Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Sci Rep. 2024 Jul 17;14(1):16568. doi: 10.1038/s41598-024-66510-2.

Reduced sialylation of airway mucin impairs mucus transport by altering the 
biophysical properties of mucin.

Harris ES(1)(2), McIntire HJ(1)(2), Mazur M(1), Schulz-Hildebrandt H(3)(4), 
Leung HM(3)(4), Tearney GJ(3)(4), Krick S(1)(2), Rowe SM(#)(5)(6)(7), Barnes 
JW(#)(8)(9).

Author information:
(1)Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama 
at Birmingham, 1900 University Blvd. Tinsley Harrison Tower, Suite 422, 
Birmingham, AL, 35294, USA.
(2)Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 
USA.
(3)Massachusetts General Hospital, Boston, MA, USA.
(4)Harvard Medical School, Boston, MA, USA.
(5)Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama 
at Birmingham, 1900 University Blvd. Tinsley Harrison Tower, Suite 422, 
Birmingham, AL, 35294, USA. smrowe@uab.edu.
(6)Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 
USA. smrowe@uab.edu.
(7)Departments of Pediatrics and Cell Developmental and Integrative Biology, 
University of Alabama at Birmingham, Birmingham, AL, USA. smrowe@uab.edu.
(8)Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama 
at Birmingham, 1900 University Blvd. Tinsley Harrison Tower, Suite 422, 
Birmingham, AL, 35294, USA. jbarnes@uabmc.edu.
(9)Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 
USA. jbarnes@uabmc.edu.
(#)Contributed equally

Update of
    Res Sq. 2024 May 31:rs.3.rs-4421613. doi: 10.21203/rs.3.rs-4421613/v1.

Mucus stasis is a pathologic hallmark of muco-obstructive diseases, including 
cystic fibrosis (CF). Mucins, the principal component of mucus, are extensively 
modified with hydroxyl (O)-linked glycans, which are largely terminated by 
sialic acid. Sialic acid is a negatively charged monosaccharide and contributes 
to the biochemical/biophysical properties of mucins. Reports suggest that mucin 
sialylation may be altered in CF; however, the consequences of reduced 
sialylation on mucus clearance have not been fully determined. Here, we 
investigated the consequences of reduced sialylation on the charge state and 
conformation of the most prominent airway mucin, MUC5B, and defined the 
functional consequences of reduced sialylation on mucociliary transport (MCT). 
Reduced sialylation contributed to a lower charged MUC5B form and decreased 
polymer expansion. The inhibition of total mucin sialylation de novo impaired 
MCT in primary human bronchial epithelial cells and rat airways, and specific 
α-2,3 sialylation blockade was sufficient to recapitulate these findings. 
Finally, we show that ST3 beta-galactoside alpha-2,3-sialyltransferase (ST3Gal1) 
expression is downregulated in CF and partially restored by correcting CFTR via 
Elexacaftor/Tezacaftor/Ivacaftor treatment. Overall, this study demonstrates the 
importance of mucin sialylation in mucus clearance and identifies decreased 
sialylation by ST3Gal1 as a possible therapeutic target in CF and potentially 
other muco-obstructive diseases.

© 2024. The Author(s).

DOI: 10.1038/s41598-024-66510-2
PMCID: PMC11255327
PMID: 39019950 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare no competing interests.


2. J Zhejiang Univ Sci B. 2024 May 15;25(6):485-498. doi: 10.1631/jzus.B2300917.

Sialyltransferase ST3GAL6 silencing reduces α2,3-sialylated glycans to regulate 
autophagy by decreasing HSPB8-BAG3 in the brain with hepatic encephalopathy.

Li X(1), Xiao Y(1), Li P(2), Zhu Y(1), Guo Y(3), Bian H(4), Li Z(5).

Author information:
(1)Laboratory for Functional Glycomics, College of Life Sciences, Northwest 
University, Xi'an 710069, China.
(2)Medical Experiment Center, Shaanxi University of Chinese Medicine, Xianyang 
712046, China.
(3)The Infectious Disease Department, Gongli Hospital, Pudong New Area, Shanghai 
200135, China. zhengli@nwu.edu.cn, gyh01678@glhospital.com.
(4)National Translational Science Center for Molecular Medicine, Department of 
Cell Biology, Fourth Military Medical University, Xi'an 710032, China. 
zhengli@nwu.edu.cn, hjbian@fmmu.edu.cn.
(5)Laboratory for Functional Glycomics, College of Life Sciences, Northwest 
University, Xi'an 710069, China. zhengli@nwu.edu.cn.

End-stage liver diseases, such as cirrhosis and liver cancer caused by hepatitis 
B, are often combined with hepatic encephalopathy (HE); ammonia poisoning is 
posited as one of its main pathogenesis mechanisms. Ammonia is closely related 
to autophagy, but the molecular mechanism of ammonia's regulatory effect on 
autophagy in HE remains unclear. Sialylation is an essential form of 
glycosylation. In the nervous system, abnormal sialylation affects various 
physiological processes, such as neural development and synapse formation. ST3 
β‍-galactoside α2,‍3-sialyltransferase 6 (ST3GAL6) is one of the significant 
glycosyltransferases responsible for adding α2,3-linked sialic acid to 
substrates and generating glycan structures. We found that the expression of 
ST3GAL6 was upregulated in the brains of mice with HE and in astrocytes after 
ammonia induction, and the expression levels of α2,3-sialylated glycans and 
autophagy-related proteins microtubule-associated protein light chain 3 (LC3) 
and Beclin-1 were upregulated in ammonia-induced astrocytes. These findings 
suggest that ST3GAL6 is related to autophagy in HE. Therefore, we aimed to 
determine the regulatory relationship between ST3GAL6 and autophagy. We found 
that silencing ST3GAL6 and blocking or degrading α2,3-sialylated glycans by way 
of Maackia amurensis lectin-II (MAL-II) and neuraminidase can inhibit autophagy. 
In addition, silencing the expression of ST3GAL6 can downregulate the expression 
of heat shock protein β8 (HSPB8) and Bcl2-associated athanogene 3 (BAG3). 
Notably, the overexpression of HSPB8 partially restored the reduced autophagy 
levels caused by silencing ST3GAL6 expression. Our results indicate that ST3GAL6 
regulates autophagy through the HSPB8-BAG3 complex.

Publisher: 
肝性脑病（HE）是肝病（如乙型肝炎引起的肝硬化和肝癌）发展到终末期之后的一个常见的并发症，氨中毒被认为是其主要的发病机制之一。氨与自噬密切相关，但其对HE的自噬调节作用的分子机制尚不清楚。唾液酸化是糖基化的一种重要形式。在神经系统中，异常的唾液酸化会影响各种生理过程，例如神经发育和突触形成。ST3 
β-半乳糖苷α2,3-唾液酸转移酶6（ST3GAL6）是一种重要的糖基转移酶，负责将α2,3-连接的唾液酸添加到底物并生成聚糖结构。在本研究中，我们发现经氨诱导后，HE小鼠大脑和星形胶质细胞中ST3GAL6的表达上调，并且在氨诱导的星形胶质细胞中，α2,3-唾液酸化聚糖和自噬相关蛋白微管相关蛋白轻链3（LC3）和Beclin-1的表达均上调。上述结果表明：ST3GAL6与HE中的自噬有关。因此，本研究将进一步确定ST3GAL6与自噬之间的调控关系。我们发现通过沉默ST3GAL6以及通过怀槐凝集素-II（MAL-II）和神经氨酸酶阻断或降解α2,3-唾液酸化聚糖可以抑制自噬。此外，沉默ST3GAL6的表达可以下调热休克蛋白β8（HSPB8）和Bcl2关联永生基因3（BAG3）的表达。值得注意的是，HSPB8的过表达可部分恢复因ST3GAL6表达沉默而导致的自噬水平降低。综上，我们的结果表明了ST3GAL6可通过HSPB8-BAG3复合物调节自噬。.

肝性脑病（HE）是肝病（如乙型肝炎引起的肝硬化和肝癌）发展到终末期之后的一个常见的并发症，氨中毒被认为是其主要的发病机制之一。氨与自噬密切相关，但其对HE的自噬调节作用的分子机制尚不清楚。唾液酸化是糖基化的一种重要形式。在神经系统中，异常的唾液酸化会影响各种生理过程，例如神经发育和突触形成。ST3 
β-半乳糖苷α2,3-唾液酸转移酶6（ST3GAL6）是一种重要的糖基转移酶，负责将α2,3-连接的唾液酸添加到底物并生成聚糖结构。在本研究中，我们发现经氨诱导后，HE小鼠大脑和星形胶质细胞中ST3GAL6的表达上调，并且在氨诱导的星形胶质细胞中，α2,3-唾液酸化聚糖和自噬相关蛋白微管相关蛋白轻链3（LC3）和Beclin-1的表达均上调。上述结果表明：ST3GAL6与HE中的自噬有关。因此，本研究将进一步确定ST3GAL6与自噬之间的调控关系。我们发现通过沉默ST3GAL6以及通过怀槐凝集素-II（MAL-II）和神经氨酸酶阻断或降解α2,3-唾液酸化聚糖可以抑制自噬。此外，沉默ST3GAL6的表达可以下调热休克蛋白β8（HSPB8）和Bcl2关联永生基因3（BAG3）的表达。值得注意的是，HSPB8的过表达可部分恢复因ST3GAL6表达沉默而导致的自噬水平降低。综上，我们的结果表明了ST3GAL6可通过HSPB8-BAG3复合物调节自噬。

DOI: 10.1631/jzus.B2300917
PMCID: PMC11199091
PMID: 38910494 [Indexed for MEDLINE]


3. Res Sq [Preprint]. 2024 May 31:rs.3.rs-4421613. doi: 
10.21203/rs.3.rs-4421613/v1.

Reduced Sialylation of Airway Mucin Impairs Mucus Transport by Altering the 
Biophysical Properties of Mucin.

Harris ES(1), McIntire HJ(1), Mazur M(1), Schulz-Hildebrandt H(2), Leung HM(2), 
Tearney GJ(2), Krick S(1), Rowe SM(1), Barnes JW(1).

Author information:
(1)Gregory Fleming James Cystic Fibrosis Research Center, Univ. of Alabama at 
Birmingham, Birmingham, AL, USA.
(2)Massachusetts General Hospital, Boston, MA, USA.

Update in
    Sci Rep. 2024 Jul 17;14(1):16568. doi: 10.1038/s41598-024-66510-2.

Mucus stasis is a pathologic hallmark of muco-obstructive diseases, including 
cystic fibrosis (CF). Mucins, the principal component of mucus, are extensively 
modified with hydroxyl (O)-linked glycans, which are largely terminated by 
sialic acid. Sialic acid is a negatively charged monosaccharide and contributes 
to the biochemical/biophysical properties of mucins. Reports suggest that mucin 
sialylation may be altered in CF; however, the consequences of reduced 
sialylation on mucus clearance have not been fully determined. Here, we 
investigated the consequences of reduced sialylation on the charge state and 
conformation of the most prominent airway mucin, MUC5B, and defined the 
functional consequences of reduced sialylation on mucociliary transport (MCT). 
Reduced sialylation contributed to a lower charged MUC5B form and decreased 
polymer expansion. The inhibition of total mucin sialylation de novo impaired 
MCT in primary human bronchial epithelial cells and rat airways, and specific 
α-2,3 sialylation blockade was sufficient to recapitulate these findings. 
Finally, we show that ST3 beta-galactoside alpha-2,3-sialyltransferase (ST3Gal1) 
expression is downregulated in CF and partially restored by correcting CFTR via 
Elexacaftor/Tezacaftor/Ivacaftor treatment. Overall, this study demonstrates the 
importance of mucin sialylation in mucus clearance and identifies decreased 
sialylation by ST3Gal1 as a possible therapeutic target in CF and potentially 
other muco-obstructive diseases.

DOI: 10.21203/rs.3.rs-4421613/v1
PMCID: PMC11160914
PMID: 38853971

Conflict of interest statement: Conflict of Interest: The authors have declared 
that no conflict of interest exists.


4. Genome Biol Evol. 2024 Jun 4;16(6):evae107. doi: 10.1093/gbe/evae107.

The Rapid Evolution of De Novo Proteins in Structure and Complex.

Chen J(1), Li Q(2)(3), Xia S(1), Arsala D(1), Sosa D(1), Wang D(2)(3), Long 
M(1).

Author information:
(1)Department of Ecology and Evolution, The University of Chicago, Chicago, IL 
60637, USA.
(2)Division of Pharmaceutical Sciences, Skaggs School of Pharmacy and 
Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, 
USA.
(3)Department of Cellular & Molecular Medicine, School of Medicine, University 
of California San Diego, La Jolla, CA 92093, USA.

Recent studies in the rice genome-wide have established that de novo genes, 
evolving from noncoding sequences, enhance protein diversity through a stepwise 
process. However, the pattern and rate of their evolution in protein structure 
over time remain unclear. Here, we addressed these issues within a surprisingly 
short evolutionary timescale (<1 million years for 97% of Oryza de novo genes) 
with comparative approaches to gene duplicates. We found that de novo genes 
evolve faster than gene duplicates in the intrinsically disordered regions (such 
as random coils), secondary structure elements (such as α helix and β strand), 
hydrophobicity, and molecular recognition features. In de novo proteins, 
specifically, we observed an 8% to 14% decay in random coils and intrinsically 
disordered region lengths and a 2.3% to 6.5% increase in structured elements, 
hydrophobicity, and molecular recognition features, per million years on 
average. These patterns of structural evolution align with changes in amino acid 
composition over time as well. We also revealed higher positive charges but 
smaller molecular weights for de novo proteins than duplicates. Tertiary 
structure predictions showed that most de novo proteins, though not typically 
well folded on their own, readily form low-energy and compact complexes with 
other proteins facilitated by extensive residue contacts and conformational 
flexibility, suggesting a faster-binding scenario in de novo proteins to promote 
interaction. These analyses illuminate a rapid evolution of protein structure in 
de novo genes in rice genomes, originating from noncoding sequences, 
highlighting their quick transformation into active, protein complex-forming 
components within a remarkably short evolutionary timeframe.

© The Author(s) 2024. Published by Oxford University Press on behalf of Society 
for Molecular Biology and Evolution.

DOI: 10.1093/gbe/evae107
PMCID: PMC11149777
PMID: 38753069 [Indexed for MEDLINE]

Conflict of interest statement: Conflict of Interest The authors have declared 
that no competing interests exist.


5. Biomacromolecules. 2023 Nov 13;24(11):4939-4957. doi: 
10.1021/acs.biomac.3c00623. Epub 2023 Oct 11.

Comprehensive Biodegradation Analysis of Chemically Modified 
Poly(3-hydroxybutyrate) Materials with Different Crystal Structures.

Julinová M(1), Šašinková D(1), Minařík A(2), Kaszonyiová M(3), Kalendová A(3), 
Kadlečková M(2), Fayyazbakhsh A(1), Koutný M(1).

Author information:
(1)Department of Environmental Protection Engineering, Faculty of Technology, 
Tomas Bata University in Zlín, Nad Ovčírnou 3685, 760 01, Zlín, Czech Republic.
(2)Department of Physics and Material Engineering, Faculty of Technology, Tomas 
Bata University in Zlín, Vavrečkova 5669, 760 01, Zlin, Czech Republic.
(3)Department of Polymer Engineering, Faculty of Technology, Tomas Bata 
University in Zlín, Vavrečkova 5669, 760 01, Zlín, Czech Republic.

This work presents a comprehensive analysis of the biodegradation of 
polyhydroxybutyrate (PHB) and chemically modified PHB with different chemical 
and crystal structures in a soil environment. A polymer modification reaction 
was performed during preparation of the chemically modified PHB films, utilizing 
2,5-dimethyl-2,5-di(tert-butylperoxy)-hexane as a free-radical initiator and 
maleic anhydride. Films of neat PHB and chemically modified PHB were prepared by 
extrusion and thermocompression. The biological agent employed was natural mixed 
microflora in the form of garden soil. The course and extent of biodegradation 
of the films was investigated by applying various techniques, as follows: a 
respirometry test to determine the production of carbon dioxide through 
microbial degradation; scanning electron microscopy (SEM); optical microscopy; 
fluorescence microscopy; differential scanning calorimetry (DSC); and X-ray 
diffraction (XRD). Next-generation sequencing was carried out to study the 
microbial community involved in biodegradation of the films. Findings from the 
respirometry test indicated that biodegradation of the extruded and chemically 
modified PHB followed a multistage (2-3) course, which varied according to the 
spatial distribution of amorphous and crystalline regions and their spherulitic 
morphology. SEM and polarized optical microscopy (POM) confirmed that the rate 
of biodegradation depended on the availability of the amorphous phase in the 
interspherulitic region and the width of the interlamellar region in the first 
stage, while dependence on the size of spherulites and thickness of spherulitic 
lamellae was evident in the second stage. X-ray diffraction revealed that 
orthorhombic α-form crystals with helical chain conformation degraded 
concurrently with β-form crystals with planar zigzag conformation. The 
nucleation of PHB crystals after 90 days of biodegradation was identified by DSC 
and POM, a phenomenon which impeded biodegradation. Fluorescence microscopy 
evidenced that the crystal structure of PHB affected the physiological behavior 
of soil microorganisms in contact with the surfaces of the films.

DOI: 10.1021/acs.biomac.3c00623
PMCID: PMC10646986
PMID: 37819211 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare no competing financial 
interest.