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Objectives: Acute Lymphoblastic Leukemia (ALL) is a multifactorial disease that results from the interaction between multiple genetic factors. ALL is characterized by uncontrolled production of hematopoietic precursor cells of the lymphoid progenitors within the bone marrow. The development of hematological malignancies has been associated with malignant-like cells that express low levels of immunogenic surface molecules, thus, facilitating their escape from cellular antineoplastic immune responses. This risk may be partly influenced by variations in polymorphic genes that control immune function and regulation. Toll-like receptors (TLRs) are well known pattern recognition receptors playing key role in innate immune response. Abnormal expression and dysregulation of TLRs will provide an opportunity for cancer cells to escape from the immune system and enhance their proliferation and angiogenesis. Toll-like receptor 2 (TLR2) play an essential role in innate immunity. Single nucleotide polymorphisms (SNPs) are present in a number of TLR genes and have been associated with various disorders. Methods: In this study, 265 subjects have been divided into two groups included 150 patients with ALL and115 healthy volunteers. All subjects were genotyped using TaqMan PCR techniques. In total, Five SNPs were statistically evaluated in the TLR2 (rs1898830 A/G, rs3804099 T/C, rs3804100 T/C, rs1339 T/C, and rs1337 C/G), which may influence the susceptibility of ALL. Minor allele frequency and genotype distribution were compared across the study groups, and the relative risk and differences between patients and controls were estimated. Moreover, the mRNA expression level was evaluated in patients with ALL and the matched healthy individuals by Real-Time Quantitative Reverse Transcription PCR (qRT-PCR). Results: TLR2 rs1898830 A/G; rs3804099 T/C; rs3804100 T/C; rs1339 T/C, were significantly decrease the risk in our population, overall and for certain subtypes and ALL samples exhibited significant increase in the mRNA levels of TLR2. Conclusions: This study shows that TLR2 could be an independent prognostic factor of ALL risks in the Saudi population. Suggesting that genetic variation in genes associated with an immune response may be important in the etiology of ALL. In addition, the results herein revealed that TLR2 overexpression is associated with ALL and has diverse biological significance in the context of the complex relationship between inflammation and cancer development. Therefore, these data could open further studies to explore the possible clinical relevance of TLRs as pathological markers for Leukemia and enhance the strategies regarding hematological malignancies prevention based on their gene expression.
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Parasitic diseases are a serious global health concern, causing many common and severe infections, including Chagas disease, leishmaniasis, and schistosomiasis. The NLRP3 inflammasome belongs to the NLR (nucleotide-binding domain leucine-rich-repeat-containing proteins) family, which are cytosolic proteins playing key roles in the detection of pathogens. NLRP3 inflammasomes are activated in immune responses to Plasmodium, Leishmania, Toxoplasma gondii, Entamoeba histolytica, Trypanosoma cruzi, and other parasites. The role of NLRP3 is not fully understood, but it is a crucial component of the innate immune response to parasitic infections and its functions as a sensor triggering the inflammatory response to the invasive parasites. However, while this response can limit the parasites' growth, it can also result in potentially catastrophic host pathology. This makes it essential to understand how NLRP3 interacts with parasites to initiate the inflammatory response. Plasmodium hemozoin, Leishmania glycoconjugate lipophosphoglycan (LPG) and E. histolytica Gal/GalNAc lectin can stimulate NLRP3 activation, while the dense granule protein 9 (GRA9) of T. gondii has been shown to suppress it. Several other parasitic products also have diverse effects on NLRP3 activation. Understanding the mechanism of NLRP3 interaction with these products will help to develop advanced therapeutic approaches to treat parasitic diseases. This review summarizes current knowledge of the NLRP3 inflammasome's action on the immune response to parasitic infections and aims to determine the mechanisms through which parasitic molecules either activate or inhibit its action.
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Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Inflamassomos/metabolismo , Inflamassomos/imunologia , Animais , Doenças Parasitárias/imunologia , Doenças Parasitárias/parasitologia , Doenças Parasitárias/metabolismo , Imunidade InataRESUMO
The specific arrangement and distribution of photoreceptors in the retina can vary among different fish species, with each species exhibiting adaptations related to its habitat, behavior, and visual requirements. Poecilia sphenops, a diurnal fish, was the focus of this study. The retinas of a total of eighteen Molly fish were investigated utilizing light and electron microscopy. The retina exhibited a square mosaic pattern of the inner segments of cones. This pattern comprised double cones positioned along the sides of a square, with two types of single cones situated at the center and corners of the square arrangement across the entire retina. The corner cones were slightly shorter than the central ones. Additionally, the outer plexiform layer contained both cone pedicles and rod spherules. The rod spherule consisted of a single synaptic ribbon arranged in a triad or quadrat junctional arrangement within the invaginating free ends of the horizontal and bipolar cell processes. On the other hand, cone pedicles have more than one synaptic ribbon in their junctional complex. The inner nuclear layer consisted of the amacrine, bipolar, Müller, and horizontal cell bodies. Müller cell processes, expressing GFAP, extended across all retinal layers, segmenting the deeper retina into alternating fascicles of optic axons and ganglion cells. The outer and inner plexiform layers showed many astrocyte cell processes expressing GFAP. In conclusion, the current study is the first record of the retinal structures of Molly fish. This study illustrated the mosaic arrangement of photoreceptors and GFAP expression patterns of astrocytes and Müller cells. The presence of three cone types, coupled with a sufficient number of rods, likely facilitates motion awareness for tasks like finding food and performing elaborate mating ceremonies.
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In poultry nutrition, zinc supplementation is typically achieved through the addition of zinc oxide or zinc sulfate to the feed. The alternative approach of organic sources utilizes an organic ligand to bind zinc (Zn), resulting in higher bioavailability. Thus, a study was conducted to assess and compare the impact of a methionine-complexed Zn versus an inorganic Zn on growth, blood biochemical profile, gut histomorphology, and fecal excretion of Zn in broilers. The experimental design included two treatments: the addition of a zinc amino acid complex or zinc oxide to the basal diet. The zinc amino acid complex was supplemented at a dose equivalent to the inorganic zinc (Zn-80), while the organic zinc was provided at levels of 20, 40, and 80 mg/kg to a total of 400 broilers. There were five treatments in total, and each treatment was replicated four times. Broilers supplemented with an organic form of Zn at the level of 80 mg/kg had significantly (p < 0.05) higher body weight gain and lower feed conversion ratio (F/G). Significantly (p < 0.05) higher Zn excretion was recorded in broilers supplemented with inorganic Zn supplementation. Significantly (p < 0.05) higher villus length and width, their ratio, and lower (p < 0.05) crypt depth were observed in birds supplemented with 80 mg/kg organic Zn. From the results of the present study, it was concluded that Zn from an organic source at the rate of 80 mg/kg was superior in terms of growth performance, intestinal histomorphology and less excretion of Zn to the environment in broilers.
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Óxido de Zinco , Zinco , Animais , Zinco/farmacologia , Zinco/química , Zinco/metabolismo , Galinhas/metabolismo , Óxido de Zinco/metabolismo , Suplementos Nutricionais , Dieta/veterinária , Metionina/metabolismo , Metionina/farmacologia , Ração Animal/análiseRESUMO
To date, no study has reported the anticoccidial effect of lemon peel powder in broilers. Coccidiosis, caused by Eimeria species, is the prevalent enteric parasitic disease in poultry. Although certain chemical drugs have been used for their control, concerns regarding drug residues and the development of resistance in chickens have arisen among consumers. In this study, a total of 300 Ross 308 broiler chicks were randomly allocated into five groups (five equal replicates of 12 animals). The first group served as the control and did not receive any specific treatment (NC). The second group, referred to as the positive control (PC) group, was deliberately exposed to Eimeria tenella. The third group was challenged with E. tenella and also received treatment with amprolium (1 g/kg) and was designated as AT. The fourth and fifth groups were challenged with E. tenella and simultaneously supplemented with lemon peel powder at a dosage of 3 g/kg (LPP3) and 6 g/kg (LPP6). Sporulated E. tenella oocysts (5 × 104/mL bird) on day 22 of the experiment were administered to the infected broiler chickens. The results indicated that in comparison with the NC, all Eimeria-treated birds exhibited significantly (p < 0.05) lower growth performance. However, a notable improvement was observed when infected birds also received a supplement of LPP3 and LPP6 in their feed. Both LPP3 and LPP6 supplementation significantly (p < 0.05) reduced mortality, lesion scores, and oocyst per gram (OPG) of feces compared with the PC group. Additionally, the histological features of the cecum revealed that villus height, villus width, and crypt depth were partially restored under supplementation with LPP3 and LPP6 in the infected birds. Overall, the results demonstrate that Eimeria-infected birds supplemented with LPP3 and LPP6 exhibited improved growth performance, reduced OPG, lowered intestinal coccidiosis lesion scores, and enhanced intestinal histological features.
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Grape by-products represent outstanding alternatives to replace conventional and unsustainable feed sources, given the substantial quantities generated annually by the winery industry. Regrettably, the majority of these by-products are wasted, resulting in significant environmental and economic repercussions. This study was conducted to assess the growth performance, feed efficiency, egg production and quality, lipid peroxidation, fertility and hatchability of reproductive laying hens during their early production stage. A total of 720 golden laying hens, all approximately 25 weeks old and with similar body weights, were randomly assigned to four experimental treatments (six replicates) as follows: control group receiving only the standard diet, (2) a group receiving the standard diet supplemented with grape seed extract at a rate of 250 g/kg (GSE1), (3) a group receiving the standarddiet supplemented with grape seed extract at a rate of 500 g/kg (GSE2), and (4) a group receiving the standarddiet supplemented with grape seed extract at a rate of 750 g/kg (GSE3). There were no significant change (p > 0.05) in feed intak, body weight gain and feed conversion ratio between the control and the experimental groups. Egg weight, egg shell thickness and egg shell weight were significantly (p < 0.05) higher in GSE250 GSE500 and GSE750 compared to the control. The results showed that hen day egg production was also significantly higher (p < 0.05) in GSE500 and GSE 750 compared to the control. Fertility level of GSE 500 and GSE750 was significantly (p < 0.5) higher compared to the control. The MDA level decreased significantly (p < 0.05) in the GSE supplemented birds compared to the control. From these findings, we concluded that GSE 750 had positive impact on egg production, reducing lipid peroxidation and improving fertility in golden laying hens.
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Extrato de Sementes de Uva , Vitis , Animais , Feminino , Dieta/veterinária , Galinhas , Extrato de Sementes de Uva/farmacologia , Peroxidação de Lipídeos , Óvulo , Suplementos Nutricionais , Fertilidade , Ração Animal/análiseRESUMO
Herein, we evaluated the in vivo effects of meloxicam and curcumin co-encapsulated PLGA nanoparticles in experimental acute models of pyrexia, nociception, and inflammation. Seven groups (n = 6) were designed for each investigation and pretreated intraperitoneally (i.p.): the control group, meloxicam (4 mg/kg b.w.), curcumin (15 mg/kg b.w.), and equivalent content containing PLGA capped nanoparticles of meloxicam (Mlx-NP) and curcumin (Cur-NP) alone and in combination (Mlx-Cur-NP; at two doses). The results showed that PLGA encapsulation significantly (p ≤ 0.05) improved the in vivo activities of each compound. Furthermore, co-encapsulation of meloxicam and curcumin potentiated the anti-pyretic effect on yeast-induced pyretic rats, anti-nociceptive effect on nociception induced in rats by formalin and heat, and anti-edematogenic activity in xylene-induced ear edema in rats in a dose-dependent manner. In carrageenan-induced paw inflammation in rats, meloxicam and curcumin co-loading (Mlx-Cur-NP) resulted in significant (p ≤ 0.05) inhibition of paw inflammation, reduction in TNF-α and PGE2 levels, downregulation of expressions of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6), as well as a decrease in histopathological changes and TNF-α immunoexpression in paw tissues. Moreover, Mlx-Cur-NP demonstrated noteworthy potentiation in pharmacological effects compared to free compounds and mono-compound-loaded nanoparticles. Thus, the association of meloxicam with curcumin in a biodegradable nanocarrier system could provide a promising anti-pyretic, anti-nociceptive, and anti-inflammatory therapeutic approach for acute conditions.
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Owing to their surface active properties, surfactants have numerous applications in different fields of life. In the present research work, the solubilization of reactive red 2 (RR2) has been studied in single and mixed micellar systems (MMS) using UV-visible spectroscopy and electrical conductivity measurements. The interaction of RR2 with ionic micelles of cetylpyridinium chloride (CPC) was investigated. In order to probe the interaction of RR2 in MMS, mixtures of CPC and TX-114 (Triton X-114, a nonionic surfactant) were used. UV-visible spectroscopy has been used to obtain the degree of solubilization of RR2 in terms of the partition coefficient (Kc) and Gibbs free energy of partitioning (ΔG°p). Electrical conductivity data have been employed to detect the critical micelle concentration (CMC) of the surfactant systems in the presence of RR2 and, accordingly, to calculate the thermodynamic parameters of the micellization. From the obtained data, it is concluded that the micellization is spontaneous at all studied temperatures. Moreover, the micellization was observed to be driven by both enthalpy and entropy. The results also indicated that MMS have better solubilizing power than single micellar solutions.
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Cancer-testis (CT) genes are typically expressed in the testes; however, they have been linked to aberrant expression in a variety of malignancies. MAGE-B family genes are an example of CT genes. Therefore, the overarching objective of this study was to examine the expressions of MAGE-B family genes in several patients with colon cancer (CC) to see if they might be employed as cancer biomarkers in the early phases of cancer detection and to improve treatment. In this investigation, RT-PCR was used to analyze MAGE-B family genes in neighboring normal colon (NC) tissue from 10 CC patients. In addition, the effect of DNA demethylation on the expression status of the MAGE-B1 gene was evaluated by RT-PCR in HCT116 and Caco-2 cells and by qRT-PCR for HCT116 only after treating both CC cell lines with varying concentrations of 5-aza-2'-deoxycytidine (1.0, 5.0, and 10.0 µM) for 48 or 72 hours. All MAGE-B family genes except for MAGE-B1 showed weak bands in several samples of NC tissues: MAGE-B2, MAGE-B3, MAGE-B4, MAGE-B5, and MAGE-B6 genes were observed in 40%, 50%, 40%, 30%, and 60% of the NC samples, respectively. Nonetheless, they had strong bands in multiple samples of CC tissues, with 70%, 90%, 60%, 50%, and 90% of the CC samples, respectively. Interestingly, MAGE-B1 was detected in 60% of CC tissues but not in NC tissues, suggesting that it is a potential biomarker for early CC detection. MAGE-B1 expression was not observed in either untreated or DMSO-treated HCT116 cells after 48 or 72 hours of treatment. However, according to the RT-PCR and qRT-PCR results, the MAGE-B1 gene was overexpressed in the HCT116 cells treated with three different concentrations of 5-aza-2'-deoxycytidine. This shows that demethylation plays a crucial role in MAGE-B1 expression activation.
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Antígenos de Neoplasias , Neoplasias do Colo , Antígenos de Neoplasias/genética , Células CACO-2 , Neoplasias do Colo/genética , Decitabina/farmacologia , Humanos , Masculino , Proteínas de Neoplasias/genéticaRESUMO
Studies indicate that female mice are more susceptible to T. gondii infection, as defined by higher mortality rates in comparison to male mice. However, whether this is due to an inability to control initial parasite multiplication or due to detrimental effects of the immune system has not been determined. Therefore, the following studies were undertaken to determine the influence of sex on early parasite multiplication and the immune response during T. gondii infection and to correlate this with disease outcome. Early parasite replication was studied through applying an in vivo imaging system (IVIS) with luciferase expressing T. gondii. In parallel immunological events were studied by cytometric bead array to quantify key immunological mediators. The results confirmed the previous findings that female mice are more susceptible to acute infection, as determined by higher mortality rates and weight loss compared with males. However, conflicting with expectations, female mice had lower parasite burdens during the acute infection than male mice. Female mice also exhibited significantly increased production of Monocyte Chemoattractant Protein-1 (MCP-1), Interferon (IFN)-γ, and Tumour Necrosis Factor (TNF)-α than male mice. MCP-1 was found to be induced by T. gondii in a dose dependent manner suggesting that the observed increased levels detected in female mice was due to a host-mediated sex difference rather than due to parasite load. However, MCP-1 was not affected by physiological concentration of estrogen or testosterone, indicating that MCP-1 differences observed between the sexes in vivo are due to an as yet unidentified intermediary factor that in turn influences MCP-1 levels. These results suggest that a stronger immune response in female mice compared with male mice enhances their ability to control parasite replication but increases their morbidity and mortality.