Membrane Layer Research Articles

Role of skin enzymes in metabolism of topical drugs

Topical drugs have gained a lot of interest with their massive market growth and are available in various dosage forms. Prodrug compounds of transdermal delivery systems can be very different and designed to convert into the form of active pharmaceutical ingredients (APIs) through enzymatic action once they enter the body. The skin, as an interfacial barrier between the body and surroundings, has demonstrated critical roles in metabolizing, filtering, and detoxifying to minimize certain side effects and improve the medication benefits of topically administered products. It is well recognized that the drug pharmacokinetics can be altered by the presence of skin enzymes driven by biotransformation reactions. To evaluate the effectiveness of a topical generic drug product, its safety, and bioequivalence with the reference one, models assessing enzyme metabolic activity are highly required for testing the amount of drugs that are metabolized or can potentially be metabolized in both healthy and compromised skin. Thus, knowledge of skin composition and enzyme expression levels is of paramount importance in mapping the relevant metabolism that may have occurred. Regulatory authorities have also been making efforts to develop efficient and harmonizable protocols to evaluate the metabolism of transdermal products. This review is a compilation of reported skin metabolizing enzymes, including their role in both drug metabolism and homeostasis regulation, along with their localization and quantification in skin equivalents (and/or membrane layers). Various aspects that potentially affect the skin enzyme metabolism study were also discussed with respect to drug development considerations.

Recycling metal-organic framework residues (MOFRs) as bifunctional additives in fabricating porous ceramic membranes

In this work, Fe-MOF residues (Fe-MOFRs) were recycled and reused as a kind of bifunctional additives in the preparation of alumina ceramic membranes. To prevent the unwanted aggregation and grain growth of Fe-MOFR derived Fe2O3 nanoparticles at elevated temperature, Fe-MOFRs were premeditatedly introduced into the alumina powder matrix to construct the composite membrane layer. Results showed that the introduction of MOFRs could reduce the thickness of the membrane layer, attributing to the sacrificial organic linkers and high activity of Fe-MOFR-derived Fe2O3 nanoparticles. However, the thickness of the formed composite membrane layer abnormally increased once MOFRs were overloaded due to the aggregation. Impressively, the surface roughness and Young modulus of the membrane layer were characterized using atomic force microscopy (AFM). The Young modulus of pure alumina membranes showed the same trend as the height, while the trend gradually reversed once Fe-MOFRs were introduced, suggesting that the binding strength between the Fe-MOFR derived Fe2O3 nanoparticles were greatly enhanced. The composite membranes showed improved pure water flux and reduced filtration resistance.

Multimodal Molecular Imaging Reveals a Novel Membrane Component in Sporangia of the Rare Actinomycete Actinoplanes missouriensis.

The bacterium Actinoplanes missouriensis belongs to the genus Actinoplanes, a prolific source of useful natural products. This microbe forms globular structures called sporangia, which contain many dormant spores. Recent studies using transmission electron microscopy have shown that the A. missouriensis sporangium membrane has an unprecedented three-layer structure, but its molecular components remain unclear. Here, we present multimodal (spontaneous Raman scattering, coherent anti-Stokes Raman scattering, second harmonic generation, sum frequency generation, and third-order sum frequency generation) label-free molecular imaging of intact A. missouriensis sporangia. Spontaneous Raman imaging assisted with multivariate curve resolution-alternating least-squares analysis revealed a novel component in the sporangium membrane that exhibits unique Raman bands at 1550 and 1615 cm-1 in addition to those characteristic of lipids. A plausible candidate for this component is an unsaturated carbonyl compound with an aliphatic moiety derived from fatty acid. Furthermore, second harmonic generation imaging revealed that a layer(s) of the sporangium membrane containing this unknown component has an ordered, noncentrosymmetric structure like fibrillar proteins and amylopectin. Our results suggest that the sporangium membrane is a new type of biological membrane, not only in terms of architecture but also in terms of components. We demonstrate that multimodal molecular imaging with Raman scattering as the core technology will provide a promising platform for interrogating the chemical components, whether known or unknown, of diverse biological structures produced by microbes.

Highly selective thin B-oriented MFI zeolite membranes on scalable modified stainless steel supports

Enhancing the separation performance of molecular sieve membranes relies significantly on precise control over their membrane morphology and microstructure. This involves creating thin, closely packed, oriented, and uniform coatings of seed crystals, enabling subsequent intergrowth to establish continuous membranes. To address industrial needs, it is crucial to generate a thin and flawless membrane efficiently producible on a large-scale support. Porous stainless supports offer scalability and easy integration into membrane modules. In this study, we present a novel and straightforward process for modifying stainless-steel supports to seed zeolite membrane layers. High-performance, b-oriented MFI zeolite membranes can be synthesized on these modified stainless-steel supports through scalable filtration seeding of MFI zeolite nanosheets followed by secondary growth. By employing a carefully designed pre-treatment procedure, we achieved the growth of well-intergrown, highly b-oriented MFI zeolite membranes on the modified stainless-steel support, establishing a robust interaction with the substrate. The membranes, fabricated through gel-free secondary growth of nanosheets deposited on a scalable stainless-steel support using this technique, demonstrate ultra-selective capabilities in separating para-xylene from ortho-xylene, with a high separation factor of 388.

Ionic liquid-triggered charge regulation of polydopamine-based surface for antibacterial nanofiltration

The charged surfaces with desirable performance are of high concern in membrane separation but there exist challenges to tailor them over a task-specific range. Herein, we propose an ionic liquid (IL)-triggered charge regulation strategy for polydopamine (PDA)-based surfaces by tuning the number and position of amino groups of ILs. By strategically manipulating the location of amino groups in either the anion, cation, or both, we realize a complete inversion in the surface charge nature of PDA coatings from highly negative to negative and even highly positive (zeta potential: −25 mV to +25 mV). This charge inversion triggered by IL is attributed to both the number of protonable groups and shielding effect provided by counter ions. Such charge flip enhances Donna effect when the PDA/IL coatings serve as the skin layer of nanofiltration membranes, thereby enabling high rejection to both negative and positive target molecules (i.e., chlorogenic acids at various pH). Despite charge regulation, ILs with dual amino groups cross link the PDA aggregates, largely narrowing the pore size distribution of the skin layer. The IL cross-linked PDA skin layer with uniform pores thus shows a nearly 100 % rejection to the target solutes. Meanwhile, the IL synchronously endow the PDA coatings with tunable charge characteristics, imidazolium functional groups and exceptional superoleophobicity, compensating for the originally inferior antibacterial activity of membranes in a wide pH range.

Influence of compression effect on the MEA structure and performance based on M−N–C electrocatalysts for PEMFC

The single-atom dispersed active sites and the thicker catalytic layer of metal-nitrogen-carbon (M-N-C) electrocatalysts based membrane electrode assembly (MEA) exhibit notable distinctions from Pt-based MEA, necessitating targeted optimization. This study systematically investigates the influence of compression on both structure and performance of the M-N-C electrocatalysts based MEA. Four compression ratios, ranging from 11.5% to 39.3%, were examined across diverse operational conditions. The variations in impedance across different electrochemical regions are observed, resulting from the superposition of distinct impedance components. It is found that the insufficient compression leads to higher porosity and the formation of cracks between catalytic layer and membrane, adversely impacting internal resistance and proton transport. Increasing compression first acts the catalytic layer, and then gradually acts on the interface, membrane and gas diffusion layer, thereby reducing internal resistance, charge transfer resistances, albeit at the expense of heightened mass transfer resistance. Among these factors, the influence of internal resistance affects significance to total performance. Furthermore, compression influenced mass transfer differently in various layers. For the catalyst layer, the effect was uniform and sustained, while for the gas diffusion layer, it initially remained constant and then experienced a sudden deterioration over a certain extent. Optimal MEA performance is achieved when the compression ratio attains 40 %, which 2.1 times higher than the low compression MEA. This finding emphasizes the necessity for higher compression on M-N-C electrocatalysts based MEA compared to Pt-based MEA.

Sandwich-structured electrospun polyvinylidene difluoride sensor for structural health monitoring of glass fiber reinforced polymer composites

Stress monitoring and interlaminar failure detection attract much attention in glass fiber reinforced polymer (GFRP) structural health monitoring area. However, due to limitations of sensing or electrode materials, existing embedding sensors cannot be designed to have both of the abilities without sacrificing mechanical properties. This work fabricated a sandwich-structured sensor, which is composed of three layers of electrospun polyvinylidene difluoride membranes. The upper and lower electrodes are flexible membranes that ensure stable signal collection in the rigid GFRP material system. The sensor can quantitatively monitor the stress based on piezoelectric effect, and interlaminar crack propagation based on parallel plate capacitors. The voltage and capacitance values have a linear relationship with the stress level and crack length (R-square of the functions is 0.999 and 0.933), respectively. Due to the porous microstructure of electrospun membranes, polymer matric can well infiltrate the polyvinylidene difluoride nanofibers while preparing the sensor embedded GFRP. Thus, the perfect bonding of the sensor within GFRP ensures the effective sensing abilities until sample failure and negligible effect (< -7%) on the mechanical properties of GFRP.

Study of interfacial competitive distribution and synergistic permeation in nanofiltration separation of Salvia divinorum acids from the aqueous extract

The contact between solution and membrane during nanofiltration separation produces the interfacial layer fluid, and the competitive distribution laws of solutes in the interfacial layer are difficult to be analyzed, giving rise to diversified separation results that are challenging to explain using traditional nanofiltration separation theory. Four Salvia divinorum phenolic acid components—sodium salvinorin, protocatechuic aldehyde, rosmarinic acid, and salvianolic acid B—which have gradient relative molecular masses and dissociation constants, were selected as the objects of study. The nanofiltration separation parameters, such as membrane flux and permeation rate of the Salvia divinorum phenolic acids and their variability with the monomer solution under the complex solution environment were systematically analyzed. Based on the correlation between the concentration of the interfacial layer and the initial concentration, membrane flux and mass transfer coefficient in the theory of concentration polarization, the concentration of the interfacial layer of the nanofiltration membrane was calculated. This was combined with the state of association characterized by the distribution of particle sizes in the solution, the research model based on the ‘Associative State-Interfacial Competition-Separation Behavior’ was constructed, and the competitive and synergistic membrane separation regulations of the constituents of salvia phenolic acids were clarified. In acidic solutions, van der Waals forces dominate the interfacial competition, and of the four phenolic acids, salvinorin acid B diffused most easily to the membrane surface, showing that the component with the larger relative molecular mass inhibited the penetration of the smaller component; In alkaline solution, Coulomb force and Van der Waals force together dominate the interfacial competition, and the more acidic sodium salvinorin, etc., would preferentially react with hydroxide. At the same time, combined with the feature that the more molecular states in the particle size distribution of the solution are more likely to form aggregates, it was proven that the dissociation of protocatechuic acid aldehyde was inhibited, and its molecular state was more complete. It was shown that the more acidic sodium salvinorin and others facilitated the less acidic protocatechuic aldehyde to pass through the membrane.

Ginsenoside Rb1-loaded bionic nanoparticles alleviate sepsis-induced acute lung injury by reducing mitochondrial oxidative stress to inhibit macrophage PANoptosis

Cytokin storms play a key role in the pathogenesis of acute lung injury (ALI) caused by sepsis, in which pulmonary macrophage PANoptosis is involved. At present, the main treatment methods for sepsis-induced ALI are antibiotics and fluid resuscitation, but the efficacy of these methods is unsatisfactory enough; therefore, the development of new therapeutic methods is urgently needed. In this study, we developed a novel bionic nanoparticle (R@ZQC NPs) using ZIF-8 nanoparticles as a carrier, internally supported with ginsenoside Rb1, and externally coated with quaternated chitosan and a macrophage membrane layer by layer. The biomimetic nanoparticles controlled the release of Rb1, had good biocompatibility, strong antibacterial activity, and targeted the inhibition of pulmonary macrophage PANoptosis. In vitro and in vivo, R@ZQC NPs effectively inhibited the activity of Escherichia coli and reduced mitochondrial damage by activating the AMPK pathway, thus alleviating the inflammatory response and ameliorating sepsis-induced ALI. In summary, this study revealed the great potential of R@ZQC NPs for antimicrobial activity, targeted inhibition of macrophage PANoptosis and reduction of the inflammatory response and represents the first attempt of R@ZQC NPs in the treatment of sepsis-induced ALI. This study provides new therapeutic ideas and strategies for the clinical treatment of sepsis-induced ALI.

Devising a technology for obtaining glued sausage casings from intestinal raw materials using electrophoresis

The object of research is the technique for obtaining glued sausage casings, in which adhesive related structures and electrophoresis for tanning are used to glue the layers of intestinal raw materials. Devising a technique for gluing sausage casings from intestinal raw materials with the use of adhesive related structures by stitching by tanning, via intensified electrophoresis, has been substantiated. The technology of glued sausage casings from intestinal raw materials, which are classified as unclaimed residues and waste, has been proposed. The technology differs from known similar technologies by applying a technique for gluing intestinal membranes using an adhesive related construct and electrophoresis during tanning. The devised gluing technique and the device for its implementation make it possible to avoid violation of the integrity of the raw material, are universal in relation to it, and are easy to operate. The rational parameters of electrophoresis, which is used to accelerate the tanning process of the place of gluing of the layers of the intestinal membranes using an adhesive related construct, have been determined. The potential difference between the electrodes and the duration of exposure of the gluing site for gluing the original intestinal raw materials: pork belly, lamb belly, beef belly were determined. At a potential difference of 100 V, the duration of exposure of the gluing site for pork and lamb bellies is 17 minutes, and for beef bellies − 20 minutes. It is noted that the results differ in the duration of exposure of the gluing site, which is probably due to the thickness of the layer of the raw material. The proposed technology would contribute to improving the efficiency of the technology of glued sausage casings from intestinal raw materials and could be used at enterprises for the processing of agricultural products and the meat processing industry

Analysis and Application of Poly(vinyl alcohol) (PVA) and Polyacrylonitrile (PAN) Nanofiber Membrane-Based Triboelectric Nanogenerators.

The triboelectric property of materials is used to harvest energy from intentional or nonintentional sources of vibration. Contact mode freestanding dielectric based nanogenerators (CFTENGs) have many advantages when compared with other modes of triboelectric nanogenerators. The property of dielectric materials plays an important role in the energy harvesting process. In this work, we aim to fabricate nanofiber membranes of poly(vinyl alcohol) (PVA) and polyacrylonitrile (PAN) and study their properties for CFTENGs. The morphology and porosity of both membranes were tested experimentally. The mechanical property is modeled with a representative volume element (RVE) technique to understand its deflection behavior. In addition, an electromechanical model is developed to predict and analyze the behavior of those membranes in the energy conversion process. Our research reveals that the PAN dielectric layer achieves a maximum open circuit voltage of 192 kV compared to the PVA dielectric layer (2.2 kV) in the CFTENG system. In comparison, the dielectric layer of the PAN nanofiber membrane reflects its flexibility to generate electrical energy in a CFTENG with the effect of contact electrification and electrostatic induction under various sources of unused energies for a wide range of applications. Moreover, the same methodology is applied to various sources of vibration, and their performance is reported. With an appropriate power management circuit, we can design a PAN membrane-based TENG for various applications.

Insights on influence of polymer molecular weight on gas sorption, transport and plasticization in glassy 6FDA-DAM polyimide membranes

It is well-known that spinning of defect-free asymmetric polyimide hollow fibers is promoted by using high polymer molecular weight. On the other hand, effects of polymer molecular weight on microstructure and separation performance of dense film 6FDA-based polyimide membranes relevant to sheath layers of composite membranes are less well-explored. In this work, gas sorption, diffusion and permeation of CO2, N2 and CH4 for 6FDA-DAM dense films are considered for 45 kDa and 176 kDa weight average molecular weights. Such molecular weights are relevant for practical hollow fiber spinning of membranes. Earlier results for polystyrene samples show similar trends in dual mode sorption model results like those noted here for the 6FDA-DAM polyimide case; however, effects on permeation like those considered here were not addressed for the polystyrene case. Here we also address actual pure and mixed gas CO2 and CH4 permeation and show higher free volumes, higher gas permeability but lower 50:50 CO2/CH4 selectivity associated with the higher molecular weight sample. Analysis using the self-consistent dual-mode sorption and transport models help understand the observed trends. Our results suggest denser packing of polymer segments exists in the Henry's law environment of the low molecular weight sample. Moreover, the higher polymer segmental packing in the Henry's law environment suppresses CO2 plasticization with a dual-mode microstructure controlling separation performance and plasticization behavior for this important member of the 6FDA polyimide family. We show evidence of effects of charge transfer complexes as possible main features in these trends. These dense film results help guide future work on dense sheath layers on composite hollow fiber membranes.

Silicon carbide ultrafiltration ceramic membrane sintered by ultra-low temperature oxidation

Silicon carbide (SiC) ceramic membranes are promising components for the efficient treatment of various wastewaters in membrane-based techniques. However, the high preparation temperature and then the high production cost inhibits their large-scale application. Here, an ultra-low temperature sintering process was proposed to prepare SiC ultrafiltration membrane. When the ceramic membrane was heated at 600 °C in air, a selective layer comprised of α-SiC and β-SiC formed without the emergence of crystalline silica. The thickness of the membrane layers was determined by the solid content and viscosity of the slurry. Well-dispersed SiC grains and homogeneous-distributed pores formed in the selective layers when using 100 nm SiC powders. The water flux and emulsion flux were investigated to verify the permeability of the ceramic membrane. Thus, this work proposes an energy-saving process for the preparation of SiC UF membrane and achieves the preparation of SiC UF membrane at ultra-low temperature.

Micro-CT structures facilitated lattice Boltzmann simulations on the water dynamics in PEMFCs GDL-Gas channel

This study employed Micro X-ray computed tomography (Micro-CT) to reconstruct the gas diffusion layer (GDL) in proton exchange membrane fuel cells (PEMFCs) and used lattice Boltzmann method (LBM) simulations to investigate the dynamic behavior of liquid water in the multiscale space of the GDL and gas channel (GC). The results showed that the transport of liquid water from GDL to GC through the interface of GDL-land and GDL-GC were divided into four stages: large pore filling, through-plane breakthrough, in-plane diffusion, and rapid transport into GC. The wettability of GC wall and GDL affects the transport and distribution of liquid water. When the contact angle on the GC wall was less than 90°, it promoted liquid water transport to the top GC wall, resulting in faster internal flow formation. Conversely, contact angles exceeding 90° caused liquid water to break through the GDL-GC interface from pores away from the GC wall. When the contact angle of the GDL was in the range of 110°–150°, both excessively large and excessively small contact angles hindered water transport and management. Maintaining the contact angle of the GDL around 130° enhanced the breakthrough path and transport speed of liquid water into the GC, and it also reduces localized liquid water accumulation.

Elastic response of layer-by-layer self-assembly nanofiltration membranes to hydraulic pressure

Membrane compaction has been often observed in pressure-driven membrane processes, resulting in deformation of membrane morphology and reduction in permeation and separation performance. Current studies on the compaction of nanofiltration (NF) membranes exclusively focused on thin-film composite (TFC) polyamide membranes prepared by interfacial polymerization (IP). The compaction of layer-by-layer (LBL) self-assembled NF membranes under high pressure has not yet been discussed. In this work, we explored the response of a flat-sheet LBL (PSS/PAH)2.5 membrane to hydraulic pressure in terms of the overall separation performance. The polysulfone (PSF) substrate of LBL membranes demonstrated an irreversible compaction similar to commercial acid-resistant KH membranes prepared by IP technology, but the polyelectrolyte (PE) selective layer surprisingly showed full recovery in the pore size and separation performance in the range of 10–40 bars. At 40 bar, the pore size of LBL membranes was enlarged, resulting in decreased rejection of MgCl2. However, in a 15% phosphoric acid feed, the LBL membranes showed slight changes in the pore size, due to stronger binding of PSS and PAH at low pH. The response of the LBL layer to pressure was related to the substrate pore size, coating layers and the binding strength of the PE pairs. For commercial acid-resistant TFC KH membranes, the decrease in substrate porosity at high pressure caused a significant reduction in the permeance but minor changes in the separation layer; the separation layer of KH membrane remained intact in water but swelled in acid with slightly increased pore size but stable salt rejection. The sharp contrast of LBL and TFC NF membranes highlighted the unique “elastic” response of LBL active layer and provided a new dimension for the design and utility of LBL membranes in different applications.

Characterization of anisotropic pore structure and dense selective layer of capillary membranes for long-term ECMO by cross-sectional ion-milling method.

Since the COVID-19 pandemic of 2020-2023, extracorporeal membrane oxygenator (ECMO) has attracted considerable attention worldwide. It is expected that ECMO with long-term durability is put into practical use in order to prepare for next emerging infectious diseases and to facilitate manufacturing for novel medical devices. Polypropylene (PP) and polymethylpentene (PMP) capillary membranes are currently the mainstream for gas exchange membrane for ECMO. ECMO support days for COVID-19-related acute hypoxemic respiratory failure have been reported to be on average for 14 or 24days. It is necessary to improve opposing functions such that promoting the permeation of oxygen and carbon dioxide and inhibiting the permeation of water vapor or plasma to develop sufficient durability for long-term use. For this purpose, accurately controlling the anisotropy of the pore structure of the entire cross section and functions of capillary membrane is significant. In this study, we focused on the cross-sectional ion-milling (CSIM) method, to precisely clarify the pore structure of the entire cross section of capillary membrane for ECMO, because there is less physical stress on the porous structure applied during the preparation of cross-sectional samples of porous capillary membranes. We attempted to observe the cross sections of commercially available PMP membranes using the CSIM method. As a result, we succeeded in fabricating fine-scale flat cross-sectional samples of PMP capillary membranes. The pore structures and the degree of anisotropy of the cross sections are quantitatively clarified. The achievements and the approaches of this study are being applied to the development of next-generation gas exchange membranes.

Incorporation of zeolitic imidazolate framework-8 (ZIF-8) in the polyamide and polysulfone layers of forward osmosis membranes for enhancing aquaculture wastewater recovery and PPCPs removal

Wastewater recovery is essential to alleviate water resource shortages, and this can be achieved through a high-energy-efficient forward osmosis (FO) process combined with an emerging material, zeolitic imidazolate framework-8 (ZIF-8). Here, we create thin-film composite FO membranes (TF-CFOMs) by incorporating ZIF-8 into the active polyamide (PA) and/or support polysulfone (PSf) layers to address the challenges of low water flux and loss of draw solutes during operation. Experimental factors included the dosage of ZIF-8 nanoparticles in PA preparation solutions and the dosages of 2-methylimidazole (2-Hmim) and zinc nitrate hexahydrate (ZNH) in n-methyl-2-pyrrolidone (NMP) to fabricate the PSf casting solutions with in-situ formed ZIF-8 nanoparticles. Successful ZIF-8 incorporation on the TF-CFOM surface was confirmed, and the ZIF-8 TF-CFOMs exhibited increased surface hydrophilicity and separation performance. Only modifying the PA layer by adding 0.025 wt% ZIF-8 nanoparticles in trimesoyl chloride (TMC) resulted in the membrane (PA0.025T-PSf0) with water flux 2.3 times higher than the pristine TF-CFOM (4.9 LMH). The pristine and modified TF-CFOMs were further applied for aquaculture wastewater (AWW) recovery and removal of pharmaceuticals and personal care products (PPCPs). Results of water recovery demonstrated that the recovery rate reached 89.1% in 3.5 days when using the dual-layer modified TF-CFOM. Results of PPCP removal indicated that both pristine and modified TF-CFOMs can achieve high PPCP rejection efficiency (>90%), with the modified TF-CFOM (PA0.025T-PSf2.0) performing the best. Overall, the PA0.025T-PSf2.0 TF-CFOM achieved high and stable separation efficiency in long-duration AWW recovery, making it well-suited for practical field applications.

The SEMA3F-NRP1/NRP2 axis is a key factor in the acquisition of invasive traits in in situ breast ductal carcinoma

BackgroundA better understanding of ductal carcinoma in situ (DCIS) is urgently needed to identify these preinvasive lesions as distinct clinical entities. Semaphorin 3F (SEMA3F) is a soluble axonal guidance molecule, and its coreceptors Neuropilin 1 (NRP1) and NRP2 are strongly expressed in invasive epithelial BC cells.MethodsWe utilized two cell line models to represent the progression from a healthy state to the mild-aggressive or ductal carcinoma in situ (DCIS) stage and, ultimately, to invasive cell lines. Additionally, we employed in vivo models and conducted analyses on patient databases to ensure the translational relevance of our results.ResultsWe revealed SEMA3F as a promoter of invasion during the DCIS-to-invasive ductal carcinoma transition in breast cancer (BC) through the action of NRP1 and NRP2. In epithelial cells, SEMA3F activates epithelialmesenchymal transition, whereas it promotes extracellular matrix degradation and basal membrane and myoepithelial cell layer breakdown.ConclusionsTogether with our patient database data, these proof-of-concept results reveal new SEMA3F-mediated mechanisms occurring in the most common preinvasive BC lesion, DCIS, and represent potent and direct activation of its transition to invasion. Moreover, and of clinical and therapeutic relevance, the effects of SEMA3F can be blocked directly through its coreceptors, thus preventing invasion and keeping DCIS lesions in the preinvasive state.

Lysophospholipase D activity on oral mucosa cells in whole mixed human saliva involves in production of bioactive lysophosphatidic acid from lysophosphatidylcholine

We reported that lysophosphatidic acid (LPA) is present at 0.8 μM in mixed human saliva (MS). In this study, we examined the distribution, origin, and enzymatic generation pathways of LPA in MS. LPA was distributed in the medium and cell pellet fraction; a true level of soluble LPA in MS was about 150 nM. The soluble LPA was assumed to be generated by ecto-type lysophospholipase D on exfoliated cells in MS from LPC that originated mainly from the major salivary gland saliva. Our results with the albumin-back extraction procedures suggest that a significant pool of LPA is kept in the outer layer of the plasma membranes of detached oral mucosal cells. Such pool of LPA may contribute to wound healing in upper digestive organs including oral cavity. We obtained evidence that the choline-producing activity in MS was mainly due to Ca2+-activated lysophospholipase D activity of glycerophosphodiesterase 7.

Clinical and Micro-CT analyses of Vertical Guided Bone Regeneration of Mandible using a d-PTFE Membrane, Autogenous Bone, and High-Temperature Processed Xenograft- A Case Series Study.

Purpose: To evaluate the efficacy of vertical guided bone regeneration (GBR) in the mandible utilizing a non-resorbable membrane and a bone graft combination of autogenous bone chips, and high-temperature processed (HTP) xenograft, through CT scans and microCT analysis. Materials and Methods: Patients underwent vertical ridge augmentation procedures prior to implant placement. The surgical procedure included flap elevation and placement of a bone graft comprising a 1:1 combination of autogenous posterior mandible-derived bone chips, and HTP xenograft graft particles covered with a d-PTFE membrane trimmed to suit the 3D shape of the bone defect. This was fastened securely with titanium screws and pins, and a layer of native collagen membrane. Post-operative complications and ridge measurements were assessed. Pre bone augmentation and pre implant placement bone parameters were obtained from CT scans. Biopsy specimens collected during implantation were examined by microCT. Results: All 13 study procedures were successful without any complications. The results revealed average vertical and horizontal bone gains of 3.35 mm and 5.15 mm respectively. A total of 33 implants were successfully placed in the augmented areas, without the need for further bone augmentation. MicroCT analysis revealed 48% bone, 15% filler material, and 37% non-calcified tissue in the augmented region compared to 65% bone, 3% filler material, and 32% non-calcified tissue in the pristine bone. Conclusions: A mixture of autogenous bone and HTP xenograft, covered with a d-PTFE membrane and a layer of native collagen membrane is effective for vertical GBR.