The first epidemiology of urolithiasis in Northern Vietnam: Urinary stone composition, age, gender, season, and clinical features study.

OBJECTIVES: The aim of this study is to analyze the compositions of urinary stones and investigate their distributions in different ages, genders, seasons, and clinical features of Northern Vietnamese patients. METHODS: A total of 231 patients with urinary stones from Northern Vietnam were collected and analyzed composition from 1/2021-12/2022. For all patients, age, sex, stone location, stone side, urine pH, and hospitalized date (month) were collected. RESULTS: Kidney stones are more frequently found in men than women with the male: female urinary stones ratio in this study being 1.96:1. The highest stone prevalence appeared between 60 and 69 years old. The most common stone composition was calcium oxalate, followed by calcium phosphate, uric acid, struvite, and cysteine. Mix stones of CaOx and CaP were more prevalent than pure stones. Males submitted more CaOx, CaP, and UA stones, whereas females were susceptible to infectious stones. Stones were more frequently found on the left side of the upper urinary tract (51.9%) than on the right side (27.3%) and lower urinary tract (7.8%). Cultural tendency leads to a smaller number of stones during the Lunar new year (February), and Ghost month (August).

Identification of Antioxidative Peptides Derived from Arthrospira maxima in the Biorefinery Process after Extraction of C-Phycocyanin and Lipids.

Arthrospira maxima has been identified as a sustainable source of rich proteins with diverse functionalities and bioactivities. After extracting C-phycocyanin (C-PC) and lipids in a biorefinery process, the spent biomass still contains a large proportion of proteins with potential for biopeptide production. In this study, the residue was digested using Papain, Alcalase, Trypsin, Protamex 1.6, and Alcalase 2.4 L at different time intervals. The resulting hydrolyzed product with the highest antioxidative activity, evaluated through their scavenging capability of hydroxyl radicals, superoxide anion, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS), was selected for further fractionation and purification to isolate and identify biopeptides. Alcalase 2.4 L was found to produce the highest antioxidative hydrolysate product after four-hour hydrolysis. Fractionating this bioactive product using ultrafiltration obtained two fractions with different molecular weights (MW) and antioxidative activity. The low-molecular-weight fraction (LMWF) with MW <3 kDa had higher DPPH scavenging activity with the IC50 value of 2.97 ± 0.33 compared to 3.76 ± 0.15 mg/mL of the high-molecular-weight fraction (HMWF) with MW >3 kDa. Two stronger antioxidative fractions (F-A and F-B) with the respective significant lower IC50 values of 0.83 ± 0.22 and 1.52 ± 0.29 mg/mL were isolated from the LMWF using gel filtration with a Sephadex G-25 column. Based on LC-MS/MS analysis of the F-A, 230 peptides derived from 108 A. maxima proteins were determined. Notably, different antioxidative peptides possessing various bioactivities, including antioxidation, were detected with high predicted scores together with in silico analyses on their stability and toxicity. This study established knowledge and technology to further value-add to the spent A. maxima biomass by optimizing hydrolysis and fraction processes to produce antioxidative peptides with Alcalase 2.4 L after two products already produced in a biorefinery. These bioactive peptides have potential applications in food and nutraceutical products.

Fear of COVID-19, healthy eating behaviors, and health-related behavior changes as associated with anxiety and depression among medical students: An online survey.

Background: Medical students' health and wellbeing are highly concerned during the COVID-19 pandemic. This study examined the impacts of fear of COVID-19 (FCoV-19S), healthy eating behavior, and health-related behavior changes on anxiety and depression. Methods: We conducted an online survey at 8 medical universities in Vietnam from 7th April to 31st May 2020. Data of 5,765 medical students were collected regarding demographic characteristics, FCoV-19S, health-related behaviors, healthy eating score (HES), anxiety, and depression. Logistic regression analyses were used to explore associations. Results: A lower likelihood of anxiety and depression were found in students with a higher HES score (OR = 0.98; 95%CI = 0.96, 0.99; p = 0.042; OR = 0.98; 95%CI = 0.96, 0.99; p = 0.021), and in those unchanged or more physical activities during the pandemic (OR = 0.54; 95%CI = 0.44, 0.66; p < 0.001; OR = 0.44; 95%CI = 0.37, 0.52; p < 0.001) as compared to those with none/less physical activity, respectively. A higher likelihood of anxiety and depression were reported in students with a higher FCoV-19S score (OR = 1.09; 95%CI = 1.07, 1.12; p < 0.001; OR = 1.06; 95%CI = 1.04, 1.08; p < 0.001), and those smoked unchanged/more during the pandemic (OR = 6.67; 95%CI = 4.71, 9.43; p < 0.001; OR = 6.77; 95%CI = 4.89, 9.38; p < 0.001) as compared to those stopped/less smoke, respectively. In addition, male students had a lower likelihood of anxiety (OR = 0.79; 95%CI = 0.65, 0.98; p = 0.029) compared to female ones. Conclusions: During the pandemic, FCoV-19S and cigarette smoking had adverse impacts on medical students' psychological health. Conversely, staying physically active and having healthy eating behaviors could potentially prevent medical students from anxiety and depressive symptoms.

Strategy for Treatment of Infected Diabetic Foot Ulcers.

Diabetic foot ulcers (DFUs) are chronic wounds that develop in 30% of diabetic patients. In DFUs, the normal wound healing process consisting of inflammation, angiogenesis, and extracellular matrix (ECM) remodeling is dysregulated and stalled. Upon injury, neutrophils and monocytes arrive at the wound and secrete matrix metalloproteinase (MMP)-8 and reactive oxygen species (ROS). ROS activates nuclear factor kappa beta (NF-κB), which upregulates MMP-9. Monocytes become macrophages, secreting tumor growth factor (TGF)-ß1 and vascular endothelial growth factor (VEGF) for angiogenesis, resulting in remodeling of the ECM. MMP-9 cleaves laminin for keratinocyte migration. MMP-8 is beneficial for remodeling the ECM and healing the wound. In DFUs, the excess unregulated MMP-9 is detrimental, destroying the ECM and preventing the wound from healing. DFUs are typically infected, many with biofilm-producing bacteria that are resistant to antibiotics. Infection increases the time for wound healing and the likelihood for a lower-limb amputation. Despite the use of antibiotics, amputations occur in 24.5% of patients with DFUs. Clearly, new strategies for treatment of DFUs are needed. With the use of an affinity resin that binds exclusively to the active forms of MMPs and proteomics, we identified two proteinases, MMP-8 and MMP-9, in wounds of diabetic mice and diabetic humans. With the use of selective inhibitors, gene ablation of MMP-9, and exogenous application of MMP-8, we demonstrated that MMP-8 is beneficial to wound repair and that MMP-9 prevents the diabetic wound from healing. Our research has shown that infection increases active MMP-9, increasing inflammation and decreasing angiogenesis. As a result, infected diabetic wounds take a longer time to heal than uninfected ones. We found that active MMP-9 and NF-κB increased in human DFUs with wound severity and infection. The best strategy for treatment of DFUs is to selectively inhibit the detrimental proteinase MMP-9 without affecting the beneficial MMP-8 so that the body can repair the wound. Lead optimization of the thiirane class of inhibitors led to the discovery of (R)-ND-336, a potent (19 nM) and selective (450-fold) MMP-9 inhibitor. (R)-ND-336 accelerated wound healing in diabetic mice by decreasing ROS and NF-κB, lowering inflammation, and increasing angiogenesis. (R)-ND-336 in combination with the antibiotic linezolid improved wound healing in infected diabetic mice by inhibiting MMP-9, which mitigated macrophage infiltration and increased angiogenesis, thereby restoring the normal wound healing process.

Fear of COVID-19 Scale-Associations of Its Scores with Health Literacy and Health-Related Behaviors among Medical Students.

The coronavirus disease 2019 (COVID-19) pandemic causes fear, as its immediate consequences for the public have produced unprecedented challenges for the education and healthcare systems. We aimed to validate the fear of COVID-19 scale (FCoV-19S) and examine the association of its scores with health literacy and health-related behaviors among medical students. A cross-sectional study was conducted from 7 to 29 April 2020 on 5423 students at eight universities across Vietnam, including five universities in the North, one university in the Center, two universities in the South. An online survey questionnaire was used to collect data on participants' characteristics, health literacy, fear of COVID-19 using the FCoV-19S, and health-related behaviors. The results showed that seven items of the FCoV-19S strongly loaded on one component, explained 62.15% of the variance, with good item-scale convergent validity and high internal consistency (Cronbach's alpha = 0.90). Higher health literacy was associated with lower FCoV-19S scores (coefficient, B, -0.06; 95% confidence interval, 95%CI, -0.08, -0.04; p < 0.001). Older age or last academic years, being men, and being able to pay for medication were associated with lower FCoV-19S scores. Students with higher FCoV-19S scores more likely kept smoking (odds ratio, OR, 1.11; 95% CI, 1.08, 1.14; p < 0.001) or drinking alcohol (OR, 1.04; 95% CI, 1.02, 1.06; p < 0.001) at an unchanged or higher level during the pandemic, as compared to students with lower FCoV-19S scores. In conclusion, the FCoV-19S is valid and reliable in screening for fear of COVID-19. Health literacy was found to protect medical students from fear. Smoking and drinking appeared to have a negative impact on fear of COVID-19. Strategic public health approaches are required to reduce fear and promote healthy lifestyles during the pandemic.

Targeting MMP-9 in Diabetic Foot Ulcers.

Diabetic foot ulcers (DFUs) are significant complications of diabetes and an unmet medical need. Matrix metalloproteinases (MMPs) play important roles in the pathology of wounds and in the wound healing process. However, because of the challenge in distinguishing active MMPs from the two catalytically inactive forms of MMPs and the clinical failure of broad-spectrum MMP inhibitors in cancer, MMPs have not been a target for treatment of DFUs until recently. This review covers the discovery of active MMP-9 as the biochemical culprit in the recalcitrance of diabetic wounds to healing and targeting this proteinase as a novel approach for the treatment of DFUs. Active MMP-8 and MMP-9 were observed in mouse and human diabetic wounds using a batimastat affinity resin and proteomics. MMP-9 was shown to play a detrimental role in diabetic wound healing, whereas MMP-8 was beneficial. A new class of selective MMP-9 inhibitors shows clinical promise for the treatment of DFUs.

Identifying miRNA-mRNA regulatory relationships in breast cancer with invariant causal prediction.

BACKGROUND: microRNAs (miRNAs) regulate gene expression at the post-transcriptional level and they play an important role in various biological processes in the human body. Therefore, identifying their regulation mechanisms is essential for the diagnostics and therapeutics for a wide range of diseases. There have been a large number of researches which use gene expression profiles to resolve this problem. However, the current methods have their own limitations. Some of them only identify the correlation of miRNA and mRNA expression levels instead of the causal or regulatory relationships while others infer the causality but with a high computational complexity. To overcome these issues, in this study, we propose a method to identify miRNA-mRNA regulatory relationships in breast cancer using the invariant causal prediction. The key idea of invariant causal prediction is that the cause miRNAs of their target mRNAs are the ones which have persistent causal relationships with the target mRNAs across different environments. RESULTS: In this research, we aim to find miRNA targets which are consistent across different breast cancer subtypes. Thus, first of all, we apply the Pam50 method to categorize BRCA samples into different "environment" groups based on different cancer subtypes. Then we use the invariant causal prediction method to find miRNA-mRNA regulatory relationships across subtypes. We validate the results with the miRNA-transfected experimental data and the results show that our method outperforms the state-of-the-art methods. In addition, we also integrate this new method with the Pearson correlation analysis method and Lasso in an ensemble method to take the advantages of these methods. We then validate the results of the ensemble method with the experimentally confirmed data and the ensemble method shows the best performance, even comparing to the proposed causal method. CONCLUSIONS: This research found miRNA targets which are consistent across different breast cancer subtypes. Further functional enrichment analysis shows that miRNAs involved in the regulatory relationships predicated by the proposed methods tend to synergistically regulate target genes, indicating the usefulness of these methods, and the identified miRNA targets could be used in the design of wet-lab experiments to discover the causes of breast cancer.

Synthesis of aromatic and indole alpha-glucosinolates.

Aromatic and indole glucosinolates are important members of the glucosinolate family of compounds du to their potential medicinal properties. They are known to exert antioxidant and anti-carcinogenic activity either by the natural products themselves, or their metabolic products including indole-3-carbinol and isothiocyanates. Natural glucosinolates are all ß-glucosinolates; however, α-glucosinolates are also promising compounds for medicinal applications and hence have to be produced synthetically for any bio-activity studies. Here we report on the successful synthesis of a series of α-glucosinolates: α-neoglucobrassicin, α-4-methoxyglucobrassicin, 2,3-dichlorophenyl-α-glucosinolate for the first time. Testing for anti-inflammatory properties of these synthetic GLs, however, did not yield the expected activity.

Redox-sensitive interaction between KIAA0132 and Nrf2 mediates indomethacin-induced expression of gamma-glutamylcysteine synthetase.

Exposure of HepG2 cells to nonsteroidal anti-inflammatory drugs (i.e., indomethacin and ibuprofen; NSAIDs) as well as resveratrol, caused increased expression of the mRNAs coding for the catalytic (Gclc) and modifier (Gclm) subunits of the glutathione synthetic enzyme, gamma-glutamylcysteine synthetase. In addition, indomethacin exposure increased intracellular glutathione content as well as inhibited glutathione depletion and cytotoxicity caused by diethyl maleate. Indomethacin-induced increases in the expression of gamma-glutamylcysteine synthetase mRNA were preceded by increases in steady state levels of intracellular pro-oxidants and glutathione disulfide accumulation. Simultaneous incubation with the thiol antioxidant N-acetylcysteine (NAC) inhibited indomethacin-mediated increases in GCLC mRNA, suggesting that increases in GCLC message were triggered by changes in intracellular oxidation/reduction (redox) reactions. Indirect immunofluorescence using intact cells demonstrated that indomethacin induced the nuclear translocation of Nrf2, a transcription factor believed to regulate GCLC expression. Immunoprecipitation studies showed that indomethacin treatment also inhibited Nrf2 tethering to KIAA0132 (the human homolog of Keap1 accession #D50922), which is believed to be a negative regulator of Nrf2. Consistent with this idea, over-expression of Nrf2 increased GCLC reporter gene expression and over-expression of KIAA0132 inhibited GCLC reporter gene activity as well as inhibited indomethacin-induced increases in the expression of GCLC. Finally, simultaneous treatment with NAC inhibited both indomethacin-induced release of Nrf2 from KIAA0132 and indomethacin-induced nuclear translocation of Nrf2. These results demonstrate that NSAIDs and resveratrol cause increases in the expression of gamma-glutamylcysteine synthetase mRNA and identify these agents as being capable of stimulating glutathione metabolism. These results also support the hypothesis that indomethacin-induced transcriptional activation of GCLC involves the redox-dependent release of KIAA0132 from Nrf2 followed by the nuclear translocation of Nrf2.