Lysosomal diseases (LDs) are a group of rare inherited disorders belonging to inborn metabolism errors. LDs are characterized by the excessive storage of undegraded substrates, most often due to the enzymatic deficiency resulting from disease-causing gene variants. LDs lead to dysregulated cellular pathways and imbalanced molecular homeostasis and can affect multiple organs and tissues. Despite being rare, LDs account for a significant incidence when considered collectively. Due to complex molecular and genetic fingerprints, considerable challenges in LD management must be overcome. Diagnosis can be significantly delayed due to the broad and nonspecific clinical manifestations and the lack of specific biomarkers. Available treatments fail to fully stop the disease progression and can alter the disease's typical phenotypes with novel manifestations. Therefore, a paradigm shift is crucial to better understand LDs and provide actionable insights. Herein, we comprehensively review the literature to demonstrate that multi-omics approaches are promising for pathophysiology elucidation, biomarker discovery, and precision therapy in LDs. We recommend adopting longitudinal study designs integrated with a multi-omics-empowered framework to facilitate mechanistic delineation, biomarker discovery, and treatment development. Relevant approaches exploring the association between LDs and common neurodegenerative disorders are also discussed, paving a potential path for improved therapeutic development and ultimately improving the patient's quality of life.

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.

In this study, twenty-five yeast strains were isolated from soil samples collected in the gold mining ore in Gia Lai, Vietnam. Among them, one isolate named GL1 T could highly tolerate Cu 2+ up to 10 mM, and the isolates could also grow in a wide range of pH (3–7), and tem perature (10–40 ℃). Dried biomass of GL1 was able to remove Cu 2+ effectively up to 90.49% with a maximal biosorption capacity of 18.1 mg/g at pH 6, temperature 30 ℃, and incuba tion time 60 min. Sequence analysis of rDNA indicated this strain was closely related to Rhodotorula mucilaginosa but with 1.53 and 3.46% nucleotide differences in the D1/D2 domain of the 28S rRNA gene and the ITS1-5.8S rRNA gene-ITS2 region sequence, respect ively. Based on phylogenetic tree analysis and the biochemical characteristics, the strain appears to be a novel Rhodotorula species, and the name Rhodotorula aurum sp. nov. is pro posed. This study provides us with more information about heavy metal-tolerant yeasts and it may produce a new tool for environmental control and metal recovery operations.

Objective: To examine the in vitro and in vivo anti-inflammatory effects of the alkaloid enriched extract (ELA) from the roots of Eurycoma longifolia. Methods: The in vitro antiinflammatory effects of ELA were evaluated by examining its inhibitory activities against nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) expressions in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The level of NO produced in the culture media was determined by Griess method. The iNOS and COX-2 protein expressions were analyzed by Western blot. The in vivo effect of ELA was evaluated on LPS-induced septic shock in mice model. Mice mortality was monitored for 5 days after injection of LPS. The chemical contents of the ELA were determined by using various chromatographic and spectroscopic techniques. Results: The ELA was found to exhibit a significant anti-inflammatory effect in both in vitro and in vivo models. The results demonstrated that ELA dose-dependently inhibited LPS-induced NO production as well as the protein iNOS and COX-2 expressions. In the septic shock model, ELA dose-dependently protected mice from LPS-induced mortality. Further study on the isolated components of ELA indicated that 9,10-dimethoxycanthin-6-one may contribute significantly to the anti-inflammatory effects of the extract. Conclusions: These results suggest that ELA exhibits the anti-inflammatory activity via suppression of pro-inflammatory mediators such as NO, iNOS, and COX-2 and protects mice from LPS-induced mortality in septic shock model.