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1.
Data Brief ; 54: 110285, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38962208

ABSTRACT

The bacterium Paenibacillus elgii YSY-1.2 was recently isolated from soil collected from Yok Don National Park in Vietnam. Previous experiments showed this bacterium possesses high chitin-degrading activity, plant-growth promotion, and biocontrol capacity. Here, we report the draft genome sequence of strain YSY-1.2 for further characterizations related to crop production. The genome sequencing was performed using the DNBSeq-G99 with the Illumina platform. The draft genome of P. elgii YSY-1.2 has 8,240,519 bp in length and comprises 135 contigs. It has an N50 of 315,408 bp and a GC% of 52.8%. The genome contains 7498 protein-coding genes, 87 tRNA genes, and 1 rRNA gene. Among the protein-coding sequences, 6610 were assigned by COG, while 3230 were assigned by KEGG. The genome possesses at least 61 genes involved in environmental adaptation and plant growth promotion. Additionally; there are 258 carbohydrate-active enzymes deduced from the genome; among them, at least 14 may contribute to the biocontrol capacity. The chitin-degrading system of strain YSY-1.2 contains 16 chitinolytic enzymes, comprising 10 chitinases, 4 ß-N-acetylhexosaminidases, and 2 auxiliary activities. Furthermore, 32 gene clusters encoding antimicrobial metabolites were identified from the genome, with 17 showing no sequence similarities to reported clusters. Data provide an insight into the genomic information of strain YSY-1.2 and could lead to valuable further explorations and applications in crop production. This is the first report describing the genome sequence of P. elgii isolated from Vietnam.

2.
BMC Infect Dis ; 24(1): 470, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38702614

ABSTRACT

BACKGROUND: Hepatitis B virus (HBV) vaccination in Vietnamese adults remains low and unequally distributed. We conducted a study on HBV-naïve adults living in Ho Chi Minh City, Viet Nam, to determine barriers associated with HBV vaccination uptake after removing the financial barrier by providing free coupons for HBV vaccination. METHODS: After being screened for HBsAg, anti-HBs, and anti-HBc, 284 HBV-naïve study participants aged 18 and over (i.e., negative for HBsAg, anti-HBs, and anti-HBc total) were provided free 3-dose HBV vaccine coupons. Next, study participants' receipt of 1st, 2nd, and 3rd doses of HBV vaccine was documented at a pre-specified study healthcare facility, where HBV vaccines were distributed at no cost to the participants. Upon study entry, participants answered questionnaires on sociodemographics, knowledge of HBV and HBV vaccination, and related social and behavioral factors. The proportions of three doses of HBV vaccine uptake and their confidence intervals were analyzed. Associations of HBV vaccine initiation with exposures at study entry were evaluated using modified Poisson regression. RESULTS: 98.9% (281 of 284) of study participants had complete data and were included in the analysis. The proportion of participants obtaining the 1st, 2nd, and 3rd doses of HBV vaccine was 11.7% (95% Confidence Interval [95% CI] 8.0-15.5%), 10.7% (95%CI 7.1-14.3%), and 8.9% (95%CI 5.6-12.2%), respectively. On the other hand, participants were more likely to initiate the 1st dose if they had adequate knowledge of transmission (adjusted relative risk [aRR] = 2.58, 95% CI 1.12-5.92), adequate knowledge of severity (aRR = 6.75, 95%CI 3.38-13.48), and annual health-checking seeking behavior (aRR = 2.04, 95%CI 1.07-3.87). CONCLUSION: We documented a low HBV vaccination uptake despite incentivization. However, increased vaccine initiation was associated with better HBV knowledge and annual health check-up adherence. When considering expanding HBV vaccination to the general adult population, we should appreciate that HBV knowledge is an independent predictor of vaccine uptake.


Subject(s)
Health Knowledge, Attitudes, Practice , Hepatitis B Vaccines , Hepatitis B , Vaccination , Humans , Male , Female , Adult , Hepatitis B Vaccines/administration & dosage , Hepatitis B/prevention & control , Vietnam , Vaccination/statistics & numerical data , Vaccination/psychology , Middle Aged , Young Adult , Adolescent , Surveys and Questionnaires , Patient Acceptance of Health Care/statistics & numerical data , Hepatitis B virus/immunology
3.
Front Plant Sci ; 14: 1271368, 2023.
Article in English | MEDLINE | ID: mdl-37908833

ABSTRACT

Plants consistently encounter environmental stresses that negatively affect their growth and development. To mitigate these challenges, plants have developed a range of adaptive strategies, including the unfolded protein response (UPR), which enables them to manage endoplasmic reticulum (ER) stress resulting from various adverse conditions. The CRISPR-Cas system has emerged as a powerful tool for plant biotechnology, with the potential to improve plant tolerance and resistance to biotic and abiotic stresses, as well as enhance crop productivity and quality by targeting specific genes, including those related to the UPR. This review highlights recent advancements in UPR signaling pathways and CRISPR-Cas technology, with a particular focus on the use of CRISPR-Cas in studying plant UPR. We also explore prospective applications of CRISPR-Cas in engineering UPR-related genes for crop improvement. The integration of CRISPR-Cas technology into plant biotechnology holds the promise to revolutionize agriculture by producing crops with enhanced resistance to environmental stresses, increased productivity, and improved quality traits.

4.
Int J Mol Sci ; 24(17)2023 Aug 23.
Article in English | MEDLINE | ID: mdl-37685921

ABSTRACT

Various stresses can affect the quality and yield of crops, including vegetables. In this study, CRISPR/Cas9 technology was employed to examine the role of the ELONGATED HYPOCOTYL 5 (HY5) gene in influencing the growth of Chinese cabbage (Brassica rapa). Single guide RNAs (sgRNAs) were designed to target the HY5 gene, and deep-sequencing analysis confirmed the induction of mutations in the bZIP domain of the gene. To investigate the response of Chinese cabbage to endoplasmic reticulum (ER) stress, plants were treated with tunicamycin (TM). Both wild-type and hy5 mutant plants showed increased growth inhibition with increasing TM concentration. However, the hy5 mutant plants displayed less severe growth inhibition compared to the wild type. Using nitroblue tetrazolium (NBT) and 3,3'-diaminobenzidine (DAB) staining methods, we determined the amount of reactive oxygen species (ROS) produced under ER stress conditions, and found that the hy5 mutant plants generated lower levels of ROS compared to the wild type. Under ER stress conditions, the hy5 mutant plants exhibited lower expression levels of UPR- and cell death-related genes than the wild type. These results indicate that CRISPR/Cas9-mediated editing of the HY5 gene can mitigate growth inhibition in Chinese cabbage under stresses, improving the quality and yield of crops.


Subject(s)
Brassica rapa , Brassica rapa/genetics , CRISPR-Cas Systems/genetics , Gene Editing , Hypocotyl , RNA, Guide, CRISPR-Cas Systems , Reactive Oxygen Species , Crops, Agricultural , Tunicamycin
5.
BMC Cancer ; 23(1): 875, 2023 Sep 18.
Article in English | MEDLINE | ID: mdl-37723439

ABSTRACT

BACKGROUND: Vietnam and Saudi Arabia have high disease burden of primary hepatocellular carcinoma (HCC). Early detection in asymptomatic patients at risk for HCC is a strategy to improve survival outcomes in HCC management. GALAD score, a serum-based panel, has demonstrated promising clinical utility in HCC management. However, in order to ascertain its potential role in the surveillance of the early detection of HCC, GALAD needs to be validated prospectively for clinical surveillance of HCC (i.e., phase IV biomarker validation study). Thus, we propose to conduct a phase IV biomarker validation study to prospectively survey a cohort of patients with advanced fibrosis or compensated cirrhosis, irrespective of etiologies, using semi-annual abdominal ultrasound and GALAD score for five years. METHODS: We plan to recruit a cohort of 1,600 patients, male or female, with advanced fibrosis or cirrhosis (i.e., F3 or F4) and MELD ≤ 15, in Vietnam and Saudi Arabia (n = 800 each). Individuals with a liver mass ≥ 1 cm in diameter, elevated alpha-fetoprotein (AFP) (≥ 9 ng/mL), and/or elevated GALAD score (≥ -0.63) will be scanned with dynamic contrast-enhanced magnetic resonance imaging (MRI), and a diagnosis of HCC will be made by Liver Imaging Reporting and Data System (LiRADS) assessment (LiRADS-5). Additionally, those who do not exhibit abnormal imaging findings, elevated AFP titer, and/or elevated GALAD score will obtain a dynamic contrast-enhanced MRI annually for five years to assess for HCC. Only MRI nearest to the time of GALAD score measurement, ultrasound and/or AFP evaluation will be included in the diagnostic validation analysis. MRI will be replaced with an abdominal computed tomography scan when MRI results are poor due to patient conditions such as movement etc. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced MRI will not be carried out in study sites in both countries. Bootstrap resampling technique will be used to account for repeated measures to estimate standard errors and confidence intervals. Additionally, we will use the Cox proportional hazards regression model with covariates tailored to the hypothesis under investigation for time-to-HCC data as predicted by time-varying biomarker data. DISCUSSION: The present work will evaluate the performance of GALAD score in early detection of liver cancer. Furthermore, by leveraging the prospective cohort, we will establish a biorepository of longitudinally collected biospecimens from patients with advanced fibrosis or cirrhosis to be used as a reference set for future research in early detection of HCC in the two countries. TRIAL REGISTRATION: Name of the registry: ClinicalTrials.gov Registration date: 22 April 2022 Trial registration number: NCT05342350 URL of trial registry record.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Female , Male , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/therapy , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/therapy , Prospective Studies , alpha-Fetoproteins , Liver Cirrhosis/complications
6.
Polymers (Basel) ; 15(18)2023 Sep 11.
Article in English | MEDLINE | ID: mdl-37765578

ABSTRACT

Chitosanases play a significant part in the hydrolysis of chitosan to form chitooligosaccharides (COS) that possess diverse biological activities. This study aimed to enhance the productivity of Paenibacillus elgii TKU051 chitosanase by fermentation from chitinous fishery wastes. The ideal parameters for achieving maximum chitosanase activity were determined: a squid pens powder amount of 5.278% (w/v), an initial pH value of 8.93, an incubation temperature of 38 °C, and an incubation duration of 5.73 days. The resulting chitosanase activity of the culture medium was 2.023 U/mL. A chitosanase with a molecular weight of 25 kDa was isolated from the culture medium of P. elgii TKU051 and was biochemically characterized. Liquid chromatography with tandem mass spectrometry analysis revealed that P. elgii TKU051 chitosanase exhibited a maximum amino acid identity of 43% with a chitosanase of Bacillus circulans belonging to the glycoside hydrolase (GH) family 46. P. elgii TKU051 chitosanase demonstrated optimal activity at pH 5.5 while displaying remarkable stability within the pH range of 5.0 to 9.0. The enzyme displayed maximum efficiency at 60 °C and demonstrated considerable stability at temperatures ≤40 °C. The presence of Mn2+ positively affected the activity of the enzyme, while the presence of Cu2+ had a negative effect. Thin-layer chromatography analysis demonstrated that P. elgii TKU051 chitosanase exhibited an endo-type cleavage pattern and hydrolyzed chitosan with 98% degree of deacetylation to yield (GlcN)2 and (GlcN)3. The enzymatic properties of P. elgii TKU051 chitosanase render it a promising candidate for application in the production of COS.

7.
Biochem Biophys Res Commun ; 670: 94-101, 2023 08 30.
Article in English | MEDLINE | ID: mdl-37290287

ABSTRACT

Protein phosphatase 2A (PP2A) is a key regulator of plant growth and development, but its role in the endoplasmic reticulum (ER) stress response remains elusive. In this study, we investigated the function of PP2A under ER stress using loss-of-function mutants of ROOTS CURL of NAPHTHYLPHTHALAMIC ACID1 (RCN1), a regulatory A1 subunit isoform of Arabidopsis PP2A. RCN1 mutants (rcn1-1 and rcn1-2) exhibited reduced sensitivity to tunicamycin (TM), an inhibitor of N-linked glycosylation and inducer of unfolded protein response (UPR) gene expression, resulting in less severe effects compared to wild-type plants (Ws-2 and Col-0). TM negatively impacted PP2A activity in Col-0 plants but did not significantly affect rcn1-2 plants. Additionally, TM treatment did not influence the transcription levels of the PP2AA1(RCN1), 2, and 3 genes in Col-0 plants. Cantharidin, a PP2A inhibitor, exacerbated growth defects in rcn1 plants and alleviated TM-induced growth inhibition in Ws-2 and Col-0 plants. Furthermore, cantharidin treatment mitigated TM hypersensitivity in ire1a&b and bzip28&60 mutants. These findings suggest that PP2A activity is essential for an efficient UPR in Arabidopsis.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Protein Phosphatase 2 , Unfolded Protein Response , Arabidopsis/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Cantharidin/pharmacology , Endoplasmic Reticulum Stress , Gene Expression Regulation, Plant , Mutation , Protein Phosphatase 2/genetics , Protein Phosphatase 2/metabolism
8.
Radiol Case Rep ; 18(3): 963-967, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36636480

ABSTRACT

Ectopic Cushing's syndrome, caused by a neuroendocrine tumor (NET), is a rare finding. NETs of the mediastinum are extremely rare. NETs arising from the anterior mediastinum are generally aggressive. They are widely characterized at clinical presentations, and may be asymptomatic or present with atypical symptoms. Prognosis is often poor due to their local recurrence and distant metastasis despite a multimodal approach. A 33-year-old male patient was admitted to our department with a femoral soft tissue abscess, diabetes, and hypokalemia. He had no typical features of Cushing's syndrome. However, with a few simple tests, that is, a basal hormone profile, and low-dose and high-dose dexamethasone suppression tests, we diagnosed this complicated condition of ectopic adrenocorticotrophic hormone (ACTH) secretion. Thoracic computed tomography revealed an anterior mediastinal mass of 35 × 22 mm. A surgical excision of the tumor was proposed, and intra-operative pathology consultation returned positive for the suspected NET. Immunohistochemically, the tumor cells were positive for CK, CD56, Chromogranin, Synaptophysin, S100, and CD117. No thymic tissue was found. The Ki-67 was 4%. A diagnosis of primary NETs of the mediastinum, intermediate grade (G2), of atypical carcinoids according to WHO 2015 was established. This patient survived with no sequelae, no distant metastasis, no recurrence, and without adjuvant radiotherapy or chemotherapy 2 years after surgery thanks to earlier diagnosis and prompt surgical intervention. Mediastinum ectopic ACTH-secreting tumors are a rare type of cancer. According to recent research, these tumors frequently display more aggressive behavior and are linked to endocrinopathies. It is noted that patient might have a better outcome and a longer survival time due to earlier detection and complete resection of malignancies.

9.
Antibiotics (Basel) ; 11(12)2022 Dec 04.
Article in English | MEDLINE | ID: mdl-36551408

ABSTRACT

Low awareness of antibiotics and antibiotic resistance may lead to inappropriate antibiotic use and contribute to the problem of antibiotic resistance. This study explored levels and determinants of antibiotic awareness in a rural community in northern Vietnam, through a cross-sectional survey of 324 households in one commune of Ha Nam Province. Awareness and knowledge of antibiotics and antibiotic resistance and determinants were evaluated using structured questionnaires. Most respondents (232/323 (71.8%)) had heard of antibiotics, but fewer could name any antibiotic (68/323 (21.1%)) or had heard of antibiotic resistance (57/322 (17.7%)). In adjusted regression models, antibiotic awareness was lower among those who lived further from health facilities (Odds Ratio (OR): 0.08; 95% Confidence Interval (CI): 0.04-0.19) but higher among those who used interpersonal sources for health information (OR: 4.06; 95% CI: 1.32-12.46). Antibiotic resistance awareness was lower among those who used private providers or pharmacies as their usual health facility (OR: 0.14; 95% CI: 0.05-0.44) but higher among those with medical insurance (OR: 3.70; 95% CI: 1.06-12.96) and those with high media use frequency (OR: 9.54; 95% CI: 2.39-38.07). Awareness of Antimicrobial Resistance (AMR) was also higher among those who sought health information from official sources (OR: 3.88; 95% CI: 1.01-14.86) or had overall high levels of health information seeking (OR: 12.85; 95% CI: 1.63-101.1). In conclusion, communication interventions need to target frequently used media platforms, such as television, as well as key health information providers, such as health workers, as channels for increasing knowledge and changing community antibiotic use behaviour.

10.
Sci Rep ; 12(1): 22512, 2022 12 29.
Article in English | MEDLINE | ID: mdl-36581706

ABSTRACT

Vietnam has high rates of antibiotic use and resistance. Measuring resistance in commensal bacteria could provide an objective indicator for evaluating the impact of interventions to reduce antibiotic use and resistance. This study aimed to evaluate the feasibility, acceptability, and bacterial recovery for different sampling strategies. We conducted a cross-sectional mixed methods study in a rural community in Ha Nam Province, northern Vietnam, and collected structured interviews, samples, and in-depth interviews from households. Out of 389 households invited, 324 participated (83%), representing 1502 individuals. Samples were collected from these individuals (1498 stool, 1002 self-administered nasal swabs, and 496 HW-administered nasopharyngeal swabs). Pneumococci were recovered from 11.1% (128/1149) of the total population and 26.2% (48/183) of those under 5-years. Recovery was higher for health-worker (HW)-administered swabs (13.7%, 48/350) than self-administered swabs (10.0%, 80/799) (OR 2.06, 95% CI 1.07-3.96). Cost per swab was cheaper for self-administered ($7.26) than HW-administered ($8.63) swabs, but the overall cost for 100 positive samples was higher ($7260 and $6300 respectively). Qualitative interviews revealed that HW-administered nasopharyngeal swabs took longer to collect, caused more discomfort, and were more difficult to take from children. Factors affecting participation included sense of contribution, perceived trade-offs between benefits and effort, and peer influence. Reluctance was related to stool sampling and negative perceptions of research. This study provides important evidence for planning community-based carriage studies, including cost, logistics, and acceptability. Self-administered swabs had lower recovery, and though cheaper and quicker, this would translate to higher costs for large population-based studies. Recovery might be improved by swab-type, transport medium, and better cold-chain to lab.


Subject(s)
Bacteria , Nose , Child , Humans , Feasibility Studies , Cross-Sectional Studies , Drug Resistance, Microbial , Anti-Bacterial Agents/pharmacology , Specimen Handling/methods
11.
Cell Death Dis ; 13(5): 448, 2022 05 11.
Article in English | MEDLINE | ID: mdl-35538058

ABSTRACT

The family of hexokinases (HKs) catalyzes the first step of glycolysis, the ATP-dependent phosphorylation of glucose to glucose-6-phosphate. While HK1 and HK2 are ubiquitously expressed, the less well-studied HK3 is primarily expressed in hematopoietic cells and tissues and is highly upregulated during terminal differentiation of some acute myeloid leukemia (AML) cell line models. Here we show that expression of HK3 is predominantly originating from myeloid cells and that the upregulation of this glycolytic enzyme is not restricted to differentiation of leukemic cells but also occurs during ex vivo myeloid differentiation of healthy CD34+ hematopoietic stem and progenitor cells. Within the hematopoietic system, we show that HK3 is predominantly expressed in cells of myeloid origin. CRISPR/Cas9 mediated gene disruption revealed that loss of HK3 has no effect on glycolytic activity in AML cell lines while knocking out HK2 significantly reduced basal glycolysis and glycolytic capacity. Instead, loss of HK3 but not HK2 led to increased sensitivity to ATRA-induced cell death in AML cell lines. We found that HK3 knockout (HK3-null) AML cells showed an accumulation of reactive oxygen species (ROS) as well as DNA damage during ATRA-induced differentiation. RNA sequencing analysis confirmed pathway enrichment for programmed cell death, oxidative stress, and DNA damage response in HK3-null AML cells. These signatures were confirmed in ATAC sequencing, showing that loss of HK3 leads to changes in chromatin configuration and increases the accessibility of genes involved in apoptosis and stress response. Through isoform-specific pulldowns, we furthermore identified a direct interaction between HK3 and the proapoptotic BCL-2 family member BIM, which has previously been shown to shorten myeloid life span. Our findings provide evidence that HK3 is dispensable for glycolytic activity in AML cells while promoting cell survival, possibly through direct interaction with the BH3-only protein BIM during ATRA-induced neutrophil differentiation.


Subject(s)
Hexokinase , Leukemia, Myeloid, Acute , Cell Survival/genetics , Glycolysis/genetics , Hexokinase/genetics , Hexokinase/metabolism , Humans , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/metabolism , Myeloid Cells/metabolism
12.
Article in English | MEDLINE | ID: mdl-35329151

ABSTRACT

Worldwide, the Satisfaction With Life Scale (SWLS) has become the most widely used measure of life satisfaction. Recently, an authorized Vietnamese-language version has been introduced. Using a convenience sample comprising community volunteers from Ho Chi Minh City (N = 1073), confirmatory support was found for the cross-national constancy of the one-dimensional structure underlying the SWLS. Corrected item-total polyserial correlations and Omega coefficient were satisfactory. Using multi-group confirmatory factor analysis, configural, metric, and scalar invariance of the SWLS factorial structure were tested by gender, age, marital status, income, and educational level. Strong evidence of scalar invariance was found for gender and education, on which relevant subgroups did not differ in terms of latent means. Partial scalar invariance was found for marital status (item 4 and 5) and income (item 4). Being involved in an intimate relationship or having a higher income were associated with higher latent means. Scalar invariance in relation to age was very poor. Accordingly, caution must be exerted when comparing age groups. A high SWLS score was predictive of good self-rated health. Implications of the findings are briefly discussed.


Subject(s)
Personal Satisfaction , Quality of Life , Factor Analysis, Statistical , Humans , Psychometrics/methods , Reproducibility of Results , Vietnam , Volunteers
13.
Front Plant Sci ; 12: 761064, 2021.
Article in English | MEDLINE | ID: mdl-34804097

ABSTRACT

Alpha-1,6-mannosyl-glycoprotein 2-ß-N-acetylglucosaminyltransferase [EC 2.4.1.143, N-acetylglucosaminyltransferase II (GnTII)] catalyzes the transfer of N-acetylglucosamine (GlcNAc) residue from the nucleotide sugar donor UDP-GlcNAc to the α1,6-mannose residue of the di-antennary N-glycan acceptor GlcNAc(Xyl)Man3(Fuc)GlcNAc2 in the Golgi apparatus. Although the formation of the GlcNAc2(Xyl)Man3(Fuc)GlcNAc2 N-glycan is known to be associated with GnTII activity in Arabidopsis thaliana, its physiological significance is still not fully understood in plants. To address the physiological importance of the GlcNAc2(Xyl)Man3(Fuc)GlcNAc2 N-glycan, we examined the phenotypic effects of loss-of-function mutations in GnTII in the presence and absence of stress, and responsiveness to phytohormones. Prolonged stress induced by tunicamycin (TM) or sodium chloride (NaCl) treatment increased GnTII expression in wild-type Arabidopsis (ecotype Col-0) but caused severe developmental damage in GnTII loss-of-function mutants (gnt2-1 and gnt2-2). The absence of the 6-arm GlcNAc residue in the N-glycans in gnt2-1 facilitated the TM-induced unfolded protein response, accelerated dark-induced leaf senescence, and reduced cytokinin signaling, as well as susceptibility to cytokinin-induced root growth inhibition. Furthermore, gnt2-1 and gnt2-2 seedlings exhibited enhanced N-1-naphthylphthalamic acid-induced inhibition of tropic growth and development. Thus, GnTII's promotion of the 6-arm GlcNAc addition to N-glycans is important for plant growth and development under stress conditions, possibly via affecting glycoprotein folding and/or distribution.

14.
Cell Rep ; 36(13): 109762, 2021 09 28.
Article in English | MEDLINE | ID: mdl-34592149

ABSTRACT

The evolutionarily conserved ULK1 kinase complex acts as gatekeeper of canonical autophagy and regulates induction of autophagosome biogenesis. To better understand control of ULK1 and analyze whether ULK1 has broader functions that are also linked to the later steps of autophagy, we perform comprehensive phosphoproteomic analyses. Combining in vivo with in vitro data, we identify numerous direct ULK1 target sites within autophagy-relevant proteins that are critical for autophagosome maturation and turnover. In addition, we highlight an intimate crosstalk between ULK1 and several phosphatase complexes. ULK1 is not only a PP2A target but also directly phosphorylates the regulatory PP2A subunit striatin, activating PP2A and serving as positive feedback to promote autophagy-dependent protein turnover. Thus, ULK1 and phosphatase activities are tightly coordinated to robustly regulate protein degradation by autophagy.


Subject(s)
Autophagy-Related Protein-1 Homolog/metabolism , Autophagy/physiology , Calmodulin-Binding Proteins/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Membrane Proteins/metabolism , Nerve Tissue Proteins/metabolism , Protein Phosphatase 2/metabolism , Autophagosomes/metabolism , Autophagy-Related Proteins/metabolism , Humans , Phosphorylation , Protein Processing, Post-Translational/physiology
15.
Matrix Biol Plus ; 11: 100066, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34435183

ABSTRACT

The human skin has a highly developed extracellular matrix (ECM) that is vital for proper skin functioning, its 3D architecture playing a pivotal role in support and guidance of resident and invading cells. To establish relevant in vitro models mimicking the complex design observed in vivo, scaffold-based and scaffold-free 3D cell culture systems have been developed. Here we show that scaffold-free systems are well suited for the analysis of ECM protein regulation. Using quantitative mass spectrometry-based proteomics in combination with magnetic 3D bioprinting we characterize changes in the proteome of skin fibroblasts and squamous cell carcinoma cells. Transferring cells from 2D to 3D without any additional scaffold induces a profound upregulation of matrisome proteins indicating the generation of a complex, tissue-like ECM.

16.
Neurosurgery ; 88(2): 375-383, 2021 01 13.
Article in English | MEDLINE | ID: mdl-32985662

ABSTRACT

BACKGROUND: Occipital nerve stimulation (ONS) has been proposed to treat refractory chronic cluster headache (rCCH) but its efficacy has only been showed in small short-term series. OBJECTIVE: To evaluate ONS long-term efficacy in rCCH. METHODS: We studied 105 patients with rCCH, treated by ONS within a multicenter ONS prospective registry. Efficacy was evaluated by frequency, intensity of pain attacks, quality of life (QoL) EuroQol 5 dimensions (EQ5D), functional (Headache Impact Test-6, Migraine Disability Assessment) and emotional (Hospital Anxiety Depression Scale [HAD]) impacts, and medication consumption. RESULTS: At last follow-up (mean 43.8 mo), attack frequency was reduced >50% in 69% of the patients. Mean weekly attack frequency decreased from 22.5 at baseline to 9.9 (P < .001) after ONS. Preventive and abortive medications were significantly decreased. Functional impact, anxiety, and QoL significantly improved after ONS. In excellent responders (59% of the patients), attack frequency decreased by 80% and QoL (EQ5D visual analog scale) dramatically improved from 37.8/100 to 73.2/100. When comparing baseline and 1-yr and last follow-up outcomes, efficacy was sustained over time. In multivariable analysis, low preoperative HAD-depression score was correlated to a higher risk of ONS failure. During the follow-up, 67 patients experienced at least one complication, 29 requiring an additional surgery: infection (6%), lead migration (12%) or fracture (4.5%), hardware dysfunction (8.2%), and local pain (20%). CONCLUSION: Our results showed that long-term efficacy of ONS in CCH was maintained over time. In responders, ONS induced a major reduction of functional and emotional headache-related impacts and a dramatic improvement of QoL. These results obtained in real-life conditions support its use and dissemination in rCCH patients.


Subject(s)
Cluster Headache/therapy , Electric Stimulation Therapy/methods , Treatment Outcome , Adult , Aged , Female , Humans , Middle Aged , Peripheral Nerves/physiology , Quality of Life
17.
PLoS One ; 15(11): e0242537, 2020.
Article in English | MEDLINE | ID: mdl-33201914

ABSTRACT

A second cluster of COVID-19 cases imported from Europe occured in Vietnam from early March 2020. We describe 44 SARS-CoV-2 RT-PCR positive patients (cycle threshold value <30) admitted to the National Hospital for Tropical Diseases in Hanoi between March 6 and April 15 2020. Whole SARS-CoV-2 genomes from these patients were sequenced using Illumina Miseq and analysed for common genetic variants and relationships to local and globally circulating strains. Results showed that 32 cases were Vietnamese with a median age of 37 years (range 15-74 years), and 23 were male. Most cases were acquired outside Vietnam, mainly from the UK (n = 15), other European countries (n = 14), Russia (n = 6) and countries in Asia (n = 3). No cases had travelled from China. Forty-one cases had symptoms at admission, typically dry cough (n = 36), fever (n = 20), sore throat (n = 14) and diarrhoea (n = 12). Hospitalisation was long with a median of 25 days, most commonly from 20-29 days. All SARS-CoV-2 genomes were similar (92-100% sequence homology) to the reference sequence Wuhan_1 (NC_045512), and 32 strains belonged to the B.1.1 lineage. The three most common variants were linked, and included C3037T, C14408T (nsp12: P323L) and A23403G (S: D614G) mutations. This group of mutations often accompanied variant C241T (39/44 genomes) or GGG 28881..28883 AAC (33/44 genomes). The prevalence of the former reflected probable European origin of viruses, and the transition D614G was dominant in Vietnam. New variants were identified; however, none could be associated with disease severity.


Subject(s)
Betacoronavirus/genetics , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Adolescent , Adult , Aged , Betacoronavirus/isolation & purification , COVID-19 , Female , Genetic Variation , Humans , Male , Middle Aged , Pandemics , Prevalence , SARS-CoV-2 , Travel-Related Illness , Vietnam , Young Adult
18.
Stem Cell Res Ther ; 11(1): 60, 2020 02 13.
Article in English | MEDLINE | ID: mdl-32054512

ABSTRACT

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. COPD results from chronic inflammation of the lungs. Current treatments, including physical and chemical therapies, provide limited results. Stem cells, particularly mesenchymal stem cells (MSCs), are used to treat COPD. Here, we evaluated the safety and efficacy of umbilical cord-derived (UC)-MSCs for treating COPD. METHODS: Twenty patients were enrolled, 9 at stage C and 11 at stage D per the Global Initiative for Obstructive Lung Disease (GOLD) classification. Patients were infused with 106 cells/kg of expanded allogeneic UC-MSCs. All patients were followed for 6 months after the first infusion. The treatment end-point included a comprehensive safety evaluation, pulmonary function testing (PFT), and quality-of-life indicators including questionnaires, the 6-min walk test (6MWT), and systemic inflammation assessments. All patients completed the full infusion and 6-month follow-up. RESULTS: No infusion-related toxicities, deaths, or severe adverse events occurred that were deemed related to UC-MSC administration. The UC-MSC-transplanted patients showed a significantly reduced Modified Medical Research Council score, COPD assessment test, and number of exacerbations. However, the forced expiratory volume in 1 s, C-reactive protein, and 6MWT values were nonsignificantly reduced after treatment (1, 3, and 6 months) compared with those before the treatment. CONCLUSION: Systemic UC-MSC administration appears to be safe in patients with moderate-to-severe COPD, can significantly improve their quality of life, and provides a basis for subsequent cell therapy investigations. TRIAL REGISTRATION: ISRCTN, ISRCTN70443938. Registered 06 July 2019.


Subject(s)
Cord Blood Stem Cell Transplantation/methods , Mesenchymal Stem Cell Transplantation/methods , Pulmonary Disease, Chronic Obstructive/therapy , Transplantation, Homologous/methods , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Pilot Projects
19.
Diabetes Metab Syndr ; 13(1): 155-160, 2019.
Article in English | MEDLINE | ID: mdl-30641689

ABSTRACT

Besides physical consequences, obesity has negative psychological effects, thereby lowering human life quality. Major psychological consequences of this disorder includes depression, impaired body image, low self-esteem, eating disorders, stress and poor quality of life, which are correlated with age and gender. Physical interventions, mainly diet control and energy balance, have been widely applied to treat obesity; and some psychological interventions including behavioral therapy, cognitive behavioral therapy and hypnotherapy have showed some effects on obesity treatment. Other psychological therapies, such as relaxation and psychodynamic therapies, are paid less attention. This review aims to update scientific evidence regarding the mental consequences and psychological interventions for obesity.


Subject(s)
Behavior Therapy , Obesity/therapy , Humans , Obesity/psychology , Quality of Life
20.
Environ Toxicol Chem ; 38(3): 503-510, 2019 03.
Article in English | MEDLINE | ID: mdl-30525225

ABSTRACT

The Mekong River Delta (Vietnam) is a flat, low-lying area formed by a dense network of main tributaries of the Tien and Hau Rivers, providing a nourishing habitat for aquatic organisms. A sediment survey of the total mercury (Hg), monomethylmercury (MMHg), and geochemical variables was carried out from the coast to 131 km upriver to establish an overview of the environmental factors affecting the bioaccumulation of Hg and MMHg in delta fish. The survey results revealed that the total Hg (12-90 ng g-1 ) and MMHg (0.014-1.5 ng g-1 ) concentrations were in the range of uncontaminated sediment. Statistical analysis using various geochemical factors demonstrated that sediment MMHg concentrations and fractions of MMHg over total Hg in sediment were higher at sites with higher total organic carbon (TOC) and total nitrogen sites. The current levels of TOC in Mekong Delta sediment are relatively low (0.2-1.5%); however, expanding dam constructions and aquacultures related to salinity intrusion are reinforcing the carbon burial rate by increasing the fine fractions. Based on the positive relationship found between MMHg and TOC in sediment, proper management efforts are necessary to reduce MMHg production in the Mekong River Delta sediment. Environ Toxicol Chem 2019;38:503-510. © 2018 SETAC.


Subject(s)
Fishes , Geologic Sediments/chemistry , Methylmercury Compounds/analysis , Water Pollutants, Chemical/analysis , Animals , Environmental Monitoring , Mercury/analysis , Rivers/chemistry , Vietnam
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