Cytokine expression of soft tissue cells cultured with titanium discs and their respective supernatants in vitro.

Objective: Titanium surface modifications improve osseointegration in dental and orthopedic implants. However, soft tissue cells can also reach the implant surface in immediate loading protocols. While previous research focused on osteogenic cells, the early response of soft tissue cells still needs to be better understood.

Toward low-friction and high-adhesion solutions: Emerging strategies for nanofibrous scaffolds in articular cartilage engineering.

Aging, trauma, pathology, and poor natural tissue regeneration are the leading causes of osteoarthritis (OA), an articular cartilage disease. Electrospun scaffolds have gained attention as potential matrices for the treatment of OA because of their high degree of ECM mimicry, which suits chondrocyte migration, adhesion, and proliferation. However, none of the products recently introduced in the market are nanofiber-based.

Discovery of benzo[c]phenanthridine derivatives with potent activity against multidrug-resistant .

(Mtb), the pathogen responsible for tuberculosis (TB), is the leading cause of bacterial disease-related death worldwide. Current antibiotic regimens for the treatment of TB remain dated and suffer from long treatment times as well as the development of drug resistance. As such, the search for novel chemical modalities that have selective or potent anti-Mtb properties remains an urgent priority, particularly against multidrug-resistant (MDR) Mtb strains.

Small Molecule Targeting PPM1A Activates Autophagy for Host-Directed Therapy.

(Mtb), the infectious agent of tuberculosis (TB), causes over 1.5 million deaths globally every year. Host-directed therapies (HDT) for TB are desirable for their potential to shorten treatment and reduce the development of antibiotic resistance.

κ-Carrageenan/poly(vinyl alcohol) functionalized films with gallic acid and stabilized with metallic ions.

Given the environmental issues caused by the extensive use of conventional petroleum-based packaging, this work proposes functional films based on commercial κ-carrageenan (κc), poly(vinyl alcohol) (PVA), and gallic acid (GA) prepared by the "casting" method. Metallic ions in the κc composition stabilized the films, supporting processability and suitable mechanical properties. However, the incorporated GA amount (6.

ATF2 orchestrates macrophage differentiation and activation to promote antibacterial responses.

The differentiation and activation of macrophages are critical regulatory programs that are central to host inflammation and pathogen defense. However, the transcriptional regulatory pathways involved in these programs are not well understood. Herein, we demonstrate that the activity and expression of the transcription factor ATF2 is precisely regulated during primary human monocyte-to-macrophage differentiation and that its activation is linked to M1 polarization and antibacterial responses.

infection triggers epigenetic changes that are enriched in a type I IFN signature.

Tuberculosis, a deadly infectious lung disease caused by (Mtb), remains the leading cause of bacterial disease-related deaths worldwide. Mtb reprograms and disables key antibacterial response pathways, many of which are regulated by epigenetic mechanisms that control the accessibility of chromatin to the transcriptional machinery. Recent reports suggest that host phosphatases, such as PPM1A, contribute to regulating chromatin accessibility during bacterial infections.

Screening costs associated with donor selection for fecal microbiota transplantation for treatment of PD-1 refractory melanoma patients.

The gut microbiome acts as a tumor-extrinsic regulator of responses to immune-checkpoint inhibitors (ICIs) targeting PD-1 and CTLA-4 receptors. Primary resistance to anti-PD-1 ICI can be reversed via responder-derived fecal microbiota transplant (FMT) in patients with refractory melanoma. Efforts to create stool banks for FMT have proved difficult.

TREM2 Promotes Immune Evasion by Mycobacterium tuberculosis in Human Macrophages.

Macrophage surface receptors are critical for pathogen defense, as they are the gatekeepers for pathogen entry and sensing, which trigger robust immune responses. TREM2 (triggering receptor expressed on myeloid cells 2) is a transmembrane surface receptor that mediates anti-inflammatory immune signaling. A recent study showed that TREM2 is a receptor for mycolic acids in the mycobacterial cell wall and inhibits macrophage activation.

An biosafety-level-2-compatible model of infection for drug susceptibility testing.

Available mouse models for tuberculosis drug susceptibility testing requires using virulent biosafety-level-3 (BSL-3) (Mtb) strains, or attenuated BSL-2 strains that lack virulence genes. Here, we present a BSL-2-compatible mouse model for tuberculosis drug susceptibility testing using the auxotrophic Mtb mc6206 strain, which retains all virulence genes. Using rifampicin and a new autophagy-boosting compound, SMIP-30, we provide a step-by-step guide for the infection, drug administration, and evaluation of Mtb burden and cytokine profiles.

A selective PPM1A inhibitor activates autophagy to restrict the survival of Mycobacterium tuberculosis.

Metal-dependent protein phosphatases (PPMs) have essential roles in a variety of cellular processes, including inflammation, proliferation, differentiation, and stress responses, which are intensively investigated in cancer and metabolic diseases. Targeting PPMs to modulate host immunity in response to pathogens is an ambitious proposition. The feasibility of such a strategy is unproven because development of inhibitors against PPMs is challenging and suffers from poor selectivity.

Exploits Focal Adhesion Kinase to Induce Necrotic Cell Death and Inhibit Reactive Oxygen Species Production.

Tuberculosis is a deadly, contagious respiratory disease that is caused by the pathogenic bacterium (Mtb). Mtb is adept at manipulating and evading host immunity by hijacking alveolar macrophages, the first line of defense against inhaled pathogens, by regulating the mode and timing of host cell death. It is established that Mtb infection actively blocks apoptosis and instead induces necrotic-like modes of cell death to promote disease progression.

Antimicrobial and cytocompatible chitosan, N,N,N-trimethyl chitosan, and tanfloc-based polyelectrolyte multilayers on gellan gum films.

In this work free-standing gels formed from gellan gum (GG) by solvent evaporation are coated with polysaccharide-based polyelectrolyte multilayers, using the layer-by-layer approach. We show that PEMs composed of iota-carrageenan (CAR) and three different natural polycationic polymers have composition-dependent antimicrobial properties, and support mammalian cell growth. Cationic polymers (chitosan (CHT), N,N,N-trimethyl chitosan (TMC), and an amino-functionalized tannin derivative (TN)) are individually assembled with the anionic iota-carrageenan (CAR) at pH 5.

Protein Kinase R Restricts the Intracellular Survival of by Promoting Selective Autophagy.

Tuberculosis (TB) is a deadly infectious lung disease caused by the pathogenic bacterium (Mtb). The identification of macrophage signaling proteins exploited by Mtb during infection will enable the development of alternative host-directed therapies (HDT) for TB. HDT strategies will boost host immunity to restrict the intracellular replication of Mtb and therefore hold promise to overcome antimicrobial resistance, a growing crisis in TB therapy.

Influence of photodynamic therapy on bond strength and adhesive interface morphology of MTA based root canal sealer to different thirds of intraradicular dentin.

Background: Photodynamic therapy (PDT) is used as an adjunct to endodontic treatment to enhance microbial reduction in the root canal system. However, studies evaluating the impact of PDT on the bond strength of the canal sealer to intraradicular dentin are scarce. Thus, this in vitro study aimed to evaluate the influence of photodynamic therapy with methylene blue (MB) photosensitizer (PS) on the bond strength and morphology of the interface between mineral trioxide aggregate (MTA) based endodontic sealer and different thirds of intraradicular dentin.

Removal of Cu(II) from aqueous solutions imparted by a pectin-based film: Cytocompatibility, antimicrobial, kinetic, and equilibrium studies.

To obtain pectin-based films is challenging due to the aqueous instability of polyelectrolyte mixtures. We overcome this issue by blending chitosan to pectin of high O-methoxylation degree (56%), followed by solvent evaporation. A durable film containing 74 wt% pectin content was produced and used as an adsorbent material toward Cu(II) ions.

Properties of a commercial κ-carrageenan food ingredient and its durable superabsorbent hydrogels.

Physical kappa-carrageenan-based hydrogels are often prepared from dilute aqueous kappa-carrageenan (κ-carrageenan) solutions at the presence of metallic ions or by mixing these solutions with proteins and other polysaccharides. The κ-carrageenan hydrogels have been used for technological purposes; however, there are no reports about the properties of a commercial GENUGEL® κ-carrageenan produced by the CP Kelco. The flame atomic absorption spectrometry shows that the commercial κ-carrageenan comprises a high content of metallic ions (K = 216.

Stathmin Is Required for Normal Mouse Mammary Gland Development and Δ16HER2-Driven Tumorigenesis.

Postnatal development of the mammary gland relies on the maintenance of oriented cell division and apicobasal polarity, both of which are often deregulated in cancer. The microtubule (MT) network contributes to control these processes; however, very little is known about the impact of altered MT dynamics in the development of a complex organ and on the role played by MT-interacting proteins such as stathmin. In this study, we report that female stathmin knock-out (STM KO) mice are unable to nurse their litters due to frank impairment of mammary gland development.

Loss of p27 increases genomic instability and induces radio-resistance in luminal breast cancer cells.

Genomic instability represents a typical feature of aggressive cancers. Normal cells have evolved intricate responses to preserve genomic integrity in response to stress, such as DNA damage induced by γ-irradiation. Cyclin-dependent kinases (CDKs) take crucial part to these safeguard mechanisms, but involvement of CDK-inhibitors, such as p27, is less clear.

p27kip1 expression limits H-Ras-driven transformation and tumorigenesis by both canonical and non-canonical mechanisms.

The tumor suppressor protein p27Kip1 plays a pivotal role in the control of cell growth and metastasis formation.Several studies pointed to different roles for p27Kip1 in the control of Ras induced transformation, although no explanation has been provided to elucidate these differences. We recently demonstrated that p27kip1 regulates H-Ras activity via its interaction with stathmin.

Radiotherapy-induced miR-223 prevents relapse of breast cancer by targeting the EGF pathway.

In breast cancer (BC) patients, local recurrences often arise in proximity of the surgical scar, suggesting that response to surgery may have a causative role. Radiotherapy (RT) after lumpectomy significantly reduces the risk of recurrence. We investigated the direct effects of surgery and of RT delivered intraoperatively (IORT), by collecting irradiated and non-irradiated breast tissues from BC patients, after tumor removal.

p27kip1 controls H-Ras/MAPK activation and cell cycle entry via modulation of MT stability.

The cyclin-dependent kinase (CDK) inhibitor p27(kip1) is a critical regulator of the G1/S-phase transition of the cell cycle and also regulates microtubule (MT) stability. This latter function is exerted by modulating the activity of stathmin, an MT-destabilizing protein, and by direct binding to MTs. We recently demonstrated that increased proliferation in p27(kip1)-null mice is reverted by concomitant deletion of stathmin in p27(kip1)/stathmin double-KO mice, suggesting that a CDK-independent function of p27(kip1) contributes to the control of cell proliferation.

SUMOylation regulates p27Kip1 stability and localization in response to TGFβ.

Exposure of normal and tumor-derived cells to TGFβ results in different outcomes, depending on the regulation of key targets. The CDK inhibitor p27(Kip1) is one of these TGFβ targets and is essential for the TGFβ-induced cell cycle arrest. TGFβ treatment inhibits p27(Kip1) degradation and induces its nuclear translocation, through mechanisms that are still unknown.