Natural flavonoids as potential therapeutics in the management of Alzheimer's disease: a review.

Alzheimer's disease (AD) is an age-dependent neurodegenerative disorder which is associated with the accumulation of proteotoxic Aß peptides, and pathologically characterized by the deposition of Aß-enriched plaques and neurofibrillary tangles. Given the social and economic burden caused by the rising frequency of AD, there is an urgent need for the development of appropriate therapeutics. Natural compounds are gaining popularity as alternatives to synthetic drugs due to their neuroprotective properties and higher biocompatibility. While natural compound's therapeutic effects for AD have been recently investigated in numerous in vitro and in vivo studies, only few have developed to clinical trials. The present review aims to provide a brief overview of the therapeutic effects, new insights, and upcoming perspectives of the preclinical and clinical trials of flavonoids for the treatment of Alzheimer's disease.

Cell membrane-based nanomaterials for therapeutics of neurodegenerative diseases.

Central nervous system (CNS) diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), glioblastoma (GBM), and peripheral nerve injury have been documented as incurable diseases, which lead to serious impacts on human health especially prevalent in the aging population worldwide. Most of the treatment strategies fail due to low efficacy, toxicity, and poor brain penetration. Recently, advancements in nanotechnology have helped alleviate the challenges associated with the application of cell membrane-based nanomaterials against CNS diseases. In the following review, the existing types of cell membrane-based nanomaterials systems which have improved therapeutic efficacy for CNS diseases would be described. A summary of recent progress in the incorporation of nanomaterials in cell membrane-based production, separation, and analysis will be provided. Addition to, challenges relate to large-scale manufacturing of cell membrane-based nanomaterials and future clinical trial of such platforms will be discussed.

Nanotechnology-Based Drug Delivery For Alzheimer's And Parkinson's Diseases.

The delivery of drugs to the brain is quite challenging in the treatment of the central nervous system [CNS) diseases due to the blood-brain barrier and the blood-cerebrospinal fluid barrier. However, significant developments in nanomaterials employed by nanoparticle drug-delivery systems have substantial potential to cross or bypass these barriers leading to enhanced therapeutic efficacies. Advances in nanoplatform, nanosystems based on lipids, polymers and inorganic materials have been extensively studied and applied in treating Alzheimer's and Parkinson's diseases. In this review, various types of brain drug delivery nanocarriers are classified, summarized, and their potential as drug delivery systems in Alzheimer's and Parkinson's diseases is discussed. Finally, challenges facing the clinical translation of nanoparticles from bench to bedside are highlighted.

Recent Advancements in Nanomaterials: A Promising Way to Manage Neurodegenerative Disorders.

Neurodegenerative diseases (NDs) such as dementia, Alzheimer's disease, Parkinson's disease, frontotemporal dementia, and amyotrophic lateral sclerosis are some of the most prevalent disorders currently afflicting healthcare systems. Many of these diseases share similar pathological hallmarks, including elevated oxidative stress, mitochondrial dysfunction, protein misfolding, excitotoxicity, and neuroinflammation, all of which contribute to the deterioration of the nervous system's structure and function. The development of diagnostic and therapeutic materials in the monitoring and treatment of these diseases remains challenging. One of the biggest challenges facing therapeutic and diagnostic materials is the blood-brain barrier (BBB). The BBB is a multifunctional membrane possessing a plethora of biochemical, cellular, and immunological features that ensure brain homeostasis by preventing the entry and accumulation of unwanted compounds. With regards to neurodegenerative diseases, the recent application of tailored nanomaterials (nanocarriers and nanoparticles) has led to advances in diagnostics and therapeutics. In this review, we provide an overview of commonly used nanoparticles and their applications in NDs, which may offer new therapeutic strategies for the prevention and treatment of neurodegenerative diseases.

Body Composition Changes Over the Menopausal Transition in Women With and Without Human Immunodeficiency Virus.

BACKGROUND: Women are at risk for weight gain during the transition to menopause, but few have examined the contribution of menopause to weight gain in women with human immunodeficiency virus (WWH). METHODS: From 2000 to 2013, participants (621 WWH; 218 without HIV [WWOH]) from the Women's Interagency HIV Study were categorized by menopausal phase using serial measures of anti-Müllerian hormone (AMH). Multivariable linear mixed models examined the association of menopausal phase with body mass index (BMI) and waist circumference (WC) trajectory, stratified by HIV status. RESULTS: In models controlled for chronologic age, the estimated effects (95% confidence interval) of menopausal phase on annual rate of BMI change across early perimenopause, late perimenopause, and menopause, respectively, compared to premenopause were -0.55% (-.80 to -.30), -0.29% (-.61 to .03), and -0.67% (-1.12 to -.20) in WWH, whereas estimated effects were 0.43% (-.01 to .87) and 0.15% (-.42 to .71) across early and late perimenopause, respectively, and -0.40% (-1.24 to .45) across menopause in WWOH. The estimated effects on rate of WC change were negative across early perimenopause (-0.21% [-.44 to .03]) and menopause (-0.12% [-.5 to .26]) and positive across late perimenopause (0.18% [-.10 to .45]) in WWH, and positive across all 3 menopausal phases in WWOH, but these effects were not statistically significant. CONCLUSIONS: In WWH, the menopausal transition was associated with BMI and WC trajectories that were mostly in a negative direction and opposite from WWOH after adjusting for age, suggesting that HIV blunts weight gain during the menopausal transition.

Graph Transformer for Drug Response Prediction.

BACKGROUND: Previous models have shown that learning drug features from their graph representation is more efficient than learning from their strings or numeric representations. Furthermore, integrating multi-omics data of cell lines increases the performance of drug response prediction. However, these models have shown drawbacks in extracting drug features from graph representation and incorporating redundancy information from multi-omics data. This paper proposes a deep learning model, GraTransDRP, to better drug representation and reduce information redundancy. First, the Graph transformer was utilized to extract the drug representation more efficiently. Next, Convolutional neural networks were used to learn the mutation, meth, and transcriptomics features. However, the dimension of transcriptomics features was up to 17737. Therefore, KernelPCA was applied to transcriptomics features to reduce the dimension and transform them into a dense presentation before putting them through the CNN model. Finally, drug and omics features were combined to predict a response value by a fully connected network. Experimental results show that our model outperforms some state-of-the-art methods, including GraphDRP and GraOmicDRP.

Predicting the risk of osteoporosis in older Vietnamese women using machine learning approaches.

Osteoporosis contributes significantly to health and economic burdens worldwide. However, the development of osteoporosis-related prediction tools has been limited for lower-middle-income countries, especially Vietnam. This study aims to develop prediction models for the Vietnamese population as well as evaluate the existing tools to forecast the risk of osteoporosis and evaluate the contribution of covariates that previous studies have determined to be risk factors for osteoporosis. The prediction models were developed to predict the risk of osteoporosis using machine learning algorithms. The performance of the included prediction models was evaluated based on two scenarios; in the first one, the original test parameters were directly modeled, and in the second the original test parameters were transformed into binary covariates. The area under the receiver operating characteristic curve, the Brier score, precision, recall and F1-score were calculated to evaluate the models' performance in both scenarios. The contribution of the covariates was estimated using the Permutation Feature Importance estimation. Four models, namely, Logistic Regression, Support Vector Machine, Random Forest and Neural Network, were developed through two scenarios. During the validation phase, these four models performed competitively against the reference models, with the areas under the curve above 0.81. Age, height and weight contributed the most to the risk of osteoporosis, while the correlation of the other covariates with the outcome was minor. Machine learning algorithms have a proven advantage in predicting the risk of osteoporosis among Vietnamese women over 50 years old. Additional research is required to more deeply evaluate the performance of the models on other high-risk populations.

In silico and in vitro studies on the anti-cancer activity of artemetin, vitexicarpin and penduletin compounds from Vitex negundo.

Vitex negundo L. (V. negundo) is one of the important medicinal and anticancer enhancer herbs. This plant is commonly used in the preparation of traditional drugs to treat numerous diseases. Inspired by the medicinal properties of this plant, the current study aimed to investigate antiproliferative potential and the primary molecular mechanisms of the apoptotic induction against human HepG2 and MCF-7 cell lines, by pure compounds isolated from targeted fractions of V. negundo which were characterized by NMR, FTIR and HRMS analysis and identified as artemetin (FLV1), vitexicarpin (FLV2), and penduletin (FLV3) compounds. The FLV1, FLV2, and FLV3 compounds were evaluated for the antiproliferative potential against HepG2 and MCF-7 cell lines by cell viability assay and exhibited IC50 values of 2.3, 23.9 and 5.6 µM and 3.9, 25.8, and 6.4 µM, respectively. In addition, those compounds increased the level of reactive oxygen species production, induced cell death occurred via apoptosis, demonstrated by Annexin V-staining cells, contributed significantly to DNA damage, and led to the activation of caspase3/caspase8 pathways.Additionally, molecular docking was also conducted to rationalize the cancer cells inhibitory and to evaluate the ability of the FLV1, FLV2, and FLV3 compounds to be developed as good drug candidates for cancers treatment.

Advances in Hydrogel-Based Drug Delivery Systems for Parkinson's Disease.

Parkinson's disease (PD) is a common central nervous system disorder (CNS) characterized by cell loss in the substantia nigra. Severe loss of dopaminergic neurons and Lewy body formation with α-synuclein inclusions are the main neuropathological features of PD. There's currently no cure for PD, but treatments are available to help relieve the symptoms and maintain quality of life. However, the variety of clinically available therapeutic molecules is mainly limited to treating symptoms rather than halting or reversing disease progression via medical interventions. As an emerging drug carrier, hydrogels loaded with therapeutic agents and cells are attracting attention as an alternative and potentially more effective approach to managing PD. The current work highlights applications of hydrogel-based biomaterials in cell culture and disease modeling as carriers for cells, medicines, and proteins as PD therapeutic models.

Evaluation of community-based screening tools for the early screening of osteoporosis in postmenopausal Vietnamese women.

BACKGROUND: Osteoporosis affects people worldwide. However, there are few validated tools for the early screening of osteoporosis in Vietnam. We set out to evaluate the performance of the osteoporosis self-assessment tool for Asians (OSTA) and the osteoporosis screening tool for Chinese (OSTC) for the early screening of osteoporosis in postmenopausal Vietnamese women. METHODS: We analyzed retrospective data from 797 postmenopausal Vietnamese women. The bone mineral density (BMD) in the lumbar vertebrae (L1-L4) and the left and right femoral necks of all participants were measured using dual-energy X-ray absorptiometry (DXA). Osteoporosis was defined as the BMD (T-score) < -2.5. The OSTA and OSTC scores were calculated from the age and weight of participants. Receiver operating characteristic analysis was conducted to compare the performance of the two tools with the BMD measurements by DXA at different anatomical sites. RESULTS: The rates of osteoporosis determined by BMD varied between anatomical sites, and ranged from 43.4% to 54.7% in the lumbar vertebrae and 29.2% and 8.9% in the left and right femoral necks, respectively. For the vertebrae, the area under the curve (AUC) for OSTA ranged from 70.9% to 73.9% and for OSTC ranged from 68.7% to 71.6%. The predictive value of both tools was higher for femoral necks, with the AUC of OSTA for the left and right femoral necks being 80.0% and 85.8%, respectively. The corresponding figures for OSTC were 80.5% and 86.4%, respectively. The highest sensitivity and specificity of OSTA were 74.6% and 81.4%, while these figures for OSTC were 73.9% and 82.6%, respectively. CONCLUSION: OSTA and OSTC were shown to be useful self-assessment tools for osteoporosis detection in Vietnam postmenopausal women. Further research is encouraged to determine the applicability of tools for other populations and settings.

The Potential Crosstalk Between the Brain and Visceral Adipose Tissue in Alzheimer's Development.

The bidirectional communication between the brain and peripheral organs have been widely documented, but the impact of visceral adipose tissue (VAT) dysfunction and its relation to structural and functional brain changes have yet to be fully elucidated. This review initially examines the clinical evidence supporting associations between the brain and VAT before visiting the roles of the autonomic nervous system, fat and glucose metabolism, neuroinflammation, and metabolites. Finally, the possible effects and potential mechanisms of the brain-VAT axis on the pathogenesis of Alzheimer's disease are discussed, providing new insights regarding future prevention and therapeutic strategies.

Reactogenicity and immunogenicity of heterologous prime-boost immunization with COVID-19 vaccine.

BACKGROUND: The objective of the present work was to assess the reactogenicity and immunogenicity of heterologous COVID-19 vaccination regimens in clinical trials and observational studies. METHODS: PubMed, Cochrane Library, Embase, MedRxiv, BioRxiv databases were searched in September 29, 2021. The PRISMA instruction for systemic review was followed. Two reviewers independently selected the studies, extracted the data and assessed risk of bias. The quality of studies was evaluated using the New Castle-Ottawa and Cochrane risk of instrument. The characteristics and study outcome (e.g., adverse events, immune response, and variant of concern) were extracted. RESULTS: Nineteen studies were included in the final data synthesis with 5 clinical trials and 14 observational studies. Heterologous vaccine administration showed a trend toward more frequent systemic reactions. However, the total reactogenicity was tolerable and manageable. Importantly, the heterologous prime-boost vaccination regimens provided higher immunogenic effect either vector/ mRNA-based vaccine or vector/ inactivated vaccine in both humoral and cellular immune response. Notably, the heterologous regimens induced the potential protection against the variant of concern, even to the Delta variant. CONCLUSIONS: The current findings provided evidence about the higher induction of robust immunogenicity and tolerated reactogenicity of heterologous vaccination regimens (vector-based/mRNA vaccine or vector-based/inactivated vaccine). Also, this study supports the application of heterologous regimens against COVID-19 which may provide more opportunities to speed up the global vaccination campaign and maximize the capacity to control the pandemic.

The 2017 Dengue virus 1 outbreak in northern Vietnam was caused by a locally circulating virus group.

BACKGROUND: Dengue virus (DENV) is a member of insect vector-borne viruses, and it causes dengue fever. Southeast Asia is the epi-center of dengue fever in the world. The characterization of the virus is essential to identify the transmission and evolution of DENV. OBJECTIVES: In 2017, there was an outbreak of Dengue virus type 1 (DENV1) in northern Vietnam and the neighboring countries. To identify the genetic character of the outbreak virus in the area, we conducted whole-genome sequencing analysis on the samples positive for the DENV1 along with real-time PCR. STUDY DESIGN: In total, 1026 blood samples were collected from patients with suspected dengue fever in Ha Nam and Hai Duong province, nearby areas of the capital of Vietnam. After screening by real-time PCR, 40 of DENV1 positive samples were subjected to whole-genome sequencing, and 28 complete coding sequences were obtained. RESULTS: All 28 sequences were genotype I of DENV1, which is dominant in the southeast and East Asian countries. The phylogenetic analysis of the E region showed that they fell into a single cluster with the reported sequences from Vietnam between 2009 and 2016, in which the isolates from other countries are very rare. Our results suggested that the 2017 outbreak in the area was caused by locally circulating viruses.

Evaluation of Anti-Hepatocellular-Cancer Properties of ß-Sitosterol and ß-Sitosterol-Glucoside from Indigofera zollingeriana Miq.

Liver cancer is the most frequent cancer, making it the leading cause of cancer death globally. Traditional medicinal plants with anticancer properties can be used as drugs or dietary adjuvants to existing therapies. This chapter presents a protocol for the preparation of ß-sitosterol and ß-sitosterol-glucoside from Indigofera zollingeriana Miq (I. zollingeriana) and the evaluation of these for anticancer activity in hepatocellular cells.

Advances of microneedles in hormone delivery.

The skin is recognized as a potential target for local and systemic drug delivery and hormone. However, the transdermal route of drug administration seems to be limited by substantial barrier properties of the skin. Recently, delivering hormone via the skin by transdermal patches is a big challenge because of the presence of the stratum corneum that prevents the application of hormone via this route. In order to overcome the limitations, microneedle (MN), consisting of micro-sized needles, are a promising approach to drill the stratum corneum and release hormone into the dermis via a minimal-invasive route. This review aimed to highlight advances in research on the development of MNs-based therapeutics for their implications in hormone delivery. The challenges during clinical translation of MNs from bench to bedside are also discussed.

Microneedles enable the development of skin-targeted vaccines against coronaviruses and influenza viruses.

Throughout the COVID-19 pandemic, many have seriously worried that the plus burden of seasonal influenza that might create a destructive scenario, resulting in overwhelmed healthcare capacities and onwards loss of life. Many efforts to develop a safe and efficacious vaccine to prevent infection by coronavirus and influenza, highlight the importance of vaccination to combat infectious pathogens. While vaccines are traditionally given as injections into the muscle, microneedle (MN) patches designed to precisely deliver cargos into the cutaneous microenvironment, rich in immune cells, provide a noninvasive and self-applicable vaccination approach, reducing overall costs and improving access to vaccines in places with limited supply. The current review aimed to highlight advances in research on the development of MNs-mediated cutaneous vaccine delivery. Concluding remarks and challenges on MNs-based skin immunization are also provided to contribute to the rational development of safe and effective MN-delivered vaccines against these emerging infectious diseases.

Lipid-Based Nanocarriers via Nose-to-Brain Pathway for Central Nervous System Disorders.

Neurodegenerative disorders are distinguished by the gradual deterioration of the nervous system's structure and function due to oxidative stress, mitochondrial dysfunction, protein misfolding, excitotoxicity, and neuroinflammation. Among these NDs, Alzheimer's disease, Huntington's disease, Parkinson's disease, and amyotrophic lateral sclerosis characterized an increasing dysfunction and loss of neuronal structure leading to neuronal cell death. Although there is currently no drug to totally reverse the effects of NDs, such novel formulations and administration routes are developed for better management and nose-to-brain delivery is one of delivery for treating NDs. This review aimed to highlight advances in research on various lipid based nanocarriers such as liposomes, solid lipid nanoparticles, nanostructured lipid carriers, microemulsion, nanoemulsion, and cubosomes which are reported to treat and alleviate the symptoms of NDs via nose-to-brain route. The challenges during clinical translation of lipid nanocarriers from bench to bed side is also discussed.

Genetic Diversity of Porcine Circovirus Subtypes from Aborted Sow Fetuses in Vietnam.

Porcine circovirus type 3 (PCV3) is an emerging circovirus that is highly distributed among swine worldwide and associated with porcine dermatitis and nephropathy syndrome, reproductive failure, and multisystemic inflammation. Here, we investigated and characterized PCV3 from aborted fetuses in Vietnam. We found that the whole genomes of PCV3 collected in these Vietnamese pig farms share 98.4-99.45% sequence identity with reference PCV3 sequences. Several distinct mutation were identified in both the Rep protein and Cap protein of these strains. These strains were clustered into two distinct subtypes (3a1 and 3b). This study contributes to a better understanding of the molecular characteristics and genetic diversity of PCV3 in Vietnam.

Nanotechnology-based drug delivery for central nervous system disorders.

Drug delivery to central nervous system (CNS) diseases is very challenging since the presence of the innate blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier that impede drug delivery. Among new strategies to overcome these limitations and successfully deliver drugs to the CNS, nanotechnology-based drug delivery platform, offers potential therapeutic approach for the treatment of some common neurological disorders like Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease. This review aimed to highlight advances in research on the development of nano-based therapeutics for their implications in therapy of CNS disorders. The challenges during clinical translation of nanomedicine from bench to bed side is also discussed.