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BACKGROUND: Systemic lupus erythematosus is a multisystemic rheumatic disease with different clinical features. Disturbance in apoptosis regulation seems to be a major factor in SLE development. OBJECTIVE: Survivin plays a key role in mitosis and inhibiting apoptosis. A study was conducted to examine the expression level of survivin and miRNAs that affect survivin transcript levels in patients with SLE. METHODS: We isolated peripheral blood mononuclear cells from 50 inactive SLE patients and 50 healthy controls. RNA is extracted and converted to cDNA. The quantitative real-time polymerase chain reaction is conducted to assess the expression levels of survivin total and its variants with effective miRNAs in PBMCs. RESULTS: Expression levels of miR-34a-5p (fold change = 1.5, p++ = 0.027), and 218-5p (fold change = 1.5, p++ = 0.020) were significantly increased. While miR-150-5p (fold change = 0.56, p++ = 0.003) was significantly decreased. The mRNA expression of survivin-WT (fold change = 0.63, p++ = 0.002) was significantly downregulated in SLE patients compared to the healthy controls. Survivin total and its two major variants (survivin-2B, and survivin-ΔEx3) did not differ significantly between SLE patients and controls. CONCLUSION: Although survivin-TS and its two variants (survivin-2B, and survivin-ΔEx3) were not differently expressed in SLE patients, survivin-WT had altered expression. Despite aberrant miRNA expression in PBMCs from SLE patients, survivin and miRNA expression were not associated with leukopenia. The pathogenesis of SLE disorder might be linked to survivin's other roles in the immune system aside from anti-apoptotic functions.
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BACKGROUND: Respiratory distress syndrome (RDS) is one of the most important and common disorders among premature infants. OBJECTIVE: This study aimed to compare the effect of the combination of surfactant and budesonide with surfactant alone on Bronchopulmonary dysplasia (BPD) and mortality rate among premature infants with RDS. METHOD: An outcome assessor-blind randomized clinical trial was conducted on 134 premature infants with RDS who were born in Ayatollah Mousavi Hospital, Zanjan, Iran in 2021. The covariate adaptive randomization method was utilized to allocate participants into two groups (surfactant alone and a combination of surfactant and budesonide). The primary outcomes were BPD and Mortality rate from admission to hospital discharge. The data in this study were analyzed using SPSS software version 18. RESULTS: Overall the comparison of mortality rate and BPD between the two groups did not show a significant difference(p > 0.05). The subgroup results showed that administering surfactant with budesonide to infants under 30 weeks of age significantly reduced the number of deaths compared to using surfactant alone (5 vs. 17). Similar positive effects were observed for the occurrence of Pulmonary Hemorrhage, the need for a second dose of surfactant, oxygen index, mean blood pressure and mean arterial pressure (MAP) in infants under 34 weeks of age compared to more than 34 weeks (p < 0.05). CONCLUSION: These findings suggest that the combination therapy of surfactant and budesonide may be beneficial, particularly in preterm infants with less than 34 weeks gestational age and 1500 birth weight. However, further studies with larger sample sizes and longer follow-up periods are needed to confirm these results and assess long-term outcomes. TRIAL REGISTRATION: The study was registered at the Iranian Registry of Clinical Trials website under the code IRCT20201222049802N1. https://en.irct.ir/user/trial/48117/view . REGISTRATION DATE: 28/02/2021. PUBLIC REPOSITORY: DATA SET: This research data set link is displayed on the Zanjan-Iran Medical Sciences website: https://repository.zums.ac.ir/cgi/users/login? target=https%3 A%2 F/repository.zums.ac.ir/id/eprint .
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Displasia Broncopulmonar , Surfactantes Pulmonares , Síndrome do Desconforto Respiratório do Recém-Nascido , Lactente , Recém-Nascido , Humanos , Recém-Nascido Prematuro , Budesonida/uso terapêutico , Tensoativos/uso terapêutico , Displasia Broncopulmonar/tratamento farmacológico , Irã (Geográfico) , Método Simples-Cego , Respiração Artificial/métodos , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Surfactantes Pulmonares/uso terapêutico , LipoproteínasRESUMO
BACKGROUND: Periodontitis is one of the most common chronic inflammatory diseases in the world, which affects oral health. Resveratrol is a polyphenol with therapeutic effects on the inflammation caused by periodontal pathogens. This study aimed to evaluate the impact of resveratrol supplementation on clinical parameters and inflammatory markers in patients with chronic periodontitis. METHODS: In this randomized, double-blind study, 40 chronic periodontitis patients underwent non-surgical therapy and were randomly assigned to two intervention and control groups, receiving either resveratrol supplements or a placebo for four weeks. Salivary levels of interleukin-8 (IL-8), interleukin-1ß (IL-1ß), and clinical parameters, including pocket depth (PD), clinical attachment level (CAL), plaque index (PI), and bleeding index (BI), were measured before and after the intervention. RESULTS: The results showed that in both the case and control groups, after four weeks of using resveratrol, only plaque index (PI) was significantly different compared to the control group (P = 0.0001). However, there were no significant differences in the mean pocket depth (PD), clinical attachment loss (CAL), bleeding index (BI), and salivary levels of IL-8 and IL-1ß between the two groups after the intervention. CONCLUSION: Resveratrol complement was helpful as an anti-inflammatory food supplement, along with other non-surgical periodontal treatments in chronic periodontitis patients.
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Periodontite Crônica , Humanos , Periodontite Crônica/tratamento farmacológico , Resveratrol/uso terapêutico , Interleucina-8 , Inflamação , Suplementos Nutricionais , Perda da Inserção Periodontal/terapia , Índice de Placa DentáriaRESUMO
OBJECTIVE: Systemic lupus erythematosus (SLE), the most common form of lupus, is a multisystemic rheumatic disease with different clinical features that generally affect women of childbearing age. The common symptoms of SLE are very similar to other autoimmune and non-autoimmune disorders, thereby it is known as a thousand faces disease. In this article, we are going to discuss some of the most updated information about immune system-related factors, cells, and cytokines involved in SLE pathogenesis. METHODS: Different electronic databases, especially PubMed/MEDLINE, Scopus, and Google Scholar, were searched to review and analyze relevant literature on the role of innate and adaptive immune cells and cytokines in the pathogenesis of SLE. A search for relevant literature was accomplished using various keywords including systemic lupus erythematosus, apoptosis, autoantibodies, immunopathogenesis of SLE, adaptive and innate immune cells, inflammatory cytokines, hormones, etc. RESULTS AND CONCLUSION: The most important characteristic of SLE is the production of antibodies against different nuclear autoantigens like double-strand DNA and RNA. The depositions of the immune complexes (ICs) that are generated between autoantibodies and autoantigens, along with aberrant clearance of them, can lead to permanent inflammation and contribute to tissue or organ damage. Related mechanisms underlying the initiation and development of SLE have not been clarified yet. Although, defects in immune tolerance, enhanced antigenic load, hyperactivity of T cells, and inappropriate regulation of B cells contribute to the pathogenic autoantibodies generation. Besides, sex hormones that influence the immune system seem to act as triggers or protectors of SLE development.
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Imunidade Adaptativa , Imunidade Inata , Lúpus Eritematoso Sistêmico , Autoanticorpos/imunologia , Autoantígenos/imunologia , Citocinas/metabolismo , Feminino , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Linfócitos T/imunologiaRESUMO
The current drug treatments against protozoan parasitic diseases including Chagas, malaria, leishmaniasis, and toxoplasmosis represent good examples of drug resistance mechanisms and have shown diverse side effects. Therefore, the identification of novel therapeutic strategies and drug compounds against such life-threatening diseases is urgent. According to the successful usage of selenium (Se) compounds-based therapy against some diseases, this therapeutic strategy has been recently further underlined against these parasitic diseases by targeting different parasite´s essential pathways. On the other hand, due to the important functions played by parasite selenoproteins in their biology (such as modulating the host immune response), they can be also considered as a novel therapeutic strategy by designing specific inhibitors against these important proteins. In addition, the immunomodulatory potentiality of these compounds to trigger T helper type 1 (Th1) cells and cytokine-mediated immune response for the substantial induction of proinflammatory cytokines, thus, Se, selenoproteins, and parasite selenoproteins could be further investigated to find possible vaccine antigens. Herein, we collect and present the results of some studies regarding Se-based therapy against protozoan parasitic diseases and highlight relevant information and some viewpoints that might be insightful to advance toward more effective studies in the future.
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Imunidade Celular , Infecções por Protozoários/tratamento farmacológico , Selênio , Selenoproteínas , Animais , Humanos , Selênio/farmacologiaRESUMO
Toxoplasma gondii is a pathogenic protozoan parasite belonging to the apicomplexan phylum that infects the nucleated cells of warm-blooded hosts leading to an infectious disease known as toxoplasmosis. Apicomplexan parasites such as T. gondii can display different mechanisms to control or manipulate host cells signaling at different levels altering the host subcellular genome and proteome. Indeed, Toxoplasma is able to modulate host cell responses (especially immune responses) during infection to its advantage through both structural and functional changes in the proteome of different infected cells. Consequently, parasites can transform the invaded cells into a suitable environment for its own replication and the induction of infection. Proteomics as an applicable tool can identify such critical proteins involved in pathogen (Toxoplasma)-host cell interactions and consequently clarify the cellular mechanisms that facilitate the entry of pathogens into host cells, and their replication and transmission, as well as the central mechanisms of host defense against pathogens. Accordingly, the current paper reviews several proteins (identified using proteomic approaches) differentially expressed in the proteome of Toxoplasma-infected host cells (macrophages and human foreskin fibroblasts) and tissues (brain and liver) and highlights their plausible functions in the cellular biology of the infected cells. The identification of such modulated proteins and their related cell impact (cell responses/signaling) can provide further information regarding parasite pathogenesis and biology that might lead to a better understanding of therapeutic strategies and novel drug targets.
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Toxoplasma , Toxoplasmose , Interações Hospedeiro-Parasita , Humanos , Proteoma/metabolismo , Proteômica , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Toxoplasma/genética , Toxoplasmose/parasitologiaRESUMO
Leishmania parasites, the causative agents of leishmaniasis, are protozoan parasites with the ability to modify the signalling pathway and cell responses of their infected host cells. These parasite strategies alter the host cell environment and conditions favouring their replication, survival and pathogenesis. Since microRNAs (miRNAs) are able to post-transcriptionally regulate gene expression processes, these biomolecules can exert critical roles in controlling Leishmania-host cell interplay. Therefore, the identification of relevant miRNAs differentially expressed in Leishmania parasites as well as in infected cells, which affect the host fitness, could be critical to understand the infection biology, pathogenicity and immune response against these parasites. Accordingly, the current review aims to address the differentially expressed miRNAs in both, the parasite and infected host cells and how these biomolecules change cell signalling and host immune responses during infection. A deep understanding of these processes could provide novel guidelines and therapeutic strategies for managing and treating leishmaniasis.
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Leishmania , Leishmaniose , MicroRNAs , Parasitos , Animais , Leishmaniose/parasitologia , MicroRNAs/genética , MicroRNAs/metabolismo , Transdução de SinaisRESUMO
The association of leishmaniasis and malignancies in human and animal models has been highlighted in recent years. The misdiagnosis of coexistence of leishmaniasis and cancer and the use of common drugs in the treatment of such diseases prompt us to further survey the molecular biology of Leishmania parasites and cancer cells. The information regarding common expressed proteins, as possible therapeutic targets, in Leishmania parasites and cancer cells is scarce. Therefore, the current study reviews proteins, and investigates the regulation and functions of several key proteins in Leishmania parasites and cancer cells. The up- and down-regulations of such proteins were mostly related to survival, development, pathogenicity, metabolic pathways and vital signalling in Leishmania parasites and cancer cells. The presence of common expressed proteins in Leishmania parasites and cancer cells reveals valuable information regarding the possible shared mechanisms of pathogenicity and opportunities for therapeutic targeting in leishmaniasis and cancers in the future.
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Leishmaniose/terapia , Neoplasias/terapia , Animais , Antineoplásicos/metabolismo , Antineoplásicos/uso terapêutico , Antiprotozoários/metabolismo , Antiprotozoários/uso terapêutico , Modelos Animais de Doenças , Humanos , Leishmaniose/imunologia , Proteínas de Neoplasias/metabolismo , Neoplasias/etiologia , Neoplasias/imunologia , Proteínas de Protozoários/metabolismoRESUMO
The mechanistic (or mammalian) target of rapamycin (mTOR) is considered as a critical regulatory enzyme involved in essential signaling pathways affecting cell growth, cell proliferation, protein translation, regulation of cellular metabolism, and cytoskeletal structure. Also, mTOR signaling has crucial roles in cell homeostasis via processes such as autophagy. Autophagy prevents many pathogen infections and is involved on immunosurveillance and pathogenesis. Immune responses and autophagy are therefore key host responses and both are linked by complex mTOR regulatory mechanisms. In recent years, the mTOR pathway has been highlighted in different diseases such as diabetes, cancer, and infectious and parasitic diseases including leishmaniasis, toxoplasmosis, and malaria. The current review underlines the implications of mTOR signals and intricate networks on pathogen infections and the modulation of this master regulator by parasites. Parasitic infections are able to induce dynamic metabolic reprogramming leading to mTOR alterations in spite of many other ways impacting this regulatory network. Accordingly, the identification of parasite effects and interactions over such a complex modulation might reveal novel information regarding the biology of the abovementioned parasites and might allow the development of therapeutic strategies against parasitic diseases. In this sense, the effects of inhibiting the mTOR pathways are also considered in this context in the light of their potential for the prevention and treatment of parasitic diseases.
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Parasitos/efeitos dos fármacos , Doenças Parasitárias/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Animais , Autofagia , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Imunidade/efeitos dos fármacos , Leishmaniose/tratamento farmacológico , Leishmaniose/parasitologia , Leishmaniose/prevenção & controle , Malária/tratamento farmacológico , Malária/parasitologia , Malária/prevenção & controle , Parasitos/fisiologia , Doenças Parasitárias/parasitologia , Doenças Parasitárias/prevenção & controle , Fosforilação , Biossíntese de Proteínas/efeitos dos fármacos , Serina-Treonina Quinases TOR/genética , Toxoplasmose/tratamento farmacológico , Toxoplasmose/parasitologia , Toxoplasmose/prevenção & controleRESUMO
Ankylosing spondylitis (AS) is a chronic autoimmune arthritis disease with a genetic background, affecting the skeletal axis, sacroiliac, and peripheral joints. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the first-line treatment for AS to alleviate the inflammation and pain. Despite the beneficial effect, their use is accompanied by a wide variety of possible side effects in the gastrointestinal and kidneys. The α-l-guluronic acid (G2013) is a new nonsteroidal anti-inflammatory patented (PCT/EP2017/067920) drug, which has shown its anti-inflammatory properties in the previous investigations. The present study revealed the oral administration effect of G2013 on COX-1 and COX-2 gene expression in AS patients. The blood samples of twelve 18-45 years old patients suffering AS and BASDAI >4, and BASFI >4, before and after 12 weeks of treatment with G2013 and 12 blood samples of healthy volunteers were collected and the effect of G2013 on the gene expression of COX-1 and COX-2 enzymes were assessed by Real-Time PCR. The results indicate that G2013 is able to reduce the gene expression level of COX-1 and COX-2 enzymes in treated AS patients compared to healthy control. Statistically significant differences were not observed between the treatment and the healthy control groups. According to the findings, G2013 might be categorized and introduced as a novel NSAID for the treatment of AS.
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Ciclo-Oxigenase 1/genética , Ciclo-Oxigenase 2/genética , Ácidos Hexurônicos/administração & dosagem , Espondilite Anquilosante/tratamento farmacológico , Espondilite Anquilosante/genética , Transcriptoma/efeitos dos fármacos , Administração Oral , Adolescente , Adulto , Ciclo-Oxigenase 1/biossíntese , Ciclo-Oxigenase 2/biossíntese , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Feminino , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Espondilite Anquilosante/metabolismo , Transcriptoma/fisiologia , Adulto JovemRESUMO
Plasmodium falciparum is the main cause of severe malaria in humans that can lead to death. There is growing evidence of drug-resistance in P. falciparum treatment, and the design of effective vaccines remains an ongoing strategy to control the disease. On the other hand, the recognition of specific diagnostic markers for P. falciparum can accelerate the diagnosis of this parasite in the early stages of infection. Therefore, the identification of novel antigenic proteins especially by proteomic tools is urgent for vaccination and diagnosis of P. falciparum. The proteome diversity of the life cycle stages of P. falciparum, the altered proteome of P. falciparum-infected human sera and altered proteins in P. falciparum-infected erythrocytes could be proposed as appropriate proteins for the aforementioned aims. Accordingly, this review highlights and proposes different proteins identified using proteomic approaches as promising markers in the diagnosis and vaccination of P. falciparum. It seems that most of the candidates identified in this study were able to elicit immune responses in the P. falciparum-infected hosts and they also played major roles in the life cycle, pathogenicity and key pathways of this parasite.
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Vacinas Antimaláricas/imunologia , Malária Falciparum , Plasmodium falciparum , Proteoma , Animais , Antimaláricos/farmacologia , Biomarcadores/metabolismo , Resistência a Medicamentos/genética , Eritrócitos/parasitologia , Genes de Protozoários , Humanos , Estágios do Ciclo de Vida/imunologia , Malária Falciparum/diagnóstico , Malária Falciparum/tratamento farmacológico , Malária Falciparum/imunologia , Plasmodium falciparum/genética , Plasmodium falciparum/imunologia , Plasmodium falciparum/metabolismo , Proteoma/imunologia , Proteoma/metabolismo , Proteômica/métodos , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismoRESUMO
According to some difficulties against tuberculosis (TB) vaccination, development of new TB vaccines has been noted in recent years. Selection of proper route for vaccination is one of the most important factors for induction of good immune responses. Hence, in this study, the effects of different administration routes, including intranasal (I.N), subcutaneous (S.C) and intramuscular (I.M) on immune responses against Mycobacterium tuberculosis ESAT-6/CFP-10 recombinant protein has been considered. Recombinant ESAT-6/CFP-10 protein with or without adjuvant (MF59 or cholera toxin B (CTB)) was administered by three routes of I.M, I.N and S.C to mice for three times. Then, the levels of specific antibodies, lymphocyte proliferation and IFN-γ/IL-5 cytokine profile have been carried out to evaluate the humoral and cellular responses. The results showed that the titers of specific antibodies were quickly elevated in S.C and I.M groups after first immunization. Otherwise, the raise of antibody has delay in the I.N immunized animals. The levels of IFN-γ and lymphocyte proliferation have been increased in all of vaccinated groups. However, the I.N immunized mice have lower levels of IL-5 production. Based on our finding, the ESAT-6/CFP-10 recombinant protein is a potent stimulator of immune responses in all of three immunization strategies. However intranasal administration of this antigen has tended to reinforcement of cellular immune responses.
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Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Mycobacterium tuberculosis/imunologia , Proteínas Recombinantes/imunologia , Vacinas contra a Tuberculose/imunologia , Tuberculose/imunologia , Administração Intranasal , Animais , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Feminino , Imunidade Celular/efeitos dos fármacos , Imunidade Celular/imunologia , Imunidade Humoral/efeitos dos fármacos , Imunidade Humoral/imunologia , Injeções Intramusculares , Injeções Subcutâneas , Camundongos , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose/microbiologia , Tuberculose/prevenção & controle , Vacinas contra a Tuberculose/administração & dosagem , Vacinação/métodosRESUMO
Ankylosing spondylitis (AS) is a debilitating chronic inflammatory disease with genetic predisposition, which is characterized by the involvement of spine and sacroiliac joints. Due to the relatively unsuccessful treatments, we designed ß-D-mannuronic (M2000) with the beneficial effects in various experimental models as a novel non-steroidal anti-inflammatory drug (NSAID). The aims of our present study were: first, to compare the therapeutic effects of M2000, as a novel designed NSAID, with naproxen and placebo in Iranian patients with AS during 12 weeks; second, to evaluate the effect of M2000 on gene expression of cyclooxygenase enzyme (COX-1/COX-2), a key enzyme in the initiation of inflammatory pathways in AS patients; and third, to assess the activity of COX-1 and COX-2 enzymes in the presence/absence of M2000 at the different doses in the murine macrophage, J774 cell line. This was a sub-study of phase II, randomized, placebo-controlled trial with three treatment arms: M2000, naproxen, and placebo. The outcome measures were the mean changes from baseline to week 12. The gene expression was assessed by real-time PCR. The COX-1 and COX-2 activities were evaluated by ELISA in J774 cell line induced by LPS and arachidonic acid (AA). Our findings demonstrated that M2000 had beneficial therapeutic effects on pain, stiffness, and inflammation, whereas no adverse effects were observed following the use of M2000 after 12 weeks. The analysis of gene expression showed that M2000 could effectively reduce the expression levels of COX-1 and COX-2 in comparison with untreated patients. In addition, the enzymatic activities in the presence of M2000 were significantly less than LPS- and AA-treated groups. Our results indicate that M2000, as a novel designed NSAID with immunosuppressive properties, can be considered as one of the therapeutic options for the treatment of inflammatory diseases without adverse events. Clinical trial identifier IRCT2013062213739N1/ http://www.IRCT.ir .
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Anti-Inflamatórios não Esteroides/uso terapêutico , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Expressão Gênica/efeitos dos fármacos , Ácidos Hexurônicos/uso terapêutico , Macrófagos/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Espondilite Anquilosante/tratamento farmacológico , Adulto , Animais , Linhagem Celular , Feminino , Humanos , Imunossupressores/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Irã (Geográfico) , Macrófagos/metabolismo , Masculino , Camundongos , Monócitos/metabolismo , Espondilite Anquilosante/metabolismoRESUMO
PURPOSE: Our purpose was to analyse the presentation, management and clinical outcome of patients treated operatively and non-operatively for Copenhagen Disease (CD). METHODS: We performed a retrospective analysis of 10 patients (n = 10) with CD, with a mean follow-up time of 14.7 years. Seven patients underwent non-operative treatment and three patients were treated operatively. Clinical presentation and radiological findings were analysed. Health-related quality of life (HRQOL) outcome measures utilized included Oswestry Disability Index (ODI), Short Form 12 Health Survey (SF-12) and visual analogue scale (VAS). RESULTS: Patients tended to present with back pain. No significant difference was detected in functional scores at time of diagnosis and when compared to last follow-up. ODI improved from 20.0 to 18.4 (p = 0.839), PCS component of SF-12 from 44.5 to 45.9 (p = 0.719), MCS component of SF-12 from 45.7 to 46.9 (p = 0.840) and VAS score remained at 2.8 (p = 1.000). There was no significant difference in functional scores when comparing operative and non-operative treatment groups. CONCLUSION: CD is likely to remain stable with time or slightly improve after treatment according to functional outcomes tests. Progression of the kyphosis can be halted at different degrees with operative and non-operative treatments although it does not correlate with changes in symptomatology.
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Dor nas Costas/etiologia , Cifose/terapia , Anormalidades Múltiplas , Adolescente , Criança , Pré-Escolar , Avaliação da Deficiência , Feminino , Seguimentos , Humanos , Lactente , Cifose/diagnóstico por imagem , Masculino , Qualidade de Vida , Radiografia , Estudos Retrospectivos , Fusão Vertebral , Escala Visual AnalógicaRESUMO
Annexins (ANXs) exert different functions in cell biological and pathological processes and are thus known as double or multi-faceted proteins. These sophisticated proteins might express on both parasite structure and secretion and in parasite-infected host cells. In addition to the characterization of these pivotal proteins, describing their mechanism of action can be also fruitful in recognizing their roles in the pathogenesis of parasitic infections. Accordingly, this study presents the most prominent ANXs thus far identified and their relevant functions in parasites and infected host cells during pathogenesis, especially in the most important intracellular protozoan parasitic infections including leishmaniasis, toxoplasmosis, malaria and trypanosomiasis. The data provided in this study demonstrate that the helminth parasites most probably express and secret ANXs to develop pathogenesis while the modulation of the host-ANXs could be employed as a crucial strategy by intracellular protozoan parasites. Moreover, such data highlight that the use of analogs of both parasite and host ANX peptides (which mimic or regulate ANXs physiological functions through various strategies) might suggest novel therapeutic insights into the treatment of parasitic infections. Furthermore, due to the prominent immunoregulatory activities of ANXs during most parasitic infections and the expression levels of these proteins in some parasitic infected tissues, such multifunctional proteins might be also potentially relevant as vaccine and diagnostic biomarkers. We also suggest some prospects and insights that could be useful and applicable to form the basis of future experimental studies.
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Leishmaniose , Malária , Parasitos , Doenças Parasitárias , Infecções por Protozoários , Animais , Humanos , Anexinas , Doenças Parasitárias/prevenção & controle , Infecções por Protozoários/diagnóstico , Malária/prevenção & controleRESUMO
To evaluate the effectiveness of targeted therapy on preventing or treating COVID-19, in this study, we want to share our experience about 14 patients (nine women, five men; average age, 59 years) who were treated with targeted therapy due to their underlying malignant disorders in our center.
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The complement system exerts crucial functions both in innate immune responses and adaptive humoral immunity. This pivotal system plays a major role dealing with pathogen invasions including protozoan parasites. Different pathogens including parasites have developed sophisticated strategies to defend themselves against complement killing. Some of these strategies include the employment, mimicking or inhibition of host's complement regulatory proteins, leading to complement evasion. Therefore, parasites are proven to use the manipulation of the complement system to assist them during infection and persistence. Herein, we attempt to study the interaction´s mechanisms of some prominent infectious protozoan parasites including Plasmodium, Toxoplasma, Trypanosoma, and Leishmania dealing with the complement system. Moreover, several crucial proteins that are expressed, recruited or hijacked by parasites and are involved in the modulation of the host´s complement system are selected and their role for efficient complement killing or lysis evasion is discussed. In addition, parasite's complement regulatory proteins appear as plausible therapeutic and vaccine targets in protozoan parasitic infections. Accordingly, we also suggest some perspectives and insights useful in guiding future investigations.
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Leishmania , Parasitos , Plasmodium , Infecções por Protozoários , Trypanosoma , Animais , Parasitos/fisiologia , Proteínas do Sistema Complemento , Infecções por Protozoários/parasitologiaRESUMO
Micro RNAs (miRNAs), as regulators of gene expression at the post-transcriptional level, can respond to/or interact with cell signaling and affect the pathogenesis of different diseases/infections. The interaction/crosstalk of miRNAs with various cellular signaling networks including mTOR (as a master regulator of signaling relevant to different cellular mechanisms) might lead to the initiation, progression or restriction of certain disease processes. There are numerous studies that have identified the crosstalk between regulatory miRNA expression and the mTOR pathway (or mTOR signaling regulated by miRNAs) in different diseases which has a dual function in pathogenesis. However, the corresponding information in parasitic infections remains scarce. miRNAs have been suggested as specific targets for therapeutic strategies in several disorders such as parasitic infections. Thus, the targeting of miRNAs (as the modulators/regulators of mTOR) by small molecules and RNA-based therapeutics and consequently managing and modulating mTOR signaling and the downstream/related cell signaling/pathways might shed some light on the design of new therapeutic strategies against parasitic diseases, including Leishmaniasis. Accordingly, the present study attempts to highlight the importance of the crosstalk between regulatory miRNAs and mTOR signaling, and to review the relevant insights into parasitic infections by focusing specifically on Leishmania.
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Leishmaniose , MicroRNAs , Doenças Parasitárias , Humanos , Imunidade , Leishmaniose/genética , Leishmaniose/parasitologia , MicroRNAs/genética , Transdução de Sinais , Serina-Treonina Quinases TOR/genéticaRESUMO
Toxoplasma gondii is a pathogenic protozoan parasite that infects the nucleated cells of warm-blooded hosts leading to an infectious zoonotic disease known as toxoplasmosis. The infection outcomes might be severe and fatal in patients with immunodeficiency, diabetes, and pregnant women and infants. The One Health approach to toxoplasmosis highlights that the health of humans is closely related to the health of animals and our common environment. The presence of drug resistance and side effects, the further improvement of sensitivity and specificity of serodiagnostic tools and the potentiality of vaccine candidates to induce the host immune response are considered as justifiable reasons for the identification of novel targets for the better management of toxoplasmosis. Thus, the identification of new critical proteins in the proteome of Toxoplasma parasites can also be helpful in designing and test more effective drugs, vaccines, and diagnostic tools. Accordingly, in this study we present important proteins found in the proteome of the life cycle-specific stages of Toxoplasma parasites that are potential diagnostic or vaccine candidates. The current study might help to understand the complexity of these parasites and provide a possible source of strategies and biomolecules that can be further evaluated in the pathobiology of Toxoplasma parasites and for diagnostics and vaccine trials against this disease.
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Human Leukocyte Antigen-G (HLA-G), a polymorphic non-classical HLA (HLA-Ib) with immune-regulatory properties in cancers and infectious diseases, presents both membrane-bound and soluble (sHLA-G) isoforms. Polymorphism has implications in host responses to pathogen infections and in pathogenesis. Differential expression patterns of HLA-G/sHLA-G or its polymorphism seem to be related to different pathological conditions, potentially acting as a disease progression biomarker. Pathogen antigens might be involved in the regulation of both membrane-bound and sHLA-G levels and impact immune responses during co-infections. The upregulation of HLA-G in viral and bacterial infections induce tolerance to infection. Recently, sHLA-G was found useful to identify the prognosis of Coronavirus disease 2019 (COVID-19) among patients and it was observed that the high levels of sHLA-G are associated with worse prognosis. The use of pathogens, such as Plasmodium falciparum, as immune modulators for other infections could be extended for the modulation of membrane-bound HLA-G in COVID-19-infected tissues. Overall, such information might open new avenues concerning the effect of some pathogens such as parasites in decreasing the expression level of HLA-G to restrict pathogenesis in some infections or to influence the immune responses after vaccination among others.