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1.
Adv Sci (Weinh) ; : e2403640, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38946588

RESUMO

Ovulation is vital for successful reproduction. Following ovulation, cumulus cells and oocyte are released, while mural granulosa cells (mGCs) remain sequestered within the post-ovulatory follicle to form the corpus luteum. However, the mechanism underlying the confinement of mGCs has been a longstanding mystery. Here, in vitro and in vivo evidence is provided demonstrating that the stiffening of mGC-layer serves as an evolutionarily conserved mechanism that prevents mGCs from escaping the post-ovulatory follicles. The results from spatial transcriptome analysis and experiments reveal that focal adhesion assembly, triggered by the LH (hCG)-cAMP-PKA-CREB signaling cascade, is necessary for mGC-layer stiffening. Disrupting focal adhesion assembly through RNA interference results in stiffening failure, mGC escape, and the subsequent development of an abnormal corpus luteum characterized by decreased cell density or cavities. These findings introduce a novel concept of "mGC-layer stiffening", shedding light on the mechanism that prevents mGC escape from the post-ovulatory follicle.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38949691

RESUMO

An essential requirement for biomedical devices is the capability of conformal adaptability on diverse irregular 3D (three-dimensional) nonflat surfaces in the human body that may be covered with liquids such as mucus or sweat. However, the development of reversible adhesive interface materials for biodevices that function on complex biological surfaces is challenging due to the wet, slippery, smooth, and curved surface properties. Herein, we present an ultra-adaptive bioadhesive for irregular 3D oral cavities covered with saliva by integrating a kirigami-metastructure and vertically self-aligning suction cups. The flared suction cup, inspired by octopus tentacles, allows adhesion to moist surfaces. Additionally, the kirigami-based auxetic metastructure with a negative Poisson's ratio relieves the stress caused by tensile strain, thereby mitigating the stress caused by curved surfaces and enabling conformal contact with the surface. As a result, the adhesive strength of the proposed auxetic adhesive is twice that of adhesives with a flat backbone on highly curved porcine palates. For potential application, the proposed auxetic adhesive is mounted on a denture and performs successfully in human subject feasibility evaluations. An integrated design of these two structures may provide functionality and potential for biomedical applications.

3.
ACS Appl Bio Mater ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38954747

RESUMO

In the realm of clinical applications, the concern surrounding biomedical device-related infections (BDI) is paramount. To mitigate the risk associated with BDI, enhancing surface characteristics such as lubrication and antibacterial efficacy is considered as a strategic approach. This study delineated the synthesis of a multifunctional copolymer, embodying self-adhesive, lubricating, and antibacterial properties, achieved through free radical polymerization and a carbodiimide coupling reaction. The copolymer was adeptly modified on the surface of stainless steel 316L (SS316L) substrates by employing a facile dip-coating technique. Comprehensive characterizations were performed by using an array of analytical techniques including Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, optical interferometry, scanning electron microscopy, and atomic force microscopy. Nanoscale tribological assessments revealed a notable reduction in the value of the friction coefficient of the copolymer-coated SS316L substrates compared to bare SS316L samples. The coating demonstrated exceptional resistance to protein adsorption, as evidenced in protein contamination models employing bovine serum albumin and fibrinogen. The bactericidal efficacy of the copolymer-modified surfaces was significantly improved against pathogenic strains such as Staphylococcus aureus and Escherichia coli. Additionally, in vitro evaluations of blood compatibility and cellular compatibility underscored the remarkable anticoagulant performance and biocompatibility. Collectively, these findings indicated that the developed copolymer coating represented a promising candidate, with its facile modification approach, for augmenting lubrication and antifouling properties in the field of biomedical implant applications.

4.
BMC Genomics ; 25(1): 650, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38951796

RESUMO

BACKGROUND: Viperin, also known as radical S-adenosyl-methionine domain containing protein 2 (RSAD2), is an interferon-inducible protein that is involved in the innate immune response against a wide array of viruses. In mammals, Viperin exerts its antiviral function through enzymatic conversion of cytidine triphosphate (CTP) into its antiviral analog ddhCTP as well as through interactions with host proteins involved in innate immune signaling and in metabolic pathways exploited by viruses during their life cycle. However, how Viperin modulates the antiviral response in fish remains largely unknown. RESULTS: For this purpose, we developed a fathead minnow (Pimephales promelas) clonal cell line in which the unique viperin gene has been knocked out by CRISPR/Cas9 genome-editing. In order to decipher the contribution of fish Viperin to the antiviral response and its regulatory role beyond the scope of the innate immune response, we performed a comparative RNA-seq analysis of viperin-/- and wildtype cell lines upon stimulation with recombinant fathead minnow type I interferon. CONCLUSIONS: Our results revealed that Viperin does not exert positive feedback on the canonical type I IFN but acts as a negative regulator of the inflammatory response by downregulating specific pro-inflammatory genes and upregulating repressors of the NF-κB pathway. It also appeared to play a role in regulating metabolic processes, including one carbon metabolism, bone formation, extracellular matrix organization and cell adhesion.


Assuntos
Cyprinidae , Inflamação , Animais , Cyprinidae/metabolismo , Cyprinidae/genética , Inflamação/metabolismo , Inflamação/genética , Imunidade Inata , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Linhagem Celular , Sistemas CRISPR-Cas , Interferon Tipo I/metabolismo , Edição de Genes , Regulação da Expressão Gênica
5.
Biochim Biophys Acta Mol Basis Dis ; : 167332, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38960056

RESUMO

Malignant cell plasticity is an important hallmark of tumor biology and crucial for metastasis and resistance. Cell plasticity lets cancer cells adapt to and escape the therapeutic strategies, which is the leading cause of cancer patient mortality. Epithelial cells acquire mobility via epithelial-mesenchymal transition (EMT), whereas mesenchymal cells enhance their migratory ability and clonogenic potential by acquiring amoeboid characteristics through mesenchymal-amoeboid transition (MAT). Tumor formation, progression, and metastasis depend on the tumor microenvironment (TME), a complex ecosystem within and around a tumor. Through increased migration and metastasis of cancer cells, the TME also contributes to malignancy. This review underscores the distinction between invasion pattern morphological manifestations and the diverse structures found within the TME. Furthermore, the mechanisms by which amoeboid-associated characteristics promote resistance and metastasis and how these mechanisms may represent therapeutic opportunities are discussed.

6.
J Biochem ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38960390

RESUMO

Erythrocytes are important vascular components that play vital roles in maintaining vascular homeostasis, in addition to carrying oxygen. Previously, we reported that the changes in the internal milieu (e.g., hyperglycemia or hypercholesterolemia) increase erythrocyte adhesion to various ECM components, potentially through altering glycosaminoglycans (GAGs). In this study, we have investigated the expression of syndecan (Sdc) family members that could be involved in mediating cytoadherence under conditions of dyslipidemia and hyperglycemia. Among the Sdc family members analyzed, we found significant overexpression of Sdc-3 in erythrocyte membranes harvested from high-fat-fed control and diabetic animals. Animal studies revealed a positive correlation between Sdc-3 expression, blood sugar levels, and erythrocyte adhesion. In the human study, diabetic cohorts with BMI >24.9 showed significantly increased expression of Sdc-3. Interestingly, blocking the Sdc-3 moiety with an anti-Sdc-3 antibody revealed that the core protein might not be directly involved in erythrocyte adhesion to fibronectin despite the GAGs bringing about adhesion. Lastly, Nano LC-MS/MS verified the presence of Sdc-3 in erythrocyte membranes. In conclusion, the high-fat diet and diabetes modulated Sdc-3 expression in the erythrocyte membrane, which may alter its adhesive properties and promote vascular complications.

7.
Adv Protein Chem Struct Biol ; 141: 361-380, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38960480

RESUMO

Multicellular organisms consist of cells and extracellular matrix (ECM). ECM creates a cellular microenvironment, and cells locally degrade the ECM according to their cellular activity. A major group of enzymes that modify ECM belongs to matrix metalloproteinases (MMPs) and play major roles in various pathophysiological events. ECM degradation by MMPs does not occur in all cellular surroundings but only where it is necessary, and cells achieve this by directionally secreting these proteolytic enzymes. Recent studies have indicated that such enzyme secretion is achieved by targeted vesicle transport along the microtubules, and several kinesin superfamily proteins (KIFs) have been identified as responsible motor proteins involved in the processes. This chapter discusses recent findings of the vesicle transport of MMPs and their roles.


Assuntos
Metaloproteinases da Matriz , Metaloproteinases da Matriz/metabolismo , Humanos , Animais , Cinesinas/metabolismo , Cinesinas/química , Matriz Extracelular/metabolismo , Transporte Biológico , Microtúbulos/metabolismo
8.
J Med Microbiol ; 73(7)2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38958241

RESUMO

Objectives. Anti-fungal agents are increasingly becoming less effective due to the development of resistance. In addition, it is difficult to treat Candida organisms that form biofilms due to a lack of ability of drugs to penetrate the biofilms. We are attempting to assess the effect of a new therapeutic agent, N-acetylcysteine (NAC), on adhesion and biofilm formation in Candida parapsilosis clinical strains. Meanwhile, to detect the transcription level changes of adhesion and biofilm formation-associated genes (CpALS6, CpALS7, CpEFG1 and CpBCR1) when administrated with NAC in C. parapsilosis strains, furthermore, to explore the mechanism of drug interference on biofilms.Hypothesis/Gap statement. N-acetylcysteine (NAC) exhibits certain inhibitory effects on adhesion and biofilm formation in C. parapsilosis clinical strains from CRBSIs through: (1) down-regulating the expression of the CpEFG1 gene, making it a highly potential candidate for the treatment of C. parapsilosis catheter-related bloodstream infections (CRBSIs), (2) regulating the metabolism and biofilm -forming factors of cell structure.Methods. To determine whether non-antifungal agents can exhibit inhibitory effects on adhesion, amounts of total biofilm formation and metabolic activities of C. parapsilosis isolates from candidemia patients, NAC was added to the yeast suspensions at different concentrations, respectively. Reverse transcription was used to detect the transcriptional levels of adhesion-related genes (CpALS6 and CpALS7) and biofilm formation-related factors (CpEFG1 and CpBCR1) in the BCR1 knockout strain, CP7 and CP5 clinical strains in the presence of NAC. To further explore the mechanism of NAC on the biofilms of C. parapsilosis, RNA sequencing was used to calculate gene expression, comparing the differences among samples. Gene Ontology (GO) enrichment analysis helps to illustrate the difference between two particular samples on functional levels.Results. A high concentration of NAC reduces the total amount of biofilm formation in C. parapsilosis. Following co-incubation with NAC, the expression of CpEFG1 in both CP7 and CP5 clinical strains decreased, while there were no significant changes in the transcriptional levels of CpBCR1 compared with the untreated strain. GO enrichment analysis showed that the metabolism and biofilm-forming factors of cell structure were all regulated after NAC intervention.Conclusions. The non-antifungal agent NAC exhibits certain inhibitory effects on clinical isolate biofilm formation by down-regulating the expression of the CpEFG1 gene, making it a highly potential candidate for the treatment of C. parapsilosis catheter-related bloodstream infections.


Assuntos
Acetilcisteína , Biofilmes , Candida parapsilosis , Candidemia , Infecções Relacionadas a Cateter , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Acetilcisteína/farmacologia , Humanos , Candida parapsilosis/efeitos dos fármacos , Candida parapsilosis/genética , Candida parapsilosis/fisiologia , Infecções Relacionadas a Cateter/microbiologia , Candidemia/microbiologia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Antifúngicos/farmacologia
9.
Glycoconj J ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958800

RESUMO

Altered glycosylation is a common feature of cancer cells. Some subsets of glycans are found to be frequently enriched on the tumor cell surface and implicated in different tumor phenotypes. Among these, changes in sialylation have long been associated with metastatic cell behaviors such as invasion and enhanced cell survival. Sialylation typically exists in three prominent linkages: α2,3, α2,6, and α2,8, catalyzed by a group of sialyltransferases. The aberrant expression of all three linkages has been related to cancer progression. The increased α2,6 sialylation on N-glycans catalyzed by ß-galactoside α2,6 sialyltransferase 1 (ST6Gal1) is frequently observed in many cancers. In contrast, functions of α2,3 sialylation on N-glycans catalyzed by at least three ß-galactoside α2,3-sialyltransferases, ST3Gal3, ST3Gal4, and ST3Gal6 remain elusive due to a possibility of compensating for one another. In this minireview, we briefly describe functions of sialylation and recent findings that different α2,3 sialyltransferases specifically modify target proteins, as well as sialylation regulatory mechanisms vis a complex formation among integrin α3ß1, Golgi phosphoprotein 3 (GOLPH3), phosphatidylinositol 4-kinase IIα (PI4KIIα), focal adhesion kinase (FAK) and sialyltransferase, which suggests a new concept for the regulation of glycosylation in cell biology.

10.
Artigo em Inglês | MEDLINE | ID: mdl-38963398

RESUMO

Here, we explored a new manufacturing strategy that uses the mask laser interference additive manufacturing (MLIAM) technique, which combines the respective strengths of laser interference lithography and mask lithography to efficiently fabricate across-scales three-dimensional bionic shark skin structures with superhydrophobicity and adhesive reduction. The phenomena and mechanisms of the MLIAM curing process were revealed and analyzed, showing the feasibility and flexibility. In terms of structural performance, the adhesive force on the surface can be tuned based on the growth direction of the bionic shark skin structures, where the maximum rate of the adhesive reduction reaches about 65%. Furthermore, the evolution of the directional diffusion for the water droplet, which is based on the change of the contact angle, was clearly observed, and the mechanism was also discussed by the models. Moreover, no-loss transportations were achieved successfully using the gradient adhesive force and superhydrophobicity on the surface by tuning the growth direction and modifying by fluorinated silane. Finally, this work gives a strategy for fabricating across-scale structures on micro- and nanometers, which have potential application in bioengineering, diversional targeting, and condenser surface.

11.
BMC Microbiol ; 24(1): 241, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961344

RESUMO

BACKGROUND: Staphylococcus aureus, a commensal bacterium, colonizes the skin and mucous membranes of approximately 30% of the human population. Apart from conventional resistance mechanisms, one of the pathogenic features of S. aureus is its ability to survive in a biofilm state on both biotic and abiotic surfaces. Due to this characteristic, S. aureus is a major cause of human infections, with Methicillin-Resistant Staphylococcus aureus (MRSA) being a significant contributor to both community-acquired and hospital-acquired infections. RESULTS: Analyzing non-repetitive clinical isolates of MRSA collected from seven provinces and cities in China between 2014 and 2020, it was observed that 53.2% of the MRSA isolates exhibited varying degrees of ability to produce biofilm. The biofilm positivity rate was notably high in MRSA isolates from Guangdong, Jiangxi, and Hubei. The predominant MRSA strains collected in this study were of sequence types ST59, ST5, and ST239, with the biofilm-producing capability mainly distributed among moderate and weak biofilm producers within these ST types. Notably, certain sequence types, such as ST88, exhibited a high prevalence of strong biofilm-producing strains. The study found that SCCmec IV was the predominant type among biofilm-positive MRSA, followed by SCCmec II. Comparing strains with weak and strong biofilm production capabilities, the positive rates of the sdrD and sdrE were higher in strong biofilm producers. The genetic determinants ebp, icaA, icaB, icaC, icaD, icaR, and sdrE were associated with strong biofilm production in MRSA. Additionally, biofilm-negative MRSA isolates showed higher sensitivity rates to cefalotin (94.8%), daptomycin (94.5%), mupirocin (86.5%), teicoplanin (94.5%), fusidic acid (81.0%), and dalbavancin (94.5%) compared to biofilm-positive MRSA isolates. The biofilm positivity rate was consistently above 50% in all collected specimen types. CONCLUSIONS: MRSA strains with biofilm production capability warrant increased vigilance.


Assuntos
Biofilmes , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Staphylococcus aureus Resistente à Meticilina/fisiologia , China/epidemiologia , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Antibacterianos/farmacologia , Genes Bacterianos/genética , Humanos
12.
Int J Biol Macromol ; 275(Pt 1): 133412, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38968915

RESUMO

Combining a biocompatible hydrogel scaffold with the cell-supportive properties of silk fibroin (SF) and the unique functionalities of ZnFe2O4 nanoparticles creates a promising platform for advanced nanobiomaterials. The research is centered on synthesizing a natural hydrogel using cellulose (Cellul) and sodium alginate (SA) combined with SF and zinc ferrite nanoparticles. A range of analytical and biological assays were conducted to determine the biological and physicochemical properties of the nanobiocomposite. The hemolysis and 2,5-diphenyl-2H-tetrazolium bromide (MTT) assays indicated that the SA-Cellul hydrogel/SF/ZnFe2O4 nanobiocomposite was a biocompatible against human dermal fibroblasts (Hu02) and red blood cells (RBC). In addition, aside from demonstrating outstanding anti-biofilm activity, the nanobiocomposite also promotes the Hu02 cells adhesion, showcasing the synergistic effect of incorporating SF and ZnFe2O4 nanoparticle. These promising results show that this nanobiocomposite has potential applications in various biomedical fields.

13.
ACS Sens ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38968930

RESUMO

DNA-based tension sensors have innovated the imaging and calibration of mechanosensitive receptor-transmitted molecular forces, such as integrin tensions. However, these sensors mainly serve as binary reporters, only indicating if molecular forces exceed one predefined threshold. Here, we have developed tandem tension sensor (TTS), which comprises two consecutive force-sensing units, each with unique force detection thresholds and distinct fluorescence spectra, thereby enabling the quantification of molecular forces with dual reference levels. With TTS, we revealed that vinculin is not required for transmitting integrin tensions at approximately 10 pN (piconewtons) but is essential for elevating integrin tensions beyond 20 pN in focal adhesions (FAs). Such high tensions have emerged during the early stage of FA formation. TTS also successfully detected changes in integrin tensions in response to disrupted actin formation, inhibited myosin activity, and tuned substrate elasticity. We also applied TTS to examine integrin tensions in platelets and revealed two force regimes, with integrin tensions surpassing 20 pN at cell central regions and 13-20 pN integrin tensions at the cell edge. Overall, TTS, especially the construct consisting of a hairpin DNA (13 pN opening force) and a shearing DNA (20 pN opening force), stands as a valuable tool for the quantification of receptor-transmitted molecular forces within living cells.

14.
Structure ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38968938

RESUMO

Contactin 2 (CNTN2) is a cell adhesion molecule involved in axon guidance, neuronal migration, and fasciculation. The ectodomains of CNTN1-CNTN6 are composed of six Ig domains (Ig1-Ig6) and four FN domains. Here, we show that CNTN2 forms transient homophilic interactions (KD ∼200 nM). Cryo-EM structures of full-length CNTN2 and CNTN2_Ig1-Ig6 reveal a T-shaped homodimer formed by intertwined, parallel monomers. Unexpectedly, the horseshoe-shaped Ig1-Ig4 headpieces extend their Ig2-Ig3 tips outwards on either side of the homodimer, while Ig4, Ig5, Ig6, and the FN domains form a central stalk. Cross-linking mass spectrometry and cell-based binding assays confirm the 3D assembly of the CNTN2 homodimer. The interface mediating homodimer formation differs between CNTNs, as do the homophilic versus heterophilic interaction mechanisms. The CNTN family thus encodes a versatile molecular platform that supports a very diverse portfolio of protein interactions and that can be leveraged to strategically guide neural circuit development.

15.
Int J Biol Macromol ; : 133655, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38969029

RESUMO

Integrated wound care, a sequential process of promoting wound hemostasis, sealing, and healing, is of great clinical significance. However, the wet environment of wounds poses formidable challenges for integrated care. Herein, we developed an epidermal growth factor (EGF)-loaded, dehydrated physical microgel (DPM)-formed adhesive hydrogel for the integrated care of wet wounds. The DPMs were designed using the rational combination of hygroscopicity and reversible crosslinking of physical hydrogels. Unlike regular bioadhesives, which consider interfacial water as a barrier to adhesion, DPMs utilize water to form desirable adhesive structures. The hygroscopicity allowed the DPMs to absorb interfacial water and subsequently, the interfacial adhesion was realized by the interactions between tissue and DPMs. The reversible crosslinks further enabled DPMs to integrate into hydrogels (DPM-Gels), thus achieving wet adhesion. Importantly, the water-absorbing gelation mode of DPMs enabled facile loading of biologically active EGF to promote wound healing. We demonstrated that the DPM-Gels possessed wet tissue adhesive performance, with about 40 times the wet adhesive strength of fibrin glue and about 4 times the burst pressure of human blood pressure. Upon application at the injury site, the EGF-loaded DPM-Gels sequentially promoted efficient wound hemostasis, stable sealing, and quick healing, achieving integrated care of wet wounds.

16.
Regen Biomater ; 11: rbae044, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962115

RESUMO

Polypropylene (PP) mesh is commonly used in abdominal wall repair due to its ability to reduce the risk of organ damage, infections and other complications. However, the PP mesh often leads to adhesion formation and does not promote functional tissue repair. In this study, we synthesized one kind of aldehyde Bletilla striata polysaccharide (BSPA) modified chitosan (CS) hydrogel based on Schiff base reaction. The hydrogel exhibited a porous network structure, a highly hydrophilic surface and good biocompatibility. We wrapped the PP mesh inside the hydrogel and evaluated the performance of the resulting composites in a bilateral 1 × 1.5 cm abdominal wall defect model in rats. The results of gross observation, histological staining and immunohistochemical staining demonstrated the positive impact of the CS hydrogel on anti-adhesion and wound healing effects. Notably, the addition of BSPA to the CS hydrogel further improved the performance of the composites in vivo, promoting wound healing by enhancing collagen deposition and capillary rearrangement. This study suggested that the BSPA-modified CS hydrogel significantly promoted the anti-adhesion, anti-inflammatory and pro-angiogenesis properties of PP meshes during the healing process. Overall, this work offers a novel approach to the design of abdominal wall repair patches.

17.
J Oral Biol Craniofac Res ; 14(4): 471-477, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962718

RESUMO

The clinical success of implanted biomaterials such as dental implants is largely determined by the molecular signaling that occurs at the tissue-implant interface. The modification of surface topography is a widely-employed strategy for optimizing tissue integration with dental implants. However, little is known regarding the direct, cellular-level effects of substratum topography on platelet signaling and adhesion, despite these cells being the first to encounter the implant surface during surgical placement. Here we compared platelet adhesion and secretion on four (4) different titanium surfaces, notably, the modifications applied to commercially available dental implants: smooth (S) titanium; acid-etched (AE), sandblasted (SB) and a combined acid-etching/sandblasting procedure (SLA). Platelets were isolated from human blood, washed, and seeded on to the 4 test surfaces; platelet adhesion was quantified by microscopy. In addition, the secretion of critical molecules stored in platelet granules (platelet factor 4, PF4; soluble P-selectin, sCD62P; transforming growth factor-beta1, TGF-ß1; platelet-derived growth factor-AB, PDGF-AB) was measured by enzyme-linked immunosorbent assay (ELISA) analysis of the supernatants. There was greater platelet adhesion to the rougher AE and SB surfaces, however, the concentration of the secreted growth factors was comparable on all surfaces. We conclude that while surface topography can be engineered to modulate initial platelet adhesion, granule secretion is likely regulated as a separate and independent process.

18.
ACS Appl Bio Mater ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38963794

RESUMO

Postoperative peritoneal adhesion (PPA) is a prevalent complication of abdominal surgery, posing a significant hindrance to postsurgical recovery. Although several strategies have been developed to alleviate and prevent adhesions, their efficacy remains unsatisfactory. For the first time, we studied the therapeutic effect and mechanism of our recently developed thermally stable oligonucleotide-based mimetics of hepatocyte growth factor (HGF DNA aptamer) to prevent PPA. The HGF DNA aptamer effectively inhibited canonical TGF-ß1 signaling transduction, partially suppressing mesothelial mesenchymal transition. Additionally, the aptamer, respectively, upregulated and downregulated the expression of tissue plasminogen activator and plasminogen activator inhibitor 1, thereby enhancing fibrinolytic activity. As a pleiotropic factor, the HGF DNA aptamer also enhanced the migratory and proliferative capacities of mesothelial cells. Finally, the aptamer demonstrated a higher level of effectiveness in preventing PPAs than the commercially available antiperitoneal adhesion barrier, Seprafilm. Due to its therapeutic benefits, excellent stability, biosafety, cost-effectiveness, and versatility, the HGF DNA aptamer demonstrates promise for preventing PPA in future clinical settings.

19.
Pathol Res Pract ; 260: 155440, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38964119

RESUMO

A cancer mass is composed of a heterogeneous group of cells, a small part of which constitutes the cancer stem cells since they are less differentiated and have a high capacity to develop cancer. Versican is an extracellular matrix protein located in many human tissues. The mRNA of versican has been shown to have "splicing patterns" as detected by RT-PCR, northern blot analysis, and cDNA sequencing. Based on this knowledge this study aims to reveal the splice variants of versican molecules, which are thought to be involved in the pathogenesis of the DU-145 human prostatic carcinoma cell line and prostatic cancer stem cells isolated from this cell line. In this study, RWPE-1 normal prostatic and DU-145 human prostate cancer cell lines have been used. Prostatic cancer stem cells and the remaining group of non-prostatic-cancer stem cells (bulk population) were isolated according to their CD133+/CD44+. RNA was isolated in all groups, and sequence analysis was accomplished for splicing variants by Illumina NextSeq 500 sequencing system. The results were analyzed by bioinformatic evaluation. As five isoforms of the versican gene in the differential transcript expression are analyzed, it was observed that a significant change was only found in the isoforms Versican 0 and Versican 1. In this study, we explored the function of this molecule which we think to be effective in cancer progression, and suggested that more valuable results can be obtained after the accomplishment of in vivo experiments.

20.
Acta Biomater ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38964526

RESUMO

Plant seeds and fruits, like those of Ocimum basilicum, develop a mucilaginous envelope rich in pectins and cellulosic fibers upon hydration. This envelope promotes adhesion for attachment to soils and other substrates for dispersal and protection of the seed for a safe germination. Initially at hydration, the mucilage envelope demonstrates low adhesion and friction, but shows increasing adhesive and frictional properties during dehydration. However, the mechanisms underlying the cellulose fiber arrangement and the mechanical properties, especially the elasticity modulus of the mucilage envelope at different hydration conditions are not fully known. In this study, which is based on scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM) and light microscopy, the structure of the seed coat and arrangement of the cellulose fibers of basil seeds were characterized. Moreover, we performed pull-off force measurements to estimate adhesive properties and JKR-tests to estimate E-modulus of the mucilage at different hydration levels. Microscopy results demonstrate that cellulose fibers are split at their free ends into smaller fibrils, which might enhance the adhesive properties of the mucilage. Adhesive forces in contact increased during dehydration and reached maximum of 33 mN shortly before complete dehydration. The E-modulus of the mucilage changed from 1.4 KPa in water to up to 2.1 MPa in the mucilage at the maximum of its adhesion performance. Obtained results showed hydrogel-like mechanical properties during dehydration and cellulose fiber structures similar to the nanofibrous systems in other organisms with strong adhesive properties. STATEMENT OF SIGNIFICANCE: This paper reveals the hierarchical cellulose fiber structure in Ocimum basilicum's mucilaginous seed coat, suggesting increased fiber splitting towards the end, potentially enhancing adhesion contact areas. Mechanical tests explore elasticity modulus and adhesion force during various hydration stages, crucial as these properties evolve with mucilage desiccation. A rare focus on mucilaginous seed coat mechanical properties, particularly cellulose-reinforced fibers, provides insight into the hydrogel-like mucilage of plant seeds. Adhesion forces peak just before complete desiccation and then decline rapidly. As mucilage water content decreases, the E-modulus rises, displaying hydrogel-like properties during early dehydration stages with higher water content. This study might bring the focus to plant seeds as inspiration for biodegradable glues and applications for hydrogel research.

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