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 RET gene point mutation is the main molecular alteration involved in medullary thyroid carcinoma (MTC) tumorigenesis. Previous studies in Vietnam mainly consisted of case reports, with limited data on larger sample sizes. In this study, we investigated RET gene mutations in exons 10, 11, and 16 and analyzed clinicopathological features of a series of Vietnamese MTC patients. Methods: We collected 33 tissue samples from patients with MTC and analyzed RET mutations using the Sanger sequencing method. The relationship between hotspot RET mutations (exons 10, 11, 16) and clinicopathological features were investigated. Results: Among the 33 analyzed cases, 17 tumors (52%) harbored RET mutations in exon 10, 11, or 16. A total of 10 distinct genetic alterations were identified, including eight missense mutations and two short indels. Of these, seven were classified as pathogenic mutations based on previous publications, with p.M918T being the most frequent (4 cases), followed by p.C634R (3 cases) and p.C618R (3 cases). Mutations were significantly associated with specific histological patterns, such as the nested/insular pattern (p=.026), giant cells (p=.007), nuclear pleomorphism (p=.018), stippled chromatin (p=.044), and amyloid deposits (p=.024). No mutations were found in germline analyses, suggesting these were somatic alterations. Conclusions: Our results provided the first comprehensive analysis of RET mutations in Vietnamese MTC patients. The most frequent mutation was p.M918T, followed by p.C634R and p.C618R. Mutations in these three exons were linked to specific histopathological features. Information on mutational profiles of patients with MTC will further aid in the development of targeted therapeutics to ensure effective disease management.

The RET gene point mutation is the main molecular alteration involved in medullary thyroid carcinoma (MTC) tumorigenesis. Previous studies in Vietnam mainly consisted of case reports, with limited data on larger sample sizes. In this study, we investigated RET gene mutations in exons 10, 11, and 16 and analyzed clinicopathological features of a series of Vietnamese MTC patients. Methods: We collected 33 tissue samples from patients with MTC and analyzed RET mutations using the Sanger sequencing method. The relationship between hotspot RET mutations (exons 10, 11, 16) and clinicopathological features were investigated. Results: Among the 33 analyzed cases, 17 tumors (52%) harbored RET mutations in exon 10, 11, or 16. A total of 10 distinct genetic alterations were identified, including eight missense mutations and two short indels. Of these, seven were classified as pathogenic mutations based on previous publications, with p.M918T being the most frequent (4 cases), followed by p.C634R (3 cases) and p.C618R (3 cases). Mutations were significantly associated with specific histological patterns, such as the nested/insular pattern (p=.026), giant cells (p=.007), nuclear pleomorphism (p=.018), stippled chromatin (p=.044), and amyloid deposits (p=.024). No mutations were found in germline analyses, suggesting these were somatic alterations. Conclusions: Our results provided the first comprehensive analysis of RET mutations in Vietnamese MTC patients. The most frequent mutation was p.M918T, followed by p.C634R and p.C618R. Mutations in these three exons were linked to specific histopathological features. Information on mutational profiles of patients with MTC will further aid in the development of targeted therapeutics to ensure effective disease management.

The RET gene point mutation is the main molecular alteration involved in medullary thyroid carcinoma (MTC) tumorigenesis. Previous studies in Vietnam mainly consisted of case reports, with limited data on larger sample sizes. In this study, we investigated RET gene mutations in exons 10, 11, and 16 and analyzed clinicopathological features of a series of Vietnamese MTC patients. Methods: We collected 33 tissue samples from patients with MTC and analyzed RET mutations using the Sanger sequencing method. The relationship between hotspot RET mutations (exons 10, 11, 16) and clinicopathological features were investigated. Results: Among the 33 analyzed cases, 17 tumors (52%) harbored RET mutations in exon 10, 11, or 16. A total of 10 distinct genetic alterations were identified, including eight missense mutations and two short indels. Of these, seven were classified as pathogenic mutations based on previous publications, with p.M918T being the most frequent (4 cases), followed by p.C634R (3 cases) and p.C618R (3 cases). Mutations were significantly associated with specific histological patterns, such as the nested/insular pattern (p=.026), giant cells (p=.007), nuclear pleomorphism (p=.018), stippled chromatin (p=.044), and amyloid deposits (p=.024). No mutations were found in germline analyses, suggesting these were somatic alterations. Conclusions: Our results provided the first comprehensive analysis of RET mutations in Vietnamese MTC patients. The most frequent mutation was p.M918T, followed by p.C634R and p.C618R. Mutations in these three exons were linked to specific histopathological features. Information on mutational profiles of patients with MTC will further aid in the development of targeted therapeutics to ensure effective disease 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.

Curcuma zedoaria (Christm.) Rosc. is a popular traditional herb to treat digestive disorders in Asian tropical countries. Previous studies indicated the presence of sesquiterpenoids, diterpenoids, and curcuminoids with various bioactivities. To enrich the phytocomposition data of this plant, this investigation was conducted.The dried rhizomes of C. zedoaria were collected in Hai Phong City (Vietnam), extracted with methanol and fractionated with n-hexane, CH2Cl2 , and EtOAc. Compounds were isolated from n-hexane soluble fraction by open column chromatography combined with thin layer chromatography from fraction n-hexane. Their chemical structures were elucidated by 1D, and 2D NMR spectra and comparison with reported data. As a result, a phytochemical investigation was conducted to isolate six sesquiterpenes from C. zedoaria. Their chemical structures were elucidated to be curcumenol (1), procurcumenol (2), neoprocurcumenol (3), 13-hydroxygermacrone (4), zederone (5), and curcumalactone (6). Among isolated compounds, compounds 1, 2, 4, and 5 were reported from C. zedoaria. Meanwhile, neoprocurcumenol (3) and curcumalactone (6) are isolated from this species for the first time. Compound 5 exhibited a mild inhibitory effect on α-glucosidase with an IC50 of 99.45 ± 0.50 μg/mL.

A new crinane-type alkaloid, 6-epihydroxypowelline (1), together with six known alkaloids, lycorine (2), 2-O-acetyllycorine (3), deacetylbowdensine (4), 1-epideacetylbowdensine (5), 8-demethyl-3-oxomaritidine (6), and (-)-marithamine (7) were isolated from the whole parts of the Crinum latifolium L. in Vietnam. The structure identification of all compounds was determined by 1D, 2D-NMR as well as HR-ESI-MS spectroscopic techniques. The absolute configuration of these compounds was established by the ECD data. In addition, in vitro inhibition of acetylcholinesterase (AChE) activities was assessed for all isolated alkaloids. All alkaloids had AChE inhibitory effects, with IC50 values ranging from 32.65 ± 2.72 to 212.76 ± 8.30 µM and compound 3 displayed the strongest inhibition of AChE, with IC50 values of 32.65 ± 2.72 µM (in comparison to the reference drug, galanthamine, which had an IC50 of 2.40 ± 0.45 µM).

Curcuma zedoaria (Christm.) Rosc. is a popular traditional herb to treat digestive disorders in Asian tropical countries. Previous studies indicated the presence of sesquiterpenoids, diterpenoids, and curcuminoids with various bioactivities. To enrich the phytocomposition data of this plant, this investigation was conducted.The dried rhizomes of C. zedoaria were collected in Hai Phong City (Vietnam), extracted with methanol and fractionated with n-hexane, CH2Cl2 , and EtOAc. Compounds were isolated from n-hexane soluble fraction by open column chromatography combined with thin layer chromatography from fraction n-hexane. Their chemical structures were elucidated by 1D, and 2D NMR spectra and comparison with reported data. As a result, a phytochemical investigation was conducted to isolate six sesquiterpenes from C. zedoaria. Their chemical structures were elucidated to be curcumenol (1), procurcumenol (2), neoprocurcumenol (3), 13-hydroxygermacrone (4), zederone (5), and curcumalactone (6). Among isolated compounds, compounds 1, 2, 4, and 5 were reported from C. zedoaria. Meanwhile, neoprocurcumenol (3) and curcumalactone (6) are isolated from this species for the first time. Compound 5 exhibited a mild inhibitory effect on α-glucosidase with an IC50 of 99.45 ± 0.50 μg/mL.

A new crinane-type alkaloid, 6-epihydroxypowelline (1), together with six known alkaloids, lycorine (2), 2-O-acetyllycorine (3), deacetylbowdensine (4), 1-epideacetylbowdensine (5), 8-demethyl-3-oxomaritidine (6), and (-)-marithamine (7) were isolated from the whole parts of the Crinum latifolium L. in Vietnam. The structure identification of all compounds was determined by 1D, 2D-NMR as well as HR-ESI-MS spectroscopic techniques. The absolute configuration of these compounds was established by the ECD data. In addition, in vitro inhibition of acetylcholinesterase (AChE) activities was assessed for all isolated alkaloids. All alkaloids had AChE inhibitory effects, with IC50 values ranging from 32.65 ± 2.72 to 212.76 ± 8.30 µM and compound 3 displayed the strongest inhibition of AChE, with IC50 values of 32.65 ± 2.72 µM (in comparison to the reference drug, galanthamine, which had an IC50 of 2.40 ± 0.45 µM).

Curcuma zedoaria (Christm.) Rosc. is a popular traditional herb to treat digestive disorders in Asian tropical countries. Previous studies indicated the presence of sesquiterpenoids, diterpenoids, and curcuminoids with various bioactivities. To enrich the phytocomposition data of this plant, this investigation was conducted.The dried rhizomes of C. zedoaria were collected in Hai Phong City (Vietnam), extracted with methanol and fractionated with n-hexane, CH2Cl2 , and EtOAc. Compounds were isolated from n-hexane soluble fraction by open column chromatography combined with thin layer chromatography from fraction n-hexane. Their chemical structures were elucidated by 1D, and 2D NMR spectra and comparison with reported data. As a result, a phytochemical investigation was conducted to isolate six sesquiterpenes from C. zedoaria. Their chemical structures were elucidated to be curcumenol (1), procurcumenol (2), neoprocurcumenol (3), 13-hydroxygermacrone (4), zederone (5), and curcumalactone (6). Among isolated compounds, compounds 1, 2, 4, and 5 were reported from C. zedoaria. Meanwhile, neoprocurcumenol (3) and curcumalactone (6) are isolated from this species for the first time. Compound 5 exhibited a mild inhibitory effect on α-glucosidase with an IC50 of 99.45 ± 0.50 μg/mL.