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PubMed1978

Effects of albumin on the phagocytosis of polystyrene spherules by rabbit polymorphonuclear leucocytes.

Polystyrene latex spherules are rapidly phagocytized by polymorphonuclear leucocytes. Surface modifications of the latex spherules can lead to an inhibition of phagocytosis, and the purpose of this study was to analyse in particular inhibition by bovine and human serum albumin. It can be shown that albumin is bound much more strongly by the PSL particle surface than by the cell surface. Furthermore, a correlation was established between the extent to which the particle surface is covered and the extent of phagocytosis inhibition. In the binding of albumin to the particle surface ionic as well as hydrophobic interactions play a role. As a result, the particle acquires a negatively charged hydrophilic coating which effectively diminishes the number of effective cell-particle collisions leading to engulfment.

Animals↗
PubMed2026

Targeted Nanoparticle Delivery CRISPR/Cas9: overcoming biological barriers, enhancing stability, and improving therapeutic precision.

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) has emerged as a promising gene-editing platform for genetic disorders; however, its in vivo application remains limited by low delivery efficiency and biological barriers. Many CRISPR payloads fail to reach target sites due to extracellular degradation, immune clearance, and intracellular trafficking limitations. This review examines the interplay between biological barriers and nanoparticle engineering strategies for CRISPR/Cas9 delivery. A barrier-oriented engineering approach is proposed as a central framework, encompassing ligand-based surface modification for enhanced targeting and uptake, improved circulation stability via PEGylation and biomimetic coatings, and optimized payload release through endosomal escape strategies. Stimulus-responsive nanoparticle systems further enable spatiotemporal control over payload release. Nuclear targeting strategies, including optimization of nuclear localization signals (NLS) and exploitation of endogenous trafficking pathways, are highlighted as key factors for improving genome-level editing efficiency. Despite these advances, major challenges-including limited intracellular delivery efficiency, insufficient targeting precision, and safety concerns-continue to hinder clinical translation. Future directions highlight artificial intelligence-driven nanoparticle design, personalized delivery systems, and next-generation CRISPR platforms. Overall, an integrated, barrier-oriented engineering strategy is essential for advancing CRISPR/Cas9 delivery toward clinical applications, ultimately advancing global good health and well-being.

CRISPR/Cas9↗
PubMed1977

Distribution of anionic sites on the oviduct ciliary membrane.

Polycationic ferritin (PCF) was used as a visual probe for anionic sites on the oviduct ciliary membrane. The binding of PCF to ciliary membranes was dependent on the concentration of the probe in the incubation media. At low concentrations (0.08-0.16 mg/ml), PCF was bound exclusively to the tip of the cilium whereas at higher concentrations (0.32-0.64 mg/ml), ferritin was located at the tip and at the base around the transition region, with occasional scattered clumps on the remainder of the membrane. The base and tip binding was fount to be associated with special surface modifications of the membrane in these regions. At the tip, PCF was bound to a filamentous glycocalyx termed the ciliary crown. Base binding was associated with a system of five to six 140-A high ridges, each of which encircled the membrane of the transition region. The ridges were equally spaced (approxamately 245 A spacing) along the length of the transition region. Since pretreatment of oviduct with either neuraminidase or protease blocked the binding of the probe, the PCF-binding sites appear to be negatively charged glycoproteins or mucopolysaccharides.

Animals↗
PubMed1979

Adaptive differences of the surface organization of horny cells.

The existence of a peculiar structural pattern of complementary villi and pores was observed on the squamous surfaces of palms and soles. These features, which might be considered as acquired and adaptive cell surface modifications, proved to be more conspicuous during a period of rat and human postnatal development.

Animals↗
PubMed1979

The role of sialated glycoproteins in endocytosis, permeability and transmural passage in the myeloid endothelium.

Changes in the anionic charge distribution at the luminal face of the endothelium of the sinusoids of the bone marrow have been studied at sites of endocytosis by large bristle coated vesicles and at the sites of molecular permeability through diaphragmed fenestrae. The anionic charge distribution has also been studied at the abluminal aspect of these vessels at sites of transmural blood cell passage. Cationic surface markers such as colloidal iron, native ferritin and polycationic ferritin used at low pH, 1.8, and the use of neuraminidase show that the nonmodified endothelial cell surface has exposed sialic acid groups, which are absent at the sites of these functional specializations. Polycationic ferritin binding over a range of pH levels indicates the prsence of another species of anionic materials present at both the nonmodified cell surface and at the sites of the cell surface modifications. This second group of anionic compounds is neuraminidase resistant and has a pKa higher than that of sialic acid (pKa:2.6).

Binding Sites↗
PubMed1979

An ultrastructural comparison of human endometrial adenocarcinoma with normal postmenopausal endometrium.

Although electron microscopy has been of limited value in detecting malignant neoplasms, some neoplasms do exhibit characteristic ultrastructural features. Intensive study of these features may offer insight into the etiology and activity of such tumors. In an attempt to characterize the ultrastructure of endometrial adenocarcinoma, tissue was examined with the electron microscope and compared with normal postmenopausal endometrium. Endometria from biopsy, hysterectomy, or curettage were processed routinely for light and electron microscopy. Several ultrastructural features of the adenocarcinoma were common both to previous descriptions of endometrium of the postovulatory phase and to the normal postmenopausal endometrium, described here, viz, atypical mitochondrial forms and cell surface modifications. Ribosomes were abundant in adenocarcinoma of the endometrium, normal postmenopausal endometrium, and normal cyclic endometrium in the preovulatory phase.

Adenocarcinoma↗
PubMed1979

Extraskeletal Ewing's sarcoma. Histologic and ultrastructural observations in three cases.

The histologic and ultrastructural morphology of three cases of Ewing's sarcoma of soft tissue are described and the fine structural features of extraskeletal Ewing's sarcoma are compared to those of similar round-cell tumors that are considered in the differential diagnosis. By light microscopy, these tumors are indistinguishable from Ewing's sarcoma of bone. Ultrastructurally, the salient features are also comparable to Ewing's sarcoma of bone and include: 1) absence of surface modifications; 2) cell-contact sites in the form of small thickenings of apposed membranes and large desmosome-like specializations; 3) undifferentiated cytoplasm usually containing abundant glycogen and occasionally nonspecific microfilaments; 4) significant variation in shape and irregularity of nuclear profiles. The ultrastructural features of extraskeletal Ewing's sarcoma are sufficiently distinctive to allow separation from from other small-cell malignant neoplasms in the majority of cases.

Adult↗
PubMed1978

The structure of the germinal disc region of the hen's ovarian follicle during the rapid growth phase.

The structure of the ovarian follicle in the region of the germinal disc, which appears as a white plaque at the surface of the oocyte, was examined by electron microscopy and compared with the non-disc region which overlies the yellow yolk mass of the oocyte in the final growth phase. The main differences concerned the granulosa cell layer and the surface layer of the oocyte. In the disc the granulosa cells were less regularly arranged and the spaces between them varied in width. Their mitotic rate was higher than that in the non-disc region, where cell division was seldom observed at maturity. The perivitelline layer was comparatively poorly developed at the periphery of the germinal vesicle in 15 mm follicles, but eventually attained a uniform thickness throughout the follicle. In the intercellular and perivitelline spaces there were smaller amounts of granular material. Marked differences were observed in the ooxyte surface layer. In 15 mm follicles the surface of the germinal disc was thrown into numerous microvilli and some narrow indentations containing macrovilli from the granulosa cells. Coated vesicles, 120 nm diameter, appeared to be invaginating from the oolemma, whereas 70 nm coated vesicles were present in the deeper cytoplasm. In follicles of more than 25 nm diameter these structural conformations were evident only at the periphery of the disc; for the most part the 120 nm coated vesicles were absent, and over the germinal vesicle microvilli were of rare occurrence. On the other hand, the bulk of the oocyte surface was highly convoluted throughout this period of growth, numerous granulosa cell macrovilli extended into deep pouches associated with 300 nm coated vesicles, and the oolemma possessed a coating of fuzzy material. These observations suggest that there is a restricted passage of yolk precursors to the surface of the germinal disc, and that the inability to transport yellow yolk into the disc is related to differences in the oolemmal surface coat and the population of coated vesicles. The surface modifications, as well as the proliferation of the granulosa cells, are likely to be influenced by the presence of the germinal vesicle.

Animals↗
PubMed1977

Effect of chemical modification of cell surface components of a brewer's yeast on the floc-forming ability.

Effects of treatments with proteolytic enzymes and protein-modifying reagents on flocculation of brewer's yeast IFO 2018 were investigated. The floc-forming ability of the yeast cells was irreversibly eliminated by treatment with papain, trypsin, chymotrypsin or pepsin, indicating that certain proteins on the cell surface participate in the yeast flocculation. Chemical modification with reagents, known to act on disulfide bridges, carboxyl and/or phosphate groups, phenolic groups, amino groups, and imidazole groups, also destroyed the ability to flocculate, although in some cases a high concentration (8 M) of urea was necessary in addition to protein-modifying reagents. Thus, it is suggested strongly that these functional groups of amino acid residues of the proteins are essential for the floc-forming ability of brewer's yeast cells.

Cell Wall↗
PubMed1977

A comparative study of the effect of modification of the surface of human platelets on the receptors for aggregated immunoglobulins and for ristocentin-von Willebrand factor.

The receptors for aggregated immunoglobulin G (IgG) (an Fc receptor) and for ristocetin-von Willebrand factor on human platelets were studied by means of various modifications of the platelet surface. The expression of these receptors was measured by the agglutination of platelets to ristocetin in the presence of von Willebrand factor, which is part of the factor VIII complex, and by the binding of aggregated IgG coupled to 3H-labelled diazobenzene. Treatment of platelets with chymotrypsin, trypsin, papain and pronase which removed protein and glycoprotein from the platelet under conditions where the release reaction was inhibited caused loss of the expression of the receptor for ristocetin-von Willebrand factor and an enhancement of that for aggregated IgG. Induction of membrane changes with ADP and of the release reaction with the ionophore A23187 abolished agglutination to ristocentin-von Willebrand factor but did not alter the receptor for aggregated IgC. Possible contributions of unspecific membrane changes, produced by protease treatment of platelets, to the modification of receptor expression were eliminated by the use of formaldehyde-treated platelets. Trypsin, papain and pronase destroyed the ability of these platelets to agglutinate to ristocetin-von Willebrand factor but produced no change in the binding of aggregated IgC. Therefore, the receptor for ristocetin-von Willebrand factor is truly sensitive to proteolysis while the Fc receptor is not, but is partially masked by protease-sensitive material.

Adenosine Diphosphate↗
PubMed1978

Chemical modification of the surfaces of bacterial cell walls.

The surfaces of the isolated cell walls of four bacterial species were studied by microelectrophoresis following chemical treatments intended to remove specific charged groups. Acid-base titrations of the walls were used to assess specificity and extent of the modifications. Carboxyl groups were specifically and completely modified by activation with a water-soluble carbodiimide and subsequent reaction with a nucleophile, such as glycinamide, to give an uncharged pH-stable product. Aqueous media and mild reaction conditions make the method suitable for modifying carboxyl groups on cell surfaces too labile to withstand the harsh conditions required for conventional esterification reactions. Use of the carbodiimide-mediated reaction for discharging carboxyl groups, along with fluorodinitrobenzene for discharging amino groups and extraction procedures for removing constituents carrying phosphoester groups (teichoic acids), made it possible to obtain information about the spatial arrangement of charged groups on the wall surfaces. Removal of the exterior negative charge dominating wall surfaces allowed underlying amino groups to become electrokinetically effective and, in the case of E. coli, also revealed a lipophilic region with an affinity for a cationic surfactant.

Bacillus↗
PubMed1978

[Effect of chemical modification of the surface of erythrocytes on their stability to the hemolytic action of sodium alkyl sulfates].

The hemolytic action of a homologous series of sodium alkyl sulfates (C8 to C15) on dog and human erythrocytes was measured. The influence of trypsin, pronase and neuraminidase treatments on the lytic resistance of human red cells was studied. A new approach evaluating the hemolytic activity of ionic surfactants is expressed as a ratio of a concentration providing 50% lysis to its CMC-value. The results obtained are examined for their bearing on the use of surfactants as a means to study the structure organization of biological membranes.

Animals↗
PubMed1978

Elimination of Escherichia coli K88 adhesion determinant by antibody in porcine gut and mammary secretions following oral immunization.

1) Although virulence of enteropathogenic E. coli in the pig is essentially associated with the K88 adhesion determinant, protection of the neonate and weanling is not necessarily dependent upon antibodies to this surface antigen. 2) Modification of the surface antigenic characteristics of enteropathogens occurs in the presence of antibody, suggesting an immune mechanism of induced loss of the genetic elements responsible for the synthesis of K88. 3) Antibodies directed against the K88 antigen do not seem to participate in the elimination of the K88 antigen. These observations provide a new concept that antibody mediated mechanisms of host defense include elimination of virulence determinants, a feature vital to maintaining the balance of the host pathogen relationship favorable to the host.

Administration, Oral↗
PubMed1977

Modification of Drosophila cell surfaces by concanavalin A.

The effect of Con A on the surface morphology of cultured cells of Drosophila melanogaster growing on coverglasses was examined by scanning electron microscopy. With low lectin concentrations (5--10 microgram/ml) surface filaments disappeared and the cells flattened and spread against the glass surface. Cytoplasmic fusion bridges were observed in areas where cells made contact. Concentrations of Con A ranging between 50--500 microgram/ml caused cell shrinkage and surface distortions without cell flattening and filament loss. These morphologic effects were not apparent if Con A binding sites were blocked by preincubation with alpha-methyl-D-mannopyranoside before application to the cell cultures. However, once the Con A-mediated changes were in effect, the cells failed to show recovery when they were returned to growth medium and a majority of the cells on the coverglasses degenerated. Presumably the cells whose morphology appears unaffected by Con A treatment are the survivors that repopulate cultures returned to growth medium.

Animals↗