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1.
J Pharm Bioallied Sci ; 16(Suppl 3): S2140-S2142, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39346438

RESUMO

The present study aimed to examine the extraction of impacted mandibular third molars by using rotatory and piezosurgery equipment. Twenty-five patients of both genders who required surgery to remove their third molars were split into two groups (control group and research group). In the surgical extraction of the impacted mandibular third molar, in the study group, a piezotome was used to remove the bone, while in the control group, a bur was used. Patients' acceptance of bone cutting, the length of the operation, discomfort and bleeding during the procedure, postoperative pain, swelling, trismus, and wound healing were evaluated. A statistically insignificant difference was observed for age and difficulty index. The intraoperative bleeding was similar in both groups. Both the groups tolerated the bone cutting well, with slightly better values for the piezo group. Based on Pederson's difficulty index, the scores of difficulty of extraction of the impacted tooth were measured between the groups. The slight difficulty was observed in 9 (36%) each in the study group and control group. The moderate difficulty in 14 (56%) of control group and 15 (60%) of study group. Severe difficulty was found among 2 (8%) in the control group and 1 (4%) in the study group. The difference was not significant (P > 0.05). Intraoral bleeding was moderately seen in 25 in both groups. Among the study and control groups respectively no intraoperative pain was seen in 14 and 16, mild intraoperative pain in 11 and 7, and moderate intraoperative pain in 0 and 2. Among group I and II acceptance to bone cutting was comfortably seen in 24 and 23, bearable in 1 and 2 respectively. The difference was not significant (P > 0.05). Piezosurgery and bur were comparable in evaluating patient acceptance, intraoperative duration, intraoperative bleeding and pain, postoperative pain, edema, trismus, and wound healing.

2.
PeerJ Comput Sci ; 10: e2062, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39145255

RESUMO

The SARS-CoV-2 virus, which induces an acute respiratory illness commonly referred to as COVID-19, had been designated as a pandemic by the World Health Organization due to its highly infectious nature and the associated public health risks it poses globally. Identifying the critical factors for predicting mortality is essential for improving patient therapy. Unlike other data types, such as computed tomography scans, x-radiation, and ultrasounds, basic blood test results are widely accessible and can aid in predicting mortality. The present research advocates the utilization of machine learning (ML) methodologies for predicting the likelihood of infectious disease like COVID-19 mortality by leveraging blood test data. Age, LDH (lactate dehydrogenase), lymphocytes, neutrophils, and hs-CRP (high-sensitivity C-reactive protein) are five extremely potent characteristics that, when combined, can accurately predict mortality in 96% of cases. By combining XGBoost feature importance with neural network classification, the optimal approach can predict mortality with exceptional accuracy from infectious disease, along with achieving a precision rate of 90% up to 16 days before the event. The studies suggested model's excellent predictive performance and practicality were confirmed through testing with three instances that depended on the days to the outcome. By carefully analyzing and identifying patterns in these significant biomarkers insightful information has been obtained for simple application. This study offers potential remedies that could accelerate decision-making for targeted medical treatments within healthcare systems, utilizing a timely, accurate, and reliable method.

3.
Nanoscale ; 16(29): 14006-14019, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-38989622

RESUMO

Local recurrence post-surgery in early-stage triple-negative breast cancer is a major challenge. To control the regrowth of a residual tumor, we have developed an autologous therapeutic hybrid fibrin glue for intra-operative implantation. Using autologous serum proteins as stabilizers, we have optimized high drug-loaded lapatinib-NanoSera (Lap-NS; ∼66% L.C.) and imiquimod-MicroSera (IMQ-MS; ∼92% L.C). Additionally, plasmonic nanosera (PNS) with an ∼67% photothermal conversion efficiency under 980 nm laser irradiation was also developed. While localized monotherapy with either Lap-NS or PNS reduced the tumor regrowth rate, their combination with IMQ-MS amplified the effect of immunogenic cell death with a high level of tumor infiltration by immune cells at the surgical site. The localized combination immunotherapy with a Nano-MicroSera based hybrid fibrin implant showed superior tumor inhibition and survival with significant promise for clinical translation.


Assuntos
Imiquimode , Feminino , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Imiquimode/química , Imiquimode/farmacologia , Lapatinib/química , Lapatinib/farmacologia , Imunoterapia , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Recidiva Local de Neoplasia/prevenção & controle , Fibrina/química , Neoplasias de Mama Triplo Negativas/terapia , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Adesivo Tecidual de Fibrina/química , Adesivo Tecidual de Fibrina/farmacologia , Camundongos Endogâmicos BALB C , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico
4.
J Stomatol Oral Maxillofac Surg ; 125(4S): 101944, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38852622

RESUMO

Throat packing is essential in oral and maxillofacial surgeries to prevent blood and tissue debris aspiration, reducing postoperative complications. Traditional oral route methods are often inadequate, especially in severe trismus cases like Oral Submucous Fibrosis (OSMF), TMJ Ankylosis, and post-traumatic conditions due to limited mouth opening. This study introduces a novel technique using a nasopharyngeal airway (NPA) for throat packing. The method involves inserting a hemostatic dressing through an NPA, ensuring minimal invasiveness and effective airway management. Proper positioning is confirmed with a laryngoscope or fiberoptic scope, and the dressing is secured to prevent dislodgement. This technique is easy, reproducible, and less injurious compared to traditional methods. At our center, throat packing via NPA was performed on 35 patients undergoing surgery under general anesthesia, resulting in high satisfaction and no reported complications.


Assuntos
Anestesia Geral , Trismo , Humanos , Trismo/cirurgia , Trismo/etiologia , Trismo/terapia , Anestesia Geral/métodos , Masculino , Feminino , Faringe/cirurgia , Adulto , Pessoa de Meia-Idade , Nasofaringe/cirurgia , Bandagens
5.
Int J Biol Macromol ; 258(Pt 2): 129051, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38159703

RESUMO

In order to deepen our understanding of the virus and help guide the creation of efficient therapies, this study uses artificial intelligence tools to thoroughly explore the genetic sequences of the SARS-CoV-2 virus. The process starts by using the Fuzzy Closure Miner for Frequent Itemsets (FCMFI) on a large corpus of SARS-CoV-2 genomic sequences to reveal hidden patterns, including nucleotides base sequences, repeating motifs, and corresponding interchanges. Then, using the Nucleotide Sequence Comprehension Engine (NSCE) technique, we were able to precisely define the genomic areas for mutation analysis. Structured and unstructured proteins are both strongly impacted by virus mutations, with spike proteins that are linked to the severity of COVID-19 pneumonia being particularly affected. Notably, the Mutagenic Anomaly Detector shows a 65 % efficiency boost in computing genome mutation rates compared to conventional point mutation analysis, while GenoAnalyzer offers a remarkable 93.33 % improvement over existing approaches in recognizing common genomic sequence patterns. These results highlight the potential of FCMFI to reveal complex genomic patterns and significant insights in COVID-19 genetic sequences when combined with mutation analysis. The Mutagenic Anomaly Detector and GenoAnalyzer show promise for revealing hidden genomic patterns and precisely estimating the SARS-CoV-2 mutation rate.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Mutagênicos , Inteligência Artificial , Mutação , Filogenia
6.
Int J Mol Sci ; 24(18)2023 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-37762579

RESUMO

Oxidative stress-mediated damage is often a downstream result of Parkinson's disease (PD), which is marked by sharp decline in dopaminergic neurons within the nigrostriatal regions of the brain, accounting for the symptomatic motor deficits in patients. Regulating the level of oxidative stress may present a beneficial approach in preventing PD pathology. Here, we assessed the efficacy of a nicotinamide adenine phosphate (NADPH) oxidase (NOX) inhibitor, an exogenous reactive oxygen species (ROS) regulator synthesized by Aptabio therapeutics with the specificity to NOX-1, 2 and 4. Utilizing N27 rat dopaminergic cells and C57Bl/6 mice, we confirmed that the exposures of alpha-synuclein preformed fibrils (PFF) induced protein aggregation, a hallmark in PD pathology. In vitro assessment of the novel compound revealed an increase in cell viability and decreases in cytotoxicity, ROS, and protein aggregation (Thioflavin-T stain) against PFF exposure at the optimal concentration of 10 nM. Concomitantly, the oral treatment alleviated motor-deficits in behavioral tests, such as hindlimb clasping, rotarod, pole, nesting and grooming test, via reducing protein aggregation, based on rescued dopaminergic neuronal loss. The suppression of NOX-1, 2 and 4 within the striatum and ventral midbrain regions including Substantia Nigra compacta (SNc) contributed to neuroprotective/recovery effects, making it a potential therapeutic option for PD.


Assuntos
Doença de Parkinson , Humanos , Camundongos , Ratos , Animais , Doença de Parkinson/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Agregados Proteicos , alfa-Sinucleína/metabolismo , Encéfalo/metabolismo , Parte Compacta da Substância Negra/metabolismo , Neurônios Dopaminérgicos/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
7.
Surg Neurol Int ; 14: 276, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37680910

RESUMO

Background: Optic nerve sheath diameter (ONSD) has been shown to be a noninvasive and quick method to calculate intracranial pressure (ICP) and subsequent neurologic outcomes, although with variable cutoffs. ICP can be indirectly assessed by noninvasive methods such as transcranial Doppler, ONSD, tympanic membrane displacement, and fundoscopy. Knowledge regarding the diagnostic accuracy of ONSD for predicting unfavorable outcomes within 72 hours (h) of moderate and severe head injury is limited. The objective of this study was to measure ONSD measurements at 24-h intervals in moderate to severe head injury patients and to find its association with clinical outcomes in the target population. Methods: This prospective observational study was done on moderate to severe head injury patients. ONSD was measured twice at 24-h intervals over 48 h. The clinical outcome was divided into the favorable group (patients who were in conservative treatment with a stable Glasgow Coma Scale [GCS] score and discharged following treatment) and the unfavorable group (patients who had a drop in GCS motor score of one or more, or expired or underwent surgical intervention) within 72 h following traumatic brain injury. The Kruskal-Wallis test, Mann- Whitney test, and receiver operating characteristic curves were used to establish the association between ONSD and clinical outcomes. Results: ONSD values measured at 24-h intervals >6.1 mm (P < 0.0146) and 6.2 mm (P < 0.0001) were found to be predictors of unfavorable outcomes (expired or underwent surgery), and hence the need for a secondary decompressive craniectomy (DC). Conclusion: ONSD is an efficient screening tool to assess neurological outcomes in severe head injury patients. It can reliably predict the need for secondary DC at an earlier stage before secondary brain damage ensues in these patients.

8.
J Maxillofac Oral Surg ; 21(3): 1015-1022, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36274883

RESUMO

Purpose: The present work was a pilot study undertaken to evaluate the effectiveness of amoxicillin and clavulanic acid impregnated plaster of paris beads for prevention of infection of third molar extraction sockets. Materials and Methods: This was a prospective, randomized, split mouth clinical trial done on 16 patients (32 sites) who required surgical extraction of mandibular third molars. Control arm patients were given Tab. amoxicillin 500 mg with clavulanic acid 125 mg (Tab. Klavimed 625 mg, Indomed, India), thrice daily for 3 days after extraction, whereas test arm patients received Antibiotic Impregnated Microbeads (AIM), containing Amoxicillin 500 mg and Clavulanic Acid 100 mg placed in situ in the extraction socket. The primary outcome parameter was infection and the secondary outcome parameters were pain, trismus, swelling and wound healing. Results: None of the patients in either group had post operative infection. There was no significant difference in pain intensity between the two groups (1st day p = 0.41; 3rd day p = 0.38, 7th day p = 0.37). Both the groups were also similar with respect to swelling (p = 0.596, 0.146, 0.871, 0.820 on 1st, 3rd, 7th, 15th post-op day ,respectively). Conclusion: Amoxycillin with clavulanic acid impregnated PoP beads appears to be as effective as oral 3 day amoxicillin with clavulanic acid regime for prevention of 3 M socket infection.

9.
RSC Adv ; 12(29): 18685-18696, 2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35873343

RESUMO

Nanoporous zinc borate (ZB) and 10% lanthanum-doped porous zinc borate (LZB) were synthesized to explore the role of porosity and doping in zinc borate during lubrication. HR-SEM, TEM, and HR-TEM authenticated nanoporous structures. The tribological properties of their blends with paraffin oil (PO) were compared by employing ASTM D4172 and ASTM D5183 norms on a four-ball tester. Vanadium selenide nanosheets (VSe2) were used to reinforce the structure of LZB for further advancement of the tribological properties. The superiority of the LZB/VSe2 over LZB and VSe2 nanosheets could be adjudged by tribological data. The porosity and lanthanum doping have yielded commendable tribological activity. The VSe2 nanosheets have strengthened the LZB matrix. The other constituent oxides of tribofilm from the LZB matrix, based on EDX analysis and XPS studies of the worn surface, ZnO, B2O3, La2O3, and V2O5, have abetted lubrication. The AFM and SEM investigations of wear track corroborated the tribological results.

10.
J Stomatol Oral Maxillofac Surg ; 123(6): e962-e972, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35803558

RESUMO

Over the recent years, Artificial Intelligence (AI) has been progressing rapidly with its ability to mimic human cognitive functions. The potential applications of AI technology in diagnosis, treatment planning, and prognosis prediction have been demonstrated in various studies. The present scoping review aimed to provide an overview of AI and Machine Learning (ML) algorithms and their applications in orthognathic surgery. A comprehensive search was conducted in databases including PubMed, Embase, Scopus, Web of Science and OVID Medline until November 2021. This scoping review was conducted following the PRISMA-ScR guidelines. After applying the inclusion and exclusion criteria, a total of 19 studies were included for final review. AI has profoundly impacted the diagnosis and prediction of orthognathic surgeries with a clinically acceptable accuracy range. Furthermore, AI reduces the work burden of the clinician by eliminating the tedious registration procedures, thereby helping in efficient and automated planning. However, focussing on the research gaps, there is a need to foster the AI models/algorithms to contemporize their efficiency in clinical decision making, diagnosis and surgical planning in future studies.


Assuntos
Cirurgia Ortognática , Procedimentos Cirúrgicos Ortognáticos , Humanos , Inteligência Artificial , Aprendizado de Máquina
11.
Int J Mol Sci ; 23(8)2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35457082

RESUMO

Parkinson's disease (PD) is a progressive neurodegenerative motor disorder without an available therapeutic to halt the formation of Lewy bodies for preventing dopaminergic neuronal loss in the nigrostriatal pathway. Since oxidative-stress-mediated damage has been commonly reported as one of the main pathological mechanisms in PD, we assessed the efficacy of a novel NOX inhibitor from AptaBio Therapeutics (C-6) in dopaminergic cells and PD mouse models. The compound reduced the cytotoxicity and enhanced the cell viability at various concentrations against MPP+ and α-synuclein preformed fibrils (PFFs). Further, the levels of ROS and protein aggregation were significantly reduced at the optimal concentration (1 µM). Using two different mouse models, we gavaged C-6 at two different doses to the PD sign-displaying transgenic mice for 2 weeks and stereotaxically PFF-injected mice for 5 weeks. Our results demonstrated that both C-6-treated mouse models showed alleviated motor deficits in pole test, hindlimb clasping, crossbeam, rotarod, grooming, and nesting analyses. We also confirmed that the compound treatment reduced the levels of protein aggregation, along with phosphorylated-α-synuclein, in the striatum and ventral midbrain and further dopaminergic neuronal loss. Taken together, our results strongly suggest that NOX inhibition can be a potential therapeutic target for PD.


Assuntos
Doença de Parkinson , alfa-Sinucleína , Animais , Modelos Animais de Doenças , Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Camundongos , Camundongos Transgênicos , Degeneração Neural/patologia , Doença de Parkinson/metabolismo , Agregados Proteicos , alfa-Sinucleína/metabolismo
13.
Natl J Maxillofac Surg ; 13(3): 457-461, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36683921

RESUMO

Introduction: Patients suffering temporomandibular joint internal disc derangement (IDD) ignore appointments after the first examination or after the first or second sessions of initial treatment. The dropout rate for these patients varies from 36% to 78% as per literature. Unfortunately, very few studies have investigated the dropout rate of these patients. Hence, the present study was undertaken to find out the dropout rate among these kinds of patients. Material and Methods: A retrospective study was done from June 2008 to December 2017 by collecting the records of the patients who were diagnosed to have IDD. Outcome variables included were age, sex, distance traveled, occupation, and education. Results: Out of 1021 patients 766 patients were included in the study after fulfilling the inclusion and exclusion criteria. The data were analyzed using Chi-square test. The level of significance was set at <0.05. In this study, there is slight male predominance (52.8%) and 63.1% (21-40 years) were among young adults and the patients in the age group of 21-30 years had shown good compliance, Postgraduate has shown the highest follow-up rate when compared with graduates and school level and the difference was found to be statistically significant. People in the job had shown good compliance when compared with business class and retired people and the patients within 50 km had shown the maximum follow-up with a statistically significant difference (P < 0.01). Conclusion: This study has shown that the dropout rate of treatment in temporomandibular joint disorder is affected by age, sex, distance traveled, occupation, and education.

15.
Cells ; 10(7)2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-34359864

RESUMO

Emerging evidence indicates that cellular senescence could be a critical inducing factor for aging-associated neurodegenerative disorders. However, the involvement of cellular senescence remains unclear in Parkinson's disease (PD). To determine this, we assessed the effects of α-synuclein preformed fibrils (α-syn PFF) or 1-methyl-4-phenylpyridinium (MPP+) on changes in cellular senescence markers, employing α-syn PFF treated-dopaminergic N27 cells, primary cortical neurons, astrocytes and microglia and α-syn PFF-injected mouse brain tissues, as well as human PD patient brains. Our results demonstrate that α-syn PFF-induced toxicity reduces the levels of Lamin B1 and HMGB1, both established markers of cellular senescence, in correlation with an increase in the levels of p21, a cell cycle-arrester and senescence marker, in both reactive astrocytes and microglia in mouse brains. Using Western blot and immunohistochemistry, we found these cellular senescence markers in reactive astrocytes as indicated by enlarged cell bodies within GFAP-positive cells and Iba1-positive activated microglia in α-syn PFF injected mouse brains. These results indicate that PFF-induced pathology could lead to astrocyte and/or microglia senescence in PD brains, which may contribute to neuropathology in this model. Targeting senescent cells using senolytics could therefore constitute a viable therapeutic option for the treatment of PD.


Assuntos
Senescência Celular , Doença de Parkinson/patologia , alfa-Sinucleína/metabolismo , 1-Metil-4-fenilpiridínio , Animais , Astrócitos/metabolismo , Astrócitos/patologia , Biomarcadores/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Linhagem Celular , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Modelos Animais de Doenças , Neurônios Dopaminérgicos/metabolismo , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Proteína HMGB1/metabolismo , Proteínas de Homeodomínio/metabolismo , Humanos , Lamina Tipo B/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Microglia/patologia , Mudanças Depois da Morte , Ratos
16.
J Virol ; 95(13): e0019221, 2021 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-33853968

RESUMO

Understanding factors that affect the infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is central to combatting coronavirus disease 2019 (COVID-19). The virus surface spike protein of SARS-CoV-2 mediates viral entry into cells by binding to the ACE2 receptor on epithelial cells and promoting fusion. We found that Epstein-Barr virus (EBV) induces ACE2 expression when it enters the lytic replicative cycle in epithelial cells. By using vesicular stomatitis virus (VSV) particles pseudotyped with the SARS-CoV-2 spike protein, we showed that lytic EBV replication enhances ACE2-dependent SARS-CoV-2 pseudovirus entry. We found that the ACE2 promoter contains response elements for Zta, an EBV transcriptional activator that is essential for EBV entry into the lytic cycle of replication. Zta preferentially acts on methylated promoters, allowing it to reactivate epigenetically silenced EBV promoters from latency. By using promoter assays, we showed that Zta directly activates methylated ACE2 promoters. Infection of normal oral keratinocytes with EBV leads to lytic replication in some of the infected cells, induces ACE2 expression, and enhances SARS-CoV-2 pseudovirus entry. These data suggest that subclinical EBV replication and lytic gene expression in epithelial cells, which is ubiquitous in the human population, may enhance the efficiency and extent of SARS-CoV-2 infection of epithelial cells by transcriptionally activating ACE2 and increasing its cell surface expression. IMPORTANCE SARS-CoV-2, the coronavirus responsible for COVID-19, has caused a pandemic leading to millions of infections and deaths worldwide. Identifying the factors governing susceptibility to SARS-CoV-2 is important in order to develop strategies to prevent SARS-CoV-2 infection. We show that Epstein-Barr virus, which infects and persists in >90% of adult humans, increases susceptibility of epithelial cells to infection by SARS-CoV-2. EBV, when it reactivates from latency or infects epithelial cells, increases expression of ACE2, the cellular receptor for SARS-CoV-2, enhancing infection by SARS-CoV-2. Inhibiting EBV replication with antivirals may therefore decrease susceptibility to SARS-CoV-2 infection.


Assuntos
Enzima de Conversão de Angiotensina 2/genética , Células Epiteliais/virologia , Herpesvirus Humano 4/fisiologia , SARS-CoV-2/fisiologia , Internalização do Vírus , Replicação Viral , Enzima de Conversão de Angiotensina 2/metabolismo , Linhagem Celular , Metilação de DNA , Células Epiteliais/metabolismo , Regulação da Expressão Gênica , Humanos , Regiões Promotoras Genéticas , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Transativadores/metabolismo , Ativação Viral
18.
J Pediatr Neurosci ; 16(4): 350-353, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-36531764

RESUMO

Rathke cleft cysts are benign lesions of the sellar and suprasellar region. Extrasellar intrasphenoidal Rathke cleft cysts are rare with only one case reported in pediatric age group. The presenting complaints described include headache and diplopia. We report a case of intrasphenoidal Rathke cleft cyst in a 15-year-old girl who presented with headache and visual disturbances. Neuroimaging showed an expansile cystic lesion involving the sphenoid sinus with mass effect over the pituitary and optic chiasma. Endoscopic decompression of the cystic lesion was done and histopathology of the cyst wall revealed it to be Rathke cleft cyst. Follow-up MRI showed total resection of the cystic lesion with residual partial left optic nerve atrophy.

19.
eNeuro ; 7(5)2020.
Artigo em Inglês | MEDLINE | ID: mdl-32887693

RESUMO

Small ubiquitin-like modifier (SUMO) is a widespread regulatory mechanism of post-translational modification (PTM) that induces rapid and reversible changes in protein function and stability. Using SUMO conjugase Ubc9-overexpressing or knock-down cells in Parkinson's disease (PD) models, we demonstrate that SUMOylation protects dopaminergic cells against MPP+ or preformed fibrils (PFFs) of α-synuclein (α-syn)-induced toxicities in cell viability and cytotoxicity assays. In the mechanism of protection, Ubc9 overexpression significantly suppressed the MPP+ or PFF-induced reactive oxygen species (ROS) generation, while Ubc9-RNAi enhanced the toxicity-induced ROS production. Further, PFF-mediated protein aggregation was exacerbated by Ubc9-RNAi in thioflavin T staining, compared with NC1 controls. In cycloheximide (Chx)-based protein stability assays, higher protein level of α-syn was identified in Ubc9-enhanced green fluorescent protein (EGFP) than in EGFP cells. Since there was no difference in endogenous mRNA levels of α-syn between Ubc9 and EGFP cells in quantitative real-time PCR (qRT-PCR), we assessed the mechanisms of SUMO-mediated delayed α-syn degradation via MG132, proteasomal inhibitor, and PMA, lysosomal degradation inducer. Ubc9-mediated SUMOylated α-syn avoided PMA-induced lysosomal degradation because of its high solubility. Our results suggest that Ubc9 enhances the levels of SUMO1 and ubiquitin on α-syn and interrupts SUMO1 removal from α-syn. In immunohistochemistry, dopaminergic axon tips in the striatum and cell bodies in the substantia nigra from Ubc9-overexpressing transgenic mice were protected from MPTP toxicities compared with wild-type (WT) siblings. Our results support that SUMOylation can be a regulatory target to protect dopaminergic neurons from oxidative stress and protein aggregation, with the implication that high levels of SUMOylation in dopaminergic neurons can prevent the pathologic progression of PD.


Assuntos
Doença de Parkinson , Enzimas de Conjugação de Ubiquitina , alfa-Sinucleína , Animais , Modelos Animais de Doenças , Neurônios Dopaminérgicos , Camundongos , Camundongos Transgênicos , Ubiquitina , alfa-Sinucleína/genética , gama-Glutamil Hidrolase
20.
Open Forum Infect Dis ; 7(4): ofaa111, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32685604

RESUMO

Targeted molecular diagnostic tests and accurate immunoassays have transformed the landscape of clinical virology, calling into question the usefulness of traditional viral culture. Here we present a case where viral culture, followed by metagenomic sequencing, was central to the diagnosis of an unexpected viral infection, with significant clinical and public health implications.

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