator-activated receptors (PPAR)-γ and arginase-I (ARG-I) in peripheral blood mononuclear cells was unaltered. However, markers for IL-10-driven monocytes/macrophages [M(IL-10)], namely soluble CD163, intramonocytic IL-10, and circulating CXCL13 were significantly increased. Monocytes/macrophages of patients with VL demonstrated an increased expression of markers for M(IL-10), along with the absence of markers for M(IL-4). Taken together, in human VL, manipulation of these IL-10 polarized monocytes-macrophages may pave the way for improved therapeutic outcomes.
Assuntos
Interleucina-10/análise , Leishmania donovani/imunologia , Leishmaniose Visceral/imunologia , Adulto , Idoso , Feminino , Humanos , Fator 4 Semelhante a Kruppel , Leishmaniose Visceral/parasitologia , Leucócitos Mononucleares/imunologia , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Explosão RespiratóriaRESUMO
Toll-like receptors (TLRs) are germline-encoded, non-clonal innate immune receptors, which are often the first receptors to recognize the molecular patterns on pathogens. Therefore, the immune response initiated by TLRs has far-reaching consequences on the outcome of an infection. As soon as the cell surface TLRs and other receptors recognize a pathogen, the pathogen is phagocytosed. Inclusion of TLRs in the phagosome results in quicker phagosomal maturation and stronger adaptive immune response, as TLRs influence co-stimulatory molecule expression and determinant selection by major histocompatibility complex (MHC) class II and MHC class I for cross-presentation. The signals delivered by the TCR-peptide-MHC complex and co-stimulatory molecules are indispensable for optimal T cell activation. In addition, the cytokines induced by TLRs can skew the differentiation of activated T cells to different effector T cell subsets. However, the potential of TLRs to influence adaptive immune response into different patterns is severely restricted by multiple factors: gross specificity for the molecular patterns, lack of receptor rearrangements, sharing of limited number of adaptors that assemble signalling complexes and redundancy in ligand recognition. These features of apparent redundancy and regulation in the functioning of TLRs characterize them as important and probable contributory factors in the resistance or susceptibility to an infection.
Assuntos
Leishmania/imunologia , Leishmaniose/imunologia , Receptores Toll-Like/imunologia , Imunidade Adaptativa , Animais , Apresentação Cruzada , Regulação da Expressão Gênica , Humanos , Imunidade Inata , Camundongos , Moléculas com Motivos Associados a Patógenos/imunologia , Fagocitose , Transdução de Sinais , Linfócitos T/imunologia , Linfócitos T/fisiologia , Receptores Toll-Like/classificação , Receptores Toll-Like/deficiência , Receptores Toll-Like/genéticaRESUMO
Itaconic acid (IA), an unsaturated 5-carbon dicarboxylic acid, is a building block platform chemical that is currently produced industrially from glucose by fermentation with Aspergillus terreus. Softwood has the potential to serve as low cost source of sugars for its production. Effective utilization of all softwood derived sugars such as glucose, mannose and galactose by the fungus for production of IA will lower the cost of its production. In this work, 20 A. terreus strains were evaluated for the first time for IA production from mannose and galactose in shake-flasks at initial pH of 3·1, 33°C and 200 rev min-1 for 7 days. Strain NRRL 1971 possesses the unique ability to produce high concentrations of IA from mannose. It produced 36·4 ± 0·2 g IA from 80 g mannose per litre with a yield of 0·46 g g-1 mannose (highest titre reported so far). This strain has the potential to be used for IA production from softwood. The maximum (1·1 ± 0·2 g) IA was produced by strain DSM 23081 from 80 g galactose per litre utilizing only 9·1 ± 0·3 g. Galactose was not suitable for IA production by these strains. This is the first detailed report on the production of IA from mannose and galactose. SIGNIFICANCE AND IMPACT OF THE STUDY: Itaconic acid (IA) is a building block platform chemical which is currently produced industrially from glucose by fermentation with Aspergillus terreus. In order to expand the use of IA, its production cost must be lowered. Softwood has the potential to serve as low cost source of sugars for its production. In this work, 20 A. terreus strains were evaluated for the first time for production of IA from mannose and galactose, sugars derived from softwood. A novel strain was found that gave the highest IA titre reported so far. Galactose was a poor substrate for IA production by A. terreus.
Assuntos
Aspergillus/metabolismo , Galactose/metabolismo , Manose/metabolismo , Succinatos/metabolismo , Fermentação , Glucose/metabolismo , Microbiologia Industrial/economia , Microbiologia Industrial/métodosRESUMO
Polyphenols can exert both, antioxidant and pro-oxidant properties, depending on cell types as well as their concentrations. Hence, it was of interest to examine if the naturally occurring resveratrol analog, trans-4,4'-dihydroxystilbene (DHS) also exert both these activities in a biphasic or cell-specific manner. In this study, we established the cytoprotective action of DHS against hydrogen peroxide (H2O2)-induced apoptotic death of the PC12 cells. DHS reduced mitochondrial membrane permeabilization and deactivated reactive oxygen species (ROS)-mediated caspase-3 activation in the H2O2-treated PC12 cells. However, it induced apoptosis in the human neuroblastoma SHSY-5Y cell line by destabilizing mitochondrial membrane, augmenting ROS and activating caspapse-3. DHS showed better activity than resveratrol in both the chosen models.
Assuntos
Apoptose/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estilbenos/farmacologia , Animais , Sobrevivência Celular , Humanos , Peróxido de Hidrogênio , Células PC12 , Ratos , Espécies Reativas de OxigênioRESUMO
Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns and results in innate immune system activation that results in elicitation of the adaptive immune response. One crucial modulator of the adaptive immune response is CD40. However, whether these molecules influence each other's expression and functions is not known. Therefore, we examined the effects of TLRs on CD40 expression on macrophages, the host cell for the protozoan parasite Leishmania major. While polyinosinic-polycytidylic acid [poly (I:C)], a TLR-3 ligand, lipopolysaccharide (LPS), a TLR-4 ligand, imiquimod, a TLR-7/8 ligand and cytosine-phosphate-guanosine (CpG), a TLR-9 ligand, were shown to enhance CD40 expression, CD40 stimulation enhanced only TLR-9 expression. Therefore, we tested the synergism between CD40 and CpG in anti-leishmanial immune response. In Leishmania-infected macrophages, CpG was found to reduce CD40-induced extracellular stress-regulated kinase (ERK)1/2 activation; with the exception of interleukin (IL)-10, these ligands had differential effects on CD40-induced IL-1α, IL-6 and IL-12 production. CpG significantly enhanced the anti-leishmanial function of CD40 with differential effects on IL-4, IL-10 and interferon (IFN)-γ production in susceptible BALB/c mice. Thus, we report the first systematic study on CD40-TLR cross-talk that regulated the experimental L. major infection.
Assuntos
Antígenos CD40/imunologia , Expressão Gênica/imunologia , Leishmania major/imunologia , Macrófagos/imunologia , Receptor Toll-Like 9/imunologia , Aminoquinolinas/imunologia , Aminoquinolinas/farmacologia , Animais , Western Blotting , Antígenos CD40/genética , Antígenos CD40/metabolismo , Células Cultivadas , MAP Quinases Reguladas por Sinal Extracelular/imunologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Citometria de Fluxo , Expressão Gênica/efeitos dos fármacos , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/imunologia , Imiquimode , Leishmania major/fisiologia , Lipopolissacarídeos/imunologia , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , Macrófagos/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Oligodesoxirribonucleotídeos/imunologia , Oligodesoxirribonucleotídeos/farmacologia , Fosforilação/efeitos dos fármacos , Fosforilação/imunologia , Receptor Cross-Talk/efeitos dos fármacos , Receptor Cross-Talk/imunologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/metabolismo , Receptores Toll-Like/genética , Receptores Toll-Like/imunologia , Receptores Toll-Like/metabolismoRESUMO
Application of Zn @ 0, 5.5 kg, 22 kg Zn ha(-1), 0.1% Zn foliar application, 5.5 kg Zn + 0.1% Znspray, increased the yield, concentration and its uptake in seed and straw in all the green gram genotypes. However, combined application of 5.5 kg Zn ha(-1) + 0.1% Zn as foliar increased the straw yield by 56.4% and seed yield by 57%, which was the highest. Maximum Zn concentration in straw and seed (5.48 and 3.5 folds over control) was achieved when combined application of soil + foliar was made. Soil + foliar application of Zn increased the seed crude protein by 26.9% over control. Seed and straw Zn content showed a significant and positive correlation with all yield attributes except branches per plant.
Assuntos
Biomassa , Fabaceae/metabolismo , Alimentos Fortificados , Sementes/metabolismo , Zinco/metabolismo , Fabaceae/crescimento & desenvolvimento , Fertilizantes , Zinco/administração & dosagemRESUMO
Childhood diarrhoea is a major public health problem in developing countries like Bangladesh which is commonly caused by intestinal infection, mainly viral. Diarrhoea is causing second leading mortality in children below 5 years, where about 2 billion cases occur globally in each year. This study was proposed to evaluate the antimicrobials utilization pattern prescribed for AWD in children below 5 years of age, in a tertiary care hospital in Bangladesh. This record based, cross-sectional, descriptive type of observational study carried out at pharmacology department of Mymensingh Medical College. A total of 205 diarrhoeal patient's up to 5 years of age, attending the paediatric OPD from January 2021 to December 2021, were enrolled in the study. Out of 205 patients 182(88.8%) were prescribed antimicrobials. Azithromycin was the most frequently prescribed antimicrobial (60.0%) and among the antiprotozoals metronidazole was the prescribed most (24.9%). ORS and Zinc were prescribed in all patients (100%). Empirical excessive use of antibiotics was observed in this study. Emphasis on educational and training programs may help in a better and judicious use of drugs in children.
Assuntos
Anti-Infecciosos , Pacientes Ambulatoriais , Humanos , Anti-Infecciosos/uso terapêutico , Bangladesh , Estudos Transversais , Diarreia/tratamento farmacológico , Centros de Atenção Terciária , Lactente , Pré-EscolarRESUMO
Chronic obstructive pulmonary disease (COPD) remains a major public health problem with relatively high prevalence rates worldwide (5-13%). COPD is a major cause of morbidity and mortality worldwide and results in an economic and social burden that is both substantial and increasing. The purpose of the study was to explore the alteration of serum calcium in patients with COPD. This cross-sectional study was carried out in the Department of Biochemistry, Mymensingh Medical College, Bangladesh from January 2021 to December 2021. Data was collected from Medicine Department of Mymensingh Medical College Hospital, Mymensingh. A total number of 120 subjects participated in this study. Out of them, 60 apparently normal healthy individuals were selected as Group I and another 60 diagnosed COPD patients were selected as Group II. Serum calcium was measured by colorimetric method using the test kit. The results were calculated and analyzed by using statistical package for social science (SPSS), windows package version 21.0. Data were expressed in mean ±SD and statistical significance was done by Student's unpaired 't' test. In this study, the mean ±SD values of serum calcium were 9.21±1.06mg/dl and 8.26±0.95mg/dl in Group I and Group II respectively. The results were highly significant (p<0.001). The result suggested that there was significant relation between COPD and alteration of serum calcium. So, by this study we recommended that routine evaluation of serum calcium is important for prevention of exacerbations, reduction of morbidity and mortality in patients with COPD.
Assuntos
Cálcio , Doença Pulmonar Obstrutiva Crônica , Humanos , Estudos Transversais , Estudos de Casos e Controles , Bangladesh/epidemiologiaRESUMO
Breast cancer stands as the prevailing invasive cancer globally, bearing high mortality rates among women. Existing evidence indicates diminished survival rates in younger patients. Consequently, this study endeavors to assess and contrast the pathological features of breast cancer in women under 40 years of age with their older counterparts. Conducted as a cross-sectional analysis, this study encompasses 560 patients diagnosed with breast cancer, seeking treatment at Mymensingh Medical College Hospital (MMCH), Community Based Medical College Bangladesh (CBMCB) and several private hospitals in Mymensingh. The gathered data incorporates information such as age, residential area, occupation, tumor histopathology, TNM classification, staging and status of hormone receptor. The patients' mean age (standard deviation) was 49.7±11.9 years, with 20.5% below 40, most were from rural areas and were housewives. Ductal carcinoma prevailed as the most common histopathologic type (87.67%). However, younger patients exhibited a higher prevalence of lobular and other rare carcinomas compared to their older counterparts (p=0.04). Additionally, the younger group demonstrated larger tumor sizes (p=0.01), lymphatic node involvement (p=0.04) and advanced staging (p=0.004). Notably, younger age showed more negativity for estrogen and/or progesterone receptors. The results suggested that women under 40 years old exhibit more aggressive tumor characteristics and a more severe form of breast cancer compared to their older counterparts.
Assuntos
Neoplasias da Mama , Carcinoma Ductal de Mama , Humanos , Feminino , Idoso , Adulto , Pessoa de Meia-Idade , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Estudos Transversais , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/terapia , Estadiamento de Neoplasias , EstrogêniosRESUMO
Two different Toll-like receptors (TLRs) have been shown to play a role in host responses to Leishmania infection. TLR-2 is involved in parasite survival in macrophages upon activation by lipophosphoglycan (LPG), a virulence factor expressed by Leishmania. In contrast, activation of TLR-9 has been shown to promote a host-protective response. However, whether there is a relationship between the interaction of LPG and TLR-2, on one hand, with the effect of TLR-9, on the other hand, remains unknown. In this study, we report that in-vitro infection of macrophages with a L. major parasite with high expression levels of LPG results in decreased TLR-9 expression compared to infection with a L. major parasite with lower expression levels of LPG. Addition of anti-LPG as well as anti-TLR-2 antibodies prevents this reduction of TLR-9 expression. Also, the addition of purified LPG to macrophages results in a decrease of TLR-9 expression, which is shown to be mediated by transforming growth factor (TGF)-ß and interleukin (IL)-10. Finally, in-vitro treatment of macrophages with anti-LPG and/or anti-TLR-2 antibodies before infection reduces the number of amastigotes in macrophages and co-treatment of mice with anti-TLR-2 antibodies and cytosine-phosphate-guanosine (CpG) reduces footpad swelling and parasite load in the draining lymph nodes, accompanied by an interferon (IFN)-γ-predominant T cell response. Thus, for the first time, we show how interactions between LPG and TLR-2 reduce anti-leishmanial responses via cytokine-mediated decrease of TLR-9 expression.
Assuntos
Glicoesfingolipídeos/imunologia , Leishmania major/imunologia , Leishmania major/patogenicidade , Receptor 2 Toll-Like/metabolismo , Receptor Toll-Like 9/metabolismo , Animais , Ilhas de CpG/imunologia , Expressão Gênica , Glicoesfingolipídeos/genética , Interações Hospedeiro-Parasita/genética , Interações Hospedeiro-Parasita/imunologia , Tolerância Imunológica , Interleucina-10/genética , Interleucina-10/metabolismo , Leishmania major/genética , Leishmaniose Cutânea/genética , Leishmaniose Cutânea/imunologia , Leishmaniose Cutânea/parasitologia , Leishmaniose Cutânea/terapia , Ativação de Macrófagos , Macrófagos/imunologia , Macrófagos/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Receptor 2 Toll-Like/antagonistas & inibidores , Receptor 2 Toll-Like/genética , Receptor Toll-Like 9/genética , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Virulência/imunologiaRESUMO
Through their receptors, prostaglandins play crucial roles in various infections. Although prostaglandin E2 (PGE2) is implicated as a susceptibility factor in Leishmania infection, the relative contributions of its four receptors--EP1, EP2, EP3 and EP4--to this infection remain unknown. We report that Leishmania major infection of BALB/c-derived peritoneal macrophages up-regulated EP1 and EP3 expressions but down-regulated EP2 and EP4 expressions. EP2 and EP4 agonists reduced parasite load, but EP1 and EP3 agonists increased parasite load in macrophages in vitro. Agonists of EP2 and EP4, antagonists of EP1 and EP3, or lentivirally expressed EP1-shRNA and EP3-shRNA significantly reduced parasite burden in susceptible BALB/c mice. These novel data suggest differential regulation and counteractive functions of EP receptor subsets.
Assuntos
Leishmania major/fisiologia , Leishmaniose Cutânea/imunologia , Macrófagos Peritoneais/imunologia , Receptores de Prostaglandina E/imunologia , Animais , Leishmaniose Cutânea/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Carga Parasitária , RNA Interferente Pequeno , Receptores de Prostaglandina E/agonistas , Receptores de Prostaglandina E/antagonistas & inibidores , Receptores de Prostaglandina E/classificaçãoRESUMO
BACKGROUND: Systemic candidiasis is an important nosocomial infection in neonatal intensive care units. The objective of this study was to identify the change in the profile of neonatal candidiasis in a tertiary neonatal intensive care unit (NICU) in eastern India in recent times. METHODS: It was a retrospective review of case records from 2014 to 2019 from a tertiary NICU of eastern India. Data of the fungal sepsis, demographic details, risk factors of fungal sepsis and mortality were collected from 103 neonates. RESULTS: One hundred and three neonates had blood culture positive for fungal species of which 91 (88.3%) infants weighed ≥1500âg and 66 (64%) infants were term. There was significant higher incidence of candidiasis among outborn (Relative risk of outborn 18.84, 95% CI 10.74-33.05). Prolonged antibiotic usage (>14 days), meropenem usage (>5 days), central catheterization (>5 days), invasive mechanical ventilation (>5 days), surgical intervention were found in 64 (62.1%), 46 (44.6%), 31(30.0%), 40 (38.8%) and 39 (37.8%) infants. Non albicans candida (NAC) was isolated as the predominant species (82/103, 79.6%). Resistance to both of fluconazole and amphotericin B were found in 19 (18.4%) babies. Presence of NAC infection and resistance to both amphotericin B and fluconazole were independent predictors of candida associated mortality in NICU. CONCLUSION: Neonatal candidiasis is found among outborn infants with higher birth weight and gestational age. NAC species are predominant organisms with resistance to common antifungal drugs.
RESUMO
Evaluation of the in vitro antibacterial activity of Chloroform extracts isolated from Henna (Lawsonia inermis) leaf against two food born & nosocomial infection causing pathogens, gram-positive Staphylococcus aureus and gram-negative Escherichia coli. This interventional study was carried out during the period of January 2021 to December 2021 in the Department of Pharmacology and Therapeutics in collaboration with the Department of Microbiology, Mymensingh Medical College, Mymensingh, Bangladesh. The antibacterial activity was tested at different concentrations of Chloroform Henna leaf extracts by using disc diffusion and broth dilution method. The extract was prepared by using solvents chloroform and 0.1% DMSO. The test microorganisms were also tested for their activity against a standard antibiotic Ciprofloxacin by broth dilution method and the result was compared with that of Chloroform extracts. Chloroform Henna Extracts (CHE) were used initially in nine different concentrations (2.5, 5, 10, 20, 50, 100, 200, 500 and 1000mg/ml) and later in selected concentrations as needed to confirm the more precise margin of antimicrobial sensitivity of the extracts. Among different concentrations of the CHE, 100mg/ml and above concentrations showed inhibitory effect against Staphylococcus aureus and 300mg/ml and above concentrations showed inhibitory effect against Escherichia coli. The MIC for Staphylococcus aureus and Escherichia coli were 100 and 350mg/ml in CHE respectively. The MIC of Ciprofloxacin was 1µg/ml against both Staphylococcus aureus and Escherichia coli. The MIC of Ciprofloxacin was the lowest in comparison to MICs of CHE for the test organisms. The present study showed that Chloroform Henna extracts demonstrated antibacterial effects against food borne pathogens. From this study, it is clearly observed that there is definite antibacterial effect of the chloroform extract of Henna leaves against Staphylococcus aureus and Escherichia coli.
Assuntos
Infecção Hospitalar , Lawsonia (Planta) , Humanos , Clorofórmio/farmacologia , Staphylococcus aureus , Escherichia coli , Extratos Vegetais/farmacologia , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , Ciprofloxacina/farmacologiaRESUMO
Chronic obstructive pulmonary disease (COPD) remains a major public health problem with relatively high prevalence rates worldwide (5.0-13.0%). COPD is a major cause of morbidity and mortality worldwide and results in an economic and social burden that is both substantial and increasing. The purpose of the study was to explore the relationship of biochemical alterations of serum magnesium and uric acid with frequent exacerbations, hypoxia, increase hospital stay, morbidity and mortality in patients with COPD. This cross-sectional study was carried out in the Department of Biochemistry, Mymensingh Medical College, Bangladesh from January 2021 to December 2021. Data was collected from Medicine Department of Mymensingh Medical College Hospital, Bangladesh. A total number of 120 subjects participated in this study. Out of them, 60 apparently normal healthy individuals were selected as Group I and another 60 diagnosed COPD patients were selected as Group II. The results were calculated and analyzed by using statistical package for social science (SPSS), windows package version 21.0. Serum magnesium was measured by photoelectric colorimetric method using the test kit and serum uric acid was measured by enzymatic colorimetric method using the test kit. Data were expressed in mean±SD and statistical significance of different parameter was done by Pearson's correlation co-efficient test. The mean±SD values of serum magnesium were 2.15±0.29mg/dl and 1.54±0.30mg/dl in Group I and Group II respectively. Result was statistically highly significant (p<0.001). The mean±SD values of serum uric acid were 5.43±2.05mg/dl and 6.86±1.61mg/dl in Group I and Group II respectively. Result was statistically highly significant (p<0.001). Pearson's correlation coefficient test showed that there was significant (p=0.001) negative correlation (r= -0.415) found between serum magnesium and serum uric acid in study group. In this study, the result suggested that there was significant relation between COPD exacerbations and alteration of these biochemical parameters. So, by this study we recommended that routine evaluation of these parameters is important for prevention of exacerbations, reduction of morbidity and mortality in patients with COPD.
Assuntos
Doença Pulmonar Obstrutiva Crônica , Ácido Úrico , Humanos , Magnésio , Estudos Transversais , Estudos de Casos e Controles , BangladeshRESUMO
Evaluation of the in vitro antibacterial activity of Methanol extracts isolated from Henna (Lawsonia inermis) leaf against two food born infection causing pathogens, gram-positive Staphylococcus aureus and gram-negative Klebsiella pneumoniae. This interventional study was carried out in the Department of Pharmacology and Therapeutics in collaboration with the Department of Microbiology, Mymensingh Medical College, Bangladesh from January 2021 to December 2021. The antibacterial activity was tested at different concentrations of Methanol Henna leaf extracts by using disc diffusion and broth dilution method. The extract was prepared by using solvents Methanol and 0.1% dimethyl sulfoxide (DMSO). The test microorganisms were also tested for their activity against a standard antibiotic Ciprofloxacin by broth dilution method and the result was compared with that of Methanol extracts. Methanol Henna Extracts (MHE) were used initially in nine different concentrations (2.5, 5, 10, 20, 50, 100, 200, 500 and 1000mg/ml) and later in selected concentrations as needed to confirm the more precise margin of antimicrobial sensitivity of the extracts. Among different concentrations of the MHE, 100mg/ml and above concentrations showed inhibitory effect against afore said bacteria. The MIC for Staphylococcus aureus and Klebsiella pneumoniae were 100mg/ml in MHE. The MIC of Ciprofloxacin was 1µg/ml against Staphylococcus aureus and 1.5µg/ml for Klebsiella pneumoniae. The MIC of Ciprofloxacin was the lowest in comparison to MICs of MHE for the test organisms. This study showed that Methanol Henna extracts demonstrated antibacterial effects against pathogens. From this study, it is clearly observed that there is definite antibacterial effect of the methanolic extract of Henna leaves (Lawsonia inermis) against Staphylococcus aureus and Klebsiella pneumoniae.
Assuntos
Lawsonia (Planta) , Metanol , Humanos , Metanol/farmacologia , Staphylococcus aureus , Klebsiella pneumoniae , Antibacterianos/farmacologia , Ciprofloxacina/farmacologia , Testes de Sensibilidade Microbiana , Extratos Vegetais/farmacologiaRESUMO
Evaluation of the in vitro antibacterial activity of Methanolic extracts isolated from Henna (Lawsonia inermis) leaf against two nosocomial infection causing pathogens, gram-positive Staphylococcus aureus and gram-negative Escherichia coli. This interventional study was carried out during the period of January 2021 to December 2021 in the Department of Pharmacology and Therapeutics in collaboration with the Department of Microbiology, Mymensingh Medical College, Mymensingh, Bangladesh. The antibacterial activity was tested at different concentrations of Methanolic Henna leaf extracts by using disc diffusion and broth dilution method. The extract was prepared by using solvents Methanol and 0.1% DMSO (Dimethyl sulfoxide). The test microorganisms were also tested for their activity against a standard antibiotic Ciprofloxacin by broth dilution method and the result was compared with that of Methanolic leaf extracts. Methanolic Henna leaf Extracts (MHE) were used initially in nine different concentrations (2.5, 5, 10, 20, 50, 100, 200, 500 and 1000 mg/ml) and later in selected concentrations as needed to confirm the more precise margin of antimicrobial sensitivity of the extracts. Among different concentrations of the MHE, 100mg/ml and above concentrations showed inhibitory effect against aforesaid bacteria. The MIC for Staphylococcus aureus and Escherichia coli were 100 and 200 mg/ml in MHE respectively. The MIC of Ciprofloxacin was 1µg/ml against both Staphylococcus aureus and Escherichia coli. The MIC of Ciprofloxacin was the lowest in comparison to MICs of MHE for the test organisms. The present study showed that Methanol Henna extracts demonstrated antibacterial effects against nosocomial infection pathogens. From this study, it is clearly observed that there are definite antibacterial effects of the methanolic extract of Henna leaves (Lawsonia inermis) against Staphylococcus aureus and Escherichia coli.