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1.
Yale J Biol Med ; 97(2): 165-177, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38947108

RESUMO

Background: Chronic rhinosinusitis (CRS) is an inflammatory condition classified into chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP). Th cells manage inflammatory cells in CRS. Suppressor of Cytokine Signaling (SOCS) proteins regulate Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway in Th cells by polarizing toward Th1, Th2, and Th17 cells. This study evaluated the levels of SOCS1,3,5 in CRS patients to find associations with Th cells. Methods: In this cross-sectional study, 20 CRSwNP patients, 12 CRSsNP patients, and 12 controls participated. The infiltration of CD4+ T cells was determined using immunohistochemistry. The expression of specific transcription factors and SOCS proteins was assessed using real-time PCR. Cytokine levels were evaluated using ELISA. SOCS protein levels were investigated using western blot analysis. Results: The expression of SOCS3 increased in the CRSwNP group compared to CRSsNP and control groups (p <0.001). SOCS3 protein levels increased in the CRSwNP group compared to CRSsNP (p <0.05) and control (p <0.001) groups. Although there was a significant difference in SOCS5 expression between CRSsNP and control groups, SOCS5 protein levels were significantly different between CRSsNP and control (p <0.001) and CRSwNP (p <0.05) groups. Conclusions: Targeted therapies may be suggested for CRS by modulating SOCS3 and SOCS5 proteins that are responsible for polarization of Th cells toward Th2 or Th1 cells, respectively. JAK-STAT pathway targeting, which encompasses numerous cells, can be limited to SOCS proteins to more effectively orchestrate Th cell differentiation.


Assuntos
Rinite , Sinusite , Proteína 3 Supressora da Sinalização de Citocinas , Proteínas Supressoras da Sinalização de Citocina , Humanos , Sinusite/metabolismo , Sinusite/imunologia , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Doença Crônica , Masculino , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Rinite/metabolismo , Rinite/imunologia , Feminino , Adulto , Pessoa de Meia-Idade , Linfócitos T Auxiliares-Indutores/metabolismo , Linfócitos T Auxiliares-Indutores/imunologia , Estudos Transversais , Pólipos Nasais/metabolismo , Citocinas/metabolismo , Proteína 1 Supressora da Sinalização de Citocina/metabolismo , Proteína 1 Supressora da Sinalização de Citocina/genética , Transdução de Sinais , Rinossinusite
2.
Sci Rep ; 14(1): 9722, 2024 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-38678138

RESUMO

Chronic rhinosinusitis with nasal polyp (CRSwNP) is a highly prevalent disorder characterized by persistent nasal and sinus mucosa inflammation. Despite significant morbidity and decreased quality of life, there are limited effective treatment options for such a disease. Therefore, identifying causal genes and dysregulated pathways paves the way for novel therapeutic interventions. In the current study, a three-way interaction approach was used to detect dynamic co-expression interactions involved in CRSwNP. In this approach, the internal evolution of the co-expression relation between a pair of genes (X, Y) was captured under a change in the expression profile of a third gene (Z), named the switch gene. Subsequently, the biological relevancy of the statistically significant triplets was confirmed using both gene set enrichment analysis and gene regulatory network reconstruction. Finally, the importance of identified switch genes was confirmed using a random forest model. The results suggested four dysregulated pathways in CRSwNP, including "positive regulation of intracellular signal transduction", "arachidonic acid metabolic process", "spermatogenesis" and "negative regulation of cellular protein metabolic process". Additionally, the S100a9 as a switch gene together with the gene pair {Cd14, Tpd52l1} form a biologically relevant triplet. More specifically, we suggested that S100a9 might act as a potential upstream modulator in toll-like receptor 4 transduction pathway in the major CRSwNP pathologies.


Assuntos
Calgranulina B , Pólipos Nasais , Rinite , Transdução de Sinais , Sinusite , Receptor 4 Toll-Like , Pólipos Nasais/metabolismo , Pólipos Nasais/genética , Humanos , Sinusite/metabolismo , Sinusite/genética , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Rinite/metabolismo , Rinite/genética , Doença Crônica , Calgranulina B/genética , Calgranulina B/metabolismo , Redes Reguladoras de Genes , Regulação da Expressão Gênica , Perfilação da Expressão Gênica , Rinossinusite
3.
Neurol Sci ; 45(2): 647-654, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37651040

RESUMO

BACKGROUND: Olfactory dysfunction has been suggested as a diagnostic and discriminative biomarker in some neurodegenerative disorders. However, there are few studies regarding the olfactory status in rare diseases including neurodegeneration with brain iron accumulation (NBIA) disorders. METHODS: Genetically-confirmed NBIA patients were enrolled. Neurological and cognitive examinations were conducted according to the Pantothenate Kinase-Associated Neurodegeneration-Disease Rating Scale (PKAN-DRS) and the Mini-Mental State Examination (MMSE) questionnaire, respectively. Olfaction was assessed in three domains of odor threshold (OT), odor discrimination (OD), odor identification (OI), and total sum (TDI) score by the Sniffin' Sticks test. The olfactory scores were compared to a control group and a normative data set. RESULTS: Thirty-seven patients, including 22 PKAN, 6 Kufor Rakeb syndrome, 4 Mitochondrial membrane Protein-Associated Neurodegeneration (MPAN), 5 cases of other 4 subtypes, and 37 controls were enrolled. The mean PKAN-DRS score was 51.83±24.93. Sixteen patients (55.2%) had normal cognition based on MMSE. NBIA patients had significantly lower olfactory scores compared to the controls in TDI and all three subtests, and 60% of them were hyposmic according to the normative data. Including only the cognitively-normal patients, still, OI and TDI scores were significantly lower compared to the controls. The phospholipase A2-Associated Neurodegeneration (PLAN) and MPAN patients had a significantly lower OI score compared to the cognitively-matched PKAN patients. CONCLUSION: Olfactory impairment as a common finding in various subtypes of NBIA disorder can potentially be considered a discriminative biomarker. Better OI in PKAN compared to PLAN and MPAN patients may be related to the different underlying pathologies.


Assuntos
Doenças Neurodegenerativas , Transtornos do Olfato , Neurodegeneração Associada a Pantotenato-Quinase , Humanos , Olfato/fisiologia , Neurodegeneração Associada a Pantotenato-Quinase/complicações , Neurodegeneração Associada a Pantotenato-Quinase/diagnóstico , Transtornos do Olfato/diagnóstico , Transtornos do Olfato/etiologia , Encéfalo , Doenças Neurodegenerativas/complicações , Ferro , Biomarcadores
4.
Plast Reconstr Surg ; 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38085998

RESUMO

BACKGROUND: The heterogeneity of nasal features across different ethnical groups is evident. This large-scale multicenter study evaluates dorsal keystone area and its relation to superficial nasal anatomy, through computed tomography (CT) scans. METHODS: Six different populations were included: South Caucasian, Middle Eastern, Black South African, Eastern Asian, Mestizo and Eastern European. Each center obtained CT scans performed between January 2020 and December 2022 from patients presenting a nasal hump and from an age and sex-matched control group. Osteocartilaginous measurements in relation to Ethmoidal-point and to Rhinion, as well as their relation to superficial nasal anatomy, were collected from nasal CT scans in midsagittal view. These were compared between populations and, in each center, compared between patient groups (nasal hump versus no nasal hump). RESULTS: The study population included 600 patients (254 with nasal hump), with a mean age of 33.98 (ranging 18 - 59) years old, and 55.6% were female. The distance from the Ethmoidal-point averaged: to Rhinion 10.1(±3.5)mm; and to nasal hump beginning point 1.68 (±0.23)mm. In 96% of cases the Ethmoidal-point was cranial or no more than 5mm caudal to the beginning of the nasal hump. S-shaped nasal bones were associated with nasal hump but its angulation (kyphion angle) did not correlate with nasal hump height. CONCLUSIONS: In most patients, the nasal hump has no ethmoid bone underneath it, and it apex is located over the septal cartilage. The Ethmoidal-point is a reliable landmark and should be considered when appreciating established and new preservation and structural rhinoplasty approaches.

5.
Int J Biol Macromol ; 253(Pt 1): 126597, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37660854

RESUMO

Chronic tympanic membrane (TM) perforation is a consequence of trauma or chronic otitis media, and these chronic TM perforations often lead to conduction hearing loss. This study focuses on the development of a patch using a combination of chitosan (CS) and polyvinyl alcohol (PVA) as graft material for repairing chronic tympanic membrane (TM) perforations. Aligned nanofibers were created using a specially designed collector (SDC) through the electrospinning method. The scanning electron microscopy (SEM) analysis revealed that the CS/PVA ratio of (15:85) resulted in uniform and bead-free nanofibers. The aligned nanofibers had a diameter of 131.11 ± 28 nm, indicating that the influence of the electrostatic field introduced by the SDC affected not only the nanofiber alignment but also the nanofiber diameter. The nanofiber angles demonstrated effective alignment. This patch is infused with thyme essential oil (TEO) for antibacterial properties. The results showed that its antibacterial property for Pseudomonas aeruginosa bacteria was enhanced in such a way that the diameter of the antibacterial halo increased from zero to 25 mm. Cell viability assays showed >80 % viability. A preclinical case study on six patients demonstrated the biocompatibility and promising potential of the fabricated patch for eardrum repair.


Assuntos
Quitosana , Nanofibras , Perfuração da Membrana Timpânica , Humanos , Perfuração da Membrana Timpânica/tratamento farmacológico , Álcool de Polivinil , Antibacterianos/farmacologia
6.
Arch Microbiol ; 204(6): 327, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35575834

RESUMO

Recent studies have established the possible role of microbiota in developing various diseases. In this regard, attention has shifted to the evaluation of microbiota changes in the paranasal sinuses and its relationship to chronic rhinosinusitis (CRS), especially CRS with nasal polyposis (CRSwNP). This study aimed to examine the bacterial communities of the sphenoidal sinus in Iranian patients with and without CRS. The investigation included 36 subjects, including 18 patients with CRSwNP who underwent Functional Endoscopic Sinus Surgery (FESS) and 18 non-CRS patients who underwent Endoscopic Endonasal Approach (EEA) for pituitary adenoma. The surgeries were performed under general anesthesia, and the sphenoidal sinus was sampled using sterile rayon-tipped swabs coated with a sheet. TaqMan quantitative real-time polymerase chain reaction (qPCR) method (the 16S rDNA gene from bacteria) was used for detection of bacterial communities in different samples. Staphylococcus haemolyticus and Pseudomonas aeruginosa were significantly more prevalent in CRS patients than non-CRS patients (P value ≤ 0.05). However, no significant difference in the frequency of Corynebacterium spp. and Staphylococcus aureus was observed between the two groups, and no Streptococcus pneumoniae or Haemophilus influenza species were isolated from any of the samples. The current study's findings indicated a significant difference in the frequency of certain bacterial species in patients with CRS vs. non-CRS patients. By establishing a link between microbial burden and CRS, it is possible to develop effective treatments or even prevent disorders in this body area.


Assuntos
Seios Paranasais , Rinite , Sinusite , Bactérias , Doença Crônica , Humanos , Irã (Geográfico)/epidemiologia , Seios Paranasais/microbiologia , Seios Paranasais/cirurgia , RNA Ribossômico 16S/genética , Rinite/microbiologia , Rinite/cirurgia , Sinusite/microbiologia , Sinusite/cirurgia
7.
BMC Res Notes ; 15(1): 174, 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35562776

RESUMO

OBJECTIVE: We aimed to evaluate cytocompatibility of hyaluronic acid (HA) and gelatin (Gela) conjugation with phenolic groups (Phs) via enzyme-mediated crosslinking. Phenolic moieties were substituted on the backbone of HA (HA-Ph) and Gela (Gela-Ph) and subsequently were subjected for horseradish peroxidase crosslinking in the presence of H2O2 as an electron donor to create a stable hybrid microenvironment for cellular behavior and cartilage tissue engineering. RESULTS: Successful synthesis of biopolymers confirmed by NRM and UV-Vis spectrophotometry. The physical characteristic of hydrogels including mechanical properties and water contact angle of hydrogels enhanced with addition of Gela-Ph in HA-based hydrogel. The Gela-Ph showed longest gelation time and highest degradation rate. The cellular studies showed cells did not attach to HA-Ph hydrogel. While, proper cell attachment and proliferation observed on blend hydrogel surface compared with the neat hydrogels which interpret by the existence of cell-adhesive motifs of utilized Gela-Ph in this hydrogel. The encapsulated cells in HA-Ph hydrogel were spheroid and just maintained their viability. Hydrogels containing Gela-Ph, the cells were spindle shape with high degrees of cytoplasmic extension. Overall, the results suggest that hybrid biomimetic hydrogel can provide a superior biological microenvironment for chondrocytes in 3D cartilage tissue engineering.


Assuntos
Hidrogéis , Engenharia Tecidual , Biomimética , Cartilagem , Ácido Hialurônico , Hidrogéis/química , Peróxido de Hidrogênio , Engenharia Tecidual/métodos
8.
J Clin Lab Anal ; 36(1): e24150, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34837714

RESUMO

BACKGROUND: Chordoma is a locally aggressive bone tumor with a high capability of recurrence. Because chordoma often occurs at critical locations next to neurovascular structures, there is an urgent need to introduce validated biomarkers. T-box transcription factor T (TBXT; OMIM: 601397) plays an important role in the pathogenesis and survival of chordoma cells. METHODS: Herein, we aimed to show whether rs2305089 polymorphism is correlated with chordoma in the Iranian population. In order to detect rs2305089, tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) was used. In total, 19 chordoma patients and 108 normal healthy individuals were recruited and screened using T-ARMS-PCR. The results were subsequently validated by Sanger sequencing. RESULTS: The genotype distributions and allele frequencies were significantly different among the patient and healthy groups (p-value <0.05). The A allele of rs2305089 showed a significant positive association with chordoma risk (p-value <0.05). DNA sequencing verified the T-ARMS-PCR results as well. This study demonstrated the association between TBXT rs2305089 and chordoma in an Iranian population using a simple, accurate, and cost-effective T-ARMS-PCR assay. CONCLUSIONS: Our results were in line with those of previous studies showing that TBXT rs2305089 is associated with chordoma development. We also developed an efficient T-ARMS-PCR assay to determine the genotype of rs2305089.


Assuntos
Cordoma , Proteínas Fetais/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Proteínas com Domínio T/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Neoplasias Ósseas/epidemiologia , Neoplasias Ósseas/genética , Estudos de Casos e Controles , Cordoma/epidemiologia , Cordoma/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Adulto Jovem
10.
Sci Rep ; 11(1): 20943, 2021 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-34686726

RESUMO

Non-functioning pituitary adenomas (NFPAs) are typical pituitary macroadenomas in adults associated with increased mortality and morbidity. Although pituitary adenomas are commonly considered slow-growing benign brain tumors, numerous of them possess an invasive nature. Such tumors destroy sella turcica and invade the adjacent tissues such as the cavernous sinus and sphenoid sinus. In these cases, the most critical obstacle for complete surgical removal is the high risk of damaging adjacent vital structures. Therefore, the development of novel therapeutic strategies for either early diagnosis through biomarkers or medical therapies to reduce the recurrence rate of NFPAs is imperative. Identification of gene interactions has paved the way for decoding complex molecular mechanisms, including disease-related pathways, and identifying the most momentous genes involved in a specific disease. Currently, our knowledge of the invasion of the pituitary adenoma at the molecular level is not sufficient. The current study aimed to identify critical biomarkers and biological pathways associated with invasiveness in the NFPAs using a three-way interaction model for the first time. In the current study, the Liquid association method was applied to capture the statistically significant triplets involved in NFPAs invasiveness. Subsequently, Random Forest analysis was applied to select the most important switch genes. Finally, gene set enrichment (GSE) and gene regulatory network (GRN) analyses were applied to trace the biological relevance of the statistically significant triplets. The results of this study suggest that "mRNA processing" and "spindle organization" biological processes are important in NFAPs invasiveness. Specifically, our results suggest Nkx3-1 and Fech as two switch genes in NFAPs invasiveness that may be potential biomarkers or target genes in this pathology.


Assuntos
Adenoma/genética , Ferroquelatase/genética , Genes de Troca/genética , Proteínas de Homeodomínio/genética , Invasividade Neoplásica/genética , Neoplasias Hipofisárias/genética , Fatores de Transcrição/genética , Adenoma/patologia , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica/genética , Redes Reguladoras de Genes/genética , Humanos , Invasividade Neoplásica/patologia , Neoplasias Hipofisárias/patologia , RNA Mensageiro/genética , Sela Túrcica/patologia
11.
Sci Rep ; 11(1): 20218, 2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34642400

RESUMO

Post-traumatic olfactory dysfunction (PTOD) is associated with a significant decrease in quality of life. The present study aimed to explore whether PTOD is associated with depression and changes in sexuality. There were two groups in this case-control study. The patient group consisted of patients with PTOD (n = 55), and the control group comprised healthy individuals without the olfactory disorder (n = 115). Olfactory function, depression, partnership, and sexual satisfaction were assessed using the Iranian version of the Sniffin' Sticks test (Ir-SST), Beck Depression Inventory (BDI), Enrich Couple Scale (ECS) and Sexual Satisfaction Scale for Women (SSSW). The BDI scores were higher in the patient group than in the control group (p < 0.001). The SSSW score was lower in the patient group than in controls (p < 0.01), although the ECS score was not significantly different between patients and controls. Also, there was no significant difference in the severity of trauma between marital satisfaction and sexual satisfaction. However, the analysis showed a statistically significant difference in depression scores in connection with the head trauma severity. In the PTOD group, depression was increased and sexual satisfaction declined. Understanding the association of olfactory dysfunction with depression and sexuality allows patients and doctors to deal with less notable consequences of this disorder.


Assuntos
Traumatismos Craniocerebrais/complicações , Depressão/epidemiologia , Transtornos do Olfato/psicologia , Orgasmo , Adulto , Estudos de Casos e Controles , Traumatismos Craniocerebrais/psicologia , Depressão/etiologia , Feminino , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Transtornos do Olfato/etiologia , Qualidade de Vida/psicologia , Índice de Gravidade de Doença , Comportamento Sexual , Adulto Jovem
12.
Biochem Biophys Rep ; 25: 100905, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33553683

RESUMO

Functional improvement after spinal cord injury remains an unsolved difficulty. Glial scars, a major component of SCI lesions, are very effective in improving the rate of this recovery. Such scars are a result of complex interaction mechanisms involving three major cells, namely, astrocytes, oligodendrocytes, and microglia. In recent years, scientists have identified two subtypes of reactive astrocytes, namely, A1 astrocytes that induce the rapid death of neurons and oligodendrocytes, and A2 astrocytes that promote neuronal survival. Moreover, recent studies have suggested that the macrophage polarization state is more of a continuum between M1 and M2 macrophages. M1 macrophages that encourage the inflammation process kill their surrounding cells and inhibit cellular proliferation. In contrast, M2 macrophages promote cell proliferation, tissue growth, and regeneration. Furthermore, the ability of oligodendrocyte precursor cells to differentiate into adult oligodendrocytes or even neurons has been reviewed. Here, we first scrutinize recent findings on glial cell subtypes and their beneficial or detrimental effects after spinal cord injury. Second, we discuss how we may be able to help the functional recovery process after injury.

13.
Med J Islam Repub Iran ; 35: 153, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35341085

RESUMO

Background :Psychophysical tests are typically used for clinical assessment of human smelling function. Given that olfactory identification is linked to the regional culture, the main aim of this study was to provide the comprehensive "sniffin' sticks" olfactory test, culturally adapted on the Iranian population as well as to examine the discriminatory power of this test between normal people and patients with olfactory disorder. Methods : This cross-sectional study consisted of 3 steps. A total of 200 healthy people were recruited to determine odor familiarity (using Likert- scale) for the first step. In the second step, based on the original sniffin' sticks test and odor familiarity, 16 odor items were selected. Odor modification was performed and the identification part of the sniffin' sticks test was created. Then, 99 patients with olfactory disorders and 214 healthy participants were tested using the Iranian sniffin' sticks test (Ir-SST). After 2 to 4 weeks, participants were reexamined and test reliability was evaluated by using a Pearson correlation coefficient test. Results : The Ir-SST showed that scores of patients with smell loss were significantly lower than normosmic participants (13.6 ± 5.24 vs 34.3 ± 3.41, P < 0.001). The sensitivity (95.2%) and specificity (93.5%) of the test were also found to be high. Test-retest reliability was as follows: composite score: r = 0.8; odor identification: r = 0.83; odor threshold: r = 0.77; and odor discrimination test: r = 0.56; P < 0.001. Conclusion : The results suggest that the Ir-SST can be effectively adapted to the Iranian population. The current study validates that the sniffin' sticks olfactory test is applicable as a useful screening tool for comprehensive assessment of olfactory function in an Iranian population.

14.
J Biomed Mater Res A ; 109(5): 649-658, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32608143

RESUMO

Current hyaluronic acid-based hydrogels often cause cytotoxicity to encapsulated cells and lack the adhesive property required for effective biomedical and tissue engineering applications. Provision of the cell-adhesive surface is an important requirement to improve its biocompatibility. An aqueous solution of hyaluronic acid possessing phenolic hydroxyl (HA-Ph) moieties is gellable via a horseradish peroxidase (HRP)-catalyzed oxidative cross-linking reaction. This study evaluates the effect of different degrees of cross-linked Ph moieties on cellular adhesiveness and proliferation on the resultant enzymatically cross-linked HA-Ph hydrogels. Mechanical characterization demonstrated that the compression force of engineered hydrogels could be tuned in the range of 0.05-35 N by changing conjugated Ph moieties in the precursor formulation. The water contact angle and water content show hydrophobicity of hydrogels increased with increasing content of cross-linked Ph groups. The seeded mouse embryo fibroblast-like cell line and human cervical cancer cell line, on the HA-Ph hydrogel, proved cell attachment and spreading with a high content of cross-linked Ph groups. The HA-Ph with a higher degree of Ph moieties shows the maximum degree of cell adhesion, spreading, and proliferation which presents this hydrogel as a suitable biomaterial for biomedical and tissue engineering applications.


Assuntos
Hidrogéis/farmacologia , Fenol/farmacologia , Animais , Adesão Celular , Encapsulamento de Células , Linhagem Celular , Força Compressiva , Reagentes de Ligações Cruzadas , Feminino , Fibroblastos , Células HeLa , Peroxidase do Rábano Silvestre/farmacologia , Humanos , Ácido Hialurônico/química , Interações Hidrofóbicas e Hidrofílicas , Testes Mecânicos , Camundongos , Água , Suporte de Carga
15.
PLoS One ; 15(9): e0239219, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32941527

RESUMO

Neurodegenerative diseases (NDDs) are increasing serious menaces to human health in the recent years. Despite exhibiting different clinical phenotypes and selective neuronal loss, there are certain common features in these disorders, suggesting the presence of commonly dysregulated pathways. Identifying causal genes and dysregulated pathways can be helpful in providing effective treatment in these diseases. Interestingly, in spite of the considerable researches on NDDs, to the best of our knowledge, no dysregulated genes and/or pathways were reported in common across all the major NDDs so far. In this study, for the first time, we have applied the three-way interaction model, as an approach to unravel sophisticated gene interactions, to trace switch genes and significant pathways that are involved in six major NDDs. Subsequently, a gene regulatory network was constructed to investigate the regulatory communication of statistically significant triplets. Finally, KEGG pathway enrichment analysis was applied to find possible common pathways. Because of the central role of neuroinflammation and immune system responses in both pathogenic and protective mechanisms in the NDDs, we focused on immune genes in this study. Our results suggest that "cytokine-cytokine receptor interaction" pathway is enriched in all of the studied NDDs, while "osteoclast differentiation" and "natural killer cell mediated cytotoxicity" pathways are enriched in five of the NDDs each. The results of this study indicate that three pathways that include "osteoclast differentiation", "natural killer cell mediated cytotoxicity" and "cytokine-cytokine receptor interaction" are common in five, five and six NDDs, respectively. Additionally, our analysis showed that Rps27a as a switch gene, together with the gene pair {Il-18, Cx3cl1} form a statistically significant and biologically relevant triplet in the major NDDs. More specifically, we suggested that Cx3cl1 might act as a potential upstream regulator of Il-18 in microglia activation, and in turn, might be controlled with Rps27a in triggering NDDs.


Assuntos
Redes Reguladoras de Genes , Microglia/imunologia , Doenças Neurodegenerativas/genética , Proteínas Ribossômicas/genética , Ubiquitinas/genética , Quimiocina CXCL1/genética , Humanos , Interleucina-18/genética
16.
Med J Islam Repub Iran ; 34: 62, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32974228

RESUMO

Background: The occurrence of anosmia/hyposmia during novel Coronavirus disease 2019 (COVID-19) may indicate a relationship between coincidence of olfactory dysfunction and coronavirus disease 2019 (COVID-19). This study aimed to assess the frequency of self-reported anosmia/hyposmia during COVID-19 epidemic in Iran. Methods: This population-based cross sectional study was performed through an online questionnaire from March 12 to 17, 2020. Cases from all provinces of Iran voluntarily participated in this study. Patients completed a 33-item patient-reported online questionnaire, including smell and taste dysfunction and their comorbidities, along with their basic characteristics and past medical histories. The inclusion criteria were self-reported anosmia/hyposmia during the past 4 weeks, from the start of COVID-19 epidemic in Iran. Results: A total of 10 069 participants aged 32.5±8.6 (7-78) years took part in this study, of them 71.13% women and 81.68% nonsmokers completed the online questionnaire. The correlation between the number of olfactory disorders and reported COVID-19 patients in all provinces up to March 17, 2020 was highly significant (Spearman correlation coefficient = 0.87, P< 0.001). A sudden onset of olfactory dysfunction was reported in 76.24% of the participations and persistent anosmia in 60.90% from the start of COVID19 epidemic. In addition, 80.38% of participants reported concomitant olfactory and gustatory dysfunctions. Conclusion: An outbreak of olfactory dysfunction occurred in Iran during the COVID-19 epidemic. The exact mechanisms by which anosmia/hyposmia occurred in patients with COVID-19 call for further investigations.

17.
Neurol Sci ; 41(9): 2331-2338, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32656713

RESUMO

BACKGROUND: Olfactory dysfunction has shown to accompany COVID-19. There are varying data regarding the exact frequency in the various study population. The outcome of the olfactory impairment is also not clearly defined. OBJECTIVE: To find the frequency of olfactory impairment and its outcome in hospitalized patients with positive swab test for COVID-19. METHODS: This is a prospective descriptive study of 100 hospitalized COVID-19 patients, randomly sampled, from February to March 2020. Demographics, comorbidities, and laboratory findings were analyzed according to the olfactory loss or sinonasal symptoms. The olfactory impairment and sinonasal symptoms were evaluated by 9 Likert scale questions asked from the patients. RESULTS: Ninety-two patients completed the follow-up (means 20.1 (± 7.42) days). Twenty-two (23.91%) patients complained of olfactory loss and in 6 (6.52%) patients olfactory loss was the first symptom of the disease. The olfactory loss was reported to be completely resolved in all but one patient. Thirty-nine (42.39%) patients had notable sinonasal symptoms while rhinorrhea was the first symptom in 3 (3.26%). Fifteen patients (16.3%) had a taste impairment. Patients with sinonasal symptoms had a lower age (p = 0.01). There was no significant relation between olfactory loss and sinonasal symptoms (p = 0.07). CONCLUSIONS: Sudden olfactory dysfunction and sinonasal symptoms have a considerable prevalence in patients with COVID-19. No significant association was noted between the sinonasal symptoms and the olfactory loss, which may suggest that other mechanisms beyond upper respiratory tract involvement are responsible for the olfactory loss.


Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico por imagem , Hospitalização/tendências , Transtornos do Olfato/diagnóstico por imagem , Seios Paranasais/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Adulto , Idoso , COVID-19 , Infecções por Coronavirus/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Olfato/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Estudos Prospectivos , SARS-CoV-2 , Resultado do Tratamento
18.
Int J Biol Macromol ; 164: 356-370, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32682976

RESUMO

One of the most effective approaches for treatment of chronic rhinosinusitis is the use of hydrogel scaffolds with the sustained release of a given required drug. With this in mind, first, we synthesized and characterized poly (lactide-co-glycolide) (PLGA) micro and nano particles loaded with dexamethasone (DEX). We observed a 7-day release of DEX from nanoparticles, while the microparticles showed a 22-day release profile. Due to their slower rate of release, the PLGA microparticles loaded with DEX (PLGADEX microparticles) were specifically chosen for this study. As a second step, chitosan/polyvinylpyrrolidone (PVP) based hydrogels were prepared in various weight ratios and the PLGADEX microparticles were optimized in their structure based on variable gelation times. The morphological studies showed PLGADEX microparticles homogenously dispersed in the hydrogels. Moreover, the effect of weight ratio in the presence and absence of optimum percentage of PLGADEX microparticles was studied. The resultant hydrogels demonstrated a range of advantages, including good mechanical strength, porous morphology, amorphous structure, high swelling ratio, controlled biodegradability rate, and antibacterial activity. Additionally, a cytotoxicity analysis confirmed that the hydrogel scaffolds do not have adverse effects on the cells; our release studies in the hydrogel with the highest PVP content also showed 80% release after 30 days. Based on these results we were able to predict and control some of the mechanical properties, including the microstructure of the scaffolds, as well as the drug release, by optimizing the polymers - microparticle concentration, plus their resulting interactions. This optimized hydrogel can become part of a suitable alternative for treatment of allergic rhinitis and chronic sinusitis.


Assuntos
Quitosana/química , Dexametasona/administração & dosagem , Portadores de Fármacos/química , Hidrogéis/química , Microesferas , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Pesquisa Biomédica/métodos , Fenômenos Químicos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Hidrólise , Tamanho da Partícula , Porosidade , Análise Espectral , Engenharia Tecidual
19.
Iran J Otorhinolaryngol ; 32(109): 65-71, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32219071

RESUMO

INTRODUCTION: Smell Identification Tests (SIT) are routinely utilized for the clinical evaluation of olfactory function. Since Iran consists of various ethnic subgroups, the reliability and validity of this test as a national SIT are required to be evaluated across the country. MATERIALS AND METHODS: This cross-sectional study evaluated the cultural adaptation of SIT administered to 420 healthy volunteers from 6 various ethnic subgroups (i.e., Fars, Turk, Kurd, Lor, Baluch, and Arab) living in 7 cities (one city for each subgroup, and Tehran [capital of Iran] with mixed ethnicities). The SIT consists of pens pre-filled with 24 odorants. The correct identification response rate was evaluated in all and each subgroup. The test was performed twice on 60 participants with a 2-week interval to assess its reliability. The SIT was further administered to 150 cases with documented abnormal olfactory function to evaluate its validity. RESULTS: The correct identification response rate was estimated at 70% for all odorants in all and each subgroup. The mean odor identification score was 21.41±1.37 (score range: 17- 24) with no significant difference among various subgroups. Moreover, the test-retest correlation coefficient was obtained at 0.77. The mean odor identification score in patients with olfactory impairment was 10.69±3.76, which was significantly different from that in healthy participants (P<0.001). The best cut-point for the beginning of olfactory impairment was 17.5 (95% CI: 9-100, Sensitivity=99, Specificity=81). Females obtained higher scores of odor identification, compared to males (P=0.025). CONCLUSION: The results indicated the reliability and validity of the SIT, which can be used nationally for the assessment of olfactory function in various ethnic subgroups across the country.

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