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We investigated the relationship between individuals' mental health traits and the characteristics of YouTube videos they watch. The mental health traits considered were stress, depression, anxiety, and self-esteem, which were measured using a survey questionnaire. We considered violence shown in a video, brightness and saturation of a video as video characteristics. We utilized the viewing history log data of the participants and analyzed the videos they watched on YouTube using computer vision techniques based on deep learning algorithms. The results revealed that viewers' consumption of violent videos was positively related to stress, depression, and anxiety, but negatively related to self-esteem. Individuals with higher levels of stress, depression, or anxiety tended to view darker videos than those with lower levels of stress, depression, or anxiety.
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Although bag sampling is a common quantification tool for volatile organic compounds (VOCs), it can serve as a major source of experimental bias, when storing even over a short duration (<24 h). To learn more about the reliability of the bag sampling method, the temporal stability of 27 VOCs (classified into five groups (i.e., aldehydes, nonpolar aromatic hydrocarbons, aliphatic carboxylic acids, phenol and methylphenols, and miscellaneous odorants) is assessed using poly-ester aluminum (PEA) bags at five intervals over a day (0.17, 1, 2, 6, and 24 h). In terms of reproducibility (e.g., relative standard error [RSEt, %]), nonpolar aromatic hydrocarbons (BTXS) exhibit the highest consistency (e.g., average RSE <1.55%). Considerable loss of VOCs is observed in the preparation of gaseous standards from a liquid phase standard when assessed by gas/liquid (G/L) ratio. Further, VOCs with lower molecular weights (e.g., propionaldehyde: 77%-94.4%) and branched molecular structures (e.g., isovaleraldehyde: 67.2%-78.9%) tend to have high G/L ratio (e.g., relative to valeraldehyde: 55.1%-66%). The overall relative recovery (RR; %) values of VOCs indicate an exponential decrease over 24 h. BTXS maintain fairly good RR values (above 94.3% at all intervals), possibly due to the nonpolar structure with uniform distribution of π electrons. In contrast, indole and skatole show the least preservation after 24 h (e.g., RR4 values of 10.9% and 24.6%, respectively) due to their highly reactive characteristics. The storability of VOCs appears to be affected by a number of variables (e.g., molecular weight, presence of ethyl branch, and time: e.g., R2 > 0.9). The results of this study offer valuable guidelines for the accurate quantification of VOC levels in air.
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Monitoramento Ambiental , Compostos Orgânicos Voláteis , Compostos Orgânicos Voláteis/análise , Monitoramento Ambiental/métodos , Poluentes Atmosféricos/análise , Reprodutibilidade dos Testes , Fatores de TempoRESUMO
Iron acquisition systems are crucial for pathogen growth and survival in iron-limiting host environments. To overcome nutritional immunity, bacterial pathogens evolved to use diverse mechanisms to acquire iron. Here, we examine a heme acquisition system that utilizes hemophores called hemophilins which are also referred to as HphAs in several Gram-negative bacteria. In this study, we report three new HphA structures from Stenotrophomonas maltophilia, Vibrio harveyi, and Haemophilus parainfluenzae. Structural determination of HphAs revealed an N-terminal clamp-like domain that binds heme and a C-terminal eight-stranded ß-barrel domain that shares the same architecture as the Slam-dependent Neisserial surface lipoproteins. The genetic organization of HphAs consists of genes encoding a Slam homolog and a TonB-dependent receptor (TBDR). We investigated the Slam-HphA system in the native organism or the reconstituted system in Escherichia coli cells and found that the efficient secretion of HphA depends on Slam. The TBDR also played an important role in heme uptake and conferred specificity for its cognate HphA. Furthermore, bioinformatic analysis of HphA homologs revealed that HphAs are conserved in the alpha, beta, and gammaproteobacteria. Together, these results show that the Slam-dependent HphA-type hemophores are prevalent in Gram-negative bacteria and further expand the role of Slams in transporting soluble proteins. IMPORTANCE: This paper describes the structure and function of a family of Slam (Type IX secretion System) secreted hemophores that bacteria use to uptake heme (iron) while establishing an infection. Using structure-based bioinformatics analysis to define the diversity and prevalence of this heme acquisition pathway, we discovered that a large portion of gammaproteobacterial harbors this system. As organisms, including Acinetobacter baumannii, utilize this system to facilitate survival during host invasion, the identification of this heme acquisition system in bacteria species is valuable information and may represent a target for antimicrobials.
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Proteínas de Bactérias , Bactérias Gram-Negativas , Heme , Bactérias Gram-Negativas/genética , Bactérias Gram-Negativas/metabolismo , Heme/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Ferro/metabolismoRESUMO
The thermocatalytic oxidative potential of various supported noble metal catalysts (SNMCs) is well-known for hazardous volatile organic compounds (VOCs), e.g., formaldehyde (FA) and toluene. However, little is known about SNMC performance against ambient VOC pollution with low concentration (subppm levels) relative to industrial effuluents with high concentrations (several hundred ppm). Here, the thermocatalytic oxidation performance of a titanium dioxide (TiO2)-supported platinum catalyst (Pt/TiO2) has been evaluated for a low-concentration binary mixture of FA and toluene at low temperatures and in the dark. A sample of TiO2 containing 1 wt% Pt with thermal reduction pre-treatment under hydrogen achieved 100 % conversion of FA (500 ppb) and toluene (100 ppb) at 130 °C and a gas hourly velocity of 59,701 h-1. Its catalytic activity was lowered by either a decrease in catalyst mass or an increase in VOC concentration, relative humidity, or flow rate. In situ diffuse reflectance infrared Fourier transform spectroscopy, density functional theory simulations, and molecular oxygen (O2) temperature-programmed desorption experiments were used to identify possible VOC oxidation pathways, reaction mechanisms, and associated surface phenomena. The present work is expected to offer insights into the utility of metal oxide-supported Pt catalysts for the low-temperature oxidative removal of gaseous VOCs in the dark, primarily for indoor air quality management.
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Herbal medicine, a multi-component treatment, has been extensively practiced for treating various symptoms and diseases. However, its molecular mechanism of action on the human body is unknown, which impedes the development and application of herbal medicine. To address this, recent studies are increasingly adopting systems pharmacology, which interprets pharmacological effects of drugs from consequences of the interaction networks that drugs might have. Most conventional network- based approaches collect associations of herb-compound, compound-target, and target-disease from individual databases, respectively, and construct an integrated network of herb-compound- target-disease to study the complex mechanisms underlying herbal treatment. More recently, rapid advances in highthroughput omics technology have led numerous studies to exploring gene expression profiles induced by herbal treatments to elicit information on direct associations between herbs and genes at the genome-wide scale. In this review, we summarize key databases and computational methods utilized in systems pharmacology for studying herbal medicine. We also highlight recent studies that identify modes of action or novel indications of herbal medicine by harnessing drug-induced transcriptome data. [BMB Reports 2022; 55(9): 417-428].
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Medicamentos de Ervas Chinesas , Medicina Herbária , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Farmacologia em Rede , Fitoterapia , TranscriptomaRESUMO
OBJECTIVE: As a component of Endosomal Sorting Complex Required for Transport (ESCRT) complex I, the tumor susceptibility gene 101 (Tsg101) carries out multiple functions. In this work, we report that oocyte-specific deletion of tumor susceptibility gene 101 (Tsg101) leads to age-dependent oocyte demise in mice. MATERIALS AND METHOD: Tsg101 floxed mice (Tsg101f/f ) were bred with Zp3cre transgenic mice to examine oocyte-specific roles of Tsg101. Multiple cellular and molecular biological approaches were taken to examine what leads to oocyte demise in the absence of Tsg101. RESULTS: The death of oocytes from Zp3cre /Tsg101f/f (Tsg101d/d thereafter) mice showed a strong correlation with sexual maturation, as gonadotropin-releasing hormone antagonist injections improved the survival rate of oocytes from 5-week-old Tsg101d/d mice. Maturation of oocytes from prepubertal Tsg101d/d mice proceeded normally, but was largely abnormal in oocytes from peripubertal Tsg101d/d mice, showing shrinkage or rupture. Endolysosomal structures in oocytes from peripubertal Tsg101d/d mice showed abnormalities, with aberrant patterns of early and late endosomal markers and a high accumulation of lysosomes. Dying oocytes showed plasma membrane blebs and leakage. Blockage of endocytosis in oocytes at 4°C prevented cytoplasmic shrinkage of oocytes from Tsg101d/d mice until 9 h. The depletion of tsg-101 in Caenorhabditis elegans increased the permeability of oocytes and embryos, suggesting a conserved role of Tsg101 in maintaining membrane integrity. CONCLUSIONS: Collectively, Tsg101 plays a dual role in maintaining the integrity of membranous structures, which is influenced by age in mouse oocytes.
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Complexos Endossomais de Distribuição Requeridos para Transporte , Oócitos , Animais , Proteínas de Ligação a DNA , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Hormônio Liberador de Gonadotropina , Camundongos , Camundongos Transgênicos , Fatores de TranscriçãoRESUMO
Nutrient acquisition systems are often crucial for pathogen growth and survival during infection, and represent attractive therapeutic targets. Here, we study the protein machinery required for heme uptake in the opportunistic pathogen Acinetobacter baumannii. We show that the hemO locus, which includes a gene encoding the heme-degrading enzyme, is required for high-affinity heme acquisition from hemoglobin and serum albumin. The hemO locus includes a gene coding for a heme scavenger (HphA), which is secreted by a Slam protein. Furthermore, heme uptake is dependent on a TonB-dependent receptor (HphR), which is important for survival and/or dissemination into the vasculature in a mouse model of pulmonary infection. Our results indicate that A. baumannii uses a two-component receptor system for the acquisition of heme from host heme reservoirs.
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Infecções por Acinetobacter/microbiologia , Acinetobacter baumannii/metabolismo , Proteínas de Bactérias/metabolismo , Heme/metabolismo , Acinetobacter baumannii/genética , Acinetobacter baumannii/crescimento & desenvolvimento , Animais , Proteínas de Bactérias/genética , Transporte Biológico , Feminino , Humanos , Camundongos Endogâmicos BALB C , Família MultigênicaRESUMO
BACKGROUND: The tumor susceptibility gene 101 (Tsg101), a component of the endosomal sorting complex required for transport (ESCRT) complex I, is involved in multiple biological processes involving endomembranous structures and the plasma membrane. The role of Tsg101 in the uterine epithelium was investigated in Tsg101 floxed mice crossed with Lactoferrin-iCre mice (Tsg101d/d). METHODS: Tsg101d/d mice were bred with stud male mice and the status of pregnancy was examined on days 4 and 6. Histological analyses were performed to examine the uterine architecture. Immunofluorescence staining of several markers was examined by confocal microscopy. Uterine epithelial cells (UECs) were isolated from Tsg101f/f and Tsg101d/d mice, and the expression of necroptosis effectors was examined by RT-PCR, western blotting, and immunofluorescence staining. UECs were also subjected to RNA expression profiling. RESULTS: Tsg101d/d female mice were subfertile with implantation failure, showing unattached blastocysts on day 6 of pregnancy. Histological and marker analyses revealed that some Tsg101d/d day 4 pregnant uteri showed a disintegrated uterine epithelial structure. Tsg101d/d UECs began to degenerate within 18 h of culture. In UECs, expression of necroptosis effectors, such as RIPK1, RIPK3, and MLKL were first confirmed. UECs responded to a stimulus to activate necroptosis and showed increased cell death. CONCLUSIONS: Tsg101 deficiency in the uterine epithelium causes implantation failure, which may be caused by epithelial defects. This study provides evidence that UECs harbor a necroptotic machinery that responds to death-inducing signals. Thus, Tsg101 expression in the uterine epithelium is required for normal pregnancy in mice.
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Proteínas de Ligação a DNA/biossíntese , Implantação do Embrião/fisiologia , Complexos Endossomais de Distribuição Requeridos para Transporte/biossíntese , Células Epiteliais/metabolismo , Fatores de Transcrição/biossíntese , Útero/metabolismo , Animais , Células Cultivadas , Proteínas de Ligação a DNA/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Células Epiteliais/patologia , Feminino , Masculino , Camundongos , Camundongos Transgênicos , Gravidez , Fatores de Transcrição/genética , Útero/patologiaRESUMO
BACKGROUND: Dasatinib is administered at a fixed starting dosage of 100 mg once daily regardless of patient-specific factors. However, such fixed dosing may not be optimal for the treatment of Asian patients with chronic myeloid leukemia in chronic phase (CP-CML). PATIENTS AND METHODS: The dose-limiting toxicities (DLTs) and molecular responses (MRs) of dasatinib therapy were evaluated using clinical data obtained from 102 patients newly diagnosed with CP-CML at 17 hospitals in South Korea. RESULTS: By 36 months after the initiation of a fixed dose regimen of dasatinib 100 mg once daily as the first-line therapy, 55.9% of patients experienced at least one type of DLT. The 3 most frequent DLTs were thrombocytopenia (45.5%), pericardial or pleural effusion (30.9%), and anemia (7.3%). Patients with higher dasatinib dose adjusted for body weight (Dose/BW) had a greater rate of DLT occurrence (logit [P] = 1.58 × [Dose/BW] - 2.27, P = .03). As median Dose/BW increased from 1.23 to 2.00 mg/kg, the rate of DLT occurrence increased from 43.5% to 66.7% (P = .03). However, Dose/BW did not affect the achievement rate of major MR (60.9% to 69.6%, P = .92). CONCLUSION: The starting dosage of dasatinib may need to be reduced (eg, 80 mg once daily or lower) for Asian patients with CP-CML, especially with lighter BW, to alleviate the risk of DLT occurrence without compromising the achievement of MR.
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Povo Asiático , Dasatinibe/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dasatinibe/efeitos adversos , Monitoramento de Medicamentos , Feminino , Humanos , Estimativa de Kaplan-Meier , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/etiologia , Masculino , Dose Máxima Tolerável , Terapia de Alvo Molecular/métodos , Razão de Chances , Inibidores de Proteínas Quinases/efeitos adversos , República da Coreia , Resultado do TratamentoRESUMO
The uterus undergoes vascular changes during the reproductive cycle and pregnancy. Steroid hormone deprivation induces macroautophagy/autophagy in major uterine cell types. Herein, we explored the functions of uterine autophagy using the Amhr2-Cre-driven atg7 deletion model. Deletion of Atg7 was confirmed by functional deficit of autophagy in uterine stromal, myometrial, and vascular smooth muscle cells, but not in endothelial cells. atg7d/d uteri exhibited enhanced stromal edema accompanied by dilation of blood vessels. Ovariectomized atg7d/d uteri showed decreased expression of endothelial junction-related proteins, such as CTNNB1/beta-catenin, with increased vascular permeability, and increased expression of VEGFA and NOS1. Nitric oxide (NO) was shown to mediate VEGFA-induced vascular permeability by targeting CTNNB1. NO involvement in maintaining endothelial junctional stability in atg7d/d uteri was confirmed by the reduction in extravasation following treatment with a NOS inhibitor. We also showed that atg7d/d uterine phenotype improved the fetal weight:placental weight ratio, which is one of the indicators of assessing the status of preeclampsia. We showed that autophagic deficit in the uterine vessel microenvironment provokes hyperpermeability through the deregulation of VEGFA, NOS1, and CTNNB1.Abbreviations: ACTA2: actin, alpha 2, smooth muscle, aortic; Amhr2: anti-Mullerian hormone type 2 receptor; ANGPT1: angiopoietin 1; ATG: autophagy-related; CDH5: cadherin 5; CLDN5: claudin 5; COL1A1: collagen, type I, alpha 1; CSPG4/NG2: chondroitin sulfate proteoglycan 4; CTNNB1: catenin (cadherin associated protein), beta 1; DES: desmin; EDN1: endothelin 1; EDNRB: endothelin receptor type B; F3: coagulation factor III; KDR/FLK1/VEGFR2: kinase insert domain protein receptor; LYVE1: lymphatic vessel endothelial hyaluronan receptor 1; MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; MCAM/CD146: melanoma cell adhesion molecule; MYL2: myosin, light polypeptide 2, regulatory, cardiac, slow; MYLK: myosin, light polypeptide kinase; NOS1/nNOS: nitric oxide synthase 1, neuronal; NOS2/iNOS: nitric oxide synthase 2, inducible; NOS3/eNOS: nitric oxide synthase 3, endothelial cell; OVX: ovariectomy; PECAM1/CD31: platelet/endothelial cell adhesion molecule 1; POSTN: periostin, osteoblast specific factor; SQSTM1: sequestosome 1; TEK/Tie2: TEK receptor tyrosine kinase; TJP1/ZO-1: tight junction protein 1; TUBB1, tubulin, beta 1 class VI; USC: uterine stromal cell; VEGFA: vascular endothelial growth factor A; VSMC: vascular smooth muscle cell.
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Autofagia , Permeabilidade Capilar , Óxido Nítrico Sintase Tipo I/metabolismo , Artéria Uterina/metabolismo , Útero/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , beta Catenina/metabolismo , Animais , Microambiente Celular , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Artéria Uterina/fisiologia , Útero/irrigação sanguínea , Útero/fisiologiaRESUMO
Cryopreserved oocytes are inevitably exposed to cold stress, which negatively affects the cellular aspects of the oocytes. Lipidomic analysis of the oocytes reveals quantitative changes in lipid classes under conditions of cold stress, leading to potential freezing-vulnerability. We had previously shown that specific phospholipids are significantly downregulated in vitrified-warmed mouse oocytes compared to those in fresh oocytes. In this study, we examined whether supplementation of polyethylene glycol 8000 (PEG 8000) during vitrification influences the lipidome of the oocytes. We used liquid chromatography with tandem mass spectrometry (LC-MS/MS) to study the alteration in the lipidome in three groups of mouse oocytes: fresh, vitrified-warmed, and vitrified with PEG 8000-warmed during vitrification. In these groups, we targeted to analyze 21 lipid classes. We profiled 132 lipid species in the oocytes and statistical analyses revealed lipid classes that were up- or downregulated in these groups. Overall, our data revealed that several classes of lipids were affected during vitrification, and that oocytes vitrified with PEG 8000 to some extent alleviated the levels of changes in phospholipid and sphingolipid contents during vitrification. These results suggest that phospholipids and sphingolipids are influenced by PEG 8000 during vitrification and that PEG 8000 can be considered as a potential candidate for preserving membrane integrity during oocyte cryopreservation.
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Lipidômica , Vitrificação , Animais , Cromatografia Líquida , Criopreservação/métodos , Suplementos Nutricionais , Camundongos , Oócitos , Polietilenoglicóis , Espectrometria de Massas em TandemRESUMO
Enhancing the radioresponsiveness of colorectal cancer (CRC) is essential for local control and prognosis. However, consequent damage to surrounding healthy cells can lead to treatment failure. We hypothesized that shortchain fatty acids (SCFAs) could act as radiosensitizers for cancer cells, allowing the administration of a lower and safer dose of radiation. To test this hypothesis, the responses of threedimensionalcultured organoids, derived from CRC patients, to radiotherapy, as well as the effects of combined radiotherapy with the SCFAs butyrate, propionate and acetate as candidate radiosensitizers, were evaluated via reverse transcriptionquantitative polymerase chain reaction, immunohistochemistry and organoid viability assay. Of the three SCFAs tested, only butyrate suppressed the proliferation of the organoids. Moreover, butyrate significantly enhanced radiationinduced cell death and enhanced treatment effects compared with administration of radiation alone. The radiationbutyrate combination reduced the proportion of Ki67 (proliferation marker)positive cells and decreased the number of S phase cells via FOXO3A. Meanwhile, 3/8 CRC organoids were found to be nonresponsive to butyrate with lower expression levels of FOXO3A compared with the responsive cases. Notably, butyrate did not increase radiationinduced cell death and improved regeneration capacity after irradiation in normal organoids. These results suggest that butyrate could enhance the efficacy of radiotherapy while protecting the normal mucosa, thus highlighting a potential strategy for minimizing the associated toxicity of radiotherapy.
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Ácido Butírico/administração & dosagem , Quimiorradioterapia Adjuvante/métodos , Neoplasias do Colo/terapia , Proteína Forkhead Box O3/metabolismo , Neoplasias Retais/terapia , Idoso , Idoso de 80 Anos ou mais , Técnicas de Cultura de Células , Colectomia , Colo/citologia , Colo/efeitos dos fármacos , Colo/patologia , Colo/efeitos da radiação , Neoplasias do Colo/patologia , Colonoscopia , Feminino , Humanos , Mucosa Intestinal/citologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Mucosa Intestinal/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Organoides , Protectomia , Neoplasias Retais/patologia , Reto/citologia , Reto/efeitos dos fármacos , Reto/patologia , Reto/efeitos da radiaçãoRESUMO
BACKGROUND: We had previously demonstrated that vitrification reduces the levels of certain phospholipid classes, and that oocytes from aged mice show a similar lipidome alteration, even without vitrification. In the current investigation, we examined if vitrification-warming of mouse oocytes from young and aged mice causes any changes in molecular aspects of lipid-associated features. METHODS: Metaphase II (MII) stage oocytes were harvested from young (10-14-week-old) and aged (45-54-week-old) mice by a superovulation regime with PMSG followed by hCG. We examined the status of the intracellular lipid pool and the integrity of the plasma membrane by staining oocytes with BODIPY 500/510 and CellMask live dyes. Expression of lipid uptake- and necroptosis-associated genes was assessed by quantitative PCR analyses, in oocytes from young and old mice, before and after vitrification. Localization patterns of two crucial necroptosis proteins, phosphorylated MLKL (pMLKL) and phosphorylated RIPK1 (pRIPK1) were examined in mouse oocytes by immunofluorescence staining. Necrostain-1 (Nec1), an inhibitor of RIPK1, was used to examine if RIPK1 activity is required to maintain oocyte quality during vitrification. RESULTS: We confirmed that vitrified-warmed oocytes from aged mice showed noticeable decrease in both CellMask and BODIPY 500/510 dyes. Among the lipid uptake-associated genes, Cd36 expression was higher in oocytes from aged mice. Necroptosis is a type of programmed cell death that involves damage to the plasma membrane, eventually resulting in cell rupture. The expression of necroptosis-associated genes did not significantly differ among groups. We observed that localization patterns of pMLKL and pRIPK1 were unique in mouse oocytes, showing association with microtubule organizing centers (MTOCs) and spindle poles. pMLKL was also localized on kinetochores of MII chromosomes. Oocytes treated with Nec1 during vitrification showed a decreased survival rate, indicating the importance of RIPK1 activity in oocyte vitrification. CONCLUSIONS: We report that oocytes from aged mice show differential expression of CD36, which suggests that CD36-mediated lipid uptake may be influenced by age. We also show for the first time that pMLKL and pRIPK1 exhibit unique localization pattern in mouse oocytes and this may suggest role(s) for these factors in non-necroptosis-associated cellular processes.
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Metabolismo dos Lipídeos/fisiologia , Necroptose/fisiologia , Oócitos/metabolismo , Fatores Etários , Animais , Células Cultivadas , Criopreservação , Feminino , Camundongos , Superovulação , VitrificaçãoRESUMO
Coronavirus disease 2019 (COVID-19), which causes serious respiratory illness such as pneumonia and lung failure, was first reported in Wuhan, the capital of Hubei, China. The etiological agent of COVID-19 has been confirmed as a novel coronavirus, now known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is most likely originated from zoonotic coronaviruses, like SARS-CoV, which emerged in 2002. Within a few months of the first report, SARS-CoV-2 had spread across China and worldwide, reaching a pandemic level. As COVID-19 has triggered enormous human casualties and serious economic loss posing global threat, an understanding of the ongoing situation and the development of strategies to contain the virus's spread are urgently needed. Currently, various diagnostic kits to test for COVID-19 are available and several repurposing therapeutics for COVID-19 have shown to be clinically effective. In addition, global institutions and companies have begun to develop vaccines for the prevention of COVID-19. Here, we review the current status of epidemiology, diagnosis, treatment, and vaccine development for COVID-19.
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Betacoronavirus , Técnicas de Laboratório Clínico , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Vacinas Virais , Betacoronavirus/imunologia , COVID-19 , Teste para COVID-19 , Vacinas contra COVID-19 , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Humanos , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , SARS-CoV-2 , Tratamento Farmacológico da COVID-19RESUMO
Safety and efficacy outcomes of imatinib treatment were evaluated using extensive clinical data collected from a total of 1003 patients with newly diagnosed chronic myeloid leukemia in chronic phase between 2001 and 2018. By 12 months of imatinib treatment at a fixed dose of 400 mg/day, 45.4% of patients experienced at least one type of dose-limiting toxicities (DLTs). The DLTs that frequently occurred first were thrombocytopenia (40.0%), neutropenia/leukopenia (14.3%) and dermatological reactions (12.1%). Patients with lighter body weight (≤ 64 kg) and older age (> 43 years) experienced a markedly higher occurrence of first DLTs by 12 months than heavier and younger patients (57.9% vs. 30.1%, p < 0.001). On the other hand, 38.9% of patients achieved major molecular response (MMR) at 12 months at the fixed dose. Female patients achieved a greater rate of MMR than male patients (45.6% vs. 35.5%, p = 0.028). In conclusion, patients with light weight and old age are more vulnerable to DLTs, whereas female patients gain more efficacy benefit at the fixed dose. The authors suggest that the initial dose of imatinib should be reduced to 300 mg/day or lower for patients vulnerable to DLTs to diminish the risk of DLTs without compromising the achievement of MMR.
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Mesilato de Imatinib/administração & dosagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Medicina de Precisão , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Peso Corporal , Feminino , Humanos , Mesilato de Imatinib/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Segurança , Trombocitopenia/induzido quimicamente , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
The present study investigated the association between single nucleotide polymorphisms (SNPs) in immune- or DNA repair-related genes and the integration pattern of human papillomavirus (HPV), a promising prognostic marker in cervical cancer. The HPV integration patterns of cervical cancer patients were determined by polymerase chain reaction and in situ hybridization, and categorized as episomal (group A), single-copy or multi-copy tandem repetition integrated (group B), and undetectable HPV types (group C). After sample and SNP quality control, 166,505 SNPs in 161 samples (38, 111, and 12 patients in groups A, B, and C, respectively) were examined. None of the SNPs reached genome-wide significance, and several candidate SNPs for future study were selected, including rs10999435 on chromosome 10q22, rs1322054 on chromosome 9q32-33, and rs10902171 on chromosome 11p15. Luciferase assay identified rs1322054 as the primary functional variant to regulate gene expression in immune cell. Further studies are needed to determine the genetic background of different integration patterns of HPV in cervical cancer patients.
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Reparo do DNA/genética , Imunidade/genética , Papillomaviridae/genética , Polimorfismo de Nucleotídeo Único , Neoplasias do Colo do Útero/genética , Integração Viral/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , DNA Viral/genética , Feminino , Genótipo , Interações Hospedeiro-Patógeno/genética , Humanos , Células Jurkat , Pessoa de Meia-Idade , Papillomaviridae/fisiologia , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/virologiaRESUMO
Human leukocyte antigen (HLA) class II alleles have been previously associated with cervical cancer. However, these associations vary widely across racial and ethnic groups. Therefore, we evaluated the effect of HLA class II alleles on cervical cancer in a Korean population. HLA-DRB1, HLA-DQB1, and HLA-DQA1 alleles were analyzed in 457 cervical cancer patients and compared to those of 926 control subjects. The odds ratio (OR) of each allele between the patients and controls was calculated using the logistic regression model. Patients, had significantly lower frequencies of HLA-DRB1 and HLA-DQB1 alleles than control subjects: HLA-DRB1*13:02:01 (4.4% vs 8.8%; OR 0.48, 95% confidence interval (CI) 0.27-0.84; pâ¯=â¯0.001), HLA-DRB1*04:06 (2.1% vs 4.7%; OR 0.44, 95% CI 0.20-0.97; pâ¯=â¯0.033), and HLA-DQB1*06:04:01 (2.3% vs 5.0%; OR 0.46, 95% CI 0.22-0.94; pâ¯=â¯0.021). No significant association was observed for HLA-DQA1. Protective associations between HLA-DRB1*13:02, HLA-DRB1*04:06, and HLA-DQB1*06:04 alleles and cervical cancer were found in the Korean population.
Assuntos
Genótipo , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Neoplasias do Colo do Útero/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Teste de Histocompatibilidade , Humanos , Coreia (Geográfico) , Modelos Logísticos , Pessoa de Meia-Idade , Polimorfismo GenéticoRESUMO
"Switchable water" is an aqueous solution containing a water-soluble amine additive that exhibits CO2 -switchable properties, such as large changes in ionic strength, by forming an ammonium bicarbonate salt. Switchable water has been used to reversibly "salt-out" organic compounds from water. This study explores the salting out of several compounds in switchable water when CO2 is present and also explores the solubility of small molecules in switchable water, compared to pure water, when CO2 is absent. The results show that organic compounds are generally more soluble in switchable water than pure water in the absence of CO2 , but less soluble in the presence of 1â atm CO2 . Exceptions include carboxylic acids and phenols which, presumably due to their acidity, are more soluble in switchable water than in pure water, even when CO2 is applied. Kirkwood-Buff solvation theory was applied to gain insights into the effects of the amine additive on the aqueous solubility of caffeine. Furthermore, the switchable properties of the additives allow for the preparation of switchable aqueous two-phase systems.
RESUMO
BACKGROUNDS/AIMS: Cysteine dioxygenase type 1 (CDO1) acts as a tumor suppressor and is silenced by promoter methylation in various malignancies. The relationship between the CDO1 methylation status and hepatocellular carcinoma (HCC) tumorigenesis was evaluated. METHODS: Using a HCC cell line (SNU423), an in vitro demethylation study was performed to confirm whether promoter methylation causes CDO1 down-regulation. The SNU423 cells transfected with the CDO1 cell function was compared to that of naïve cells. An in vivo study using immunohistochemical staining of HCC specimens that were collected from patients who underwent curative liver resection was also performed. RESULTS: CDO1 was activated after demethylation treatment in the HCC specimens. Moreover, tumor cell proliferation, colony-forming, migration, and invasion activities significantly decreased after CDO1 transfection (p<0.05). The percentage of tumors that were larger than 5 cm was higher in patients who had a lower expression of CDO1 (p=0.030). Vascular invasion and histological grade were independent prognostic factors for poor overall and recurrence-free survival. The degree of CDO1 expression was not an independent prognostic factor in this study's population. CONCLUSIONS: These results suggested that methylation down-regulated CDO1 expression in the HCC cells. CDO1 methylation may be a potentially valuable diagnostic biomarker for HCC.
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PURPOSE: The standard chemoradiation therapy currently used for locally advanced cervical cancer (LACC) patients does not reflect the biological heterogeneity of this disease, and there is an increasing need for the development of biomarkers that can help guide the individualized treatment regimens. The purpose of this study was to investigate the prognostic value of the integration pattern of human papillomavirus (HPV) in LACC patients. METHODS AND MATERIALS: The HPV integration pattern was determined by in situ hybridization and polymerase chain reaction, and the tumors were classified as the episomal pattern (group A), as the single-copy integrated or multicopy tandem repetition-integrated pattern (group B), or as undetectable HPV (group C). Ninety-eight LACC patients were included in a development dataset and 106 independent patients in a validation dataset. The multivariate Cox model was used to examine the effect of the HPV integration pattern on disease-free survival (DFS). The model was validated internally by the leave-one-out cross-validation method and externally by an independent dataset. RESULTS: After adjustment for significant prognostic factors (stage, histologic grade, histologic type, and tumor size), the HPV integration pattern was significantly associated with DFS in the development (P=.032) and validation (P=.023) datasets. Survival was worst in group C and best in group A. The multivariate model with HPV integration pattern as an explanatory variable showed good discrimination ability and could separate patients with different risk profiles. CONCLUSIONS: This study identified the HPV integration pattern, as determined by in situ hybridization and polymerase chain reaction, as a strong prognostic biomarker for DFS in LACC patients treated by chemoradiation therapy. This finding may open the possibility of personalized treatment of these patients.