Corrigendum: Effectiveness of perindopril/amlodipine fixed-dose combination in the treatment of hypertension: a systematic review.

[This corrects the article DOI: 10.3389/fphar.2023.1156655.].

Time-course cross-species transcriptomics reveals conserved hepatotoxicity pathways induced by repeated administration of cyclosporine A.

Cyclosporine A (CsA) has shown efficacy against immunity-related diseases despite its toxicity in various organs, including the liver, emphasizing the need to elucidate its underlying hepatotoxicity mechanism. This study aimed to capture the alterations in genome-wide expression over time and the subsequent perturbations of corresponding pathways across species. Six data from humans, mice, and rats, including animal liver tissue, human liver microtissues, and two liver cell lines exposed to CsA toxic dose, were used. The microtissue exposed to CsA for 10 d was analyzed to obtain dynamically differentially expressed genes (DEGs). Single-time points data at 1, 3, 5, 7, and 28 d of different species were used to provide additional evidence. Using liver microtissue-based longitudinal design, DEGs that were consistently up- or down-regulated over time were captured, and the well-known mechanism involved in CsA toxicity was elucidated. Thirty DEGs that consistently changed in longitudinal data were also altered in 28-d rat in-house data with concordant expression. Some genes (e.g. TUBB2A, PLIN2, APOB) showed good concordance with identified DEGs in 1-d and 7-d mouse data. Pathway analysis revealed up-regulations of protein processing, asparagine N-linked glycosylation, and cargo concentration in the endoplasmic reticulum. Furthermore, the down-regulations of pathways related to biological oxidations and metabolite and lipid metabolism were elucidated. These pathways were also enriched in single-time-point data and conserved across species, implying their biological significance and generalizability. Overall, the human organoids-based longitudinal design coupled with cross-species validation provides temporal molecular change tracking, aiding mechanistic elucidation and biologically relevant biomarker discovery.

Pulmonary artery penetration due to fish bone ingestion: A rare case report.

Accidental fish bone ingestion is a common manifestation at emergency departments. In most cases, ingested foreign bodies usually pass uneventfully through the gastrointestinal tract and complications only present in less than 5% of all patients. In this report, we present the first documented case of pulmonary artery injury due to a fish bone in a 63-year-old male patient hospitalized with hemoptysis after accidentally swallowing a fish bone 30 days ago. This patient subsequently had surgery and endoscopy to safely remove the foreign body and then recovered well on a follow-up examination. For cases of fish bone ingestion, contrast-enhanced chest computed tomography is one of the most essential tools to assess vascular problems and associated mediastinal infections-risk factors for life-threatening and long-term recurrent inflammation. Reconstructing planes along the foreign body axis and changing windows when analyzing CT scans is necessary to avoid missing lesions and dilemmas.

Germinoma of basal ganglia.

Basal ganglia germinomas (BGGs) are rare lesions. Because of the atypical features of early-stage clinical symptoms and imaging characteristics, BGGs are easily misdiagnosed with non-tumorous conditions. This article presented cases of 2 young male patients who came to the hospital due to right arm weakness. Brain Magnetic Resonance Imaging (MRI) images in the first case revealed a lobulated mixed component mass on the left basal ganglia. The solid part showed restricted diffusion on diffusion-weighted imaging, heterogeneous strong enhancement, and no signal of calcification or bleeding. The second case in the left putamen showed hypointensity on T2*, mild enhancement, and atrophy of the ipsilateral cerebral peduncle, increased choline, and decreased n-acetyl-aspartate (NAA) on spectroscopy. Follow-up MRI after 6 months showed a mass increase in size and hypointensity part on T2*. BGGs have been confirmed on biopsy in both cases. With isolated chemotherapy application, there is no sign of remission in the first patient. The second patient was treated with chemotherapy and radiotherapy, and MRI images after treatment showed a complete response.

Factors in the Neonatal Period Associated With Pulmonary Hypertension at 28 Days of Life in Broncho-Pulmonary Dysplasia.

Objectives. To identify factors associated with pulmonary hypertension (PH) at 28 days of life in preterm infants with bronchopulmonary dysplasia (BPD). Methods. This observational study included 128 premature infants with BPD between January 2022 and February 2023 from the neonatal intensive care unit of Vietnam National Children's Hospital. Results. PH was observed using echocardiography in 29 patients (22.66%). The prevalence of severe BPD in the PH group (62.07%) was significantly higher than that in the non-PH group (18.18%). The multivariate logistic regression showed 2 predictors of PH in BPD: invasive mechanical ventilation up to 28 days of life (odds ratio [OR]:9.440; 95% confidence interval [CI]: 3.090-28.833; P < .001) and history of shock (OR: 2.962; 95% CI: 1.067-8.225; P = .037). Conclusion. We found 2 predictors of PH at 28 days of life in BPD: invasive mechanical ventilation up to 28 days of life and history of shock.

Cyclosporine A-induced systemic metabolic perturbations in rats: A comprehensive metabolome analysis.

A better understanding of cyclosporine A (CsA)-induced nephro- and hepatotoxicity at the molecular level is necessary for safe and effective use. Utilizing a sophisticated study design, this study explored metabolic alterations after long-term CsA treatment in vivo. Rats were exposed to CsA with 4, 10, and 25 mg/kg for 4 weeks and then sacrificed to obtain liver, kidney, urine, and serum for untargeted metabolomics analysis. Differential network analysis was conducted to explore the biological relevance of metabolites significantly altered by toxicity-induced disturbance. Dose-dependent toxicity was observed in all biospecimens. The toxic effects were characterized by alterations of metabolites related to energy metabolism and cellular membrane composition, which could lead to the cholestasis-induced accumulation of bile acids in the tissues. The unfavorable impacts were also demonstrated in the serum and urine. Intriguingly, phenylacetylglycine was increased in the kidney, urine, and serum treated with high doses versus controls. Differential correlation network analysis revealed the strong correlations of deoxycytidine and guanosine with other metabolites in the network, which highlighted the influence of repeated CsA exposure on DNA synthesis. Overall, prolonged CsA administration had system-level dose-dependent effects on the metabolome in treated rats, suggesting the need for careful usage and dose adjustment.

Metabolic phenotyping and global functional analysis facilitate metabolic signature discovery for tuberculosis treatment monitoring.

Tracking alterations in polar metabolite and lipid levels during anti-tuberculosis (TB) interventions is an emerging biomarker discovery and validation approach due to its sensitivity in capturing changes and reflecting on the host status. Here, we employed deep plasma metabolic phenotyping to explore the TB patient metabolome during three phases of treatment: at baseline, during intensive phase treatment, and upon treatment completion. Differential metabolites (DMs) in each period were determined, and the pathway-level biological alterations were explored by untargeted metabolomics-guided functional interpretations that bypassed identification. We identified 41 DMs and 39 pathways that changed during intensive phase completion. Notably, levels of certain amino acids including histidine, bile acids, and metabolites of purine metabolism were dramatically increased. The altered pathways included those involved in the metabolism of amino acids, glycerophospholipids, and purine. At the end of treatment, 44 DMs were discovered. The levels of glutamine, bile acids, and lysophosphatidylinositol significantly increased compared to baseline; the levels of carboxylates and hypotaurine declined. In addition, 37 pathways principally associated with the metabolism of amino acids, carbohydrates, and glycan altered at treatment completion. The potential of each DM for diagnosing TB was examined using a cohort consisting of TB patients, those with latent infections, and controls. Logistic regression revealed four biomarkers (taurine, methionine, glutamine, and acetyl-carnitine) that exhibited excellent performance in differential diagnosis. In conclusion, we identified metabolites that could serve as useful metabolic signatures for TB management and elucidated underlying biological processes affected by the crosstalk between host and TB pathogen during treatment.

Imaging features of shoulder tuberculosis with rice bodies formation: A case report.

Osteoarticular tuberculosis is less common than pulmonary tuberculosis and is often overlooked in the differential diagnosis of people with joint disease. In this article, we present a case of a 71-year-old female patient admitted to the hospital because of pain and limited movement of her right shoulder for a year. The patient had diabetes for 10 years, and no history of tuberculosis or previous history of tuberculosis exposure. Blood test results showed inflammatory condition and positive IGRA test. X-ray, ultrasound and magnetic resonance imaging images revealed osteolytic and sclerotic lesions of the humeral head, diffuse thickening of the synovial membrane, and loose bodies in the joint and bursa. The clinical diagnosis was tuberculous inflammatory osteoarthritis of the right shoulder. The patient underwent arthroscopy surgery to remove loose bodies and the inflamed portion of the synovium and send them to the pathology department. Histopathological examination of the loose bodies and synovial membrane revealed features suggestive of tuberculosis of the shoulder joint. Afterward, the patient was treated with antituberculosis drugs according to the guideline and rehabilitation exercises. After 3 months of treatment, the clinical symptoms were reduced, the pain rating was decreased and the range of motion was increased.

Push forward LC-MS-based therapeutic drug monitoring and pharmacometabolomics for anti-tuberculosis precision dosing and comprehensive clinical management.

The spread of tuberculosis (TB), especially multidrug-resistant TB and extensively drug-resistant TB, has strongly motivated the research and development of new anti-TB drugs. New strategies to facilitate drug combinations, including pharmacokinetics-guided dose optimization and toxicology studies of first- and second-line anti-TB drugs have also been introduced and recommended. Liquid chromatography-mass spectrometry (LC-MS) has arguably become the gold standard in the analysis of both endo- and exo-genous compounds. This technique has been applied successfully not only for therapeutic drug monitoring (TDM) but also for pharmacometabolomics analysis. TDM improves the effectiveness of treatment, reduces adverse drug reactions, and the likelihood of drug resistance development in TB patients by determining dosage regimens that produce concentrations within the therapeutic target window. Based on TDM, the dose would be optimized individually to achieve favorable outcomes. Pharmacometabolomics is essential in generating and validating hypotheses regarding the metabolism of anti-TB drugs, aiding in the discovery of potential biomarkers for TB diagnostics, treatment monitoring, and outcome evaluation. This article highlighted the current progresses in TDM of anti-TB drugs based on LC-MS bioassay in the last two decades. Besides, we discussed the advantages and disadvantages of this technique in practical use. The pressing need for non-invasive sampling approaches and stability studies of anti-TB drugs was highlighted. Lastly, we provided perspectives on the prospects of combining LC-MS-based TDM and pharmacometabolomics with other advanced strategies (pharmacometrics, drug and vaccine developments, machine learning/artificial intelligence, among others) to encapsulate in an all-inclusive approach to improve treatment outcomes of TB patients.

Impact of COVID-19 on patterns of drug utilization: A case study at national hospital.

BACKGROUND: The Coronavirus disease of 2019 (COVID-19) pandemic and the corresponding mitigation measures have had a discernible impact on drug utilization among outpatients. However, limited research exists on the prescription trends in the elderly population during the pandemic period in Viet Nam. OBJECTIVES: This study aims to analyze the effects of COVID-19 on outpatient drug utilization patterns at a national geriatric hospital in Ho Chi Minh City before and after the early onset of the pandemic. METHODS: Data was collected from the prescriptions and administration claims, encompassing the period from January 2016 to December 2022. The dataset was divided into two periods: Period 1: January 2016 to December 2020 and Period 2: January 2021 to December 2022. The drug utilization was measured using DDD/1000P (defined daily doses-DDD per 1000 prescriptions) on a monthly basis. The analysis employed interrupted time series using Autoregressive Integrated Moving Average (ARIMA) to detect changes in drug use levels and rates. RESULTS: A total of 1,060,507 and 644,944 outpatient prescriptions from Thong Nhat Hospital were included in Period 1 and Period 2, respectively. The median age of the patients were 58 in Period 1 and 67 years old in Period 2. The most common comorbidities were dyslipidemia, hypertension, and diabetes mellitus. In terms of medication utilization, cardiovascular drugs were the most frequently prescribed, followed by drugs active on the digestive and hormonal systems. The study observed significant surges in the number of prescriptions and the average number of drugs per prescription. However, there were no significant changes in the overall consumption of all drugs. Among the drug groups related to the cardiovascular system, three subgroups experienced a sudden and significant increase: cardiac therapy, beta-blocking agents, and antihypertensives, with increasing consumption levels of 1,177.73 [CI 95%: 79.29; 2,276.16], 73.32 [CI 95%: 28.18; 118.46], and 36.70 [CI 95%: 6.74; 66.66] DDD/1000P, respectively. On the other hand, there was a significant monthly decrease of -31.36 [CI 95%: -57.02; -5.70] DDD/1000P in the consumption of anti-inflammatory and antirheumatic products. Interestingly, there was a significant increase of 74.62 [CI 95%: -0.36; 149.60] DDD/1000P in the use of antigout preparations. CONCLUSION: COVID-19 resulted in a sudden, non-significant increase in overall drug consumption levels among outpatients. Notably, our findings highlight significant increases in the utilization of three drug groups related to the cardiovascular system, specifically cardiac therapy, beta-blocking agents, and antihypertensives. Intriguingly, there was a statistically significant increase in the consumption of antigout preparations, despite a decline in the monthly consumption rate of non-steroidal anti-flammatory drugs (NSAIDs). Further studies in the following years are necessary to provide a more comprehensive understanding of the impact of COVID-19 on outpatient drug utilization patterns.

Effect of metal dopants on the electrochromic performance of hydrothermally-prepared tungsten oxide materials.

Electrochromic (EC) glass has the potential to significantly improve energy efficiency in buildings by controlling the amount of light and heat that the building exchanges with its exterior. However, the development of EC materials is still hindered by key challenges such as slow switching time, low coloration efficiency, short cycling lifetime, and material degradation. Metal doping is a promising technique to enhance the performance of metal oxide-based EC materials, where adding a small amount of metal into the host material can lead to lattice distortion, a variation of oxygen vacancies, and a shorter ion transfer path during the insertion and de-insertion process. In this study, we investigated the effects of niobium, gadolinium, and erbium doping on tungsten oxide using a single-step solvothermal technique. Our results demonstrate that both insertion and de-insertion current density of a doped sample can be significantly enhanced by metal elements, with an improvement of about 5, 4 and 3.5 times for niobium, gadolinium and erbium doped tungsten oxide, respectively compared to a pure tungsten oxide sample. Moreover, the colouration efficiency increased by 16, 9 and 24% when doping with niobium, gadolinium and erbium, respectively. These findings suggest that metal doping is a promising technique for improving the performance of EC materials and can pave the way for the development of more efficient EC glass for building applications.

A Fluorescent Chemosensor for Detection pH and Cu2+ Ion Base on 7-((2-Aminoethyl)amino)-5-Bromo-6-Hydroxy-1-Methylquinolin-1-ium-3-Sulfonate: Experimental and DFT Calculation.

A quinoline derivative 7-((2-aminoethyl)amino)-5-bromo-6-hydroxy-1-methylquinolin-1-ium-3-sulfonate (QEt) containing quinoline ring, -[Formula: see text] sulfonate, -OH phenol, and amine groups was synthesized and studied luminescence properties. The aqueous solutions QEt 10µM change luminescence color from green (λem = 490 nm) to yellow (λem = 563 nm) as increasing pH and the intensity at a peak of 563 nm is linearly proportional with pH value in the range of pH = 3,0-4,0. The QEt solution can be used as a chemosensor for Cu2+ with an LOD value at 0.66 [Formula: see text]. Along with the experiment, the structure, absorption and emission spectra of QEt have been investigated by TD-DFT calculation. The result shows that the absorption band centered at 420 nm is due to the electron transition from HOMO to LUMO (π → π*). The results also help to assign emission band centered at 490 nm is due to the S1 → S0 transition (LUMO → HOMO singlet transition), at 563 nm is due to the T1 → S0 transition (LUMO → HOMO triplet transition). The dependence of the relative intensity of each emission peak on pH, which is experimentally recorded, is explained based on the results of theoretical TD-DFT calculation.

Alterations of lipid-related genes during anti-tuberculosis treatment: insights into host immune responses and potential transcriptional biomarkers.

Background: The optimal diagnosis and treatment of tuberculosis (TB) are challenging due to underdiagnosis and inadequate treatment monitoring. Lipid-related genes are crucial components of the host immune response in TB. However, their dynamic expression and potential usefulness for monitoring response to anti-TB treatment are unclear. Methodology: In the present study, we used a targeted, knowledge-based approach to investigate the expression of lipid-related genes during anti-TB treatment and their potential use as biomarkers of treatment response. Results and discussion: The expression levels of 10 genes (ARPC5, ACSL4, PLD4, LIPA, CHMP2B, RAB5A, GABARAPL2, PLA2G4A, MBOAT2, and MBOAT1) were significantly altered during standard anti-TB treatment. We evaluated the potential usefulness of this 10-lipid-gene signature for TB diagnosis and treatment monitoring in various clinical scenarios across multiple populations. We also compared this signature with other transcriptomic signatures. The 10-lipid-gene signature could distinguish patients with TB from those with latent tuberculosis infection and non-TB controls (area under the receiver operating characteristic curve > 0.7 for most cases); it could also be useful for monitoring response to anti-TB treatment. Although the performance of the new signature was not better than that of previous signatures (i.e., RISK6, Sambarey10, Long10), our results suggest the usefulness of metabolism-centric biomarkers. Conclusions: Lipid-related genes play significant roles in TB pathophysiology and host immune responses. Furthermore, transcriptomic signatures related to the immune response and lipid-related gene may be useful for TB diagnosis and treatment monitoring.

Evaluation of the impact before and after the application of an antimicrobial stewardship program at Dong Thap General Hospital, Vietnam, from 2017 to 2021.

Background: Vietnam has one of the highest rates of antibiotic resistance in Asia. In 2020, the Vietnam Minister of Health introduced new legislation for the implementation of an antimicrobial stewardship program (ASP). The evidence for the effectiveness of ASP in small hospitals and hospitals located in provinces was limited compared with larger-scale and central city hospitals. Aim: Evaluation of the impact before and after the introduction of an antimicrobial stewardship program at Dong Thap General Hospital, from 2017 to 2021. Methods: Retrospective data was collected from June 2017 to June 2021. The impact of the ASP on changes in antibiotic use and the clinical outcome associated with the implementation of the ASP was evaluated using autoregressive integrated moving average modelling of controlled interrupted time-series analysis. Results: There was a significant and sustained decrease in antibiotic consumption level (step change) in 2 indicators, DOT/1000PD (129.55; P<0.01) and LOT/1000PD (99.95, P<0.01), immediately after the ASP intervention. There were no statistically significant changes identified in terms of consumption with DDD/1000PD, or in the clinical outcomes. The results showed no statistically significant change in consumption trend (ramps) in all evaluated indicators. No statistically significant changes in consumption levels and trends were observed in the control group. Conclusion: The ASP implemented in Dong Thap General Hospital from 2017 to 2021 showed a considerable influence on antibiotic consumption as indicated by the DOT/1000 PD and LOT/1000 PD during the initial stages. Moreover, controlling antibiotic consumption did not negatively impact patient outcomes.

Prevalence of arterial hypertension in Vietnamese seafarers aboard merchant vessels: a cross-sectional study.

BACKGROUND: Hypertension is one of the leading causes of morbidity and mortality globally. It is a major risk factor for major cardiovascular events such as stroke, myocardial infarction, heart failure, kidney failure, and blindness. The aim of this research is to assess the prevalence and some factors related to arterial hypertension on Vietnamese seafarers aboard merchant vessels. MATERIALS AND METHODS: Seven hundred eight Vietnamese seafarers working aboard merchant ships were examined at the Institute of Marine Medicine before going to sea during the period from January 2022 to December 2022. It was a cross-sectional descriptive epidemiological study. The following parameters were measured: blood pressure, height, weight, waist circumference, buttock circumference to assess the prevalence of hypertension, overweight, and obesity. Seafarers we directly interviewed about workplace on ships and physical exercise, smoking tobacco, alcohol abuse, and anxiety symptoms to identify several factors associated with hypertension. RESULTS: The prevalence of hypertension in seafarers was 32.9%, prehypertension 26.4%, overweight 32.4%, obesity 13.3%, abdominal obesity 47.7%. Factors related to hypertension of seafarers included: job duration at sea > 10 years, odds ratio (OR) = 8.23 (95% confidence interval [CI] 4.34-17.27); non-officers, OR = 2.11 (95% CI 1.45-2.82); engine room crew, OR = 2.11 (95% CI 1.45-3.58); obesity, OR = 3.34 (95% CI 2.15-5.63); abdominal obesity, OR = 9.12 (95% CI 4.23-18.45); current smoking, OR = 1.32 (95% CI 1.02-1.99); irregular exercise, OR =1.43 (95% CI 1.03-2.18); anxiety symptoms, OR = 1.56 (95% CI 1.08-2.27). CONCLUSIONS: Hypertension is a health problem for Vietnamese seafarers. To minimise hypertension, seafarers need to adjust their lifestyle, increase regular exercise and improve psychological issues on board.

Strongyloides stercoralis infection reduces Fusicatenibacter and Anaerostipes in the gut and increases bacterial amino-acid metabolism in early-stage chronic kidney disease.

Understanding gut bacterial composition and proteome changes in patients with early-stage chronic kidney disease (CKD) could lead to better methods of controlling the disease progression. Here, we investigated the gut microbiome and microbial functions in patients with S. stercoralis infection (strongyloidiasis) and early-stage CKD. Thirty-five patients with early stages (1-3) of CKD were placed in two groups matched for population characteristics and biochemical parameters, 12 patients with strongyloidiasis in one group and 23 uninfected patients in the other. From every individual, a sample of their feces was obtained and processed for 16S rRNA sequencing and metaproteomic analysis using tandem liquid chromatography-mass spectrometry (LC-MS/MS). Strongyloides stercoralis infection per se did not significantly alter gut microbial diversity. However, certain genera (Bacteroides, Faecalibacterium, Fusicatenibacter, Sarcina, and Anaerostipes) were significantly more abundant in infection-free CKD patients than in infected individuals. The genera Peptoclostridium and Catenibacterium were enriched in infected patients. Among the significantly altered genera, Fusicatenibacter and Anaerostipes were the most correlated with renal parameters. The relative abundance of members of the genus Fusicatenibacter was moderately positively correlated with estimated glomerular filtration rate (eGFR) (r = 0.335, p = 0.049) and negatively with serum creatinine (r = -0.35, p = 0.039). Anaerostipes, on the other hand, showed a near-significant positive correlation with eGFR (r = 0.296, p = 0.084). Individuals with S. stercoralis infection had higher levels of bacterial proteins involved in amino-acid metabolism. Analysis using STITCH predicted that bacterial amino-acid metabolism may also be involved in the production of colon-derived uremic toxin (indole), a toxic substance known to promote CKD. Strongyloides stercoralis infection is, therefore, associated with reduced abundance of Fusicatenibacter and Anaerostipes (two genera possibly beneficial for kidney function) and with increased bacterial amino-acid metabolism in the early-stages of CKD, potentially producing uremic toxin. This study provides useful information for prevention of progression of CKD beyond the early stages.

Optimal forest management for carbon sequestration, timber, and bioenergy production in Vietnam using an extended full-cycle carbon accounting method.

Using an extended full-cycle carbon model from the Faustmann framework, which allows for management strategies of several uses concurrently implemented in the same area of forest, this paper investigates the selection of management objectives that are beneficial and optimal for forest plantations in Vietnam. Three scenarios are considered: Scenario 1 investigates the management objective of maximizing the land economic value (LEV) of timber as a single production. Scenario 2 investigates the joint production of timber and bioenergy sources. Scenario 3 analyzes the joint production of timber, bioenergy production, and carbon sequestration. The findings reveal that if growers pursue a timber management objective (Scenario 1), the farming business only provides considerable benefits under the government-subsidized credit scheme of 8.4%. For a higher non-subsidized interest rate of 15.24% of commercial banks, such gains reduce substantially and become negative value under the mean interest rate of 19.08% of private credit sources. Altering the management objective to a joint production of timber and raw bioenergy production (Scenario 2) will boost the LEV by a moderate level, but at the expense of timber production and thus carbon stock. However, the reduction tendency of timber and carbon balance is not substantial due mainly to the relatively small proportion of bioenergy production compared to timber production; therefore, decision-making frameworks targeting carbon uptake may be capable of incorporating such levels of confliction. Further internalizing the carbon value of the forest into management objectives generally leads to a longer rotation length, thus improving both carbon sequestration and income gains. Shifting the current timber-dominant management objective to a joint production of timber and bioenergy sources, or, alternatively, a joint production of timber, bioenergy production, and carbon sequestration when the carbon market is emerging, is a good alternative strategy for forest management in Vietnam.

Pathway-level multi-omics analysis of the molecular mechanisms underlying the toxicity of long-term tacrolimus exposure.

Tacrolimus (TAC)-based treatment is associated with nephrotoxicity and hepatotoxicity; however, the underlying molecular mechanisms responsible for this toxicity have not been fully explored. This study elucidated the molecular processes underlying the toxic effects of TAC using an integrative omics approach. Rats were sacrificed after 4 weeks of daily oral TAC administration at a dose of 5 mg/kg. The liver and kidney underwent genome-wide gene expression profiling and untargeted metabolomics assays. Molecular alterations were identified using individual data profiling modalities and further characterized by pathway-level transcriptomics-metabolomics integration analysis. Metabolic disturbances were mainly related to an imbalance in oxidant-antioxidant status, as well as in lipid and amino acid metabolism in the liver and kidney. Gene expression profiles also indicated profound molecular alterations, including in genes associated with a dysregulated immune response, proinflammatory signals, and programmed cell death in the liver and kidney. Joint-pathway analysis indicated that the toxicity of TAC was associated with DNA synthesis disruption, oxidative stress, and cell membrane permeabilization, as well as lipid and glucose metabolism. In conclusion, our pathway-level integration of transcriptome and metabolome and conventional analyses of individual omics profiles, provided a more comprehensive picture of the molecular changes resulting from TAC toxicity. This study also serves as a valuable resource for subsequent investigations aiming to understand the mechanism underlying the molecular toxicology of TAC.

Untargeted Metabolomics Approach for the Differentiation between Panax vietnamensis var. vietnamensis and Panax vietnamensis var. fuscidiscus.

Panax vietnamensis var. vietnamensis (PVV) and Panax vietnamensis var. fuscidiscus (PVF) both belong to Panax vietnamensis species and are chemically and morphologically similar, making it hard to distinguish for the consumer. Herein, 42 PVF and 12 PVV samples were collected in Quang Nam and Lai Chau Province, respectively, and subsequently characterized by ITSr-DNA sequence data to verify their origins. Next, untargeted metabolomics combined with multivariate statistical analysis was developed to differentiate PVV and PVF. The metabolic profiles of PVV and PVF were found to be distinct and classified well using Partial Least-Squares Discriminant Analysis (PLS-DA) in the training set. Among them, seven ginsenosides were of high abundance in PVV, while six were of high abundance in PVF. Next, the test set was used to validate 13 putative differential markers found in the training set, illustrating a complete match with the expression patterns of these ginsenosides in the training set. Finally, PLS-DA and linear Support Vector Machine models both indicated distinct ginsenoside profiles of PVV and PVF without misclassification in the test set. Conclusively, the developed untargeted metabolomics approach might serve as a powerful tool for the authentication of PVV and PVF at the metabolome level.

Lipid class-dependent alterations of Caenorhabditis elegans under harmane exposure.

Altered lipid patterns in Caenorhabditis elegans (C. elegans) resulting from exposure to harmane remain to be explored. In this study, untargeted lipidomics was carried out to elucidate the effects of acute exposure to harmane on the lipidome of C. elegans. Exposure to the compound was evaluated based on the reproduction ability of the worms at 0.1 and 1 µg/mL. No significant effects of harmane were observed at these concentrations. Furthermore, we found that the modulatory effects of harmane on the lipidome of C. elegans at 1 µg/mL were lipid class dependent. In particular, harmane-treated worms were enriched in triglycerides and fatty acids, regardless of the degree of saturation. Glycerophospholipids were generally down-regulated. Furthermore, functional analyses suggested that there was a reduction in lipid membrane bilayer-related terms, and in some related to the mitochondria, and endoplasmic reticulum of C. elegans when treated with harmane. Lipid droplets and storage appeared to be up-regulated. In conclusion, our findings suggest that harmane exposure affects the lipidome of C. elegans in a sophisticated manner. Further investigations are required to elucidate the molecular mechanisms underlying these lipid pattern changes.