Past, Present, and Future of Liver-Brain Axis in Alzheimer's Disease: A Bibliometric Review.

Background: No effective drugs currently exist to cure Alzheimer's disease (AD) due to its complexity and the lack of understanding of the involved molecular signaling and pathways. The relationship between liver health and AD is now widely recognized. Still, molecular links and shared pathways between the liver and brain remain unclear, making the liver-brain axis in AD therapies a new area for exploration. However, bibliometric studies on this topic are lacking. Objective: This study aims to review the liver-brain axis in AD and identify future research hotspots and trends through bibliometric analysis. Methods: Articles and reviews related to AD and liver and its related diseases were searched in the Web of Science Core Collection (WoSCC) database up to 2024. Data were processed and visually analyzed using VOSviewer, CiteSpace, and Pajek. Results: We collected 1,777 articles on AD and liver and its related diseases from 2,517 institutions across 80 countries. Keyword cluster analysis identified 11 clusters, with 'insulin resistance,' 'amyloid-beta,' 'apolipoprotein-E,' 'oxidative stress,' and 'inflammation' appearing most frequently, and exhibiting strong total link strength. These results indicate that these topics have been the primary focus of research on the liver-brain axis in AD. Conclusions: This study is the first to comprehensively analyze the liver-brain axis in AD using bibliometric methods. The research results identify recent research frontiers and hotspots, aiding scholars in gaining a deeper understanding of the correlation between AD and the liver.

Meroterpenoids from Marine Sponge Hyrtios sp. and Their Anticancer Activity against Human Colorectal Cancer Cells.

Two new meroterpenoids, hyrtamide A (1) and hyrfarnediol A (2), along with two known ones, 3-farnesyl-4-hydroxybenzoic acid methyl ester (3) and dictyoceratin C (4), were isolated from a South China Sea sponge Hyrtios sp. Their structures were elucidated by NMR and MS data. Compounds 2-4 exhibited weak cytotoxicity against human colorectal cancer cells (HCT-116), showing IC50 values of 41.6, 45.0, and 37.3 µM, respectively. Furthermore, compounds 3 and 4 significantly suppressed the invasion of HCT-116 cells while also downregulating the expression of vascular endothelial growth factor receptor 1 (VEGFR-1) and vimentin proteins, which are key markers associated with angiogenesis and epithelial-mesenchymal transition (EMT). Our findings suggest that compounds 3 and 4 may exert their anti-invasive effects on tumor cells by inhibiting the expression of VEGFR-1 and impeding the process of EMT.

Palladium- and Brønsted acid-catalyzed enantio-, site- and E/Z-selective addition of alkylidenecyclopropanes with imines.

Transition-metal catalyzed functionalization of ACPs has been widely investigated in cycloaddition and 1,3-difunctionalization reactions. However, the transition metal catalyzed nucleophilic reactions of ACPs have rarely been reported. In this article, an enantio-, site- and E/Z-selective addition of ACPs with imines for the synthesis of dienyl substituted amines has been developed via palladium- and Brønsted acid co-catalysis. A range of synthetically valuable dienyl substituted amines were effectively prepared with good to excellent yields and excellent enantio- and E/Z-selectivities.

Palladium-Catalyzed Nucleophilic Reaction of Alkylidenecyclopropanes with ß,γ-Unsaturated α-Ketoesters: Ligand-Controlled Divergent Synthesis.

A palladium-catalyzed ligand-controlled selective 1,4-addition and cycloaddition reaction of ß,γ-unsaturated α-ketoesters with alkylidenecyclopropanes (ACPs) has been developed. Using ACPs and ß,γ-unsaturated α-ketoesters as starting materials, γ-dienyl-α-ketoesters and dihydro-2H-pyrans could be prepared selectively by modulating the ligand. A range of multisubstituted α-ketoesters and dihydro-2H-pyrans were obtained in moderate to excellent yields with excellent regioselectivities.

Copper catalyzed borocarbonylation of benzylidenecyclopropanes through selective proximal C-C bond cleavage: synthesis of γ-boryl-γ,δ-unsaturated carbonyl compounds.

A copper catalyzed borocarbonylation of BCPs via proximal C-C bond cleavage for the synthesis of γ-boryl-γ,δ-unsaturated carbonyl compounds has been developed. Using substituted benzylidenecyclopropanes (BCPs) and chloroformates as starting material, a broad range of γ-boryl-γ,δ-unsaturated esters were prepared in moderate to excellent yields with excellent regio- and stereoselectivity. Besides, when aliphatic acid chlorides were used in this reaction, γ-boryl-γ,δ-unsaturated ketones could be produced in excellent yields. When substituted BCPs were used as substrates, the borocarbonylation occurred predominantly at the proximal C-C bond trans to the phenyl group in a regio- and stereoselective manner, which leads to the Z-isomers as the products. This efficient methodology involves the cleavage of a C-C bond and the formation of a C-C bond as well as a C-B bond, and provides a new method for the proximal C-C bond difunctionalization of BCPs.

Palladium Catalyzed Dicarbonylation of α-Iodo-Substituted Alkylidenecyclopropanes: Synthesis of Carbamoyl Substituted Indenones.

A palladium catalyzed dicarbonylation of α-iodo-substituted ACPs for the synthesis of carbamoyl substituted indenones has been developed. Two carbonyl groups were incorporated into the product with the cleavage of the proximal C-C bond of the ACPs. A broad range of carbamoyl substituted indenones were efficiently prepared in good to excellent yields.

New Bioactive Polyacetylenes from the Marine Sponge Petrosia sp.

Three new polyacetylenes, pellynols P (1), Q (2), and R (3) were isolated from the marine sponge Petrosia sp., along with the known compound pellynol H (4). Their structures were determined by analyses of extensive NMR, HR-MS, and ESI-MS/MS data. All compounds displayed potent cytotoxicities against human hepatocellular carcinoma HepG2, human melanoma A375, and human colorectal carcinoma HT29 cell lines with IC50 values at the range of 1.4-4.4 µM.

Copper-catalyzed 1,2-Borylacylation of 1,3-Enynes: synthesis of ß-Alkynyl ketones.

A copper catalyzed 1,2-borylacylation of 1,3-enynes with B2pin2 and acid chlorides has been developed. Using readily available 1,3-enynes, B2pin2 and acid chlorides as substrates, a range of highly functionalized α,α-disubstituted ß-alkynyl ketones were readily prepared under mild conditions in moderate to good yields. The borylacylated products can be easily derivatized to give several valuable structures. Notably, treatment of the products with NaBO3·4H2O provided 1,2-allenyl ketones, which is proposed to proceed via a retro-aldol process of the corresponding homopropargyl alcohols.

Palladium-Catalyzed Carbonylative Sonogashira/Annulation Reaction: Synthesis of Indolo[1,2-b]isoquinolines.

A palladium-catalyzed carbonylative Sonogashira/annulation reaction for the synthesis of indolo[1,2-b]isoquinolines has been developed. Tetracyclic 6/5/6/6 indoline skeletons were synthesized in moderate to good yields from easily available 2-bromo-N-(2-iodophenyl)benzamides and terminal alkynes. Notably, this efficient methodology established three C-C bonds and a C-N bond through a one-step transformation and provided a new method for the synthesis of indolo[1,2-b]isoquinoline derivatives.

Unprecedented Multicomponent Reaction of Indoles, CS2 and Nitroarenes: Stereoselective Synthesis of (Z)-3-((Arylamino)methylene)indoline-2-thiones.

An efficient method for the stereoselective synthesis of (Z)-3-((arylamino)methylene)indoline-2-thiones have been developed via a novel multicomponent reaction of indoles, CS2 and nitroarenes. A range of functionalized indoline-2-thiones were prepared in moderate to good yields from easily available starting materials. The indoline-2-thione products can be easily derivatized to give biologically active thieno[2,3-b]indole and thiopyrano[2,3-b]indole skeletons in high yields.

Association of genetic polymorphisms in HSD17B1, HSD17B2 and SHBG genes with hepatocellular carcinoma risk.

Genetic polymorphisms of enzymes involved in estrogen synthesizing/transporting can influence the risk of hormone-dependent diseases. The incidence rate and relative risk for hepatocellular carcinoma (HCC) are higher in men than in women. This study was conducted to explore the relationship of single nucleotide polymorphisms (SNPs) in 17 ß-Hydroxysteroid dehydrogenases (HSD17B1 and HSD17B2) and sex hormone-binding globulin (SHBG) genes with the risk of HCC within Chinese Han population. Polymorphisms of HSD17B1 rs676387, HSD17B2 rs8191246 and SHBG rs6259 were genotyped in 253 HCC patients and 438 healthy control subjects using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Significantly increased HCC risk was found to be associated with T allele of rs676387 and G allele of rs8191246. Increased HCC risks were found in different genetic model (TT genotype in a recessive model, T allele carriers in a dominant model, TT genotype and TG genotype in a codominant model for HSD17B1 rs676387, G allele carriers in a dominant model and AG genotype in a codominant model for HSD17B2 rs8191246, respectively). No association between SHBG rs6259 and HCC risk was observed. The present study provided evidence that HSD17B1 rs676387 and HSD17B2 rs8191246 were association with HCC development. Further studies in diverse ethnic population with larger sample size were recommended to confirm the findings.

[Plexiform angiomyxoid myofibroblastic tumor of stomach].

OBJECTIVE: To study the clinicopathologic features, immunophenotype and differential diagnosis of plexiform angiomyxoid myofibroblastic tumor (PAMT) of the stomach. METHODS: The clinical and pathologic findings of 3 cases of PAMT in the gastric antrum were retrospectively analyzed. Immunohistochemical study was carried out and the literature was reviewed. RESULTS: The age of patients ranged from 31 to 47 years. The male-to-female ratio was 1:2. The clinical presentation included epigastric pain and distension. Endoscopically, the tumor mass protruded into the gastric cavity at the antrum and ranged from 4.5 cm to 8.0 cm in greatest dimension. One of the tumors studied was associated with surface ulceration. Histologically, the tumors were located in the gastric wall. They were composed of bland spindle cells and small vessels arranged in a plexiform or nodular pattern within a myxoid stroma. Immunohistochemical study showed that the spindle cells were consistently positive for smooth muscle actin and muscle-specific actin. There was focal staining for h-caldesmon, desmin in case 3 and focal positive for epithelial membrane antigen, CAM5.2 in case 1. Further, CD10 and progesterone receptor were positive in case 3. CONCLUSIONS: PAMT represents a rare novel mesenchymal tumor of the stomach, with a propensity of gastric antral involvement. The distinctive pathologic features help to differentiate this entity from other benign and malignant tumors.