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1.
Biochem Genet ; 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39320417

RESUMO

The c-Jun N-terminal kinase (JNK) pathway is a signal transduction pathway that plays a critical role in cell growth and survival. Its dysregulation is related to various cancers, including adult T-cell leukemia/lymphoma (ATLL), an aggressive peripheral T-cell malignancy caused by human T-cell lymphotropic virus type 1 (HTLV-1) infection. There is currently no vaccine or definitive treatment for ATLL. This research aimed to identify the JNK-MAPK pathway checkpoints to identify possible therapeutic targets using Boolean network analysis. First, the genes involved in the JNK pathway and their interactions were identified and mapped. Next, a Boolean network analysis was performed using the R programming language, which suggested protein kinase B (AKT) and MAP kinase phosphatase (MKP) for further evaluation. Finally, to confirm the effect of these two genes, a clinical study was conducted among ATLL patients and healthy individuals. The quantitative real time polymerase chain reaction (qRT‒PCR) results revealed a statistically significant decrease in the expression of AKT and MKP in ATLL patients compared to normal controls. This highlights the potential role of these two genes as potential therapeutic targets in ATLL.

2.
Microb Pathog ; 176: 105995, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36681203

RESUMO

Despite the availability of an effective hepatitis B virus (HBV) vaccine and universal immunization schedules, HBV has remained a health problem in various stages such as occult hepatitis B infection (OBI), chronic hepatitis B (CHB), and hepatocellular carcinoma (HCC), which is considered one of the possible phases during chronic HBV infection. OBI is defined as the persistence of HBV genomes in hepatocytes of patients with a negative HBV surface antigen (HBsAg) test and detectable or undetectable HBV DNA in the blood. OBI is occasionally associated with infection caused by mutant viruses that produce a modified HBsAg that is undetected by diagnostic procedures or with replication-defective variations. Many aspects of HBV (OBI more than any other stage) including prevalence, pathobiology, and clinical implications has remained controversial. According to a growing body of research, non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been linked to the development and progression of a number of illnesses, including viral infectious disorders. Despite a shortage of knowledge regarding the expression and biological activities of lncRNAs and miRNAs in HBV infection, Hepatitis B remains a major global public health concern. This review summarizes the role of lncRNAs in the diagnosis and treatment of different stages of hepatitis B infection.


Assuntos
Carcinoma Hepatocelular , Hepatite B Crônica , Hepatite B , Neoplasias Hepáticas , MicroRNAs , RNA Longo não Codificante , Humanos , Antígenos de Superfície da Hepatite B , Neoplasias Hepáticas/patologia , DNA Viral , Vírus da Hepatite B/genética , Hepatite B Crônica/complicações
3.
Rev Med Virol ; 32(2): e2282, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34339073

RESUMO

To date, seven human coronaviruses (HCoVs) have been detected: HCoV-NL63, HCoV-229E, HCoV-HKU1, HCoV-OC43, severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV-2. Four of these viruses, including HCoV-NL63, -229E, -HKU1 and -OC43, usually cause mild-to-moderate respiratory diseases with a seasonal pattern. Since 2000, three new HCoVs have emerged with a significant mortality rate. Although SARS-CoV and MERS-CoV caused an epidemic in some countries, SARS-CoV-2 escalated into a pandemic. All HCoVs can cause severe complications in the elderly and immunocompromised individuals. The bat origin of HCoVs, the presence of intermediate hosts and the nature of their viral replication suggest that other new coronaviruses may emerge in the future. Despite the fact that all HCoVs share similarities in viral replication, they differ in their accessory proteins, incubation period and pathogenicity. This study aims to review these differences between the seven HCoVs.


Assuntos
COVID-19 , Coronavirus Humano 229E , Coronavirus Humano NL63 , Coronavirus Humano OC43 , Idoso , Humanos , SARS-CoV-2
4.
Rev Med Virol ; 32(4): e2316, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34873779

RESUMO

The complement system, as a vital part of innate immunity, has an important role in the clearance of pathogens; however, unregulated activation of this system probably has a key role in the pathogenesis of acute lung injury, which is induced by highly pathogenic viruses (i.e. influenza A viruses and severe acute respiratory syndrome [SARS] coronavirus). The novel coronavirus SARS-CoV-2, which is the causal agent for the ongoing global pandemic of the coronavirus disease 2019 (Covid-19), has recently been spread to almost all countries around the world. Although most people are immunocompetent to SARS-CoV-2, a small group develops hyper-inflammation that leads to complications like acute respiratory distress syndrome, disseminated intravascular coagulation, and multi-organ failure. Emerging evidence demonstrates that the complement system exerts a crucial role in this inflammatory reaction. Additionally, patients with the severe form of Covid-19 show over-activation of the complement in their skin, sera, and lungs. This study aims to summarise current knowledge concerning the interaction of SARS-CoV-2 with the complement system and to critically appraise complement inhibition as a potential new approach for Covid-19 treatment.


Assuntos
Tratamento Farmacológico da COVID-19 , Síndrome do Desconforto Respiratório , Proteínas do Sistema Complemento , Humanos , Inflamação , Pandemias , SARS-CoV-2
5.
Can J Infect Dis Med Microbiol ; 2023: 4263309, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36644336

RESUMO

Hepatitis A virus (HAV) is one of the well-known viruses that cause hepatitis all around the globe. Although this illness has decreased in developed countries due to extensive immunization, numerous developing and under-developed countries are struggling with this virus. HAV infection can be spread by oral-fecal contact, and there are frequent epidemics through nutrition. Improvements in socioeconomic and sanitary circumstances have caused a shift in the disease's prevalence worldwide. Younger children are usually asymptomatic, but as they become older, the infection symptoms begin to appear. Symptoms range from slight inflammation and jaundice to acute liver failure in older individuals. While an acute infection may be self-limiting, unrecognized persistent infections, and the misapplication of therapeutic methods based on clinical guidelines are linked to a higher incidence of cirrhosis, hepatocellular carcinoma, and mortality. Fortunately, most patients recover within two months of infection, though 10-15% of patients will relapse within the first six months. A virus seldom leads to persistent infection or liver damage. The mainstay of therapy is based on supportive care. All children from 12-23 months, as well as some susceptible populations, should receive routine vaccinations, according to the Centers for Disease Control and Prevention and the American Academy of Pediatrics. Laboratory diagnosis of HAV is based on antigen detection, checking liver enzyme levels, and antibody screening. Furthermore, polymerase chain reaction (PCR) technology has identified HAV in suspected nutrition sources; therefore, this technique is used for preventative measures and food-related laws.

6.
Przegl Epidemiol ; 77(2): 136-145, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37823628

RESUMO

Introduction: Subacute thyroiditis (SAT), also known as de Quatrain's thyroiditis or granulomatous thyroiditis, is an inflammatory disease of the thyroid. Most of the time, it manifests in the thirties to fifties and is more common in women. SAT can have either viral or post-viral origin. Some viruses, like influenza, COVID-19, Epstein-Barr virus, cytomegalovirus, hepatitis, coxsackievirus 16, and mumps virus, have been linked to SAT development. The COVID-19 pandemic has affected people's lives all around the world and has changed our attitude toward the treatment of many diseases. It has also made us look deeper into the subject in a way that we would be able to treat this sort of disease with a newer insight. Objective: Regarding the importance of this issue, we decided to summarize our extensive searches from online databases, including PubMed, Google Scholar, Medline, Web of Science, and Scopus until February 2023, which we found effective in elucidating the association of subacute thyroiditis and viral diseases. Method: Different online databases were searched for narrative review articles, systemic review articles, and original articles, which were published until February 2023. Result: According to the included studies, we found that there is a correlation between SAT and several viruses such as Epstein-Barr virus, influenza virus, human immunodeficiency virus, cytomegalovirus, oral and cervical virus, hepatitis, dengue virus, and SARS-COV-2. The effect of each of the viral diseases mentioned in the SAT is given in the text. Conclusions: According to the results mentioned in the text, because SAT may be challenging for early diagnosis, due to the potential of classic symptoms as well as the interference of similar clinical symptoms between thyrotoxicosis and viral reactions, the correlation between SAT and viral diseases should be considered so that we can avoid misdiagnosis and lateness.


Assuntos
COVID-19 , Infecções por Vírus Epstein-Barr , Influenza Humana , Tireoidite Subaguda , Feminino , Humanos , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4 , Pandemias , Polônia , SARS-CoV-2 , Tireoidite Subaguda/complicações , Tireoidite Subaguda/diagnóstico
7.
Virol J ; 19(1): 206, 2022 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-36463213

RESUMO

In December 2019, Coronavirus Disease 2019 (COVID-19) was reported in Wuhan, China. Comprehensive strategies for quick identification, prevention, control, and remedy of COVID-19 have been implemented until today. Advances in various nanoparticle-based technologies, including organic and inorganic nanoparticles, have created new perspectives in this field. These materials were extensively used to control COVID-19 because of their specific attribution to preparing antiviral face masks, various safety sensors, etc. In this review, the most current nanoparticle-based technologies, applications, and achievements against the coronavirus were summarized and highlighted. This paper also offers nanoparticle preventive, diagnostic, and treatment options to combat this pandemic.


Assuntos
COVID-19 , Nanopartículas , Humanos , Antivirais/uso terapêutico , COVID-19/diagnóstico , Pandemias/prevenção & controle
8.
Mol Biol Rep ; 49(1): 647-656, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34648139

RESUMO

The severe acute respiratory syndrome (SARS-CoV-2), a newly emerging of coronavirus, continues to infect humans in the absence of a viable treatment. Neutralizing antibodies that disrupt the interaction of RBD and ACE2 has been under the spotlight as a way of developing the COVID-19 treatment. Some animals, such as llamas, manufacture heavy-chain antibodies that have a single variable domain (VHH) instead of two variable domains (VH/VL) as opposed to typical antibodies. Nanobodies are antigen-specific, single-domain, changeable segments of camelid heavy chain-only antibodies that are recombinantly produced. These types of antibodies exhibit a wide range of strong physical and chemical properties, like high solubility, and stability. The VHH's high-affinity attachment to the receptor-binding domain (RBD) allowed the neutralization of SARS-CoV-2. To tackle COVID-19, some nanobodies are being developed against SARS-CoV-2, some of which have been recently included in clinical trials. Nanobody therapy may be useful in managing the COVID-19 pandemic as a potent and low-cost treatment. This paper describes the application of nanobodies as a new class of recombinant antibodies in COVID-19 treatment.


Assuntos
Tratamento Farmacológico da COVID-19 , Anticorpos de Domínio Único , Animais , Anticorpos Neutralizantes/química , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/farmacologia , Anticorpos Antivirais/química , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/farmacologia , COVID-19/imunologia , COVID-19/terapia , Humanos , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/imunologia , Anticorpos de Domínio Único/química , Anticorpos de Domínio Único/imunologia , Anticorpos de Domínio Único/farmacologia , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo
9.
Biotechnol Appl Biochem ; 69(4): 1348-1353, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34056785

RESUMO

Rabies virus as a neurotropic agent causes rabies in humans and animals. Rabies virus transmission usually occurs through direct contact with saliva of rabid animals. However, serological and molecular tests commonly are used in diagnosing rabies but all the detection methods of rabies have some limitations. It is necessary to develop a rapid, effective, and low-cost biosensor as an alternative tool to detect rabies virus. In this review, we studied related biosensor researches to rabies virus detection for comparing it with other detection test including serological and molecular methods. Given that very limited studies have been conducted in this field, biosensors as quick, effective, and high sensitivity tools can be used in diagnostic of rabies as an alternative tool instead of other detection methods. According to the important role of rapid detection of rabies in the control of infection and public health measures, development of a biosensor as a quick tool can be very significant in the diagnosis of rabies.


Assuntos
Técnicas Biossensoriais , Vírus da Raiva , Raiva , Animais , Humanos , Raiva/diagnóstico , Raiva/prevenção & controle
10.
J Clin Lab Anal ; 36(1): e24151, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34851526

RESUMO

BACKGROUND: To provide information about pathogens' coinfection prevalence with SARS-CoV-2 could be a real help to save patients' lives. This study aims to evaluate the pathogens' coinfection prevalence among COVID-19 patients. METHOD: In order to find all of the relevant articles, we used systematic search approach. Research-based databases including PubMed, Web of Science, Embase, and Scopus, without language restrictions, were searched to identify the relevant bacterial, fungal, and viral coinfections among COVID-19 cases from December 1, 2019, to August 23, 2021. In order to dig deeper, other scientific repositories such as Medrxiv were probed. RESULTS: A total of 13,023 studies were found through systematic search. After thorough analysis, only 64 studies with 61,547 patients were included in the study. The most common causative agents of coinfection among COVID-19 patients were bacteria (pooled prevalence: 20.97%; 95% CI: 15.95-26.46; I2 : 99.9%) and less frequent were virus coinfections (pooled prevalence: 12.58%; 95% CI: 7.31-18.96; I2 : 98.7%). The pooled prevalence of fungal coinfections was also 12.60% (95% CI: 7.84-17.36; I2 : 98.3%). Meta-regression analysis showed that the age sample size and WHO geographic region did not influenced heterogeneity. CONCLUSION: We identified a high prevalence of pathogenic microorganism coinfection among COVID-19 patients. Because of this rate of coinfection empirical use of antibacterial, antifungal, and antiviral treatment are advisable specifically at the early stage of COVID-19 infection. We also suggest running simultaneously diagnostic tests to identify other microbiological agents' coinfection with SARS-CoV-2.


Assuntos
Infecções Bacterianas/epidemiologia , COVID-19/epidemiologia , Coinfecção/epidemiologia , Micoses/epidemiologia , COVID-19/microbiologia , Humanos , Prevalência
11.
Virol J ; 18(1): 248, 2021 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-34903252

RESUMO

BACKGROUND: Vaccination against HCV is an effective measure in reduction of virus-related public health burden and mortality. However, no prophylactic vaccine is available as of yet. DNA-based immunization is a promising modality to generate cellular and humoral immune responses. The objective of this study is to provide a systematic review of HCV DNA vaccines and investigate and discuss the strategies employed to optimize their efficacies. METHODS: MEDLINE (PubMed), Web of Science, Scopus, ScienceDirect, and databases in persian language including the Regional Information Centre for Science & Technology (RICeST), the Scientific Information Database and the Iranian Research Institute for Information Science and Technology (IranDoc) were examined to identify studies pertaining to HCV nucleic acid vaccine development from 2000 to 2020. RESULTS: Twenty-seven articles were included. Studies related to HCV RNA vaccines were yet to be published. A variety of strategies were identified with the potential to optimize HCV DNA vaccines such as incorporating multiple viral proteins and molecular tags such as HBsAg and Immunoglobulin Fc, multi-epitope expression, co-expression plasmid utilization, recombinant subunit immunogens, heterologous prime-boosting, incorporating NS3 mutants in DNA vaccines, utilization of adjuvants, employment of less explored methods such as Gene Electro Transfer, construction of multi- CTL epitopes, utilizing co/post translational modifications and polycistronic genes, among others. The effectiveness of the aforementioned strategies in boosting immune response and improving vaccine potency was assessed. CONCLUSIONS: The recent progress on HCV vaccine development was examined in this systematic review to identify candidates with most promising prophylactic and therapeutic potential.


Assuntos
Hepatite C , Vacinas de DNA , Vacinas contra Hepatite Viral , Animais , Hepacivirus/genética , Humanos , Irã (Geográfico) , Camundongos , Camundongos Endogâmicos BALB C , Vacinas de DNA/genética , Vacinas contra Hepatite Viral/genética
12.
Acta Med Indones ; 53(1): 86-95, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33818411

RESUMO

The global widespread mortality after the emergence of SARS-CoV-2 infection in China, has become a critical concern all around the world. Convalescent plasma (CP) therapy is one of the methods elevating the survival rate for COVID-19 infection cases. This technique, as a practicable therapy, was used in previous viral outbreaks including influenza, SARS and MERS. In CP therapy, the blood plasma is collected from persons rehabilitated from that specific infection in order to develop a passive immunity in other patients. Therefore, this review aimed to point out the role of CP therapy in aforementioned viral infections and illustrate different factors influencing the efficacy of CP therapy.


Assuntos
COVID-19/terapia , Infecções por Coronavirus/terapia , SARS-CoV-2/imunologia , Síndrome Respiratória Aguda Grave/terapia , Anticorpos Antivirais/sangue , COVID-19/epidemiologia , COVID-19/imunologia , Humanos , Imunização Passiva/métodos , Resultado do Tratamento , Soroterapia para COVID-19
13.
Acta Med Indones ; 53(3): 339-348, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34611075

RESUMO

In this era, the novel Coronavirus, referred to as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a life-threatening virus with a high mortality rate (4.2%) and with no absolute treatment as of yet, may ultimately result in acute respiratory distress syndrome (ARDS). ARDS is one of the fatal complications, highlighted by pulmonary infiltration and severe hypoxemia. This condition can be developed from primary lung inflammation caused by various viruses, particularly influenza viruses, some of the most common human pathogens. Due to this issue, many studies explored several approaches for ARDS treatment. Lung transplantation has been claimed as an efficient cure for severe ARDS and Influenza, which can also be offered for treating critical lung complications of SARS-CoV-2. Thereupon, to the best of our knowledge for the first time, we aimed to review all available data about capability of lung transplantation for the treatment of critically ill patients with ARDS, Influenza, and SARS-CoV-2.


Assuntos
COVID-19/cirurgia , Influenza Humana/cirurgia , Transplante de Pulmão , Pneumonia Viral , COVID-19/diagnóstico , Humanos , Influenza Humana/diagnóstico , Transplante de Pulmão/efeitos adversos , Transplante de Pulmão/métodos , Orthomyxoviridae/isolamento & purificação , Pneumonia Viral/etiologia , Pneumonia Viral/cirurgia , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença
14.
ACS Appl Mater Interfaces ; 15(36): 42251-42270, 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37647536

RESUMO

Dysfunctional clinical outcomes following spinal cord injury (SCI) result from glial scar formation, leading to the inhibition of new axon growth and impaired regeneration. Nevertheless, nerve regeneration after SCI is possible, provided that the state of neuron development in the injured environment is improved. Hence, biomaterial-based therapy would be a promising strategy to endow a desirable environment for tissue repair. Herein, we designed a novel multifunctional injectable hydrogel with antioxidant, neuroprotective, and neuroregenerative effects. Bucladesine-encapsulated chitosan nanoparticles (BCS NPs) were first prepared and embedded in a matrix of thiol-functionalized hyaluronic acid modified with ferulic acid (HASH-FA). The target hydrogel (HSP-F/BCS) was then created through Michael-type addition between HASH-FA containing BCS NPs and four-arm polyethylene glycol-maleimide (4-Arm-PEG-Mal). The obtained hydrogel with shear thinning behavior showed viscoelastic and mechanical properties similar to the normal nerve tissue. FA conjugation significantly improved the antioxidant activity of HA, and suppressed intracellular ROS formation. In situ injection of the HSP-F/BCS hydrogel in a rat contusion model of SCI inhibited glial scar progression, reduced microglia/macrophage infiltration, promoted angiogenesis, and induced myelinated axon regeneration. As a result, a significant improvement in motor performance was observed compared to other experimental groups. Taken together, the HSP-F/BCS hydrogel developed in this study could be a promising system for SCI repair.


Assuntos
Traumatismos da Medula Espinal , Regeneração da Medula Espinal , Animais , Ratos , Bucladesina , Axônios , Gliose , Traumatismos da Medula Espinal/tratamento farmacológico , Antioxidantes/farmacologia , Hidrogéis/farmacologia
15.
Virusdisease ; 34(1): 21-28, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37009253

RESUMO

Neuraminidase inhibitors are the only FDA-approved class of antiviral agents against influenza B viruses. Resistance to these drugs has been reported from different parts of the world; however, there seems to be not enough information about this issue in Iran. We aimed to study the genetic evolution of these viruses as well as the presence of possible mutations concerning drug resistance in northern Iran. RNA was extracted from naso- and oropharyngeal swabs and amplified by one-step RT-PCR for detection and sequencing of the neuraminidase gene. All the data were edited and assembled utilizing BioEdit DNASequence Alignment Editor Software, and the phylogenetic tree was constructed via MEGA software version 10. Finally, resistance-associated mutations and B-cell epitopes substitutions were assessed by comparing our sequences with the counterparts in the reference strains. Comparing our sequences with reference strains revealed that the analyzed isolates of influenza B pertained to the B-Yamagata lineage, had a few B-cell epitopes alterations, and contained no particular mutations concerning resistance against neuraminidase inhibitors, such as oseltamivir. Our findings suggest that all the strains circulating in northern Iran and hopefully other parts of the country can be considered sensitive to this class of drugs. Although it is promising, we strongly recommend additional investigations to evaluate the impact of such drug-resistant mutations in other regions, which in turn will assist the public health agencies in taking immediate and effective therapeutic measures into account when needed.

16.
Iran J Microbiol ; 15(3): 475-481, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37448673

RESUMO

Background and Objectives: HTLV-1 is responsible for two important diseases, HAM/TSP and ATLL. Approximately 10 to 20 million people are infected with HTLV-1 worldwide. Identifying altered genes in different cancers is crucial for finding potential treatment strategies. One of the proteins of the RAS/MAPK signaling pathway is MEK1, which is made from the MAP2K1 gene. The effects of the MAP2K1 gene on the MAPK signaling pathway are not yet fully elucidated. The current study aims to determine the MAP2K1 gene mutations and the level of MAP2K1 gene expression in ATLL patients compared to healthy individuals. Materials and Methods: Ten ATLL and 10 healthy control individuals were investigated in this study. We used ELISA test to screen anti-HTLV-I antibodies and PCR for confirmation of infection. Then, we extracted total RNA from fresh whole blood, and cDNA was synthesized. The expression levels of the MAP2K1 gene were examined by qRT-PCR, and to check possible mutations in the MAP2K1 gene; all samples were sequenced and analyzed by BioEdite Software. Results: MAP2K1 gene expression in the ATLL group was significantly higher than in the healthy control (P=0.001). The mutational sequencing analysis showed nucleotide 212 (S→R) change and identification mutations at different nucleotides that were entirely different from the nucleotide mutations defined in the UniProt database. Conclusion: These results could be a perspective in the prevention, prognosis, and targeted treatment of diseases in which the MAP2K1 gene plays a vital role.

17.
Life Sci ; 329: 121990, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37524159

RESUMO

AIM: Parkinson's Disease (PD) is a common age-related neurodegenerative disorder with a rising prevalence. Human pluripotent stem cells have emerged as the most promising source of cells for midbrain dopaminergic (mDA) neuron replacement in PD. This study aimed to generate transplantable mDA progenitors for treatment of PD. MATERIALS AND METHODS: Here, we optimized and fine-tuned a differentiation protocol using a combination of small molecules and growth factors to induce mDA progenitors to comply with good manufacturing practice (GMP) guidelines based on our clinical-grade human embryonic stem cell (hESC) line. KEY FINDINGS: The resulting mDA progenitors demonstrated robust differentiation and functional properties in vitro. Moreover, cryopreserved mDA progenitors were transplanted into 6-hydroxydopamine-lesioned rats, leading to functional recovery. SIGNIFICANCE: We demonstrate that our optimized protocol using a clinical hESC line is suitable for generating clinical-grade mDA progenitors and provides the ground work for future translational applications.


Assuntos
Células-Tronco Embrionárias Humanas , Doença de Parkinson , Células-Tronco Pluripotentes , Humanos , Ratos , Animais , Doença de Parkinson/terapia , Doença de Parkinson/metabolismo , Neurônios Dopaminérgicos/fisiologia , Diferenciação Celular , Dopamina/metabolismo , Mesencéfalo/metabolismo
18.
Infect Agent Cancer ; 18(1): 12, 2023 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-36841815

RESUMO

BACKGROUND: Adult T-cell Lymphoma/Leukemia (ATLL) is characterized by the malignant proliferation of T-cells in Human T-Lymphotropic Virus Type 1 and a high mortality rate. Considering the emerging roles of microRNAs (miRNAs) in various malignancies, the analysis of high-throughput miRNA data employing computational algorithms helps to identify potential biomarkers. METHODS: Weighted gene co-expression network analysis was utilized to analyze miRNA microarray data from ATLL and healthy uninfected samples. To identify miRNAs involved in the progression of ATLL, module preservation analysis was used. Subsequently, based on the target genes of the identified miRNAs, the STRING database was employed to construct protein-protein interaction networks (PPIN). Real-time quantitative PCR was also performed to validate the expression of identified hub genes in the PPIN network. RESULTS: After constructing co-expression modules and then performing module preservation analysis, four out of 15 modules were determined as ATLL-specific modules. Next, the hub miRNA including hsa-miR-18a-3p, has-miR-187-5p, hsa-miR-196a-3p, and hsa-miR-346 were found as hub miRNAs. The protein-protein interaction networks were constructed for the target genes of each hub miRNA and hub genes were identified. Among them, UBB, RPS15A, and KMT2D were validated by Reverse-transcriptase PCR in ATLL patients. CONCLUSION: The results of the network analysis of miRNAs and their target genes revealed the major players in the pathogenesis of ATLL. Further studies are required to confirm the role of these molecular factors and to discover their potential benefits as treatment targets and diagnostic biomarkers.

19.
Zebrafish ; 19(4): 137-147, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35905303

RESUMO

The dopaminergic system, a spinal cord (SC) motor circuit regulator, is administrated by sexual hormones and evolutionary conserved in all vertebrates. Accordingly, we hypothesized that the dopamine receptor (DAR) expression pattern may be dissimilar in female and male zebrafish SC auto repair. We implemented an uncomplicated method to induce spinal cord injury (SCI) on fully reproductive adult zebrafish, in both genders. SCI was induced using a 28-gauge needle at 9th-10th vertebra without skin incision. Thereupon, lesioned SC was harvested for DAR gene expression analysis; zebrafish were tracked routinely for any improvement in swim distance, speed, and their roaming capabilities/preference. Our findings revealed discrepancies between drd2a, drd2b, drd3, drd4a, and drd4b expression patterns at 1, 7, and 14 days postinjury (DPI) between female and male zebrafish. The receptors were mostly upregulated at 7 DPI in both genders, whereas drd2a and drd2b were mostly maximized in females. Surprisingly, drd3 was measured greater even in intact SC in males. In addition, female zebrafish were able to swim farther distances more accelerated, in multiple directions, by engaging more caudal muscles compared with males, of course with no statistical significance. Indeed, females were able to generate whole-body rotation and move forward using the muscles downstream to the lesion site, whereas the coordinated movement in males was accomplished by rostral muscles. In conclusion, there are differences in DAR gene expression pattern throughout SC autonomous recovery between adult female and male zebrafish, and also, female locomotion seems to ameliorate more rapidly.


Assuntos
Traumatismos da Medula Espinal , Peixe-Zebra , Animais , Dopamina/metabolismo , Feminino , Expressão Gênica , Locomoção/fisiologia , Masculino , Receptores Dopaminérgicos/genética , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/metabolismo , Peixe-Zebra/genética , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
20.
Front Mol Biosci ; 9: 804109, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35495619

RESUMO

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has led to huge concern worldwide. Some SARS-CoV-2 infected patients may experience post-COVID-19 complications such as multisystem inflammatory syndrome, defined by symptoms including fever and elevated inflammatory markers (such as elevation of C reactive protein (CRP), erythrocyte sedimentation rate, fibrinogen, procalcitonin test, D-dimer, ferritin, lactate dehydrogenase or IL-6, presence of neutrophilia, lymphopenia, decreased albumin, and multiple organ dysfunction). Post-COVID-19 complications may also manifest as autoimmune diseases such as Guillain-Barré syndrome and systemic lupus erythematosus. Signaling disorders, increased inflammatory cytokines secretion, corticosteroid use to treat COVID-19 patients, or impaired immune responses are suggested causes of autoimmune diseases in these patients. In this review, we discuss the molecular and pathophysiological mechanisms and therapeutic opportunities for multisystem inflammatory syndrome and autoimmune diseases following SARS-CoV-2 infection with the aim to provide a clear view for health care providers and researchers.

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