Discovery of Alkyl Triphenylphosphonium Pinostrobin Derivatives as Potent Anti-Breast Cancer Agents.

Pinostrobin demonstrated anticancer properties, but its hydrophobic feature led to a reduction in bioavailability. The mitochondria-targeted approach successfully synthesized eight new alkyl triphenylphosphonium pinostrobin derivatives (1-8) with good yield in this study. Seven compounds (1-3, 5-8) showed greater cytotoxic potency against the human MCF-7 breast cancer cell line than pinostrobin. Molecular docking studies were performed with two important targets in hormone-dependent anticancer strategies, estrogen receptor α (ERα) ligand binding domains, 3ERT (antagonist recognition and antiproliferative function), and 1GWR (agonist recognition and pro-proliferative function). In addition, the MD simulation study of the two most potent compounds (2 and 3) complexed with both ERα forms suggested that compounds 2 and 3 could serve as favourable antagonists. Furthermore, the in silico ADMET prediction indicated that compounds 2 and 3 could be potential drug candidates.

In vitro biological evaluation and in silico studies of linear diarylheptanoids from Curcuma aromatica Salisb. as urease inhibitors.

Plants of the Zingiberaceae family, specifically those belonging to the Curcuma species, are commonly under consideration as potential therapeutic agents for the management of gastrointestinal diseases. In this study, we carried out a phytochemical study on Curcuma aromatica Salisb. (or so-called "Nghe trang" in Vietnamese) grown in Vietnam, which yields three newly discovered 3,5-diacetoxy diarylheptanoids (1-3) and six known 3,5-dihydroxyl diarylheptanoids (4-9). The bioactivity assessment shows that all isolated compounds, except compounds 3, 7, and 8, could inhibit urease. Compounds 4 and 9 significantly inhibit urease, with an IC50 value of 9.6 and 21.4 µM, respectively, more substantial than the positive control, hydroxyurea (IC50 = 77.4 µM). The structure-activity relationship (SAR) of linear diarylheptanoids was also established, suggesting that the hydroxyl groups at any position of skeleton diarylheptanoids are essential for exerting anti-urease action. Through a comparative analysis of the binding sites of hydroxyurea and diarylheptanoid compounds via our constructed in silico model, the mechanism of action of diarylheptanoid compounds is predicted to bind to the dynamic region close to the dinickel active center, resulting in a loss of catalytic activity. Such insights certainly help design and/or find diarylheptanoid-based compounds for treating gastric ulcers through inhibiting urease.

Generation of parthenocarpic tomato plants in multiple elite cultivars using the CRISPR/Cas9 system.

Tomato (Solanum lycopersicum L.) is one of the most important crops in the world for its fruit production. Advances in cutting-edge techniques have enabled the development of numerous critical traits related to the quality and quantity of tomatoes. Genetic engineering techniques, such as gene transformation and gene editing, have emerged as powerful tools for generating new plant varieties with superior traits. In this study, we induced parthenocarpic traits in a population of elite tomato (ET) lines. At first, the adaptability of ET lines to genetic transformation was evaluated to identify the best-performing lines by transforming the SlANT1 gene overexpression cassette and then later used to produce the SlIAA9 knockout lines using the CRISPR/Cas9 system. ET5 and ET8 emerged as excellent materials for these techniques and showed higher efficiency. Typical phenotypes of knockout sliaa9 were clearly visible in G0 and G1 plants, in which simple leaves and parthenocarpic fruits were observed. The high efficiency of the CRISPR/Cas9 system in developing new tomato varieties with desired traits in a short period was demonstrated by generating T-DNA-free homozygous sliaa9 knockout plants in the G1 generation. Additionally, a simple artificial fertilization method was successfully applied to recover seed production from parthenocarpic plants, securing the use of these varieties as breeding materials. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01452-1.

Beyond hot flashes: Exploring the role of estrogen therapy in postmenopausal women for myocardial infarction prevention and recovery.

Myocardial infarction (MI) commonly known as "heart attack" results from the blockage of blood flow to the heart. Postmenopausal women face an elevated risk of MI due to declining estrogen levels, a hormone pivotal in maintaining cardiovascular health. It promotes vasodilation, reduce inflammation, and improves lipid profiles. While estrogen therapy shows promise in mitigating MI risk for postmenopausal woman, its efficacy in prevention and recovery remains a subject of debate. This review provides a critical assessment of existing evidence on estrogen therapy's cardioprotective effects for postmenopausal women. It delves into estrogen's role in vascular function enhancement, inflammation reduction, and lipid metabolism modulation. Additionally, it addresses the various forms of estrogen therapy, administration methods, dosage considerations, safety implications, and associated risks. The review highlights the existing controversies and knowledge gaps related to estrogen therapy for MI prevention. It underscores the urgency for in-depth research to decipher the nexus between estrogen therapy and MI risk, especially concerning primary prevention and specific postmenopausal subgroups. Future studies should investigate optimal formulations, doses, and administration routes of estrogen therapy as well as assess treatment timing and duration. Comparative studies and long-term follow-up are necessary to inform clinical decision-making and improve patient care. Addressing these research gaps will empower clinicians to make more judicious choices about estrogen therapy for MI prevention and recovery in postmenopausal women, aiming for enhanced patient outcomes.

Mental Health Among Healthcare Workers During the COVID-19 Pandemic in Vietnam.

OBJECTIVES: The objective of this study was to characterize mental health issues among Vietnamese healthcare workers (HCWs) and to identify related factors. METHODS: A cross-sectional study was conducted with 990 HCWs in 2021. Their mental health status was measured using the Depression, Anxiety, and Stress Scale. RESULTS: In total, 49.9%, 52.3%, and 29.8% of respondents were found to have depression, anxiety, and stress, respectively. The multivariable linear regression model revealed that factors associated with increased anxiety scores included depression scores (ß, 0.45; 95% confidence interval [CI], 0.39 to 0.51) and stress scores (ß, 0.46; 95% CI, 0.41 to 0.52). Factors associated with increased depression scores included being frontline HCWs (ß, 0.57; 95% CI, 0.10 to 1.10), stress scores (ß, 0.50; 95% CI, 0.45 to 0.56), and anxiety scores (ß, 0.41; 95% CI, 0.36 to 0.47), while working experience was associated with reduced depression scores (ß, -0.08; 95% CI, -0.16 to -0.01). Factors associated with increased stress scores included working experience (ß, 0.08; 95% CI, 0.00 to 0.16), personal protective equipment interference with daily activities (ß, 0.55; 95% CI, 0.07 to 1.00), depression scores (ß, 0.54; 95% CI, 0.48 to 0.59), and anxiety scores (ß, 0.45; 95% CI, 0.39 to 0.50), while age was associated with reduced stress scores (ß, -0.12; 95% CI, -0.20 to -0.05). CONCLUSIONS: Specific interventions are necessary to enhance and promote the mental health of HCWs so they can successfully cope with the circumstances of the pandemic.

A new apotirucallane-type protolimonoid from the leaves of Paramignya trimera.

This study presents a phytochemical analysis of the leaves of Paramignya trimera, revealing the isolation of a new apotirucallane-type protolimonoid, identified as 25-O-methyl-1,2-dihydroprotoxylocarpin D (1), along with two known compounds (2 and 3). The known compounds were identified as (20S,21R,23R)-21,23-epoxy-7α,24,25-trihydroxy-21-O-methyl-3-oxoapotirucalla-14-ene (2) and 7α,24,25-trihydroxy-3-oxoapotirucalla-14-en-21,23-olide (3). The three apotirucallane-type protolimonoids (1-3) did not exhibit cytotoxicity against MCF-7 cells at a concentration of 100 µM. Interestingly, when MCF-7 cells were treated with compound 1 at various concentrations, a notable stimulatory response was observed, leading to a significant increase in cell viability, up to 127%.

Erratum: Closing the gap for cervical cancer research in Vietnam: current perspectives and future opportunities: a report from the 5th Gynecologic Cancer InterGroup (GCIG) Cervical Cancer Research Network (CCRN) Education Symposium.

This corrects the article on p. e88 in vol. 34, PMID: 37668081.

Contribution of the Nuclear Localization Sequences of Influenza A Nucleoprotein to the Nuclear Import of the Influenza Genome in Infected Cells.

Replication of the RNA genome of influenza A virus occurs in the nucleus of infected cells. The influenza nucleoprotein (NP) associated with the viral RNA into ribonucleoprotein complexes (vRNPs) is involved in the nuclear import of the viral genome. NP has two nuclear localization sequences (NLSs), NLS1 and NLS2. Most studies have concentrated on the role of NP's NLSs using in vitro-assembled or purified vRNPs, which may differ from incoming vRNPs released in the cytoplasm during an infection. Here, we study the contribution of the NP's NLSs to the nuclear import of vRNPs in a cell culture model system for influenza infection: human lung carcinoma cells infected with viruses containing NP-carrying mutations in NLS1 or NLS2 (NLS2MT), generated by reverse genetics. We found that cells infected with these mutant viruses were defective in the nuclear import of incoming vRNPs and produced reduced amounts of newly synthesized NP, newly assembled vRNP, and progeny virus. In addition, NLS2MT-infected cells were also defective in the nucleolar accumulation of NP, confirming the nucleolar localization role of NLS2. Our findings indicate that both NLS1 and NLS2 have to be present for successful infection and demonstrate the crucial role of these two NLSs in the infection cycle of the influenza A virus.

A Hybrid Structure-Based Machine Learning Approach for Predicting Kinase Inhibition by Small Molecules.

Kinases have been the focus of drug discovery programs for three decades leading to over 70 therapeutic kinase inhibitors and biophysical affinity measurements for over 130,000 kinase-compound pairs. Nonetheless, the precise target spectrum for many kinases remains only partly understood. In this study, we describe a computational approach to unlocking qualitative and quantitative kinome-wide binding measurements for structure-based machine learning. Our study has three components: (i) a Kinase Inhibitor Complex (KinCo) data set comprising in silico predicted kinase structures paired with experimental binding constants, (ii) a machine learning loss function that integrates qualitative and quantitative data for model training, and (iii) a structure-based machine learning model trained on KinCo. We show that our approach outperforms methods trained on crystal structures alone in predicting binary and quantitative kinase-compound interaction affinities; relative to structure-free methods, our approach also captures known kinase biochemistry and more successfully generalizes to distant kinase sequences and compound scaffolds.

SBcoyote: An extensible Python-based reaction editor and viewer.

SBcoyote is an open-source cross-platform biochemical reaction viewer and editor released under the liberal MIT license. It is written in Python and uses wxPython to implement the GUI and the drawing canvas. It supports the visualization and editing of compartments, species, and reactions. It includes many options to stylize each of these components. For instance, species can be in different colors and shapes. Other core features include the ability to create alias nodes, alignment of groups of nodes, network zooming, as well as an interactive bird-eye view of the network to allow easy navigation on large networks. A unique feature of the tool is the extensive Python plugin API, where third-party developers can include new functionality. To assist third-party plugin developers, we provide a variety of sample plugins, including, random network generation, a simple auto layout tool, export to Antimony, export SBML, import SBML, etc. Of particular interest are the export and import SBML plugins since these support the SBML level 3 layout and render standard, which is exchangeable with other software packages. Plugins are stored in a GitHub repository, and an included plugin manager can retrieve and install new plugins from the repository on demand. Plugins have version metadata associated with them to make it install plugin updates. Availability: https://github.com/sys-bio/SBcoyote.

SBcoyote: An Extensible Python-Based Reaction Editor and Viewer.

SBcoyote is an open-source cross-platform biochemical reaction viewer and editor released under the liberal MIT license. It is written in Python and uses wxPython to implement the GUI and the drawing canvas. It supports the visualization and editing of compartments, species, and reactions. It includes many options to stylize each of these components. For instance, species can be in different colors and shapes. Other core features include the ability to create alias nodes, alignment of groups of nodes, network zooming, as well as an interactive bird-eye view of the network to allow easy navigation on large networks. A unique feature of the tool is the extensive Python plugin API, where third-party developers can include new functionality. To assist third-party plugin developers, we provide a variety of sample plugins, including, random network generation, a simple auto layout tool, export to Antimony, export SBML, import SBML, etc. Of particular interest are the export and import SBML plugins since these support the SBML level 3 layout and render standard, which is exchangeable with other software packages. Plugins are stored in a GitHub repository, and an included plugin manager can retrieve and install new plugins from the repository on demand. Plugins have version metadata associated with them to make it install plugin updates. Availability: https://github.com/sys-bio/SBcoyote.

Sleep Quality and Poor Sleep-related Factors Among Healthcare Workers During the COVID-19 Pandemic in Vietnam.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has increased the workload of healthcare workers (HCWs), impacting their health. This study aimed to assess sleep quality using the Pittsburgh Sleep Quality Index (PSQI) and identify factors associated with poor sleep among HCWs in Vietnam during the COVID-19 pandemic. METHODS: In this cross-sectional study, 1000 frontline HCWs were recruited from various healthcare facilities in Vietnam between October 2021 and November 2021. Data were collected using a 3-part self-administered questionnaire, which covered demographics, sleep quality, and factors related to poor sleep. Poor sleep quality was defined as a total PSQI score of 5 or higher. RESULTS: Participants' mean age was 33.20±6.81 years (range, 20.0-61.0), and 63.0% were women. The median work experience was 8.54±6.30 years. Approximately 6.3% had chronic comorbidities, such as hypertension and diabetes mellitus. About 59.5% were directly responsible for patient care and treatment, while 7.1% worked in tracing and sampling. A total of 73.8% reported poor sleep quality. Multivariate logistic regression revealed significant associations between poor sleep quality and the presence of chronic comorbidities (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.17 to 5.24), being a frontline HCW directly involved in patient care and treatment (OR, 1.59; 95% CI, 1.16 to 2.16), increased working hours (OR, 1.84; 95% CI,1.37 to 2.48), and a higher frequency of encountering critically ill and dying patients (OR, 1.42; 95% CI, 1.03 to 1.95). CONCLUSIONS: The high prevalence of poor sleep among HCWs in Vietnam during the COVID-19 pandemic was similar to that in other countries. Working conditions should be adjusted to improve sleep quality among this population.

A novel diphenylbutenoid-type compound from the rhizomes of Zingiber montanum (J.Koenig) Link ex A.Dietr. (Zingiberaceae).

From the EtOAc-soluble extract of the rhizomes of Zingiber montanum (J.Koenig) Link ex A.Dietr., a novel diphenylbutenoid, montadinin A (1) and a previously unreported phenylbutenoid compound, 1-(3,4-dimethoxyphenyl)but-3-en-2-ol (7), in natural source were isolated. Additionally, seven known phenylbutenoids were also identified. The structures of all compounds were elucidated through NMR spectroscopic interpretation. Compounds cis-3-(3,4-dimethoxyphenyl)-4-[(E)-3,4-dimethoxystyryl]cyclohex-1-ene (2), cis-4-[(E)-3,4-dimethoxystyryl]-3-(2,4,5-trimethoxyphenyl)cyclohex-1-ene (3), trans-3-(3,4,-dimethoxyphenyl)-4-[(E)-2,4,5-trimethoxystyryl]cyclohex-1-ene (5), and cis-3-(3,4-dimethoxyphenyl)-4-[(Z)-2,4,5-trimethoxylstyryl]cyclohex-1-ene (6) showed weak cytotoxicity against HepG2 cells with IC50 values of 122.9, 127.3, 257.5, and 168.5 µM, respectively.

Novel Therapeutic Targets for Fibrodysplasia Ossificans Progressiva: Emerging Strategies and Future Directions.

Fibrodysplasia ossificans progressiva (FOP), also known as Stoneman syndrome, is a rare genetic disorder characterized by abnormal bone development caused by activating mutations of the ACVR1 gene. FOP affects both the developmental and postnatal stages, resulting in musculoskeletal abnormalities and heterotopic ossification. Current treatment options for FOP are limited, emphasizing the need for innovative therapeutic approaches. Challenges in the development of management criteria for FOP include difficulties in recruitment due to the rarity of FOP, disease variability, the absence of reliable biomarkers, and ethical considerations regarding placebo-controlled trials. This narrative review provides an overview of the disease and explores emerging strategies for FOP treatment. Gene therapy, particularly the CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats-associated protein 9) system, holds promise in treating FOP by specifically targeting the ACVR1 gene mutation. Another gene therapy approach being investigated is RNA interference, which aims to silence the mutant ACVR1 gene. Small molecule inhibitors targeting glycogen synthase kinase-3ß and modulation of the bone morphogenetic protein signaling pathway are also being explored as potential therapies for FOP. Stem cell-based approaches, such as mesenchymal stem cells and induced pluripotent stem cells, show potential in tissue regeneration and inhibiting abnormal bone formation in FOP. Immunotherapy and nanoparticle delivery systems provide alternative avenues for FOP treatment.

Primary Cardiac Angiosarcoma: A Review.

Primary cardiac angiosarcoma is a rare and aggressive malignancy originating from the endothelial lining of cardiac blood vessels. This review covers various aspects of the disease, including its pathogenesis, clinical presentation, diagnosis, treatment, and prognosis. The primary characteristic of cardiac angiosarcoma is the rapid growth of abnormal blood vessels that invade the heart muscle, leading to the destruction of healthy tissue. Due to its infiltrative nature and early spread, diagnosing and treating cardiac angiosarcoma present significant challenges. Transesophageal echocardiography (TEE) plays a crucial role in diagnosing cardiac tumors such as angiosarcoma due to its high sensitivity. Additional imaging techniques such as computed tomography (CT) and cardiac magnetic resonance imaging (MRI) help assess tumor anatomy and identify metastases. Histopathological examination and immunohistochemistry are essential for confirming the diagnosis, as they reveal distinct histological features and specific endothelial markers associated with primary cardiac angiosarcoma. Targeted therapies directed at the angiogenic mechanisms and molecular abnormalities hold promise for improving treatment outcomes. Early detection of primary cardiac angiosarcoma remains challenging due to its rarity, and the prognosis is generally poor due to advanced disease at the time of diagnosis. The review emphasizes the importance of a multidisciplinary approach and collaboration among different specialties to optimize the diagnosis, treatment, and follow-up care of patients with primary cardiac angiosarcoma. The ultimate goal is to enhance diagnostic methods and therapeutic approaches by advancing knowledge and promoting further research into this aggressive malignancy.

A Study on the Health-Related Issues and Behavior of Vietnamese Migrants Living in Japan: Developing Risk Communication in the Tuberculosis Response.

Ensuring a healthy lifestyle for the increasing number of Vietnamese migrants living in Japan is a key public health issue, including infectious disease responses such as tuberculosis (TB). To develop risk communication in relation to the TB response, this study aimed to explore the health issues and health-related behaviors of Vietnamese migrants living in Japan using a mixed method. A survey was conducted on Vietnam-born migrants, aged 18 years and over, in Tokyo. The survey consisted of questions on the following components: (1) demographics; (2) health-related issues and behavior; and (3) health-seeking behavior, information, and communication. A total 165 participants participated in the survey. The majority of the participants were young adults. 13% of the participants responded that they were concerned about their health. Moreover, 22% and 7% of the participants reported weight loss and respiratory symptoms, respectively. 44% of the participants answered they had no one to consult about their health in Japan when they needed it, and 58% answered they had no awareness of any Vietnamese-language health consultation services. Logistic regression analysis revealed that people who contact family members living in Vietnam or overseas using social networking services (SNSs) when they needed to consult someone about their health (adjusted odds ratio (AOR) = 6.09, 95% confidence interval (CI) 1.52-24.43) were more likely to present with one or more of the typical TB symptoms, compared to those who did not consult someone in this manner. Current smokers (OR = 3.08, 95% CI 1.15-8.23) were more likely to have health problems compared to non-smokers. The key informant interviews revealed that individual factors, the health system, and socio-environmental factors may hinder Vietnamese migrants' health-seeking and health-information-seeking behaviors in Japan. TB risk communication approaches for migrants need to be developed considering their health-related behaviors while addressing their health needs.

A human model of asthma exacerbation reveals transcriptional programs and cell circuits specific to allergic asthma.

Asthma is a chronic disease most commonly associated with allergy and type 2 inflammation. However, the mechanisms that link airway inflammation to the structural changes that define asthma are incompletely understood. Using a human model of allergen-induced asthma exacerbation, we compared the lower airway mucosa in allergic asthmatics and allergic non-asthmatic controls using single-cell RNA sequencing. In response to allergen, the asthmatic airway epithelium was highly dynamic and up-regulated genes involved in matrix degradation, mucus metaplasia, and glycolysis while failing to induce injury-repair and antioxidant pathways observed in controls. IL9-expressing pathogenic TH2 cells were specific to asthmatic airways and were only observed after allergen challenge. Additionally, conventional type 2 dendritic cells (DC2 that express CD1C) and CCR2-expressing monocyte-derived cells (MCs) were uniquely enriched in asthmatics after allergen, with up-regulation of genes that sustain type 2 inflammation and promote pathologic airway remodeling. In contrast, allergic controls were enriched for macrophage-like MCs that up-regulated tissue repair programs after allergen challenge, suggesting that these populations may protect against asthmatic airway remodeling. Cellular interaction analyses revealed a TH2-mononuclear phagocyte-basal cell interactome unique to asthmatics. These pathogenic cellular circuits were characterized by type 2 programming of immune and structural cells and additional pathways that may sustain and amplify type 2 signals, including TNF family signaling, altered cellular metabolism, failure to engage antioxidant responses, and loss of growth factor signaling. Our findings therefore suggest that pathogenic effector circuits and the absence of proresolution programs drive structural airway disease in response to type 2 inflammation.

Microsurgery of large falcine meningiomas: postoperative results at 1 year: a cross-sectional study.

Performing microsurgery with the support of navigation in falcine meningioma management shows significant impacts in short and middle-time follow-up, including unilaterally skull opening with smallest and nearest skin incision, lessen the surgical duration, limit blood transfusion and prevent tumours from recurrence. Materials and methods: Sixty-two falcine meningioma patients treated by microoperation applying neuronavigation were enroled from July 2015 to March 2017. Patients are evaluated before and 1 year after surgery according to The Karnofsky Performance Scale (KPS) for comparison. Results: Histopathology: the most common was fibrous meningioma with 32.26%; meningothelial meningioma was 19.35% and transitional meningioma was 16.13%. KPS I before surgery was 6.45% and after was 83.87%. KPS III who needed assistance in activities preoperation was 64.52% and postoperation was 1.61%. After surgery, there was no disabled patient. All patients were followed up a year after surgery and received MRI to evaluate the recurrence. After 12 months, there were three recurrent cases, accounted for 4.84%. Conclusions: Microsurgery under neuronavigation help brings significant improvement in patient's functional abilities and low recurrence of falcine meningiomas within 1-year post-surgery. Further studies with large sample size and longer follow-up duration should be performed to reliably evaluate safety and effectiveness of microsurgical neuronavigation in the management of the disease.

A new ß-carboline-type alkaloid from the flowers of Calotropis gigantea (L.) W.T.Aiton.

In our antioxidant screening of some Vietnamese plant extracts, the CHCl3-soluble fraction from Calotropis gigantea (L.) W.T.Aiton flowers showed moderate DPPH free radical scavenging activity with an IC50 value of 55.8 µg/mL. Thus, a further phytochemical study was carried out to obtain five alkaloids, including a new ß-carboline-type alkaloid, caloside H (1). These known compounds were identified as 5-hydroxy-(2-methoxymethyl)pyridine (2), nicotinic acid (3), p-(acetylamino)phenol (4), and thymine (5). These structures were determined based on the NMR spectroscopic analysis. In antioxidant assay, caloside H at concentration of 100 µM showed DPPH radical scavenging capacity with a percentage of inhibition of 40.2%. In addition, a plausible biosynthetic pathway for the formation of caloside H was proposed based on the Schiff base formation and Mannich-like reaction.