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1.
Allergy ; 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38037751

RESUMO

BACKGROUND: Atopic dermatitis (AD) is a complex condition characterized by impaired epithelial barriers and dysregulated immune cells. In this study, we demonstrated Forsythia velutina Nakai extract (FVE) simultaneously inhibits basophils, macrophages, keratinocytes, and T cells that are closely interrelated in AD development. METHODS: We analyzed the effect of FVE on nitric oxide and reactive oxygen species (ROS) production in macrophages, basophil degranulation, T cell activation, and tight junctions in damaged keratinocytes. Expression of cell-type-specific inflammatory mediators was analyzed, and the underlying signaling pathways for anti-inflammatory effects of FVE were investigated. The anti-inflammatory effects of FVE were validated using a DNCB-induced mouse model of AD. Anti-inflammatory activity of compounds isolated from FVE was validated in each immune cell type. RESULTS: FVE downregulated the expression of inflammatory mediators and ROS production in macrophages through TLR4 and NRF2 pathways modulation. It significantly reduced basophil degranulation and expression of type 2 (T2) and pro-inflammatory cytokines by perturbing FcεRI signaling. Forsythia velutina Nakai extract also robustly inhibited the expression of T2 cytokines in activated T cells. Furthermore, FVE upregulated the expression of tight junction molecules in damaged keratinocytes and downregulated leukocyte attractants, as well as IL-33, an inducer of T2 inflammation. In the AD mouse model, FVE showed superior improvement in inflammatory cell infiltration and skin structure integrity compared to dexamethasone. Dimatairesinol, a lignan dimer, was identified as the most potent anti-inflammatory FVE compound. CONCLUSION: Forsythia velutina Nakai extract and its constituent compounds demonstrate promising efficacy as a therapeutic option for prolonged AD treatment by independently inhibiting various cell types associated with AD and disrupting the deleterious link between them.

2.
Small ; 18(40): e2202912, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36058645

RESUMO

Development of efficient surface passivation methods for semiconductor devices is crucial to counter the degradation in their electrical performance owing to scattering or trapping of carriers in the channels induced by molecular adsorption from the ambient environment. However, conventional dielectric deposition involves the formation of additional interfacial defects associated with broken covalent bonds, resulting in accidental electrostatic doping or enhanced hysteretic behavior. In this study, centimeter-scaled van der Waals passivation of transition metal dichalcogenides (TMDCs) is demonstrated by stacking hydrocarbon (HC) dielectrics onto MoSe2 field-effect transistors (FETs), thereby enhancing the electric performance and stability of the device, accompanied with the suppression of chemical disorder at the HC/TMDCs interface. The stacking of HC onto MoSe2 FETs enhances the carrier mobility of MoSe2 FET by over 50% at the n-branch, and a significant decrease in hysteresis, owing to the screening of molecular adsorption. The electron mobility and hysteresis of the HC/MoSe2 FETs are verified to be nearly intact compared to those of the fabricated HC/MoSe2 FETs after exposure to ambient environment for 3 months. Consequently, the proposed design can act as a model for developing advanced nanoelectronics applications based on layered materials for mass production.

3.
J Biol Chem ; 294(35): 12957-12974, 2019 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-31296660

RESUMO

Transcriptional regulator KAISO plays a critical role in cell cycle arrest and apoptosis through modulation of p53 acetylation by histone acetyltransferase p300. KAISO potently stimulates apoptosis in cells expressing WT p53, but not in p53-mutant or p53-null cells. Here, we investigated how KAISO transcription is regulated by p53, finding four potential p53-binding sites (p53-responsive DNA elements; p53REs) located in a distal 5'-upstream regulatory element, intron 1, exon 2 coding sequence, and a 3'-UTR region. Transient transcription assays of pG5-p53RE-Luc constructs with various p53REs revealed that p53 activates KAISO (ZBTB33) transcription by acting on p53RE1 (-4326 to -4227) of the 5'-upstream region and on p53RE3 (+2929 to +2959) of the exon 2 coding region during early DNA damage responses (DDRs). ChIP and oligonucleotide pulldown assays further disclosed that p53 binds to the p53RE1 and p53RE3 sites. Moreover, ataxia telangiectasia mutated (ATM) or ATM-Rad3-related (ATR) kinase-mediated p53 phosphorylation at Ser-15 or Ser-37 residues activated KAISO transcription by binding its p53RE1 or p53RE3 sites during early DDR. p53RE1 uniquely contained three p53-binding half-sites, a structural feature important for transcriptional activation by phosphorylated p53 Ser-15·Ser-37. During the later DDR phase, a KAISO-mediated acetylated p53 form (represented by a p53QRQ acetyl-mimic) robustly activated transcription by acting on p53RE1 in which this structural feature is not significant, but it provided sufficient KAISO levels to confer a p53 "apoptotic code." These results suggest that the critical apoptosis regulator KAISO is a p53 target gene that is differently regulated by phosphorylated p53 or acetylated p53, depending on DDR stage.


Assuntos
Apoptose , Fatores de Transcrição/metabolismo , Ativação Transcricional , Proteína Supressora de Tumor p53/metabolismo , Acetilação , Células Cultivadas , Humanos , Fosforilação , Fatores de Transcrição/genética
4.
J Biol Chem ; 294(1): 299-313, 2019 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-30409904

RESUMO

Even in the face of physiological DNA damage or expression of the tumor suppressor protein p53, B cell CLL/lymphoma 6 (BCL6) increases proliferation and antagonizes apoptotic responses in B cells. BCL6 represses TP53 transcription and also appears to inactivate p53 at the protein level, and additional findings have suggested negative mutual regulation between BCL6 and p53. Here, using Bcl6-/- knockout mice, HEK293A and HCT116 p53-/- cells, and site-directed mutagenesis, we found that BCL6 interacts with p53 and thereby inhibits acetylation of Lys-132 in p53 by E1A-binding protein p300 (p300), a modification that normally occurs upon DNA damage-induced cellular stress and whose abrogation by BCL6 diminished transcriptional activation of p53 target genes, including that encoding caspase-1. Conversely, we also found that BCL6 protein is degraded via p53-induced, caspase-mediated proteolytic cleavage, and the formation of a BCL6-p53-caspase-1 complex. Our results suggest that p53 may block oncogenic transformation by decreasing BCL6 stability via caspase-1 up-regulation, whereas aberrant BCL6 expression inactivates transactivation of p53 target genes, either by inhibiting p53 acetylation by p300 or repressing TP53 gene transcription. These findings have implications for B cell development and lymphomagenesis.


Assuntos
Linfócitos B/metabolismo , Caspase 1/sangue , Transformação Celular Neoplásica/metabolismo , Regulação Enzimológica da Expressão Gênica , Proteínas Proto-Oncogênicas c-bcl-6/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Linfócitos B/patologia , Caspase 1/genética , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Células HCT116 , Células HEK293 , Humanos , Camundongos , Camundongos Knockout , Proteínas Proto-Oncogênicas c-bcl-6/genética , Proteína Supressora de Tumor p53/genética
5.
Biochem Biophys Res Commun ; 530(3): 588-596, 2020 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-32753315

RESUMO

KLHL4 is a member of the KLHL protein family, many of whom bind the Cul3 E3 ligase, and mediate the ubiquitination of interacting proteins. The KLHL4 gene, localized on the X chromosome, associates with a disorder known as X-linked cleft palate (CPX). However, the biological functions of KLHL4 are largely unknown. In this study, microarray analysis of HEK293A embryonic kidney cells, expressing ectopic p53, showed a 3-fold increase of KLHL4 mRNA. Moreover, both KLHL4 mRNA and protein expression were elevated by p53 or DNA damage, suggesting that KLHL4 might be a p53 target gene. We also found that KLHL4 activates transcription of p21WAF/CDKN1A, a p53 target gene encoding a major negative regulator of the cell-cycle. KLHL4 interacted with p53 to increase its binding to p53 response element of the p21WAF/CDKN1A gene, resulting in transcriptional upregulation. Furthermore, we observed that KLHL4 can interact with the Cul3 ubiquitin ligase, to possibly play a role in ubiquitin-mediated proteasomal degradation, and Klhl4 knocked-out MEF mouse embryonic fibroblasts proliferated faster than WT MEF cells. These results suggest that KLHL4 upregulation by p53 may inhibit cell proliferation, by activating p21WAF/CDKN1A.


Assuntos
Inibidor de Quinase Dependente de Ciclina p21/genética , Proteínas do Citoesqueleto/genética , Proteína Supressora de Tumor p53/genética , Proliferação de Células , Dano ao DNA , Células HCT116 , Células HEK293 , Células HeLa , Humanos , RNA Mensageiro/genética , Ativação Transcricional , Regulação para Cima
6.
Biol Res ; 49(1): 41, 2016 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-27716424

RESUMO

BACKGROUND: Asthma is an increasing global health problem, and novel strategies to prevent or ameliorate the condition are needed. Here, the effects of 80 % ethanol extracts of Salvia plebeia R. Br. (SE) on an induced inflammatory response were investigated. RESULTS: Salvia plebeia R. Br. inhibited production of pro-inflammatory cytokines, such as TNF-α and IL-6, as well as nitric oxide (NO) in LPS-stimulated RAW 264.7 cells. NO and pro-inflammatory cytokine production was suppressed more effectively by SE of the aerial parts (SE-A) than of the roots (SE-R) of S. plebeia. In BEAS-2B cells, both SE-A and SE-R inhibited the increase in production of the inflammatory cytokines IL-6 and IL-8. We also investigated the anti-asthmatic effects of SE in an ovalbumin (OVA)-induced BALB/c mouse model. SE-A treatment significantly reduced the number of airway eosinophils, IL-4 and IL-13 levels, mucus production, and inflammatory infiltration, as compared with the corresponding levels in the untreated, OVA-induced mice, and had similar effects to dexamethasone. CONCLUSIONS: Salvia plebeia ethanol extract ameliorated the induced inflammatory response in RAW 264.7 and BEAS-2B cells, with more effective inhibition noted for SE-A than for SE-R. SE-A treatment was effective in improving the histopathological changes in the lungs of asthma model mice via modulation of eosinophils and Th2 cytokines. These results suggest that SE-A can be considered as a therapeutic agent that can potentially relieve asthma.


Assuntos
Antiasmáticos/farmacologia , Anti-Inflamatórios/farmacologia , Asma/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Animais , Asma/induzido quimicamente , Canfanos , Células Cultivadas , Citocinas/análise , Citocinas/efeitos dos fármacos , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Etanol/farmacologia , Feminino , Lipopolissacarídeos/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico/análise , Ovalbumina , Panax notoginseng , Componentes Aéreos da Planta/química , Células RAW 264.7 , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Salvia miltiorrhiza
7.
J Infect Chemother ; 20(1): 38-42, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24462423

RESUMO

We conducted a retrospective analysis of acute bacterial prostatitis (ABP) secondary to manipulation to document clinical features, management and microbiology based on the route of prior manipulation, which can be divided into two subgroups: transrectal and transurethral procedure. The medical records of 158 cases compatible with a confirmed diagnosis of ABP secondary to manipulation from 7 urological centers between 2001 and 2012 were reviewed. When subcategorized according to route of prior manipulation of the lower urinary tract, there were distinct differences between transrectal and transurethral manipulation group with regard to clinical and microbiological features. Escherichia coli was the most common causative bacterium in both groups, but Pseudomonas spp. were much more dominant pathogens in the group by transurethral manipulation than transrectal manipulation group. The susceptibilities to second-, third- and fourth-generation cephalosporins, amikacin, carbapenem and aztreonam were shown to be very low in the transurethral manipulation group. Therefore, it will take account the difference in antibiotic selection in the patients with ABP secondary to manipulation according to the manipulation route.


Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Prostatite/tratamento farmacológico , Prostatite/microbiologia , Sistema Urinário/efeitos dos fármacos , Sistema Urinário/microbiologia , Doença Aguda , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
8.
J Med Food ; 27(3): 242-249, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38354279

RESUMO

This study aimed to test the hypothesis that long-term and low-dose supplementation with an ethanol extract of Ecklonia stolonifera may confer protection against high-fat diet (HFD)-induced obesity in mice. Male C57BL/6J mice were divided into two groups, one of which was fed an HFD (40 kcal% fat) and the other an HFD+E. stolonifera (0.006%, w/w, ∼5 mg/kg body weight/day) for 16 weeks. E. stolonifera supplementation significantly reduced body weight from week 3 and until the end of the experiment. E. stolonifera-supplemented mice also exhibited lower fat mass (epididymal, perirenal, and mesenteric fat) and smaller adipocyte size than HFD control mice. The two groups displayed similar food intakes, but E. stolonifera markedly decreased lipogenesis and increased lipolysis and fatty acid oxidation in adipose tissue. Moreover, E. stolonifera significantly decreased plasma and hepatic lipid levels, hepatic lipid droplet accumulation, plasma aminotransferase levels, and liver weight by decreasing lipogenesis and increasing fatty acid oxidation. As E. stolonifera-supplemented mice showed improvements in hyperglycemia, insulin resistance, and inflammation, compared to control mice, it is possible that the beneficial effects of E. stolonifera on obesity might be associated with decreased inflammation and insulin resistance. Collectively, these results indicate that E. stolonifera could be used as a novel means of preventing and treating obesity and obesity-related metabolic disorders.


Assuntos
Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Masculino , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Camundongos Obesos , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BL , Fígado/metabolismo , Obesidade/tratamento farmacológico , Obesidade/etiologia , Inflamação/tratamento farmacológico , Extratos Vegetais/farmacologia , Ácidos Graxos/metabolismo
9.
Heliyon ; 10(10): e30835, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38770307

RESUMO

Periodontal disease represents a condition that exhibits substantial global morbidity, and is characterized by the infection and inflammation of the periodontal tissue effectuated by bacterial pathogens. The present study aimed at evaluating the therapeutic efficacy of BenTooth, an edible natural product mixture comprising burdock root extract, persimmon leaf extract and quercetin, against periodontitis both in vitro and in vivo. BenTooth was examined for antimicrobial properties and its impact on cellular responses related to inflammation and bone resorption. Its effects were also assessed in a rat model of ligature-induced periodontitis. BenTooth demonstrated potent antimicrobial activity against P. gingivalis and S. mutans. In RAW264.7 cells, it notably diminished the expression of inducible nitric oxide synthase and cyclooxygenase-2, as well as reduced interleukin-6 and tumor necrosis factor-α levels triggered by P. gingivalis-derived lipopolysaccharide. Furthermore, BenTooth inhibited osteoclastogenesis mediated by the receptor activator of nuclear factor κB ligand. In the rat model, BenTooth consumption mitigated the ligature-induced expansion in distance between the cementoenamel junction and the alveolar bone crest and bolstered the bone volume fraction. These results present BenTooth as a potential therapeutic candidate for the prevention and remediation of periodontal diseases.

10.
Urol Int ; 90(2): 144-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23295780

RESUMO

OBJECTIVE: This study aims to examine the relationship between chronic prostatic inflammation and prostatic calculi, and clinical parameters of benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: This study was based on 225 patients who underwent transurethral resection of the prostate for BPH. Chronic inflammation was graded as 0 (n = 44), I (n = 54), II (n = 88) or III (n = 39) according to severity. Prostatic calculi were classified into types A (n = 66), B (n = 44), M (n = 77) and N (n = 38). The relationship between inflammation and calculus type was analyzed, and clinical parameters of BPH were compared for each group. RESULTS: There was no correlation between severity of inflammation and calculus type. Prostatic volume increased with the severity of inflammation and showed significant differences between G2, G3 and G0. The International Prostate Symptom Score also increased with increasing inflammation. There was no significant difference between each clinical parameter according to calculus type. CONCLUSIONS: Prostatic calculi had no significant association with chronic inflammation and clinical parameters of BPH. Chronic inflammation was associated with the volume of the prostate and storage symptoms; thus, it is not only presumed to be related to the progression of BPH, but may also be one of the causes of lower urinary tract symptoms.


Assuntos
Cálculos/cirurgia , Próstata/patologia , Hiperplasia Prostática/complicações , Hiperplasia Prostática/fisiopatologia , Ressecção Transuretral da Próstata/métodos , Idoso , Cálculos/complicações , Humanos , Inflamação/fisiopatologia , Sintomas do Trato Urinário Inferior/diagnóstico , Masculino , Pessoa de Meia-Idade , Próstata/cirurgia , Prostatite/complicações , Prostatite/diagnóstico , Estudos Retrospectivos
11.
Korean J Anesthesiol ; 2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37599607

RESUMO

Tranexamic acid (TXA) is a synthetic antifibrinolytic agent that has been used for several decades to reduce blood loss during surgery and after trauma. TXA was traditionally used to reduce bleeding in various clinical settings such as menorrhagia, hemophilia, or other bleeding disorder . Numerous studies have demonstrated the efficacy of TXA in reducing blood loss and the need for transfusions. Interest in the potential applications of TXA beyond its traditional use has been growing recently, with studies investigating the use of TXA in postpartum hemorrhage, cardiac surgery, trauma, neurosurgery, and orthopedic surgery. Despite its widespread use and expanding indications, data regarding the safe and appropriate use of TXA is lacking. Recent clinical trials have found various potential risks and limitations in the long-term benefits of TXA. This narrative review summarizes the clinical applications and limitations of TXA.

12.
Brain Sci ; 13(7)2023 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-37508986

RESUMO

This study aimed to investigate differences in prefrontal cortex activation between older adults with and without depressive symptoms during cognitive tasks using functional near-infrared spectroscopy (fNIRS). We examined 204 older participants without psychiatric or neurological disorders who completed the Geriatric Depression Scale, digit span, Verbal Fluency Test, and Stroop test. At the same time, prefrontal cortex activation was recorded using fNIRS. During the Stroop test, significantly reduced hemodynamics were observed in the depressive-symptom group. The mean accΔHbO2 of all channel averages was 0.14 µM in the control group and -0.75 µM in the depressive-symptom group (p = 0.03). The right hemisphere average was 0.13 µM and -0.96 µM, respectively (p = 0.02), and the left hemisphere average was 0.14 µM and -0.54 µM, respectively (p = 0.12). There was no significant difference in hemodynamic response (mean accΔHbO2) between the two groups during the digit span backward and VFT. In conclusion, reduced hemodynamics in the frontal cortex of the depressive-symptom group has been observed. The frontal fNIRS signal and the Stroop task may be used to measure depressive symptoms sensitively in the elderly.

13.
Biochim Biophys Acta Gene Regul Mech ; 1866(2): 194931, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37011832

RESUMO

ZBTB7A overexpressed in many human cancers is a major oncogenic driver. ZBTB7A promotes tumorigenesis by regulating transcription of the genes involved in cell survival and proliferation, apoptosis, invasion, and migration/metastasis. One unresolved issue is the mechanism underlying the aberrant overexpression of ZBTB7A in cancer cells. Interestingly, inhibition of HSP90 decreased ZBTB7A expression in a variety of human cancer cells. ZBTB7A interacts with and is stabilized by HSP90. Inhibition of HSP90 by 17-AAG resulted in p53-dependent proteolysis of ZBTB7A via increased p53 expression and upregulation of the CUL3-dependent E3 ubiquitin ligase, KLHL20. Down-regulation of ZBTB7A resulted in the derepression of a major negative regulator of cell cycle progression, p21/CDKN1A. We discovered a new function of p53 regulating ZBTB7A expression through KLHL20-E3 ligase and proteasomal protein degradation system.


Assuntos
Proteínas de Ligação a DNA , Neoplasias , Humanos , Proteínas Adaptadoras de Transdução de Sinal/genética , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Neoplasias/genética , Proto-Oncogenes , Fatores de Transcrição/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação
14.
Viruses ; 15(1)2023 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-36680213

RESUMO

The rapid emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has resulted in the ongoing global coronavirus disease 2019 (COVID-19) pandemic. Thus, the rapid development of a platform to detect a broad range of SARS-CoV-2 variants is essential for successful COVID-19 management. In this study, four SARS-CoV-2 spike protein-specific single-chain variable fragments (scFvs) were isolated from a synthetic antibody library using phage display technology. Following the conversion of these scFvs into monoclonal antibodies (mAbs) (K104.1-K104.4) and production and purification of the mAbs, the antibody pair (K104.1 and K104.2) that exhibited the highest binding affinity (K104.1 and K104.2, 1.3 nM and 1.9 nM) was selected. Biochemical analyses revealed that this antibody pair specifically bound to different sites on the S2 subunit of the spike protein. Furthermore, we developed a highly sensitive sandwich immunoassay using this antibody pair that accurately and quantitatively detected the spike proteins of wild-type SARS-CoV-2 and multiple variants, including Alpha, Beta, Gamma, Delta, Kappa, and Omicron, in the picomolar range. Conclusively, the novel phage display-derived mAbs we have developed may be useful for the rapid and efficient detection of the fast-evolving SARS-CoV-2.


Assuntos
Anticorpos Monoclonais , Bacteriófagos , SARS-CoV-2 , Anticorpos de Cadeia Única , Humanos , Anticorpos Monoclonais/genética , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19 , SARS-CoV-2/genética , Anticorpos de Cadeia Única/genética , Glicoproteína da Espícula de Coronavírus
15.
PLoS One ; 18(9): e0291537, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37708114

RESUMO

In a short time, several types of injectable and oral therapeutics have been developed and used to effectively manage patients with coronavirus disease 2019 (COVID-19). BEN815 is an improved mixture of three extracts (Psidium guajava, Camellia sinensis, and Rosa hybrida) recognized by the Ministry of Food and Drug Safety of Korea as a health food ingredient that alleviates allergic rhinitis. The current animal efficacy study was performed to assess its probability of improving COVID-19 symptoms. BEN815 treatment significantly increased the survival of K18-hACE2 transgenic mice and reduced viral titers in the lungs at 5 days post infection (DPI). Furthermore, the lungs of the treated mice showed mild tissue damage at 5 DPI and nearly complete recovery from COVID-19 at 14 DPI. BEN815 appears to be an effective and minimally toxic anti-SARS-CoV-2 agent in mice and has potential for clinical applications.


Assuntos
COVID-19 , Camellia sinensis , Animais , Camundongos , Animais de Laboratório , SARS-CoV-2 , Camundongos Transgênicos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
16.
World J Clin Cases ; 11(6): 1419-1425, 2023 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-36926132

RESUMO

BACKGROUND: Transverse myelitis (TM) is characterized by sudden lower extremity progressive weakness and sensory impairment, and most patients have a history of advanced viral infection symptoms. A variety of disorders can cause TM in association with viral or nonviral infection, vascular, neoplasia, collagen vascular, and iatrogenic, such as vaccination. Vaccination has become common through the global implementation against coronavirus disease 2019 (COVID-19) and reported complications like herpes zoster (HZ) activation has increased. CASE SUMMARY: This is a 68-year-old woman who developed multiple pustules and scabs at the T6-T9 dermatome site 1 wk after vaccination with the COVID-19 vaccine (Oxford/AstraZeneca ([ChAdOx1S{recombinant}]). The patient had a paraplegia aggravation 3 wk after HZ symptoms started. Spinal magnetic resonance imaging (MRI) showed transverse myelitis at the T6-T9 Level. Treatment was acyclovir with steroids combined with physical therapy. Her neurological function was slowly restored by Day 17. CONCLUSION: HZ developed after COVID-19 vaccination, which may lead to more severe complications. Therefore, HZ treatment itself should not be delayed. If neurological complications worsen after appropriate management, an immediate diagnostic procedure, such as magnetic resonance imaging and laboratory tests, will start and should treat the neurological complications.

17.
World J Clin Cases ; 11(24): 5789-5796, 2023 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-37727714

RESUMO

BACKGROUND: Atrial arrhythmias such as paroxysmal supraventricular tachycardia (PSVT) and atrial flutter (AF) are common in the perioperative setting. They commonly resolve spontaneously. However, occasionally, they may continually progress to fatal arrhythmias or cause complications. Therefore, prompt and appropriate management is important. CASE SUMMARY: A 46-year-old female patient diagnosed with cervical C6-7 radiculopathy characterized by decreased sensation in the right third, fourth and fifth fingers underwent C6-7 anterior cervical disc fusion surgery. Electrocardiography showed PSVT and ventricular tachycardia during C6-7 disc retraction. However, the patient remained stable. Initial treatment with esmolol and lidocaine for ventricular tachycardia was ineffective. Carotid massage and Valsalva maneuver were attempted but PSVT did not resolve. The surgery was paused, and the patient's fraction of inspired oxygen was set to 100%. Adenosine was administered for pharmacological management of PSVT. The arrhythmia temporarily resolved. However, it then transformed into AF. Diltiazem was administered, which briefly decreased blood pressure, which immediately recovered. Surgery resumed while the patient was in normal sinus rhythm. She was discharged safely on postoperative day 6 without complications or abnormalities. Currently, she is living a healthy life without arrhythmia recurrence. CONCLUSION: Ganglia associated with cardiac arrhythmias in the surgical site should be identified during cervical spine surgery.

18.
Cell Death Differ ; 30(10): 2309-2321, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37704840

RESUMO

Gastrointestinal stromal tumors (GISTs) frequently show KIT mutations, accompanied by overexpression and aberrant localization of mutant KIT (MT-KIT). As previously established by multiple studies, including ours, we confirmed that MT-KIT initiates downstream signaling in the Golgi complex. Basic leucine zipper nuclear factor 1 (BLZF1) was identified as a novel MT-KIT-binding partner that tethers MT-KIT to the Golgi complex. Sustained activation of activated transcription factor 6 (ATF6), which belongs to the unfolded protein response (UPR) family, alleviates endoplasmic reticulum (ER) stress by upregulating chaperone expression, including heat shock protein 90 (HSP90), which assists in MT-KIT folding. BLZF1 knockdown and ATF6 inhibition suppressed both imatinib-sensitive and -resistant GIST in vitro. ATF6 inhibitors further showed potent antitumor effects in GIST xenografts, and the effect was enhanced with ER stress-inducing drugs. ATF6 activation was frequently observed in 67% of patients with GIST (n = 42), and was significantly associated with poorer relapse-free survival (P = 0.033). Overall, GIST bypasses ER quality control (QC) and ER stress-mediated cell death via UPR activation and uses the QC-free Golgi to initiate signaling.

19.
ACS Omega ; 8(50): 48019-48027, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38144078

RESUMO

Diffuse-type gastric cancer (GC) is a type of stomach cancer that occurs in small clusters of cells that are widely spread. It does not typically manifest with symptoms until the advanced stages and often goes undetected in routine imaging tests. In addition, there is no specific targeted therapy for diffuse-type GC and it has a high mortality risk. Hence, it is worthwhile to discover molecules against this cancer. In this study, the extract of Heloniopsis koreana, which is endemic to Korea, exhibited cytotoxicity against two diffuse-type GC cell lines, MKN1 and SNU668. This led to the isolation of 10 compounds, including a new cinnamic acid glycoside. Of the compounds, saponin Th (4) and SNF 11 (5) showed potent activities with IC50 values of 3.66 and 3.85 µM, respectively, in MKN1 cells, and 1.8 and 1.98 µM, respectively, in SNU668 cells. These compounds prevented cancer cell division, invasion, and colony formation in both cell lines. In addition, these compounds induced cancer cell death through conventional cell death pathways, showing an increase in ADP-ribose polymerase, caspase 3, and BAX and a decrease in BCL2.

20.
World J Clin Cases ; 10(32): 11967-11973, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36405277

RESUMO

BACKGROUND: The trigeminocardiac reflex (TCR) is usually caused by an increased parasympathetic tone when pressure or traction is applied to the surrounding tissue of the trigeminal nerve. However, the inexperienced anesthesiologists may have challenges on the management of TCR patients. CASE SUMMARY: This is the case of an 18-year-old woman diagnosed with hemangioma of the upper lip. During the operation, about 1 h after surgery started, a constant 1:1 premature ventricular complex was detected, and blood pressure was decreased when approaching the deeper part with more strong traction for exposure of the part. Although the management of arrhythmias, such as lidocaine and atropine, was injected, arrhythmia induced by surgical stimulation could not be eliminated completely. As the traction repeated, bradycardia was also repeated, despite injecting additional atropine. Therefore, the anesthesiologist and the surgeon decided to perform the operation only to the extent that the vascular tissue was selectively removed only at the site without the reflex. CONCLUSION: With TCR, anesthesiologists should perform appropriate monitoring. In addition to proper drug administration, surgeons should be consulted to cope with stopping the surgery and setting the scope of the surgery even if the site is superficial.

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