Matrix Molecules Research Articles

Multidrug-Resistant Methicillin-Resistant Staphylococcus aureus Associated with Hospitalized Newborn Infants.

Multidrug resistance (MDR) is a significant challenge in healthcare management, and addressing it requires a comprehensive approach. In this study, we employed a combination of phenotypic and genotypic approaches, along with whole genome sequencing (WGS) to investigate five hospital-associated MDR methicillin-resistant Staphylococcus aureus (MRSA) strains that were isolated from newborn infants. Our analysis revealed the following for the MDR-MRSA strains: SauR31 was resistant to three antimicrobial classes; SauR12, SauR91 and SauR110 were resistant to four antimicrobial classes; and SauR23 exhibited resistance to seven classes. All the MDR-MRSA strains were capable of producing slime and biofilms, harbored SCCmec type IV, and belonged to different spa types (t022, t032, and t548), with varying profiles for microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) and virulence genes. The WGS data for the MDR SauR23 and SauR91 strains revealed that most of the antimicrobial resistance genes were present in the chromosomes, including blaZ, mecA, norA, lmrS, and sdrM, with only the ermC gene found in a small (<3 kb) plasmid. The presence of MDR-MRSA strains among neonates raises public concern, hence implementation of multifaceted interventions is recommended to address this issue. In addition, metadata is needed to improve the investigation of antimicrobial resistance genes in MDR isolates.

Extracellular matrix inclusion in immunoisolating alginate-based microcapsules promotes longevity, reduces fibrosis, and supports function of islet allografts in vivo.

Immunoisolation of pancreatic-islets in alginate-microcapsules is applied to treat diabetes. However, long-term islet function is limited, which might be due to damaged and lack of contact with pancreatic extracellular matrix (ECM) components. Herein we investigated the impact of collagen IV combined with laminin sequences, either RGD, LRE, or PDSGR, on graft-survival of microencapsulated bioluminescent islets in vivo. Collagen IV with RGD had the most pronounced effect. It enhanced after 8-week implantation in immune-incompetent mice the bioluminescence of allogeneic islets by 3.2-fold, oxygen consumption rate by 14.3-fold and glucose-induced insulin release by 9.6-fold. Transcriptomics demonstrated that ECM enhanced canonical pathways involving insulin-secretion and that it suppressed pathways related to inflammation and hypoxic stress. Also, 5.8-fold fewer capsules were affected by fibrosis. In a subsequent longevity study in immune-competent mice, microencapsulated allografts containing collagen IV and RGD had a 2.4-fold higher functionality in the first week after implantation and remained at least 2.1-fold higher during the study. Islets in microcapsules containing collagen IV and RGD survived 211 ± 24.1 days while controls survived 125 ± 19.7 days. Our findings provide in vivo evidence for the efficacy of supplementing immunoisolating devices with specific ECM components to enhance functionality and longevity of islet-grafts in vivo. STATEMENT OF SIGNIFICANCE: Limitations in duration of survival of immunoisolated pancreatic islet grafts is a major obstacle for application of the technology to treat diabetes. Accumulating evidence supports that incorporation of extracellular matrix (ECM) molecules in the capsules enhances longevity of pancreatic islets. After selection of the most efficacious laminin sequence in vitro, we show in vivo that inclusion of collagen IV and RGD in alginate-based microcapsules enhances survival, insulin secretion function, and mitochondrial function. It also suppresses fibrosis by lowering proinflammatory cytokines secretion. Moreover, transcriptomic analysis shows that ECM-inclusion promotes insulin-secretion related pathways and attenuates inflammation and hypoxic stress related pathways in islets. We show that inclusion of ECM in immunoisolating devices is a promising strategy to promote long-term survival of islet-grafts.

Regenerative Capability of Human Nucleus Pulposus Cells in Degenerated Disc Under Hydrostatic Pressure Mimicking Physiologically Relevant Intradiscal Pressure In Vitro.

Isolated human nucleus pulposus (hNP) cells from the degenerated intervertebral disc (IVD) were incubated under hydrostatic pressure (HP) and evaluated for regenerative potential. To characterize metabolic turnover in hNP cells isolated from degenerated IVDs classified by Pfirrmann grade under physiologically relevant HP at high osmolality in vitro. We demonstrated that bovine caudal nucleus pulposus cells isolated from healthy cows produced more extracellular matrix under cyclic HP followed by constant pressure (mimicking physiological intradiscal pressure in humans) than under no pressure in vitro. We assessed the effects of pressure on human degenerated cells isolated under the same regimen of pressure used for bovine cells. hNP cells isolated from discarded tissue classified as Pfirrmann grade 2 to 3 (n = 13: age, 46.7 ± 14.0) and grade 4 (n = 13: age, 53.0 ± 11.5) were incubated under cyclic HP at 0.2 to 0.7 MPa, 0.5 Hz for 2 days followed by constant pressure at 0.3 MPa for 1 day, repeated twice over 6 days. The gene expression and immunohistology of matrix molecules and catabolic and anticatabolic proteins were evaluated. Aggrecan and collagen type II expression were significantly more upregulated under HP in grades 2 to 3 than in grade 4 tissues (both, P < 0.01). Linear regression analysis showed a positive correlation between matrix metalloproteinase 13 and tissue inhibitor for metalloproteinase 2 expression in grades 2 to 3, whereas a negative correlation was found in grade 4 ( P < 0.05). Immunohistological staining revealed the activation of a mechanoreceptor, transient receptor potential vanilloid 4, under HP. Resident cells in mild-moderate degenerated discs classified as Pfirrmann grade 2 to 3 have the potential to promote extracellular matrix production and maintain adequate cell viability under physiological spinal loading. This study explored the potential of degenerated remnant nucleus pulposus cells under a physiological environment, possibly leading to establishing strategies for IVD regeneration.

Cooperation between primary cilia signaling and integrin receptor extracellular matrix engagement regulates progenitor proliferation and neuronal differentiation in the developing cerebellum.

Neural progenitors and their neuronal progeny are bathed in extrinsic signals that impact critical decisions like the mode of cell division, how long they should reside in specific neuronal laminae, when to differentiate, and the timing of migratory decisions. Chief among these signals are secreted morphogens and extracellular matrix (ECM) molecules. Among the many cellular organelles and cell surface receptors that sense morphogen and ECM signals, the primary cilia and integrin receptors are some of the most important mediators of extracellular signals. Despite years of dissecting the function of cell-extrinsic sensory pathways in isolation, recent research has begun to show that key pathways work together to help neurons and progenitors interpret diverse inputs in their germinal niches. This mini-review utilizes the developing cerebellar granule neuron lineage as a model that highlights evolving concepts on the crosstalk between primary cilia and integrins in the development of the most abundant neuronal type in the brains of mammals.

The phenotypes and genotypes associated with biofilm formation among methicillin-susceptible Staphylococcus aureus (MSSA) isolates collected from a tertiary hospital in Terengganu, Malaysia.

Methicillin-susceptible Staphylococcus aureus (MSSA) is an important nosocomial pathogen worldwide. This study aims to investigate the in vitro biofilm-forming ability of clinical MSSA isolated from various sources in the main public tertiary referral hospital in Terengganu, Malaysia and to detect the presence of biofilm-associated and regulatory genes among these isolates. A total of 104 MSSA isolates [pus (n = 75), blood (n = 24), respiratory secretions (n = 2), eye (n = 2), and urine (n = 1)] were investigated for slime production and biofilm formation using Congo red agar and crystal violet microtitre plate, respectively. Fifteen MSSA isolates with varying degrees of biofilm formation were selected for validation via a real-time cell analyser. All isolates were screened for microbial surface components recognising adhesive matrix molecules (MSCRAMM) and accessory gene regulator (agr) using polymerase chain reaction assay. A total of 76.0% (79/104) isolates produced slime layer, while all isolates developed biofilm as follows: 52.8% (55/104) strong biofilm producers, 40.4% (42/104) intermediate biofilm producers, and 6.7% (7/104) weak biofilm producers. A total of 98.1% (102/104) isolates carried at least one of the screened MSCRAMM gene(s) with the eno gene detected at the highest rate (87.5%, 91/104), while the sasG gene was significantly associated with strong biofilm production (p = 0.015). Three agr groups, 1, 2, and 3, were detected among the MSSA isolates with a predominance of agr-3 (32.7%, 34/104). In conclusion, biofilm formation varied greatly among clinical MSSA isolates, and the presence of sasG gene and agr-1 may play important role in initiating MSSA infections via biofilm formation.

Space Omics and Tissue Response in Astronaut Skeletal Muscle after Short and Long Duration Missions.

The molecular mechanisms of skeletal muscle adaptation to spaceflight are as yet not fully investigated and well understood. The MUSCLE BIOPSY study analyzed pre and postflight deep calf muscle biopsies (m. soleus) obtained from five male International Space Station (ISS) astronauts. Moderate rates of myofiber atrophy were found in long-duration mission (LDM) astronauts (~180 days in space) performing routine inflight exercise as countermeasure (CM) compared to a short-duration mission (SDM) astronaut (11 days in space, little or no inflight CM) for reference control. Conventional H&E scout histology showed enlarged intramuscular connective tissue gaps between myofiber groups in LDM post vs. preflight. Immunoexpression signals of extracellular matrix (ECM) molecules, collagen 4 and 6, COL4 and 6, and perlecan were reduced while matrix-metalloproteinase, MMP2, biomarker remained unchanged in LDM post vs. preflight suggesting connective tissue remodeling. Large scale proteomics (space omics) identified two canonical protein pathways associated to muscle weakness (necroptosis, GP6 signaling/COL6) in SDM and four key pathways (Fatty acid β-oxidation, integrin-linked kinase ILK, Rho A GTPase RHO, dilated cardiomyopathy signaling) explicitly in LDM. The levels of structural ECM organization proteins COL6A1/A3, fibrillin 1, FBN1, and lumican, LUM, increased in postflight SDM vs. LDM. Proteins from tricarboxylic acid, TCA cycle, mitochondrial respiratory chain, and lipid metabolism mostly recovered in LDM vs. SDM. High levels of calcium signaling proteins, ryanodine receptor 1, RyR1, calsequestrin 1/2, CASQ1/2, annexin A2, ANXA2, and sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA1) pump, ATP2A, were signatures of SDM, and decreased levels of oxidative stress peroxiredoxin 1, PRDX1, thioredoxin-dependent peroxide reductase, PRDX3, or superoxide dismutase [Mn] 2, SOD2, signatures of LDM postflight. Results help to better understand the spatiotemporal molecular adaptation of skeletal muscle and provide a large scale database of skeletal muscle from human spaceflight for the better design of effective CM protocols in future human deep space exploration.

Molecular Simulation Study on the Aging Mechanism of NEPE Propellant Matrix

Polyethylene glycols (PEG) and toluene diisocyanate (TDI) are often used as the main components of binders and curing agents in solid propellants, and their aging is an important issue in the storage and use of propellants. To study the aging behavior and aging mechanism of nitrate ester plasticized polyether propellant (NEPE) matrix during storage, the transition states of aging reactions of binder and curing agent were optimized at the (U)B3LYP/6-311G(d,p) level of theory, and the rate coefficients over the temperature range of 298-1000 K were calculated by CVT theory. The results showed that there were five kinds of aging reactions for binder, which included decomposition, nitration, H abstraction, oxidation, and crosslinking reactions. Among them, theenergy barriers of oxidation and H abstraction reactions were relatively low (79.3-91.2 kJ·mol-1) and the main reaction types of binder aging. The main aging reaction of curing agent was decomposition. Compared with the aging reactions of binder, the energy barriers of curing agent are higher (196.6-282.7 kJ·mol-1) and the reaction is more difficult to occur. By comparing the energy barriers and rate constants of different reactions, it is found that the aging of NEPE propellant matrix can be divided into two stages. In the first stage, the propellant matrix mainly undergoes H abstraction and oxidation reaction, and as the reaction proceeds, the products crosslink to form -O-O-, -C-C-, and -C-O-C- bonds. At this time, the long chain molecules of the propellant matrix crosslink, and the molecular weight increases. This stage corresponds to the rising stage of mechanical properties in the aging process of the propellant. In the second stage, the propellant matrix mainly undergoes decomposition and nitration, resulting in degradation, the reduction of molecular weights, and the appearance of holes and microcracks in the matrix. This stage corresponds to the decline of mechanical properties in the aging process of the propellant. The above simulation results are in good agreement with the aging experimental phenomena, revealing the microscopic mechanism of the changes in the macroscopic properties of NEPE propellant during the aging process, and providing a theoretical basis for the related research on the aging properties and anti-aging technology of NEPE propellant.

The injections of mitochondrial fusion promoter M1 during proestrus disrupt the progesterone secretion and the estrous cycle in the mouse

After ovulation, the mitochondrial enzyme CYP11A1 cleavage the cholesterol into pregnenolone for progesterone synthesis, suggesting that mitochondrial dynamics play a vital role in the female reproductive system. The changes in the mitochondria dynamics throughout the ovarian cycle have been reported in literature, but the correlation to its role in the ovarian cycle remains unclear. In this study, mitochondrial fusion promotor, M1, was used to study the impact of mitochondria dynamics in the female reproductive system. Our results showed that M1 treatment in mice can lead to the disruptions of estrous cycles in vagina smears. The decrease in serum LH was recorded in the animal. And the inhibitions of progesterone secretion and ovulations were observed in ovarian culture. Although no significant changes in mitochondrial networks were observed in the ovaries, significant up-regulation of mitochondrial respiratory complexes was revealed in M1 treatments through transcriptomic analysis. In contrast to the estrogen and steroid biosynthesis up-regulated in M1, the molecules of extracellular matrix, remodeling enzymes, and adhesion signalings were decreased. Collectively, our study provides novel targets to regulate the ovarian cycles through the mitochondria. However, more studies are still necessary to provide the functional connections between mitochondria and the female reproductive systems.

Axon guidance gene-targeted siRNA delivery system improves neural stem cell transplantation therapy after spinal cord injury

BackgroundNeural stem cells (NSCs) derived from the embryonic spinal cord are excellent candidates for the cellular regeneration of lost neural cells after spinal cord injury (SCI). Semaphorin 3 A (Sema3A) is well known as being implicated in the major axon guidance of the growth cone as a repulsive function during the development of the central nervous system, yet its function in NSC transplantation therapy for SCI has not been investigated. Here, we report for the first time that embryonic spinal cord-derived NSCs significantly express Sema3A in the SCI environment, potentially facilitating inhibition of cell proliferation after transplantation.MethodssiRNA-Sema3A was conjugated with poly-l-lysin-coated gold nanoparticles (AuNPs) through a charge interaction process. NSCs were isolated from embryonic spinal cords of rats. Then, the cells were embedded into a dual-degradable hydrogel with the siRNA- Sema3A loaded-AuNPs and transplanted after complete SCI in rats.ResultsThe knockdown of Sema3A by delivering siRNA nanoparticles via dual-degradable hydrogels led to a significant increase in cell survival and neuronal differentiation of the transplanted NSCs after SCI. Of note, the knockdown of Sema3A increased the synaptic connectivity of transplanted NSC in the injured spinal cord. Moreover, extracellular matrix molecule and functional recovery were significantly improved in Sema3A-inhibited rats compared to those in rats with only NSCs transplanted.ConclusionsThese findings demonstrate the important role of Sema3A in NSC transplantation therapy, which may be considered as a future cell transplantation therapy for SCI cases.Graphical

Stimulation of Chondrogenesis in a Developmental Model of Endochondral Bone Formation by Pulsed Electromagnetic Fields.

Notable characteristics of the skeleton are its responsiveness to physical stimuli and its ability to remodel secondary to changing biophysical environments and thereby fulfill its physiological roles of stability and movement. Bone and cartilage cells have many mechanisms to sense physical cues and activate a variety of genes to synthesize structural molecules to remodel their extracellular matrix and soluble molecules for paracrine signaling. This review describes the response of a developmental model of endochondral bone formation which is translationally relevant to embryogenesis, growth, and repair to an externally applied pulsed electromagnetic field (PEMF). The use of a PEMF allows for the exploration of morphogenesis in the absence of distracting stimuli such as mechanical load and fluid flow. The response of the system is described in terms of the cell differentiation and extracellular matrix synthesis in chondrogenesis. Emphasis is placed upon dosimetry of the applied physical stimulus and some of the mechanisms of tissue response through a developmental process of maturation. PEMFs are used clinically for bone repair and have other potential clinical applications. These features of tissue response and signal dosimetry can be extrapolated to the design of clinically optimal stimulation.

Antimicrobial susceptibility and biofilm forming ability of staphylococci from subclinical buffalo mastitis.

The starting objective of this research communication was to determine the prevalence of subclinical mastitis in buffalo in Turkey. We also seeked to isolate and identify staphylococci, determine their antimicrobial susceptibilities and biofilm-forming abilities as well as investigating the presence of biofilm-related genes and microbial surface components recognizing adhesive matrix molecules. A total of 107 (66.9%) staphylococci (28 S. aureus and 79 coagulase-negative staphylococci, CoNS) were isolated from 160 mastitic milk samples collected from 200 lactating water buffalos. The staphylococci were especially resistant to beta-lactams except for cefoxitin but were less resistant to the other antimicrobials that were tested. Based on the Congo red agar method, 92.9% of the S. aureus and 70.9% of the CoNS isolates were positive for biofilm-forming ability, while all S. aureus and 97.5% of CoNS isolates were positive by a microtiter plate analysis. The presence of icaA and icaD genes was not always correlated with biofilm synthesis, and even in the absence of these genes, the isolates were able to synthesize biofilm.

Hyaluronan in the Cancer Cells Microenvironment.

The presence of the glycosaminoglycan hyaluronan in the extracellular matrix of tissues is the result of the cooperative synthesis of several resident cells, that is, macrophages and tumor and stromal cells. Any change in hyaluronan concentration or dimension leads to a modification in stiffness and cellular response through receptors on the plasma membrane. Hyaluronan has an effect on all cancer cell behaviors, such as evasion of apoptosis, limitless replicative potential, sustained angiogenesis, and metastasis. It is noteworthy that hyaluronan metabolism can be dramatically altered by growth factors and matrikines during inflammation, as well as by the metabolic homeostasis of cells. The regulation of HA deposition and its dimensions are pivotal for tumor progression and cancer patient prognosis. Nevertheless, because of all the factors involved, modulating hyaluronan metabolism could be tough. Several commercial drugs have already been described as potential or effective modulators; however, deeper investigations are needed to study their possible side effects. Moreover, other matrix molecules could be identified and targeted as upstream regulators of synthetic or degrading enzymes. Finally, co-cultures of cancer, fibroblasts, and immune cells could reveal potential new targets among secreted factors.

Urine-based multi-omic comparative analysis of COVID-19 and bacterial sepsis-induced ARDS

BackgroundAcute respiratory distress syndrome (ARDS), a life-threatening condition during critical illness, is a common complication of COVID-19. It can originate from various disease etiologies, including severe infections, major injury, or inhalation of irritants. ARDS poses substantial clinical challenges due to a lack of etiology-specific therapies, multisystem involvement, and heterogeneous, poor patient outcomes. A molecular comparison of ARDS groups holds the potential to reveal common and distinct mechanisms underlying ARDS pathogenesis.MethodsWe performed a comparative analysis of urine-based metabolomics and proteomics profiles from COVID-19 ARDS patients (n = 42) and bacterial sepsis-induced ARDS patients (n = 17). To this end, we used two different approaches, first we compared the molecular omics profiles between ARDS groups, and second, we correlated clinical manifestations within each group with the omics profiles.ResultsThe comparison of the two ARDS etiologies identified 150 metabolites and 70 proteins that were differentially abundant between the two groups. Based on these findings, we interrogated the interplay of cell adhesion/extracellular matrix molecules, inflammation, and mitochondrial dysfunction in ARDS pathogenesis through a multi-omic network approach. Moreover, we identified a proteomic signature associated with mortality in COVID-19 ARDS patients, which contained several proteins that had previously been implicated in clinical manifestations frequently linked with ARDS pathogenesis.ConclusionIn summary, our results provide evidence for significant molecular differences in ARDS patients from different etiologies and a potential synergy of extracellular matrix molecules, inflammation, and mitochondrial dysfunction in ARDS pathogenesis. The proteomic mortality signature should be further investigated in future studies to develop prediction models for COVID-19 patient outcomes.

Effects of Electrical Stimulation on Articular Cartilage Regeneration with a Focus on Piezoelectric Biomaterials for Articular Cartilage Tissue Repair and Engineering.

There is increasing evidence that chondrocytes within articular cartilage are affected by endogenous force-related electrical potentials. Furthermore, electrical stimulation (ES) promotes the proliferation of chondrocytes and the synthesis of extracellular matrix (ECM) molecules, which accelerate the healing of cartilage defects. These findings suggest the potential application of ES in cartilage repair. In this review, we summarize the pathogenesis of articular cartilage injuries and the current clinical strategies for the treatment of articular cartilage injuries. We then focus on the application of ES in the repair of articular cartilage in vivo. The ES-induced chondrogenic differentiation of mesenchymal stem cells (MSCs) and its potential regulatory mechanism are discussed in detail. In addition, we discuss the potential of applying piezoelectric materials in the process of constructing engineering articular cartilage, highlighting the important advances in the unique field of tissue engineering.

Stromal cells support the survival of human primary chronic lymphocytic leukemia (CLL) cells through Lyn-driven extracellular vesicles.

In chronic lymphocytic leukemia (CLL), the tumor cells receive survival support from stromal cells through direct cell contact, soluble factors and extracellular vesicles (EVs). The protein tyrosine kinase Lyn is aberrantly expressed in the malignant and stromal cells in CLL tissue. We studied the role of Lyn in the EV-based communication and tumor support. We compared the Lyn-dependent EV release, uptake and functionality using Lyn-proficient (wild-type) and -deficient stromal cells and primary CLL cells. Lyn-proficient cells caused a significantly higher EV release and EV uptake as compared to Lyn-deficient cells and also conferred stronger support of primary CLL cells. Proteomic comparison of the EVs from Lyn-proficient and -deficient stromal cells revealed 70 significantly differentially expressed proteins. Gene ontology studies categorized many of which to organization of the extracellular matrix, such as collagen, fibronectin, fibrillin, Lysyl oxidase like 2, integrins and endosialin (CD248). In terms of function, a knockdown of CD248 in Lyn+ HS-5 cells resulted in a diminished B-CLL cell feeding capacity compared to wildtype or scrambled control cells. CD248 is a marker of certain tumors and cancer-associated fibroblast (CAF) and crosslinks fibronectin and collagen in a membrane-associated context. Our data provide preclinical evidence that the tyrosine kinase Lyn crucially influences the EV-based communication between stromal and primary B-CLL cells by raising EV release and altering the concentration of functional molecules of the extracellular matrix.

Molecular Analysis of Pathogenicity, Adhesive Matrix Molecules (MSCRAMMs) and Biofilm Genes of Coagulase-Negative Staphylococci Isolated from Ready-to-Eat Food.

This paper provides a snapshot on the pathogenic traits within CoNS isolated from ready-to-eat (RTE) food. Eighty-five strains were subjected to biofilm and slime production, as well as biofilm-associated genes (icaA, icaD, icaB, icaC, eno, bap, bhp, aap, fbe, embP and atlE), the insertion sequence elements IS256 and IS257 and hemolytic genes. The results showed that the most prevalent determinants responsible for the primary adherence were eno (57.6%) and aap (56.5%) genes. The icaADBC operon was detected in 45.9% of the tested strains and was correlated to slime production. Moreover, most strains carrying the icaADBC operon simultaneously carried the IS257 insertion sequence element. Among the genes encoding for surface proteins involved in the adhesion to abiotic surfaces process, atlE was the most commonly (31.8%) followed by bap (4.7%) and bhp (1.2%). The MSCRAMMs, including fbe and embp were detected in the 11.8% and 28.2% of strains, respectively. A high occurrence of genes involved in the hemolytic toxin production were detected, such as hla_yiD (50.6%), hlb (48.2%), hld (41.2%) and hla_haem (34.1%). The results of the present study revealed an unexpected occurrence of the genes involved in biofilm production and the high hemolytic activity among the CoNS strains, isolated from RTE food, highlighting that this group seems to be acquiring pathogenic traits similar to those of S. aureus, suggesting the need to be included in the routine microbiological analyses of food.

Macrophage scavenger receptors: Tumor support and tumor inhibition.

Tumor-associated macrophages (TAMs) are a heterogeneous population of myeloid cells that constitute up to 50% of the cell mass of human tumors. TAMs interact with the components of the tumor microenvironment (TME) by using scavenger receptors (SRs), a large superfamily of multifunctional receptors that recognize, internalize and transport to the endosomal/lysosomal pathway apoptotic cells, cytokines, matrix molecules, lipid modified lipoproteins and other unwanted-self ligands. In our review, we summarized state-of-the art for the role of macrophage scavenger receptors in tumor development and their significance as cancer biomarkers. In this review we focused on functional activity of TAM-expressing SRs in animal models and in patients, and summarized the data for different human cancer types about the prognostic significance of TAM-expressed SRs. We discussed the role of SRs in the regulation of cancer cell biology, cell-cell and cell-matrix interaction in TME, immune status in TME, angiogenesis, and intratumoral metabolism. Targeting of tumor-promoting SRs can be a promising therapeutic approach in anti-cancer therapy. In our review we provide evidence for both tumor supporting and tumor inhibiting functions of scavenger receptors expressed on TAMs. We focused on the key differences in the prognostic and functional roles of SRs that are specific for cancer types. We highlighted perspectives for inhibition of tumor-promoting SRs in anti-cancer therapy.

Unexpected Crosslinking Effects of a Human Thyroid Stimulating Monoclonal Autoantibody, M22, with IGF1 on Adipogenesis in 3T3L-1 Cells.

To study the effects of the crosslinking of IGF1 and/or the human thyroid-stimulating monoclonal autoantibody (TSmAb), M22 on mouse adipocytes, two- and three-dimensional (2D or 3D) cultures of 3T3-L1 cells were prepared. Each sample was then subjected to the following analyses: (1) lipid staining, (2) a real-time cellular metabolic analysis, (3) analysis of the mRNA expression of adipogenesis-related genes and extracellular matrix (ECM) molecules including collagen (Col) 1, 4 and 6, and fibronectin (Fn), and (4) measurement of the size and physical properties of the 3D spheroids with a micro-squeezer. Upon adipogenic differentiation (DIF+), lipid staining and the mRNA expression of adipogenesis-related genes in the 2D- or 3D-cultured 3T3-L1 cells substantially increased. On adding IGF1 but not M22 to DIF+ cells, a significant enhancement in lipid staining and gene expressions of adipogenesis-related genes was detected in the 2D-cultured 3T3-L1 cells, although some simultaneous suppression or enhancement effects by IGF1 and M22 against lipid staining or Fabp4 expression, respectively, were detected in the 3D 3T3-L1 spheroids. Real-time metabolic analyses indicated that monotherapy with IGF1 or M22 shifted cellular metabolism toward energetic states in the 2D 3T3-L1 cells upon DIF+, although no significant metabolic changes were induced by DIF+ alone in 2D cultures. In addition, some synergistical effects on cellular metabolism by IGF1 and M22 were also observed in the 2D 3T3-L1 cells as well as in cultured non-Graves' orbitopathy-related human orbital fibroblasts (n-HOFs), but not in Graves' orbitopathy-related HOFs (GHOFs). In terms of the physical properties of the 3D 3T3-L1 spheroids, (1) their sizes significantly increased upon DIF+, and this increase was significantly enhanced by the presence of both IGF1 and M22 despite downsizing by monotreatment, and (2) their stiffness increased substantially, and no significant effects by IGF-1 and/or M22 were observed. Regarding the expression of ECM molecules, (1) upon DIF+, significant downregulation or upregulation of Col1 and Fn (3D), or Col4 and 6 (2D and 3D) were observed, and (2) in the presence of IGF-1 and/or M22, the mRNA expression of Col4 was significantly downregulated by M22 (2D and 3D), but the expression of Col1 was modulated in different manners by monotreatment (upregulation) or the combined treatment (downregulation) (3D). These collective data suggest that the human-specific TSmAb M22 induced some unexpected simultaneous crosslinking effects with IGF-1 with respect to the adipogenesis of 2D-cultured 3T3-L1 cells and the physical properties of 3D 3T3-L1 spheroids.

Anion dynamics and motional decoupling in a glycerol-choline chloride deep eutectic solvent studied by one- and two-dimensional 35Cl NMR.

Chlorine-35 is among the few nuclides that provide an experimental handle on the anion dynamics in choline based deep eutectic solvents. By combining several nuclear magnetic resonance (NMR) techniques, the present work examines the Cl- motions within glyceline, a glycerol : choline chloride 2 : 1 solution, in a large temperature range down to the glass transition temperature Tg. The applied methods include spin relaxometry, second-order line shape analysis, as well as two-dimensional central-transition exchange and stimulated-echo spectroscopy. The finding of unstructured central-transition NMR spectra characterized by a relatively small average quadrupolar coupling attests to a highly disordered, essentially nondirectional anionic coordination in glyceline. For temperatures larger than about 1.3Tg the chlorine motions are well coupled to those of the glycerol and the choline moieties. At lower temperatures the local translational anion dynamics become Arrhenian and increasingly faster than the motion of glyceline's matrix molecules. Upon further cooling, the overall ionic conductivity continues to display a super-Arrhenius behavior, implying that the choline cations rather than the Cl anions dominate the long-range charge transport also near Tg.

Amphoteric waterborne polyurethane with unsaturated carboxyl group as crosslinker to improve cohesive strength of soybean protein-based adhesive for excellent cold-pressing adhesion

The cold-pressing performance of adhesives is important for the preparation of wood-based panels. Adhesives for wood-based panels must have appropriate viscosity, strong interfacial adhesion to wood substrates with hydration layers, and excellent cohesive strength at ambient temperature for cold-pressing adhesion. However, bio-based adhesives synthesized using conventional modification approaches still struggle to meet these standards. Herein, an amphoteric waterborne polyurethane with an unsaturated carboxyl group (AWPU-UC) is prepared as a crosslinker to modify soybean meal (SM) matrix, and prepare a soybean protein-based adhesive with excellent cold-pressing adhesion and mildew resistance. The unsaturated carboxyl groups form electrostatic interactions with tertiary ammonium groups of polyurethane and amino groups of protein molecules in the SM matrix. These bonds enhance both the cohesion of adhesive molecular network and the interaction between the adhesive and wood surface with “hydration layers”. Consequently, the cold-pressing bonding strength of the adhesives SM/AWPU-UC-4 reaches 271% of that of pure SM adhesive. In addition, the quaternary ammonium structure formed by electrostatic interactions in the AWPU-UC system endows the adhesive with mildew resistance. This study provides a simple and effective method for producing high-performance protein-based adhesives with outstanding cold-pressing adhesion and mildew resistance. • An amphoteric waterborne polyurethane emulsion with unsaturated carboxyl groups was synthesized. • The emulsion facilitated diffusion and creation of interaction of adhesives with the wood substrate. • The electrostatic interaction between unsaturated carboxyl groups and aminos on protein promoted cohesive crosslinking. • The quaternary ammonium structure produced by electrostatic interaction made it possess bactericidal ability. • The bio-adhesives had excellent cold-pressing performance and mildew resistance with AWPU-UC as a crosslinker.