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1.
JCO Glob Oncol ; 10: e2300463, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38723216

RESUMO

PURPOSE: We aimed to assess knowledge, attitudes, and perceived barriers among health care professionals (HCPs), policymakers, and regulators in Vietnam related to opioid therapy for cancer pain. METHODS: We conducted a cross-sectional study in Vietnam from June to August 2022. Participants completed a questionnaire on their demographic characteristics, knowledge and attitudes toward opioid therapy, and barriers to accessing opioids for cancer pain. RESULTS: Two hundred seven HCPs and 15 policymakers/regulators completed the questionnaire. Poor knowledge about opioids in cancer pain was found in 63.3% of HCPs and 80.0% of policymakers/regulators. Poor knowledge was associated with a lack of training in cancer pain management or palliative care (PC; prevalence ratio [PR], 1.14 [95% CI, 1.04 to 1.24]). Negative attitudes toward opioid therapy in cancer pain were held by 64.7% of HCPs and 80.0% of policymakers/regulators. Negative attitudes were associated with the unavailability of oral morphine in the workplace (PR, 1.10 [95% CI, 1.01 to 1.20]). The most common major barriers reported were the absence of national policy on pain management and PC (34.7%), inadequate training in opioid use for cancer pain (33.8%), lockdown of health facilities during the COVID-19 pandemic (32.4%), limited opioid availability in local health facilities (32.4%), and excessively restrictive regulation of opioid dispensing in pharmacies (32.4%). CONCLUSION: This study found a knowledge deficit and negative attitudes toward opioid therapy for cancer pain among HCPs and policymakers/regulators. Improving education and training in opioid therapy is essential. Recognizing major barriers can guide strategies to enhance safe opioid accessibility for cancer pain management in Vietnam.


Assuntos
Analgésicos Opioides , Dor do Câncer , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde , Manejo da Dor , Humanos , Vietnã , Estudos Transversais , Analgésicos Opioides/uso terapêutico , Dor do Câncer/tratamento farmacológico , Dor do Câncer/psicologia , Masculino , Feminino , Adulto , Pessoal de Saúde/psicologia , Pessoal de Saúde/educação , Pessoa de Meia-Idade , Manejo da Dor/métodos , Inquéritos e Questionários , Atitude do Pessoal de Saúde , COVID-19/epidemiologia , COVID-19/prevenção & controle , Cuidados Paliativos/métodos
2.
Heliyon ; 10(9): e29539, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38698995

RESUMO

Background: Probiotics are intellectually rewarding for the discovery of their potential as a source of functional food. Investigating the economic and beauty sector dynamics, this study conducted a comprehensive review of scholarly articles to evaluate the capacity of probiotics to promote hair growth and manage dandruff. Methods: We used the PRISMA 2020 with Embase, Pubmed, ClinicalTrials.gov, Scopus, and ICTRP databases to investigate studies till May 2023. Meta-analyses utilizing the random effects model were used with odds ratios (OR) and standardized mean differences (SMD). Result: Meta-analysis comprised eight randomized clinical trials and preclinical studies. Hair growth analysis found a non-significant improvement in hair count (SMD = 0.32, 95 % CI -0.10 to 0.75) and a significant effect on thickness (SMD = 0.92, 95 % CI 0.47 to 1.36). In preclinical studies, probiotics significantly induced hair follicle count (SMD = 3.24, 95 % CI 0.65 to 5.82) and skin thickness (SMD = 2.32, 95 % CI 0.47 to 4.17). VEGF levels increased significantly (SMD = 2.97, 95 % CI 0.80 to 5.13), while IGF-1 showed a non-significant inducement (SMD = 0.53, 95 % CI -4.40 to 5.45). For dandruff control, two studies demonstrated non-significant improvement in adherent dandruff (OR = 1.31, 95 % CI 0.13-13.65) and a significant increase in free dandruff (OR = 5.39, 95 % CI 1.50-19.43). Hair follicle count, VEGF, IGF-1, and adherent dandruff parameters were recorded with high heterogeneity. For the systematic review, probiotics have shown potential in improving hair growth and controlling dandruff through modulation of the immune pathway and gut-hair axis. The Wnt/ß-catenin pathway, IGF-1 pathway, and VEGF are key molecular pathways in regulating hair follicle growth and maintenance. Conclusions: This review found significant aspects exemplified by the properties of probiotics related to promoting hair growth and anti-dandruff effect, which serve as a roadmap for further in-depth studies to make it into pilot scales.

3.
Pathology ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38777739

RESUMO

Haemophilus influenzae, a causative agent of severe invasive infections such as meningitis, sepsis and pneumonia, is classified into encapsulated or typeable (represented by serotypes A to F) and non-typeable varieties (NTHi) by the presence or absence of the polysaccharide capsule. Invasive disease caused by H. influenzae type B (HIB) can be prevented through vaccination which remains the main disease control intervention in many countries. This study examined the genomic diversity of circulating H. influenzae strains associated with invasive disease in New South Wales, Australia, before and during the COVID-19 pandemic. Ninety-six isolates representing 95 cases of invasive H. influenzae infections (iHi) diagnosed between January 2017 and September 2022 were typed and characterised using whole genome sequencing. These cases were caused by serotypes A (n=24), B (n=35), E (n=3), F (n=2) and NTHi (n=32). There was an apparent decline in the number of iHi infections during the COVID-19 pandemic, with a corresponding increase in the proportion of iHi cases caused by serotype A (HIA), which returned to pre-pandemic levels in 2022. Fifteen isolates associated with HIB or non-typeable iHi were resistant to ß-lactams due to a PBP3 mutation or carriage of blaTEM-1. Further, capsular gene duplication was observed in HIB isolates but was not found in HIA. These findings provide important baseline genomic data for ongoing iHi surveillance and control.

4.
Brief Bioinform ; 25(3)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38754407

RESUMO

Predicting cancer drug response using both genomics and drug features has shown some success compared to using genomics features alone. However, there has been limited research done on how best to combine or fuse the two types of features. Using a visible neural network with two deep learning branches for genes and drug features as the base architecture, we experimented with different fusion functions and fusion points. Our experiments show that injecting multiplicative relationships between gene and drug latent features into the original concatenation-based architecture DrugCell significantly improved the overall predictive performance and outperformed other baseline models. We also show that different fusion methods respond differently to different fusion points, indicating that the relationship between drug features and different hierarchical biological level of gene features is optimally captured using different methods. Considering both predictive performance and runtime speed, tensor product partial is the best-performing fusion function to combine late-stage representations of drug and gene features to predict cancer drug response.


Assuntos
Antineoplásicos , Genótipo , Neoplasias , Redes Neurais de Computação , Humanos , Neoplasias/genética , Neoplasias/tratamento farmacológico , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Aprendizado Profundo , Genômica/métodos , Biologia Computacional/métodos
5.
BMC Bioinformatics ; 25(1): 193, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755527

RESUMO

We have developed AMRViz, a toolkit for analyzing, visualizing, and managing bacterial genomics samples. The toolkit is bundled with the current best practice analysis pipeline allowing researchers to perform comprehensive analysis of a collection of samples directly from raw sequencing data with a single command line. The analysis results in a report showing the genome structure, genome annotations, antibiotic resistance and virulence profile for each sample. The pan-genome of all samples of the collection is analyzed to identify core- and accessory-genes. Phylogenies of the whole genome as well as all gene clusters are also generated. The toolkit provides a web-based visualization dashboard allowing researchers to interactively examine various aspects of the analysis results. Availability: AMRViz is implemented in Python and NodeJS, and is publicly available under open source MIT license at https://github.com/amromics/amrviz .


Assuntos
Genoma Bacteriano , Genômica , Software , Genômica/métodos , Farmacorresistência Bacteriana/genética , Filogenia , Bactérias/genética , Bactérias/efeitos dos fármacos , Antibacterianos/farmacologia
6.
PLoS One ; 19(5): e0299791, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38728261

RESUMO

BACKGROUND: Depression is one of the most common mental health disorders among older people. Depressive symptoms are often overlooked and untreated in primary care settings. This study aims to assess the prevalence of depressive symptoms and associated factors among older people in Vietnam. METHOD: The study analyzed data from the Vietnam National Aging Survey (VNAS) conducted in 2022 with a nationally representative sample of 3,006 older people aged 60 and over in 12 provinces. The 15-item Geriatric Depression Scale (GDS-15) was used to assess depressive symptoms. Bivariate and multiple logistic regression analyses were used to explore the association between depressive symptoms and other related factors such as sociodemographic and economic characteristics, social support, health status, Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) limitations, chronic diseases, cigarette smoking status, alcoholic drinking, and domestic violence. RESULTS: The prevalence of depressive symptoms among older people was 20.2%. The associated factors that increase the odds of having depression among older people were female gender (OR = 2.21, 95% CI 1.34-3.62), living in rural areas (OR = 1.83, 95% CI 1.15-2.89), the poorest quintile (OR = 2.26, 95% CI 1.39-3.66), self-rated poor health (OR = 11.68, 95% CI 4.96-27.49), ADL limitations (OR = 2.12, 95% CI 1.51-2.99), IADL limitation (OR = 1.61 95% CI 1.16-2.25), and experiencing domestic violence in the last 12 months (OR = 6.66, 95% CI 4.00-11.05). CONCLUSION: Depression symptoms were prevalent among older people in Vietnam. Depression screening for older people should be included in primary care settings for early identification and treatment of depression.


Assuntos
Atividades Cotidianas , Depressão , Humanos , Masculino , Feminino , Idoso , Vietnã/epidemiologia , Depressão/epidemiologia , Pessoa de Meia-Idade , Prevalência , Idoso de 80 Anos ou mais , Envelhecimento/psicologia , Fatores de Risco , Inquéritos Epidemiológicos , Nível de Saúde
7.
Clin Transl Sci ; 17(5): e13828, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38783568

RESUMO

As a treatment for relapsed or refractory multiple myeloma (MM), carfilzomib has been associated with a significant risk of cardiovascular adverse events (CVAE). The goals of our study were to evaluate the metabolomic profile of MM patients to identify those at high risk prior to carfilzomib treatment and to explore the mechanisms of carfilzomib-CVAE to inform potential strategies to protect patients from this cardiotoxicity. Global metabolomic profiling was performed on the baseline and post-baseline plasma samples of 60 MM patients treated with carfilzomib-based therapy, including 31 who experienced CVAE, in a prospective cohort study. Baseline metabolites and post-baseline/baseline metabolite ratios that differ between the CVAE and no-CVAE patients were identified using unadjusted and adjusted methods. A baseline metabolomic risk score was created to stratify patients. We observed a lower abundance of tauroursodeoxycholic acid (T-UDCA) in CVAE patients at baseline (odds ratio [OR] = 0.47, 95% confidence interval [CI] = 0.21-0.94, p = 0.044) compared with the no-CVAE patients. A metabolite risk score was able to stratify patients into three risk groups. The area under the receiver-operating curve of the model with clinical predictors and metabolite risk score was 0.93. Glycochenodeoxycholic acid (OR = 0.56, 95% CI = 0.31-0.87, p = 0.023) was significantly lower in post-baseline/baseline ratios of CVAE patients compared with no-CVAE patients. Following metabolomic analysis, we created a baseline metabolite risk score that can stratify MM patients into different risk groups. The result also provided intriguing clues about the mechanism of carfilzomib-CVAE and potential cardioprotective strategies.


Assuntos
Cardiotoxicidade , Metabolômica , Mieloma Múltiplo , Oligopeptídeos , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/sangue , Oligopeptídeos/efeitos adversos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Cardiotoxicidade/etiologia , Cardiotoxicidade/sangue , Cardiotoxicidade/diagnóstico , Metabolômica/métodos , Estudos Prospectivos , Metaboloma/efeitos dos fármacos , Idoso de 80 Anos ou mais , Fatores de Risco
8.
Cell Stem Cell ; 31(5): 676-693.e10, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38626772

RESUMO

Frontotemporal dementia (FTD) is an incurable group of early-onset dementias that can be caused by the deposition of hyperphosphorylated tau in patient brains. However, the mechanisms leading to neurodegeneration remain largely unknown. Here, we combined single-cell analyses of FTD patient brains with a stem cell culture and transplantation model of FTD. We identified disease phenotypes in FTD neurons carrying the MAPT-N279K mutation, which were related to oxidative stress, oxidative phosphorylation, and neuroinflammation with an upregulation of the inflammation-associated protein osteopontin (OPN). Human FTD neurons survived less and elicited an increased microglial response after transplantation into the mouse forebrain, which we further characterized by single nucleus RNA sequencing of microdissected grafts. Notably, downregulation of OPN in engrafted FTD neurons resulted in improved engraftment and reduced microglial infiltration, indicating an immune-modulatory role of OPN in patient neurons, which may represent a potential therapeutic target in FTD.


Assuntos
Demência Frontotemporal , Neurônios , Osteopontina , Proteínas tau , Osteopontina/metabolismo , Osteopontina/genética , Demência Frontotemporal/genética , Demência Frontotemporal/patologia , Demência Frontotemporal/metabolismo , Humanos , Neurônios/metabolismo , Neurônios/patologia , Animais , Proteínas tau/metabolismo , Camundongos , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/patologia , Microglia/metabolismo , Microglia/patologia , Mutação/genética
9.
Biostatistics ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579199

RESUMO

The study of treatment effects is often complicated by noncompliance and missing data. In the one-sided noncompliance setting where of interest are the complier and noncomplier average causal effects, we address outcome missingness of the latent missing at random type (LMAR, also known as latent ignorability). That is, conditional on covariates and treatment assigned, the missingness may depend on compliance type. Within the instrumental variable (IV) approach to noncompliance, methods have been proposed for handling LMAR outcome that additionally invoke an exclusion restriction-type assumption on missingness, but no solution has been proposed for when a non-IV approach is used. This article focuses on effect identification in the presence of LMAR outcomes, with a view to flexibly accommodate different principal identification approaches. We show that under treatment assignment ignorability and LMAR only, effect nonidentifiability boils down to a set of two connected mixture equations involving unidentified stratum-specific response probabilities and outcome means. This clarifies that (except for a special case) effect identification generally requires two additional assumptions: a specific missingness mechanism assumption and a principal identification assumption. This provides a template for identifying effects based on separate choices of these assumptions. We consider a range of specific missingness assumptions, including those that have appeared in the literature and some new ones. Incidentally, we find an issue in the existing assumptions, and propose a modification of the assumptions to avoid the issue. Results under different assumptions are illustrated using data from the Baltimore Experience Corps Trial.

10.
J Oncol Pharm Pract ; : 10781552241248057, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38651319

RESUMO

BACKGROUND: Colitis was the third most common immune-related adverse effect in melanoma patients treated with immune-checkpoint inhibitor (ICI). With the limitation of real-world data in the UK population, this study was conducted in a UK hospital where a fresh colitis guidance was introduced to evaluate the overall grading (OG) to assess colitis severity and guide the treatment. AIMS: This study aimed to investigate colitis severity by Common Terminology Criteria for Adverse Events (CTCAE) grade and overall grade at time of presentation. Colitis treatment and outcome were evaluated to compare the impact of these two categories. METHODS: A single-center, retrospective observational study was performed in melanoma patient developing colitis symptoms. RESULTS: A total of 44 advanced melanoma patient with colitis symptoms were included. Median time to colitis onset was 67 days (range 4-890). Majority of patients developed G1/ G2 of CTCAE scale (70.4%) but moderate or severe overall grade (84.1%). There were 65.9% of patients treated with steroids, and 38.2% with infliximab and 4.5% with vedolizumab. The median time of colitis resolution was 28 days (range 0-282). Both treatment modality and time to resolution were associated with severity of colitis assessed by complete OG(p<0.0001) rather than CTCAE grading (p>0.05). CONCLUSIONS: This study provided a comprehensive description about ICI-induced colitis management in a single center of the UK. The more completed OG was proposed to stratify colitis patient and guide the investigation and treatment decision at presenting time, replacing the old CTCAE grading.

11.
Heliyon ; 10(7): e28118, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38596094

RESUMO

In this study, a series of secondary metabolites from Ganoderma sp. were screened against Staphylococcus aureus protein targets, including as phosphotransacetylase, clumping factor A, and dihydrofolate reductase, using molecular docking simulations. The chemicals that showed the strongest binding energy with the targeted proteins were ganodermanontriol, lucidumol B, ganoderic acid J, ergosterol, ergosterol peroxide, 7-oxoganoderic acid Z, ganoderic acid AM1, ganosinoside A, ganoderic acid D, and 24R-ergosta-7,2E-diene-3ß,5α,6ß-triol. Interestingly, ganosinoside A showed the greatest affinity for the protein clumping factor A, a result validated by molecular dynamic simulation. Additionally, three natural Ganoderma sp. Strains as Ganoderma lingzhi VNKKK1903, Ganoderma lingzhi VNKK1905A2, and Amauroderma subresinosum VNKKK1904 were collected from Kon Ka Kinh National Park in central land of Vietnam and evaluated for their antibacterial activity against Staphylococcus aureus using an agar well diffusion technique. These results suggest that the fungal extracts and secondary metabolites may serve as valuable sources of antibiotics against Staphylococcus aureus. These findings provided an important scientific groundwork for further exploration of the antibacterial mechanisms of compounds derived from Ganoderma sp. in future research.

12.
J Funct Biomater ; 15(3)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38535257

RESUMO

BACKGROUND: Recent developments in addressing dental aesthetic concerns, encompassing issues like teeth discoloration and halitosis, underscore the demand for safer alternative solutions. PURPOSE: This study aims to confirm the effects of lactic acid bacteria (LAB) from kimchi on artificial teeth bleaching and their potential impact in terms of preventing halitosis-related bacteria. MATERIALS AND METHODS: To evaluate the antimicrobial effects against oral pathogens, disc diffusion tests and broth microdilution methods were used. Additionally, crystal violet analysis was performed to confirm the biofilm inhibition effect. The bleaching effects on stained artificial teeth were analyzed using the CIEDE2000 colorimetric method. Statistical analyses were performed using GraphPad Prism 9 with one-way and two-way ANOVA, with the significance level set at α < 0.05. RESULTS: The strain THK-30, isolated from kimchi, exhibited antibacterial activity against Streptococcus mutans, Porphyromonas gingivalis, and Fusobacterium nucleatum, and was identified as Pediococcus inopinatus. Moreover, THK-30 showed a synergistic antibacterial effect against Gram-negative oral pathogens with 8% sodium hexametaphosphate (SHMP). In the stained artificial teeth bleaching test and artificial teeth biofilm inhibition test, the cell-free supernatant of THK-30 displayed significant teeth bleaching effects and caused the inhibition of biofilm formation, both independently and in combination with SHMP 8%. CONCLUSIONS: This study has demonstrated the potential applicability of LAB in teeth discoloration and halitosis. These findings are poised to provide a foundation for the development of research pertaining to the control of oral bacteria.

13.
Cult Health Sex ; : 1-17, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38478464

RESUMO

Women living with HIV often face intersecting challenges of stigma and gender inequality. In Vietnam, this issue is potentially exacerbated by the patriarchal culture. From December 2021 to March 2022, we conducted in-depth interviews with 30 women living with HIV in Hanoi to better understand their experiences and the coping mechanisms to navigate HIV stigma, cultural beliefs and gender norms. The interviews explored various topics including women's social and family roles in Vietnam, HIV-related beliefs, stigma and its impact on one's health and coping strategies. Participants reported stereotypes that assumed that women living with HIV had either engaged in sex work or behaved promiscuously. These stereotypes render them vulnerable to judgement and discrimination owing to widespread expectations of female virtue. As a result, women living with HIV often enacted non-disclosure and self-isolation to avoid stigma. This self-stigmatisation negatively impacted their healthcare-seeking, employment opportunities and ability to fulfil traditional family-caring roles. Conversely, many participants exhibited resilience with the support of family and peers. Overall, the complex interplay between gender, culture and HIV stigma underscores the importance of developing culturally appropriate, multifaceted approaches to engaging family and peers, modifying gender-based discriminatory social practices and enhancing women's self-efficacy and empowerment in Vietnam.

14.
Reprod Health ; 21(1): 34, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38468301

RESUMO

BACKGROUND: Human Immunodeficiency Virus (HIV) remains a significant public health concern worldwide. Women living with HIV/AIDS (WLHA) have the additional and unique need to seek sexual and reproductive health services. WLHA's maternal health journeys can be shaped by the cultural norms and resources that exist in their society. This study sought to understand if and how WLHA's family planning, pregnancy, and motherhood experiences could be influenced by the patriarchal culture, gender roles, and HIV stigma in Vietnam, specifically. METHODS: Between December 2021 and March 2022, 30 WLHA with diverse socioeconomic backgrounds and childbirth experiences were interviewed in Hanoi, Vietnam. These semi-structured interviews covered topics including HIV stigma, gender norms, pregnancy experiences, and child-rearing challenges. Interviews were audio recorded, transcribed, and analysed using ATLAS.ti. RESULTS: Qualitative analyses of participant quotes revealed how limited information on one's health prospects and reproductive options posed a significant challenge to family planning. Societal and familial expectations as well as economic circumstances also influenced reproductive decision-making. WLHA often encountered substandard healthcare during pregnancy, labor, and delivery. Stigma and lack of provider attentiveness resulted in cases where women were denied pain relief and other medical services. Communication breakdowns resulted in failure to administer antiretroviral therapy for newborns. Motherhood for WLHA was shadowed by concerns for not only their own health, but also the wellbeing of their children, as HIV stigma affected their children at school and in society as well. Many WLHA highlighted the constructive or destructive role that family members could play in their childbirth decision-making and care-giving experiences. CONCLUSIONS: Overall, this study underscores the complex ways that cultural expectations, family support, and stigma in healthcare impact WLHA. Efforts to educate and engage families and healthcare providers are warranted to better understand and address the needs of WLHA, ultimately improving their reproductive and maternal health.


HIV-related stigma and discrimination have consequential impacts on health and quality of life for women living with HIV (WLHA). WLHA in Vietnam must navigate the additional challenges of a traditionally patriarchal and hierarchical society. Women typically face less educational and occupational opportunities and are often expected to defer to expectations of family and virtue. Stigma among family members, friends, employers, and healthcare providers poses a significant challenge to WLHA autonomy, especially as it relates to their reproductive health decision-making and maternal health experiences. This study aims to better understand the experiences of WLHA throughout family planning, pregnancy, and motherhood. The findings will hopefully shed light on strategies to empower WLHA and to combat HIV- and gender-based stigma not only in Vietnam, but also globally.


Assuntos
Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Gravidez , Humanos , Feminino , Recém-Nascido , HIV , Saúde Materna , Vietnã/epidemiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Pesquisa Qualitativa
15.
Funct Integr Genomics ; 24(2): 59, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38498207

RESUMO

Rice is an essential but highly stress-susceptible crop, whose root system plays an important role in plant development and stress adaptation. The rice root system architecture is controlled by gene regulatory networks involving different phytohormones including auxin, jasmonate, and gibberellin. Gibberellin is generally known as a molecular clock that interacts with different pathways to regulate root meristem development. The exogenous treatment of rice plantlets with Gibberellin reduced the number of crown roots, whilst the exogenous jasmonic acid treatment enhanced them by involving a Germin-like protein OsGER4. Due to those opposite effects, this study aims to investigate the effect of Gibberellin on crown root development in the rice mutant of the plasmodesmal Germin-like protein OsGER4. Under exogenous gibberellin treatment, the number of crown roots significantly increased in osger4 mutant lines and decreased in the OsGER4 overexpressed lines. GUS staining showed that OsGER4 was strongly expressed in rice root systems, particularly crown and lateral roots under GA3 application. Specifically, OsGER4 was strongly expressed from the exodermis, epidermis, sclerenchyma to the endodermis layers of the crown root, along the vascular bundle and throughout LR primordia. The plasmodesmal protein OsGER4 is suggested to be involved in crown root development by maintaining hormone homeostasis, including Gibberillin.


Assuntos
Giberelinas , Glicoproteínas , Oryza , Giberelinas/farmacologia , Giberelinas/metabolismo , Oryza/metabolismo , Raízes de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ácidos Indolacéticos/farmacologia , Ácidos Indolacéticos/metabolismo
16.
JCI Insight ; 9(8)2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483541

RESUMO

Glioblastoma (GBM) remains an incurable disease, requiring more effective therapies. Through interrogation of publicly available CRISPR and RNAi library screens, we identified the α-ketoglutarate dehydrogenase (OGDH) gene, which encodes an enzyme that is part of the tricarboxylic acid (TCA) cycle, as essential for GBM growth. Moreover, by combining transcriptome and metabolite screening analyses, we discovered that loss of function of OGDH by the clinically validated drug compound CPI-613 was synthetically lethal with Bcl-xL inhibition (genetically and through the clinically validated BH3 mimetic, ABT263) in patient-derived xenografts as well neurosphere GBM cultures. CPI-613-mediated energy deprivation drove an integrated stress response with an upregulation of the BH3-only domain protein, Noxa, in an ATF4-dependent manner, as demonstrated by genetic loss-of-function experiments. Consistently, silencing of Noxa attenuated cell death induced by CPI-613 in model systems of GBM. In patient-derived xenograft models of GBM in mice, the combination treatment of ABT263 and CPI-613 suppressed tumor growth and extended animal survival more potently than each compound on its own. Therefore, combined inhibition of Bcl-xL along with disruption of the TCA cycle might be a treatment strategy for GBM.


Assuntos
Compostos de Anilina , Caprilatos , Glioblastoma , Complexo Cetoglutarato Desidrogenase , Sulfetos , Sulfonamidas , Mutações Sintéticas Letais , Ensaios Antitumorais Modelo de Xenoenxerto , Proteína bcl-X , Animais , Humanos , Camundongos , Fator 4 Ativador da Transcrição/metabolismo , Fator 4 Ativador da Transcrição/genética , Compostos de Anilina/farmacologia , Proteína bcl-X/metabolismo , Proteína bcl-X/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/tratamento farmacológico , Linhagem Celular Tumoral , Ciclo do Ácido Cítrico/efeitos dos fármacos , Glioblastoma/patologia , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/tratamento farmacológico , Complexo Cetoglutarato Desidrogenase/metabolismo , Complexo Cetoglutarato Desidrogenase/genética , Complexo Cetoglutarato Desidrogenase/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Sulfonamidas/farmacologia
17.
Nucleic Acids Res ; 52(9): 5016-5032, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38471819

RESUMO

Viruses are master remodelers of the host cell environment in support of infection and virus production. For example, viruses typically regulate cell gene expression through modulating canonical cell promoter activity. Here, we show that Epstein Barr virus (EBV) replication causes 'de novo' transcription initiation at 29674 new transcription start sites throughout the cell genome. De novo transcription initiation is facilitated in part by the unique properties of the viral pre-initiation complex (vPIC) that binds a TATT[T/A]AA, TATA box-like sequence and activates transcription with minimal support by additional transcription factors. Other de novo promoters are driven by the viral transcription factors, Zta and Rta and are influenced by directional proximity to existing canonical cell promoters, a configuration that fosters transcription through existing promoters and transcriptional interference. These studies reveal a new way that viruses interact with the host transcriptome to inhibit host gene expression and they shed light on primal features driving eukaryotic promoter function.


Assuntos
Herpesvirus Humano 4 , Regiões Promotoras Genéticas , Replicação Viral , Humanos , Replicação Viral/genética , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/fisiologia , Sítio de Iniciação de Transcrição , Iniciação da Transcrição Genética , Interações Hospedeiro-Patógeno/genética , Proteínas Virais/metabolismo , Proteínas Virais/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Transcrição Gênica , TATA Box/genética
18.
J Comput Chem ; 45(18): 1552-1561, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38500409

RESUMO

Investigation of Lewis acid-base interactions has been conducted by ab initio calculations and machine learning (ML) models. This study aims to resolve two critical tasks that have not been quantitatively investigated. First, ML models developed from density functional theory (DFT) calculations predict experimental BF3 affinity with Pearson correlation coefficients around 0.9 and mean absolute errors around 10 kJ mol-1. The ML models are trained by DFT-calculated BF3 affinity of more than 3000 adducts, with input features readily obtained by rdkit. Second, the ML models have the capability of predicting the relative strength of Lewis base binding atoms in Lewis polybases, which is either an extremely challenging task to conduct experimentally or a computationally expensive task for ab initio methods. The study demonstrates and solidifies the potential of combining DFT calculations and ML models to predict experimental properties, especially those that are scarce and impractical to empirically acquire.

19.
ISME J ; 18(1)2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38365233

RESUMO

Microbial community dynamics on sinking particles control the amount of carbon that reaches the deep ocean and the length of time that carbon is stored, with potentially profound impacts on Earth's climate. A mechanistic understanding of the controls on sinking particle distributions has been hindered by limited depth- and time-resolved sampling and methods that cannot distinguish individual particles. Here, we analyze microbial communities on nearly 400 individual sinking particles in conjunction with more conventional composite particle samples to determine how particle colonization and community assembly might control carbon sequestration in the deep ocean. We observed community succession with corresponding changes in microbial metabolic potential on the larger sinking particles transporting a significant fraction of carbon to the deep sea. Microbial community richness decreased as particles aged and sank; however, richness increased with particle size and the attenuation of carbon export. This suggests that the theory of island biogeography applies to sinking marine particles. Changes in POC flux attenuation with time and microbial community composition with depth were reproduced in a mechanistic ecosystem model that reflected a range of POC labilities and microbial growth rates. Our results highlight microbial community dynamics and processes on individual sinking particles, the isolation of which is necessary to improve mechanistic models of ocean carbon uptake.


Assuntos
Microbiota , Água do Mar , Carbono , Sequestro de Carbono
20.
J Food Sci ; 89(4): 2512-2521, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38380711

RESUMO

In recent years, concerns have been raised regarding the contamination of grapes with pesticide residues. As consumer demand for safer food products grows, regular monitoring of pesticide residues in food has become essential. This study sought to develop a rapid and sensitive technique for detecting two specific pesticides (phosmet and paraquat) present on the grape surface using the surface-enhanced Raman spectroscopy (SERS) method. Gold nanostars (AuNS) particles were synthesized, featuring spiky tips that act as hot spots for localized surface plasmon resonance, thereby enhancing Raman signals. Additionally, the roughened surface of AuNS increases the surface area, resulting in improved interactions between the substrate and analyte molecules. Prominent Raman peaks of mixed contaminants were acquired and used to characterize and quantify the pesticides. It was observed that the SERS intensity of the Raman peaks changed in proportion to the concentration ratio of phosmet and paraquat. Moreover, AuNS exhibited superior SERS enhancement compared to gold nanoparticles. The results demonstrate that the lowest detectable concentration for both pesticides on grape surfaces is 0.5 mg/kg. These findings suggest that SERS coupled with AuNS constitutes a practical and promising approach for detecting and quantifying trace contaminants in food. PRACTICAL APPLICATION: This research established a novel surface-enhanced Raman spectroscopy (SERS) method coupled with a simplified extraction protocol and gold nanostar substrates to detect trace levels of pesticides in fresh produce. The detection limits meet the maximum residue limits set by the EPA. This substrate has great potential for rapid measurements of chemical contaminants in foods.


Assuntos
Nanopartículas Metálicas , Resíduos de Praguicidas , Praguicidas , Fosmet , Vitis , Resíduos de Praguicidas/análise , Ouro/química , Paraquat , Nanopartículas Metálicas/química , Praguicidas/análise , Análise Espectral Raman/métodos
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