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Sulfation of chondroitin and bile acids converges to antagonize Wnt/β-catenin signaling and inhibit APC deficiency-induced gut tumorigenesis

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1241-1256页

作者： Pengfei Xu Yue Xi Jong-Won Kim Junjie Zhu Min Zhang Meishu Xu Songrong Ren Da Yang Xiaochao Ma Wen Xie Center for Pharmacogenetics and department of Pharmaceutical Sciences University of PittsburghPittsburghPA 15261USA department of Hepatobiliary and Pancreatic Surgery Zhongnan Hospital of Wuhan UniversitySchool of Pharmaceutical SciencesWuhan UniversityWuhan 430071China department of pharmacology&Chemical Biology University of PittsburghPittsburghPA 15261USA

Sulfation is a crucial and prevalent conjugation reaction involved in cellular processes and mammalian physiology.3’-Phosphoadenosine 5’-phosphosulfate(PAPS)synthase 2(PAPSS2)is the primary enzyme to generate the universal sulfonate donor *** involvement of PAPSS2-mediated sulfation in adenomatous polyposis coli(APC)mutation-promoted colonic carcinogenesis has not been ***,we showed that the expression of PAPSS2 was decreased in human colon tumors along with cancer stages,and the lower expression of PAPSS2 was correlated with poor prognosis in advanced colon *** epithelial-specific heterozygous Apc deficient and Papss2-knockout(Apc^(Δgut-Het)Papss2^(Δgut))mice were created,and the phenotypes were compared to the spontaneous intestinal tumorigenesis of Apc^(Δgut-Het)***^(Δgut-Het)Papss2^(Δgutmice) were more sensitive to gut tumorigenesis,which was mechanistically accounted for by the activation of Wnt/β-catenin signaling pathway due to the suppression of chondroitin sulfation and inhibition of the farnesoid X receptor(FXR)-transducin-like enhancer of split 3(TLE3)gene regulatory *** sulfate supplementation in Apc^(Δgut-Het)Papss2^(Δgutmice) alleviated intestinal *** summary,we have uncovered the protective role of PAPSS2-mediated chondroitin sulfation and bile acids-FXR-TLE3 activation in the prevention of gut carcinogenesis via the antagonization of Wnt/β-catenin *** sulfate may be explored as a therapeutic agent for Papss2 deficiency-associated colonic carcinogenesis.

关键词： Colon cancer APC Wnt/b-catenin PAPSS2 Chondroitin sulfate Sulfation Bile acids FXR

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CD9 role in proliferation, rejuvenation, and therapeutic applications

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Genes & Diseases 2024年第3期11卷 95-97页

作者： Sai Priyanka Kodam Neda Baghban Mujib Ullah Institutefor Immunityand Transplantation Stem Cell Biology and Regenerative MedicineSchool of MedicineMolecular Medicine Department of MedicineStanford UniversityPaloAltoCA94304USA

The CD9 gene,also known as the Tspan29 gene,codes for a protein called CD9,which is a member of the tetraspanin family of transmembrane proteins.^(1) The CD9 protein is involved in various cellular processes,including cell proliferation,differentiation,adhesion,and migration.^(1,2) CD9 has also been found to play a role in the regulation of stem cell proliferation and differentiation.

关键词： migration. therapeutic CD9

Neural membrane repair at the core of regeneration

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Neural Regeneration Research 2024年第7期19卷 1399-1400页

作者： Catarina Dias Jesper Nylandsted Danish Cancer Institute Membrane IntegrityCopenhagenDenmark Champalimaud Research Champalimaud FoundationLisbonPortugal department of molecular Medicine University of Southern DenmarkOdenseDenmark

Loss of plasma membrane integrity can compromise cell functioning and *** countera ct this eminent threat,euka ryotic cells have developed efficient repair mechanisms,which seem to have co-evolved with the emergence of vital membrane processes(Cooper and McNeil,2015).This relationship between basic cellular functioning and membrane repair highlights the fundamental significance of preserving membrane integrity for cellular life.

关键词： repair preserving integrity

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Bone-targeted lipoplex-loaded three-dimensional bioprinting bilayer scaffold enhanced bone regeneration

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Regenerative Biomaterials 2024年第4期3卷 138-148页

作者： Woo-Jin Kim Jeong-Hyun Ryu Ji Won Kim Ki-Tae Kim Hye-Rim Shin Heein Yoon Hyun-Mo Ryoo Young-Dan Cho department of molecular Genetics School of Dentistry and Dental Research InstituteSeoul National UniversitySeoul03080Republic of Korea department of Periodontology School of Dentistry and Dental Research InstituteSeoul National University and Seoul National University Dental HospitalSeoul03080Republic of Korea

Clinical bone-morphogenetic protein 2(BMP2)treatment for bone regeneration,often resulting in complications like soft tissue inflammation and ectopic ossification due to high dosages and non-specific delivery systems,necessitates research into improved biomaterials for better BMP2 stability and *** tackle this challenge,we introduced a groundbreaking bone-targeted,lipoplex-loaded,three-dimensional bioprinted bilayer scaffold,termed the polycaprolactone-bioink-nanoparticle(PBN)scaffold,aimed at boosting bone *** encapsulated BMP2 within the fibroin nanoparticle based lipoplex(Fibroplex)and functionalized it with DSS6 for bone tissue-specific targeting.3D printing technology enables customized,porous PCL scaffolds for bone healing and soft tissue growth,with a two-step bioprinting process creating a cellular lattice structure and a bioink grid using gelatin-alginate hydrogel and DSS6-Fibroplex,shown to support effective nutrient exchange and cell growth at specific pore *** PBN scaffold is predicted through in silico analysis to exhibit biased BMP2 release between bone and soft tissue,a finding validated by in vitro osteogenic differentiation *** PBN scaffold was evaluated for critical calvarial defects,focusing on sustained BMP2 delivery,prevention of soft tissue cell infiltration and controlled fiber membrane pore size in *** PBN scaffold demonstrated a more than eight times longer BMP2 release time than that of the collagen sponge,promoting osteogenic differentiation and bone regeneration in a calvarial defect *** findings suggest that the PBN scaffold enhanced the local concentration of BMP2 in bone defects through sustained release and improved the spatial arrangement of bone formation,thereby reducing the risk of heterotopic ossification.

关键词： 3D bioprinting bone-targeting lipoplex BMP2 bone regeneration

Mesenchymal stem cells’“garbage bags”at work:Treating radial nerve injury with mesenchymal stem cell-derived exosomes

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World Journal of Stem Cells 2024年第5期16卷 467-478页

作者： Mazhar Mushtaq Doaa Hussein Zineldeen Muhammad Abdul Mateen Khawaja Husnain Haider department of Basic Sciences Sulaiman AlRajhi UniversityAlbukairiyah 52736AlQaseemSaudi Arabia Medical Biochemistry and molecular Biology department Faculty of MedicineTanta UniversityTanta 6632110Egypt

Unlike central nervous system injuries,peripheral nerve injuries(PNIs)are often characterized by more or less successful axonal ***,structural and functional recovery is a senile process involving multifaceted cellular and molecular *** contemporary treatment options are limited,with surgical intervention as the gold-standard method;however,each treatment option has its associated limitations,especially when the injury is severe with a large *** advancements in cell-based therapy and cell-free therapy approaches using stem cell-derived soluble and insoluble components of the cell secretome are fast-emerging therapeutic approaches to treating acute and chronic *** recent pilot study is a leap forward in the field,which is expected to pave the way for more enormous,systematic,and well-designed clinical trials to assess the therapeutic efficacy of mesenchymal stem cell-derived exosomes as a bio-drug either alone or as part of a combinatorial approach,in an attempt synergize the best of novel treatment approaches to address the complexity of the neural repair and regeneration.

关键词： Exosome Mesenchymal stem cells Nerve injury Stem cells Secretome Regeneration

Modeling tuberous sclerosis complex with human induced pluripotent stem cells

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World Journal of Pediatrics 2024年第3期20卷 208-218页

作者： Weibo Niu Benjamin Siciliano Zhexing Wen department of Psychiatry and Behavioral Sciences Emory University School of MedicineWhitehead Research Building 447615 Michael StreetAtlantaGA 30322USA The Graduate Program in molecular and Systems pharmacology Laney Graduate SchoolEmory UniversityAtlanta.GA 30322.USA department of Cell Biology Emory University School of MedicineWhitehead Research Building 447615 Michael StreetAtlantaGA30322USA department of Neurology Emory University School of MedicineWhitehead Research Building 447.615 Michael StreetAtlantaGA 30322USA

Background Tuberous sclerosis complex(TSC)is an autosomal dominant genetic disorder with a birth incidence of I:6000 in the United States that is characterized by the growth of non-cancerous tumors in multiple organ systems including the brain,kidneys,lungs,and ***,TSCis also associated with signicant neurological manifestations including epilepsy TSC-associated neuropsychiatric disorders,intellectual disabilities,and autism spectrum *** in the TSCI or TSC2 genes are well-established causes of TSC,which lead to TSC1/TSC2 deficiency in organs and hyper-activation of the mammalian target of rapamycin signaling *** models have been widely used to study the effect of TSCl/2 genes on the development and function of the *** considerable progress in understanding the molecular mechanisms underlying TSC in animal models,a human-specific model is urgently needed to investigate the effects of TSCl/2 mutations that are unique to human *** sources Literature reviews and research articles were published in PubMed-indexed *** Human-induced pluripotent stem cells(iPSCs),which capture risk alleles that are identical to their donors and have the capacity to differentiate into virtually any cell type in the human body,pave the way for the empirical study of previously inaccessible biological systems such as the developing human *** In this review,we present an overview of the recent progress in modeling TSC with human iPSC models,the existing limitations,and potential directions for future research.

关键词： Induced pluripotent stem cells Three-dimensional cultures Tuberous sclerosis complex Two-dimensional cultures

TransCell:In Silico Characterization of Genomic Landscape and cellular Responses by Deep Transfer Learning

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Genomics, Proteomics & Bioinformatics 2024年第2期22卷 157-170页

作者： Shan-Ju Yeh Shreya Paithankar Ruoqiao Chen Jing Xing Mengying Sun Ke Liu Jiayu Zhou Bin Chen department of Pediatrics and Human Development Michigan State UniversityGrand RapidsMI 49503USA department of pharmacology and Toxicology Michigan State UniversityGrand RapidsMI 49503USA department of Computer Science and Engineering Michigan State UniversityEast LansingMI 48824USA

Gene expression profiling of new or modified cell lines becomes routine today;however,obtaining comprehensive molecular characterization and cellular responses for a variety of cell lines,including those derived from underrepresented groups,is not trivial when resources are *** gene expression to predict other measurements has been actively explored;however,systematic investigation of its predictive power in various measurements has not been well ***,we evaluated commonly used machine learning methods and presented TransCell,a two-step deep transfer learning framework that utilized the knowledge derived from pan-cancer tumor samples to predict molecular features and *** these models,TransCell had the best performance in predicting metabolite,gene effect score(or genetic dependency),and drug sensitivity,and had comparable performance in predicting mutation,copy number variation,and protein ***,TransCell improved the performance by over 50%in drug sensitivity prediction and achieved a correlation of 0.7 in gene effect score ***,predicted drug sensitivities revealed potential repurposing candidates for new 100 pediatric cancer cell lines,and predicted gene effect scores reflected BRAF resistance in melanoma cell ***,we investigated the predictive power of gene expression in six molecular measurement types and developed a web portal(http://***/transcell/)that enables the prediction of 352,000 genomic and cellular response features solely from gene expression profiles.

关键词： Genomics Transcriptomics Cancer dependency Drug repurposing Transfer learning

Charcoal Nanoparticles as a Delivery System for Doxorubicin and Sorafenib in Treatment of Hepatocellular Carcinoma

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Advances in Nanoparticles 2024年第3期13卷 45-60页

作者： Aisha Elgurashi Abdulla Toga Khalid Mohamed Gader Marvit Osman Widdatallah Omer Abdullah E. Gouda Samah Mamdouh Mohamed A. Shemis department of Clinical Pharmacy Faculty of Pharmacy University of Medical Sciences and Technology Khartoum Sudan department of pharmacology Faculty of Pharmacy University of Medical Sciences and Technology Khartoum Sudan department of Biochemistry and molecular Biology Theodor Bilharz Research Institute Giza Egypt

Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and one of the leading causes of cancer-related death worldwide. Advanced HCC displays strong resistance to chemotherapy, and traditional chemotherapy drugs do not achieve satisfactory therapeutic efficacy. The delivery of therapeutic compounds to the target site is a major challenge in the treatment of many diseases. Objective: This study aims to evaluate activated charcoal nanoparticles as a drug delivery system for anticancer agents (Sorafenib and Doxorubicin) in Hepatocellular Cancer Stem Cells. Method: The percent efficiency of entrapment (% EE) of the doxorubicin and sorafenib entrapped onto the activated charcoal was obtained by determining the free doxorubicin and sorafenib concentration in the supernatant-prepared solutions. Then the characterizations of nanoparticles were formed by determination of the particle size distribution, zeta potential, and polydispersity index (PDI). The anticancer activity of activated Charcoal, Doxorubicin-ACNP, sorafenib-ACNP, free doxorubicin, and free sorafenib solutions was measured based on cell viability percentage in HepG2 cell lines (ATCC-CCL 75). In vitro RBC’s toxicity of Doxorubicin/sorafenib loaded charcoal was estimated by hemolysis percentage. Results: The synthesized Doxorubicin-ACNP and Sorafenib-ACNP were evaluated and their physiochemical properties were also examined. Essentially, the percent Efficiency of Entrapment (EE %) was found to be 87.5% and 82.66% for Doxorubicin-ACNP and Sorafenib-ACNP, respectively. The loading capacity was 34.78% and 24.31% for Doxorubicin-ACNP and Sorafenib-ACNP. Using the Dynamic Light scattering [DLS] for the determination of the hydrodynamic size and surface zeta potential, a narrow sample size distribution was obtained of (18, 68, and 190 nm for charcoal, 105, 255, and 712 nm for doxorubicin, and 91, 295, and 955 nm for sorafenib), respectively. A surface charge of −13.2, −15.6 and −17 was obta

关键词： Activated Charcoal Nanoparticles (ACNP) Drug Delivery System Sorafenib and Doxorubicin Hepatocellular Cancer Stem Cells

Parallelogram 3d-4f-5d heterometallic clusters based on trilacunary tungstoantimonates with excellent proton conductivity

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Chinese Chemical Letters 2024年第3期35卷 528-531页

作者： Haiying Wang Han Xu Chaolong Chen Yingjie Zhu Yikang Zhang Dongdi Zhang Jingyang Niu Henan Key Laboratory of Polyoxometalate Chemistry College of Chemistry and Molecular SciencesHenan UniversityKaifeng 475004China School of Pharmaceutical Science&Yunnan Key Laboratory of pharmacology for Natural Products Kunming Medical UniversityKunming 650500China Collaborative Innovation Center of Chemistry for Energy Materials State Key Laboratory of Physical Chemistry of Solid Surface and Department of ChemistryCollege of Chemistry and Chemical EngineeringXiamen UniversityXiamen 361005China

Two 3d-4f-5d heterometallic cluster-containing polyoxometalates,formulated as Na_(22){(SbW_(9)O_(33))_(4)[La_(3)W_(6)MO_(18)(H_(2)O)_(8)(CH_(3)COO)_(4)]_(2)}·nH_(2)O(abbreviated as La_(6)M_(2),M=Co/Mn)were synthesized and structurally ***-crystal X-ray diffraction analyses reveal that the polyanions of La_(6)Co_(2)and La_(6)Mn_(2)consist of the uncommon 3d-4f-5d clusters{La_(6)W_(12)Co_(2)}and{La_(6)W_(12)Mn_(2)},which are encapsulated by four trilacunary Keggin tungstoantimonates to form the parallelogram-shaped title ***,the polyanions can be extended into a two-dimensional(2D)frame by the linkage of peripheral Na+*** inner space of the 2D layer was filled with water molecules and thus an H-bonded network was formed,which is expected to exhibit a fascinating proton *** study of water-assisted proton conduction demonstrated that La_(6)Co_(2)and La_(6)Mn_(2)were temperature-and humiditydependent proton conductors,respectively,and the proton conductivities could reach 1.3×10^(-2)and 2.3×10^(-2)S/cm at 65℃and 90%RH conditions.

关键词： Polyoxometalate Parallelogram Heterometallic 3d-4f-5d cluster Proton conductivity

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