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Mei-Jung Lin

Publications and source records attributed to Mei-Jung Lin.

7 recordsLinked to original sources
PubMed2025

Hepatocyte-specific CLSTN3B ablation impairs lipid droplet maturation and alleviates diet-induced steatohepatitis in mice.

Excessive lipid accumulation in hepatocytes, a hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD), can lead to progressive liver damage. Understanding the molecular mechanisms governing lipid storage in hepatocytes is essential for identifying therapeutic targets to halt MASLD progression. Here, we show a pivotal role for the protein calsyntenin 3β (CLSTN3B) in promoting lipid droplet (LD) maturation and lipid storage in hepatocytes. Previously characterized as an endoplasmic reticulum (ER)-LD contact protein that facilitates LD maturation in adipocytes, we now show that CLSTN3B expression is strongly induced in mouse hepatocytes by peroxisome proliferator-activated receptor gamma (PPARγ) in response to dietary caloric excess. Hepatocyte-specific deletion of CLSTN3B in mice significantly increases energy expenditure, reduces metabolic efficiency, and protects against diet-induced hepatic steatosis and fibrosis. Mechanistically, CLSTN3B deficiency causes reduced LD phospholipid coverage and increased lipase recruitment. This results in enhanced fatty acid oxidation driven by a futile cycle of lipolysis and re-esterification. Notably, human clinical data reveal a positive correlation between hepatic CLSTN3B expression and MASLD severity and progression, emphasizing its relevance to human disease. Together, our findings establish CLSTN3B as a key regulator of hepatocyte lipid storage and metabolic efficiency and highlight its potential as a therapeutic target in MASLD.

Journal Article↗
PubMed2004

Combinatorial synthesis of biheterocyclic benzimidazoles by microwave irradiation.

Liquid phasel synthesis of biheterocyclic benzimidazoles by controlled microwave irradiation was investigated. Polymer immobilized o-phenylenediamines was synthesized under microwave irradiation. The resulting PEG bound diamines was N-acylated with 4-fluoro-3-nitrobenzoic acid selectively in primary aromatic amino moiety. Nucleophilic aromatic substitution of amide was performed with various amines then cyclized to form the first benzimidazole scaffold in acidic condition. Successive reduction, cyclization with isothiocyanates yielded 5-(benzimidazol-2-yl)benzimidazoles. The desired products were released from the polymer support to afford the tri-substituted bis-benzimidazoles in good yields and purity.

Acylation↗
PubMed2003

Microwave-enhanced liquid-phase synthesis of thiohydantoins and thioxotetrahydropyrimidinones.

An efficient, microwave-assisted method for the liquid-phase combinatorial synthesis of 3,5-disubstituted thiohydantoins and 3,5-disubstituted 2-thioxotetrahydropyrimidin-4-ones has been developed. In synthesizing thiohydantoins, Fmoc-protected amino acids were coupled with polymer support and then deprotected to give primary amines. While in synthesizing thioxotetrahydropyrimidinones, 3-chloropropionyl chloride was immobilized to the support and subsequently reacted with various amines to form secondary amines. The PEG bound primary/secondary amines then were incorporated with various isothiocyanates to give thiourea intermediates and concomitant cyclization/cleavage steps occurred under mild basic condition. The desired products were then liberated from the soluble matrix in good yield and purity. All reactions described here were performed under microwave irradiation.

Amines↗
PubMed2003

Microwave-assisted polymer-supported combinatorial synthesis.

Lead identification and optimization is always a challenge to the medicinal chemists in drug discovery. Numbers of simple to complex and smaller to bigger organic compounds are prepared to meet the screening purpose of biological targets. Conventional solution phase synthetic methodologies are lacking the speed to run along with the need of medicinally interesting compounds due to their long reaction time, tedious work-up and purification problems. Alternatively opted polymer-supported synthesis of combinatorial libraries has been emerged as a promising tool in generating large numbers of structurally diverse molecules in a manner rapid and parallel. Microwave-assisted solid/liquid phase combinatorial synthetic techniques have been proved efficient in reducing the reaction time from days & hours to minutes & seconds and more promisingly to produce improved yields with high purities. This review briefs about the theory behind microwave chemical technology and glimpses of recent advancements in its application on polymer supported combinatorial synthesis.

Combinatorial Chemistry Techniques↗
PubMed2003

Traceless liquid phase synthesis of piperazinediones.

Liquid phase combinatorial synthesis (LPCS) of piperazinediones by the use of soluble polymer support is explored to generate libraries. Proline anchored polyethylene glycol monomethyl ether (PEG) underwent dipeptide formation with different Fmoc-amino acids in the presence of dicyclohexyl carbodiimide (DCC). Deprotection of Fmoc accompanied with the cleavage from polymer support with cyclization of dipeptide to piperazinediones offers a facile and effective way to prepare diverse combinatorial libraries. Excellent yields and purities were achieved by simple wash and precipitation method.

Amino Acids↗
PubMed2003

Advances in angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs).

Hypertension remains one of the most unmet medical needs of this century. While many drugs are available for treating hypertension, efforts are still insufficient to find potent therapeutic agents since cause for hypertension in all patients is not the same. Angiotensin-converting enzyme inhibitors (ACEIs) have emerged as an important class of drugs in the treatment of hypertension, congestive heart failure (CHF), protenuric renal disease, myocardial infarction and stroke. This class of drugs blocks the conversion of angiotensin I to angiotensin II and prevents bradykinin breakdown. However, the lack of specificity of ACEIs leads to the frequent side effects like cough and angio-oedema. Recently developed, specific non-peptide and orally active angiotensin receptor blockers (ARBs) have become the prime therapeutics as they alone or co-administration with ACE inhibitors can control the renin angiotensin disorders. This review explores recent developments in the design, synthesis, and structural modifications of ACE inhibitors as well as angiotensin receptor blockers.

Angiotensin Receptor Antagonists↗