MicroRNA regulators of vascular pathophysiology in chronic kidney disease.

Coronary artery disease (CAD) is a severe comorbidity in chronic kidney disease (CKD) due to heavy calcification in the medial layer and inflamed plaques. Chronic inflammation, endothelial dysfunction and vascular calcification are major contributors that lead to artherosclerosis in CKD. The lack of specific symptoms and signs of CAD and decreased accuracy of noninvasive diagnostic tools result in delayed diagnosis leading to increased mortality. MicroRNAs (miRNAs) are post-transcriptional regulators present in various biofluids throughout the body. In the circulation, miRNAs have been reported to be encapsulated in extracellular vesicles and serve as stable messengers for crosstalk among cells. miRNAs are involved in pathophysiologic mechanisms including CAD and can potentially be extended from basic research to clinical translational practice.

The mutation spectrum of SLC25A13 gene in citrin deficiency: identification of novel mutations in Vietnamese pediatric cohort with neonatal intrahepatic cholestasis.

BACKGROUND: Citrin deficiency (CD), a disorder caused by mutations in the SLC25A13 gene, may result in neonatal intrahepatic cholestasis. This study was purposely to explore the mutation spectrum of SLC25A13 gene in Vietnamese CD patients. METHODS: The 292 unrelated CD patients were first screened for four high-frequency mutations by PCR/PCR-RFLP. Then, Sanger sequencing was performed directly for heterozygous or undetected patients. Novel mutations identified would need to be confirmed by their parents. RESULTS: 12 pathogenic SLC25A13 mutations were identified in all probands, including three deletions c.851_854del (p.R284Rfs*3), c.70-63_133del (p.Y24_72Ifs*10), and c.[1956C>A;1962del] (p.[N652K;F654Lfs*45]), two splice-site mutations (IVS6+5G>A and IVS11+1G>A), one nonsense mutations c.1399C>T (p.R467*), one duplication mutation c.1638_1660dup (p.A554fs*570), one insertion IVSl6ins3kb (p.A584fs*585), and four missense mutation c.2T>C (p.M1T), c.1231G>A (p.V411M), c.1763G>A (p.R588Q), and c.135G>C (p.L45F). Among them, c.851_854del (mut I) was the most identified mutant allele (91.78%) with a total of 247 homozygous and 42 heterozygous genotypes of carriers. Interestingly, two novel mutations were identified: c.70-63_133del (p.Y24_72Ifs*10) and c.[1956C>A;1962del] (p.[N652K;F654Lfs*45]). CONCLUSION: The SLC25A13 mutation spectrum related to intrahepatic cholestasis infants in Vietnam revealed a quite similar pattern to Asian countries' reports. This finding supports the use of targeted SLC25A13 mutation for CD screening in Vietnam and contributed to the SLC25A13 mutation spectra worldwide. It also helps emphasize the role of DNA analysis in treatment, genetic counseling, and prenatal diagnosis.

Masked face recognition with convolutional neural networks and local binary patterns.

Face recognition is one of the most common biometric authentication methods as its feasibility while convenient use. Recently, the COVID-19 pandemic is dramatically spreading throughout the world, which seriously leads to negative impacts on people's health and economy. Wearing masks in public settings is an effective way to prevent viruses from spreading. However, masked face recognition is a highly challenging task due to the lack of facial feature information. In this paper, we propose a method that takes advantage of the combination of deep learning and Local Binary Pattern (LBP) features to recognize the masked face by utilizing RetinaFace, a joint extra-supervised and self-supervised multi-task learning face detector that can deal with various scales of faces, as a fast yet effective encoder. In addition, we extract local binary pattern features from masked face's eye, forehead and eyebow areas and combine them with features learnt from RetinaFace into a unified framework for recognizing masked faces. In addition, we collected a dataset named COMASK20 from 300 subjects at our institution. In the experiment, we compared our proposed system with several state of the art face recognition methods on the published Essex dataset and our self-collected dataset COMASK20. With the recognition results of 87% f1-score on the COMASK20 dataset and 98% f1-score on the Essex dataset, these demonstrated that our proposed system outperforms Dlib and InsightFace, which has shown the effectiveness and suitability of the proposed method. The COMASK20 dataset is available on https://github.com/tuminguyen/COMASK20 for research purposes.

Decades of emerging infectious disease, food safety, and antimicrobial resistance response in Vietnam: The role of One Health.

Since facing outbreaks of severe acute respiratory syndrome and avian influenza A in 2003, Vietnam has increasingly applied a One Health approach to address emerging infectious diseases of animal origin. Here, we reflect on the challenges and opportunities of One Health in the context of zoonoses, food safety, and antimicrobial resistance, drawing on a stocktake of One Health training, policy, and research in Vietnam. We also report on the results of a virtual consultation workshop held on July 2021 with representatives from 32 institutions in Vietnam to explore future One Health directions. As Vietnam approaches nearly two decades of disease preparedness and response, we hope our experiences can provide practical insights to support countries in developing coordination mechanisms and moving the One Health agenda forward toward better public health outcomes.

miRNA as a Modulator of Immunotherapy and Immune Response in Melanoma.

Immune checkpoint inhibitors are a promising therapy for the treatment of cancers, including melanoma, that improved benefit clinical outcomes. However, a subset of melanoma patients do not respond or acquire resistance to immunotherapy, which limits their clinical applicability. Recent studies have explored the reasons related to the resistance of melanoma to immune checkpoint inhibitors. Of note, miRNAs are the regulators of not only cancer progression but also of the response between cancer cells and immune cells. Investigation of miRNA functions within the tumor microenvironment have suggested that miRNAs could be considered as key partners in immunotherapy. Here, we reviewed the known mechanism by which melanoma induces resistance to immunotherapy and the role of miRNAs in immune responses and the microenvironment.

Forager and farmer evolutionary adaptations to malaria evidenced by 7000 years of thalassemia in Southeast Asia.

Thalassemias are inherited blood disorders that are found in high prevalences in the Mediterranean, Southeast Asia and the Pacific. These diseases provide varying levels of resistance to malaria and are proposed to have emerged as an adaptive response to malaria in these regions. The transition to agriculture in the Holocene has been suggested to have influenced the selection for thalassemia in the Mediterranean as land clearance for farming encouraged interaction between Anopheles mosquitos, the vectors for malaria, and human groups. Here we document macroscopic and microscopic skeletal evidence for the presence of thalassemia in both hunter-gatherer (Con Co Ngua) and early agricultural (Man Bac) populations in northern Vietnam. Firstly, our findings demonstrate that thalassemia emerged prior to the transition to agriculture in Mainland Southeast Asia, from at least the early seventh millennium BP, contradicting a long-held assumption that agriculture was the main driver for an increase in malaria in Southeast Asia. Secondly, we describe evidence for significant malarial burden in the region during early agriculture. We argue that the introduction of farming into the region was not the initial driver of the selection for thalassemia, as it may have been in other regions of the world.

miR-524-5p reduces the progression of the BRAF inhibitor-resistant melanoma.

BRAF inhibitors were approved for the treatment of BRAF-mutant melanoma. However, most patients acquire the resistance to BRAF inhibitors after several months of treatment. miR-524-5p is considered as a tumor suppressor in many cancers, including melanoma. In this study, we investigated the biological functions of miR-524-5p in melanoma with acquired resistance to BRAF inhibitor and evaluated the endogenous miR-524-5p expression as a biomarker for melanoma. The results showed that the expression of miR-524-5p was 0.481-fold lower in melanoma tissues (n = 117) than in nevus tissues (n = 40). Overexpression of miR-524-5p significantly reduced proliferative, anchorage-independent growth, migratory and invasive abilities of BRAF inhibitor-resistant melanoma cells. Moreover, the introduction of miR-524-5p led to a reduced development of BRAF inhibitor-resistant melanoma in vivo. Remarkably, the MAPK/ERK signaling pathway was decreased after treatment with miR-524-5p. Furthermore, next-generation sequencing analysis implied that the complement system, leukocyte extravasation, liver X receptor/retinoid-X-receptor activation, and cAMP-mediated signaling may be related to miR-524-5p-induced pathways in the resistant cells. The miR-524-5p level was higher on average in complete response and long-term partial response patients than in progressive disease and short-term partial response patients treated with BRAF inhibitors. Our results proposed that miR-524-5p could be considered as a target for treatment BRAF inhibitor-resistant melanoma and a prognostic marker in the response of patients to BRAF inhibitors for melanoma.

RP-HPLC and UV Spectrophotometric Analysis of Paracetamol, Ibuprofen, and Caffeine in Solid Pharmaceutical Dosage Forms by Derivative, Fourier, and Wavelet Transforms: A Comparison Study.

Different signal-transforming algorithms were applied for UV spectrophotometric analysis of paracetamol, ibuprofen, and caffeine in ternary mixtures. Phosphate buffer pH 7.2 was used as the spectrophotometric solvent. Severe overlapping spectra could be resolved into individual bands in the range of wavelengths 200-300 nm by using Savitzky-Golay smoothing and differentiation, trigonometric Fourier series, and mother wavelet functions (i.e., sym6, haar, coif3, and mexh). To optimize spectral recoveries, the concentration of various types of divisors (single, double, and successive) was tested. The developed spectrophotometric methods showed linearity over the ranges 20-40 mg/L for paracetamol, 12-32 mg/L for ibuprofen, and 1-3.5 mg/L for caffeine (R 2 > 0.990). They could be successfully applied to the assay and dissolution test of paracetamol, ibuprofen, and caffeine in their combined tablets and capsules, with accuracy (99.1-101.5% recovery) and precision (RSD < 2%). For comparison, an isocratic RP-HPLC analysis was also developed and validated on an Agilent ZORBAX Eclipse XDB-C18 (150 × 4.6 mm, 5 µm) at an ambient temperature. A mixture of methanol : phosphate buffer 0.01 M pH 3 (30 : 70 v/v) was used as the mobile phase delivered at 2 mL/min, and the effluent was monitored at 225 nm. It was shown that spectrophotometric data were statistically comparable to HPLC (p > 0.05), suggesting possible interchange between UV spectrophotometric and HPLC methods for routine analysis of paracetamol, ibuprofen, and caffeine in their solid pharmaceutical dosage forms.

Community Participatory Interventions to Improve Farmer Knowledge and Practices of Household Biogas Unit Operation in Ha Nam Province, Vietnam.

CONTEXT: The use of biogas systems to treat livestock waste is a common practice in Vietnam. However, farmers' knowledge and practices of the safe and appropriate use of household biogas units (HBUs) are still limited and could negatively impact human, animal, and environmental health. OBJECTIVE: To assess the effectiveness of an intervention to improve knowledge and practices of biogas operation among farmers in 2 communes of Ha Nam Province, Vietnam. DESIGN: A community-based intervention approach. SETTING: This study was conducted from 2015 to 2016 in 2 communes of Ha Nam Province, Vietnam. PARTICIPANTS: Only farmers with HBUs (N = 399) participated in this research. Farmers were assigned to either an intervention group or a control group at a ratio of 1:2. INTERVENTION: Two intervention steps were implemented over a 6-month period as follows: (i) the core farmer group trained in 6 steps of HBU safe handling practice; and (ii) the core farmer group conducted peer-to-peer communication with its neighbors in the commune using the provided material. MAIN OUTCOME MEASURE(S): Farmers' knowledge and practices in biogas operation were assessed by a structured questionnaire. The questionnaire was administered before (baseline) and after the intervention (follow-up) to both the control and intervention groups. RESULTS: There was a significant difference in the knowledge and practices of biogas operation between the 2 groups, in which farmers in the intervention group demonstrated better understanding of the related topic than the control group (P < .05, t test). A linear regression model indicated that baseline and follow-up scores in both knowledge and practices of the intervention group were higher than those of the control group. After the intervention, the mean difference score in knowledge and practices between the intervention and control groups was 5.0 and 2.0 points, respectively (P < .01). CONCLUSION: A community-based intervention approach could be applied to improve knowledge and practices among farmers in using biogas systems. However, further studies should be conducted to assess the sustainability and effectiveness of this model.

Antigen Analysis of Pre-Eclamptic Plasma Antibodies Using Escherichia Coli Proteome Chips.

Pre-eclampsia is one of the main causes of perinatal mortality and morbidity. Many biomarkers for diagnosing pre-eclampsia have been found but most have low accuracy. Therefore, a potential marker that can detect pre-eclampsia with high accuracy is required. Infection has been reported as a cause of pre-eclampsia. In recent years, protein microarray chips have been recognized as a strong and robust tool for profiling antibodies for infection diagnoses. The purpose of the present study was to profile antibodies in the human plasma of healthy and pre-eclamptic pregnancies to identify suitable biomarkers. In this study, an Escherichia coli chip was probed with samples from 29 individuals (16 pre-eclamptic women and 13 healthy pregnant women) to profile plasma antibodies. Bioinformatics tools were used to analyze the results, discover conserved motifs, compare against the entire human proteome, and perform protein functional analysis. An antibody classifier was identified using k-top scoring pairs and additional samples for a blinded test were collected. The findings indicated that compared with the healthy women, the pre-eclamptic women exhibited 108 and 130 differentially immunogenic proteins against human immunoglobulins G and M, respectively. In addition, pre-eclamptic women developed more immunoglobulin G but less immunoglobulin M against bacterial surface proteins compared with healthy women. The k-top scoring pairs identified five pairs of immunogenic proteins as classifiers with a high accuracy of 90% in the blind test. [AG] [ISV] GV [AE] L [LF] and [IV] [IV] RI [AG] [AD] E were the consensus motifs observed in immunogenic proteins in the immunoglobulin G and immunoglobulin M of pre-eclamptic women, respectively, whereas GA [AG] [AL] L [LF] and [SRY] [IQML] [ILV] [ILV] [ACG] GI [GH] [AEF] [AK] [ATY] [RG] N [IV] were observed in the immunoglobulins G and immunoglobulin M of healthy women, respectively.

Diarrhea risks by exposure to livestock waste in Vietnam using quantitative microbial risk assessment.

OBJECTIVES: The aim of this paper was to assess the diarrhea risks caused by various pathogens among those exposed to biogas wastewater through different activities. METHODS: Application of quantitative microbial risk assessment (QMRA) of biogas wastewater was conducted in Hanam Province, Vietnam. A total of 451 representatives from households that use biogas were interviewed about their practices of handling biogas plant and reuse of biogas effluent for irrigation. In addition, 150 samples of biogas wastewater were analyzed for Escherichia coli, Cryptosporidium parvum, and Giardia lamblia. Risk characterization was calculated using Monte Carlo simulation. RESULTS: The annual diarrhea risk caused by exposure to biogas effluent through irrigation activities ranged from 17.4 to 21.1% (E. coli O157:H7), 1.0 to 2.3% (G. lamblia), and 0.2 to 0.5% (C. parvum), while those caused through unblocking drains connected to biogas effluent tanks were 22.0% (E. coli), 0.7% (G. lamblia), and 0.5% (C. parvum). CONCLUSIONS: Further measures are needed to reduce the risk by either improving the microbial quality of biogas effluent or by ensuring the use of personal protective measures when exposed to biogas wastewater.

Ameliorative Effect of Curcumin-Encapsulated Hyaluronic Acid-PLA Nanoparticles on Thioacetamide-Induced Murine Hepatic Fibrosis.

In this study, we developed curcumin-encapsulated hyaluronic acid-polylactide nanoparticles (CEHPNPs) to be used for liver fibrosis amelioration. CD44, the hyaluronic acid (HA) receptor, is upregulated on the surface of cancer cells and on activated hepatic stellate cells (aHSCs) rather than normal cells. CEHPNPs could bind to CD44 and be internalized effectively through endocytosis to release curcumin, a poor water-soluble liver protective agent. Thus, CEHPNPs were potentially not only improving drug efficiency, but also targeting aHSCs. HA and polylactide (PLA) were crosslinked by adipic acid dihydrazide (ADH). The synthesis of HA-PLA was monitored by Fourier-transform infrared (FTIR) and Nuclear Magnetic Resonance (NMR). The average particle size was approximately 60-70 nm as determined by dynamic light scattering (DLS) and scanning electron microscope (SEM). Zeta potential was around -30 mV, which suggested a good stability of the particles. This drug delivery system induced significant aHSC cell death without affecting quiescent HSCs, hepatic epithelial, and parenchymal cells. This system reduced drug dosage without sacrificing therapeutic efficacy. The cytotoxicity IC50 (inhibitory concentration at 50%) value of CEHPNPs was approximately 1/30 to that of the free drug treated group in vitro. Additionally, the therapeutic effects of CEHPNPs were as effective as the group treated with the same curcumin dose intensity in vivo. CEHPNPs significantly reduced serum aspartate transaminase/alanine transaminase (ALT/AST) significantly, and attenuated tissue collagen production and cell proliferation as revealed by liver biopsy. Conclusively, the advantages of superior biosafety and satisfactory therapeutic effect mean that CEHPNPs hold great potential for treating hepatic fibrosis.

Evidence for Public Health Risks of Wastewater and Excreta Management Practices in Southeast Asia: A Scoping Review.

The use of wastewater and excreta in agriculture is a common practice in Southeast Asia; however, concerns remain about the potential public health risks of this practice. We undertook a scoping review to examine the extent, range, and nature of literature, as well as synthesize the evidence for associations between wastewater and excreta management practices and public health risks in Southeast Asia. Three electronic databases (PubMed, CAB Direct, and Web of Science) were searched and a total of 27 relevant studies were included and evaluated. The available evidence suggested that possible occupational health risks of wastewater and excreta management practices include diarrhea, skin infection, parasitic infection, bacterial infection, and epilepsy. Community members can be at risk for adverse health outcomes through consuming contaminated fish, vegetables, or fruits. Results suggested that practices including handling, treatment, and use of waste may be harmful to human health, particularly farmer's health. Many studies in this review, however, had limitations including lack of gender analyses, exposure assessment, and longitudinal study designs. These findings suggest that more studies on identifying, quantitatively assessing, and mitigating health risks are needed if sustainable benefits are to be obtained from wastewater and excreta reuse in agriculture in Southeast Asia.

Tabula diptycha: differential HIV knowledge, stigma and intended behavioural outcomes amongst visitors at Vietnam's Pain and Hope exhibition.

Stigma reduction efforts in Vietnam have been encumbered by contradictory and dynamic views of people living with HIV and the epidemic over the past two decades. World AIDS Day 2010 saw the launch of Pain and Hope, a museum exhibition showcasing the lives and experiences of Vietnamese people living with AIDS at the Vietnam Museum of Ethnology (VME). Between December 2010 and May 2011, a random sample of visitors completed exit surveys regarding their attitudes towards the exhibition and Vietnamese living with HIV/AIDS. The survey sought to determine what kind of visitors the museum and exhibition attracted, and the stigma-related impacts of this kind of exposure and parasocial contact. Of 2500 Vietnamese visitors randomly selected, 852 completed the computer surveys (response rate of 34.1%), 92.3% of whom had seen Pain and Hope. We found two sub-strata or types of visitors attending the exhibition, with varying demographic characteristics, HIV-related knowledge, some differences in stigma ideation, and clear differences in intended behaviours specifically attributable to the exhibition. Social desirability biases notwithstanding, there has emerged a diptych typology of visitors to the VME, for whom the experience of the exhibition is likely interacting with divergent prior knowledge, experiences, interests and motivations.

Impaired muscle regeneration in ob/ob and db/db mice.

In obesity and type 2 diabetes, efficient skeletal muscle repair following injury may be required, not only for restoring muscle structure and function, but also for maintaining exercise capacity and insulin sensitivity. The hypothesis of this study was that muscle regeneration would be impaired in ob/ob and db/db mice, which are common mouse models of obesity and type 2 diabetes. Muscle injury was produced by cardiotoxin injection, and regeneration was assessed by morphological and immunostaining techniques. Muscle regeneration was delayed in ob/ob and db/db mice, but not in a less severe model of insulin resistance - feeding a high-fat diet to wild-type mice. Angiogenesis, cell proliferation, and myoblast accumulation were also impaired in ob/ob and db/db mice, but not the high-fat diet mice. The impairments in muscle regeneration were associated with impaired macrophage accumulation; macrophages have been shown previously to be required for efficient muscle regeneration. Impaired regeneration in ob/ob and db/db mice could be due partly to the lack of leptin signaling, since leptin is expressed both in damaged muscle and in cultured muscle cells. In summary, impaired muscle regeneration in ob/ob and db/db mice was associated with reduced macrophage accumulation, angiogenesis, and myoblast activity, and could have implications for insulin sensitivity in the skeletal muscle of obese and type 2 diabetic patients.

Macrophage-specific expression of urokinase-type plasminogen activator promotes skeletal muscle regeneration.

Macrophages (Mp) and the plasminogen system play important roles in tissue repair following injury. We hypothesized that Mp-specific expression of urokinase-type plasminogen activator (uPA) is sufficient for Mp to migrate into damaged muscle and for efficient muscle regeneration. We generated transgenic mice expressing uPA only in Mp, and we assessed the ability of these mice to repair muscle injury. Mp-only uPA expression was sufficient to induce wild-type levels of Mp accumulation, angiogenesis, and new muscle fiber formation. In mice with wild-type uPA expression, Mp-specific overexpression further increased Mp accumulation and enhanced muscle fiber regeneration. Furthermore, Mp expression of uPA regulated the level of active hepatocyte growth factor, which is required for muscle fiber regeneration, in damaged muscle. In vitro studies demonstrated that uPA promotes Mp migration through proteolytic and nonproteolytic mechanisms, including proteolytic activation of hepatocyte growth factor. In summary, Mp-derived uPA promotes muscle regeneration by inducing Mp migration, angiogenesis, and myogenesis.

Urokinase-type plasminogen activator increases hepatocyte growth factor activity required for skeletal muscle regeneration.

The plasminogen system plays a crucial role in the repair of a variety of tissues, including skeletal muscle. We hypothesized that urokinase-type plasminogen activator (uPA) promotes muscle regeneration by activating hepatocyte growth factor (HGF), which, in turn, stimulates proliferation of myoblasts required for regeneration. In our studies, levels of active HGF and phosphorylation of the HGF receptor c-met were increased after muscle injury in wild-type mice. Compared with wild-type animals, mice deficient in uPA (uPA(-/-)) had markedly reduced HGF levels and c-met activation after muscle damage. This reduced HGF activity in uPA(-/-) animals was associated with decreased cell proliferation, myoblast accumulation, and new muscle fiber formation. On the other hand, HGF activity was enhanced at early time points in PAI-1(-/-) mice compared with wild-type mice and the PAI-1(-/-) animals exhibited accelerated muscle fiber regeneration. Furthermore, administration of exogenous uPA rescued HGF levels and muscle regeneration in uPA(-/-) mice, and an HGF-blocking antibody reduced HGF activity and muscle regeneration in wild-type mice. We also found that uPA promotes myoblast proliferation in vitro through its proteolytic activity, and this process was inhibited by an HGF-blocking antibody. Together, our findings demonstrate that uPA promotes muscle regeneration through HGF activation and subsequent myoblast proliferation.

Endogenous interferon-gamma is required for efficient skeletal muscle regeneration.

The inflammatory response is thought to play important roles in tissue healing. The hypothesis of this study was that the inflammatory cytokine interferon (IFN)-gamma is produced endogenously following skeletal muscle injury and promotes efficient healing. We show that IFN-gamma is expressed at both mRNA and protein levels in skeletal muscle following injury, and that the time course of IFN-gamma expression correlated with the accumulation of macrophages, T-cells, and natural killer cells, as well as myoblasts, in damaged muscle. Cells of each type were isolated from injured muscle, and IFN-gamma expression was detected in each cell type. We also demonstrate that administration of an IFN-gamma receptor blocking antibody to wild-type mice impaired induction of interferon response factor-1, reduced cell proliferation, and decreased formation of regenerating fibers. IFN-gamma null mice showed similarly impaired muscle healing associated with impaired macrophage function and development of fibrosis. In vitro studies demonstrated that IFN-gamma and its receptor are expressed in the C2C12 muscle cell line, and that the IFN-gamma receptor blocking antibody reduced proliferation and fusion of these muscle cells. In summary, our results indicate that IFN-gamma promotes muscle healing, in part, by stimulating formation of new muscle fibers.

Discovery of a second human molar and cranium fragment in the late Middle to Late Pleistocene cave of Ma U'Oi (Northern Vietnam).

In November 2002, during the second season of work by a Vietnamese-French-Japanese team, we discovered a human molar and a fragment of an occipital bone in the late Middle to Late Pleistocene cave of Ma U'Oi (Bacon et al., Geobios. 37 (2004) 305). The layer from which this material comes is the same as that in which a human lower molar was found in 2001. Both molars can be attributed to archaic Homo, and both exhibit archaic and modern traits.