Conditioned medium of human mesenchymal stromal/stem cells cultured on decellularized extracellular matrix promotes murine skeletal muscle repair after acute injury.

Mesenchymal stromal/stem cells (MSCs) and their secretome are known to exert beneficial effects in many pathological states. However, MSCs therapeutic properties can be reduced due to unsuitable in vitro maintenance conditions. Standard culture protocols neglect the fact that MSCs exist in vivo in the closest connection with the extracellular matrix (ECM), the complex protein network providing an instructive microenvironment.

The Decellularized Cell-Derived Extracellular Matrix Enhances the Paracrine Function of Human Mesenchymal Stromal/Stem Cells.

The mesenchymal stromal/stem cells (MSCs) are known to secrete pleiotropic paracrine factors, contributing to tissue regeneration. This unique ability makes MSCs promising therapeutic tools for many diseases, including even those that were previously untreatable. Thus, the development of preconditioning approaches aimed at enhancing the paracrine function of MSCs attracts great interest.

Atopic Polygenic Risk Score Is Associated with Paradoxical Eczema Developing in Patients with Psoriasis Treated with Biologics.

Biologic therapies for psoriasis can cause paradoxical eczema. The role of genetic factors in its pathogenesis is unknown. To identify risk variants, we conducted a GWAS of 3,212 patients with psoriasis, of whom 88 developed paradoxical eczema.

Scalable optical-to-terahertz converter with a prism-coupled plane-parallel lithium niobate plate.

A nonlinear optical converter of femtosecond laser pulses to terahertz radiation, which combines the tilted-pulse-front pumping and prism coupling techniques, is proposed and experimentally tested. In contrast to the conventional tilted-pulse-front scheme with a prism-shaped LiNbO crystal, the converter consists of a plane-parallel LiNbO plate sandwiched between two dielectric prisms. One prism is used to couple the pump beam into the LiNbO plate, another prism couples the generated terahertz radiation out of the plate.

Management of the Two-Week Wait Pathway for Skin Cancer Patients, before and during the Pandemic: Is Virtual Consultation an Option?

Background: Although telemedicine emerged more than 100 years ago, the recent pandemic underlined the role of remote assessment of different diseases. The diagnoses of cutaneous conditions, especially malignant lesions, have placed significant stress on the fast-track pathway for general practitioners (GPs), dermatologists, and plastic surgeons. The aim of the study was to compare (pre- and during the pandemic) the ability of professionals to face the challenge.

Monovalent ions and stress-induced senescence in human mesenchymal endometrial stem/stromal cells.

Monovalent ions are involved in growth, proliferation, differentiation of cells as well as in their death. This work concerns the ion homeostasis during senescence induction in human mesenchymal endometrium stem/stromal cells (hMESCs): hMESCs subjected to oxidative stress (sublethal pulse of HO) enter the premature senescence accompanied by persistent DNA damage, irreversible cell cycle arrest, increased expression of the cell cycle inhibitors (p53, p21) cell hypertrophy, enhanced β-galactosidase activity. Using flame photometry to estimate K, Na content and Rb (K) fluxes we found that during the senescence development in stress-induced hMESCs, Na/Kpump-mediated K fluxes are enhanced due to the increased Na content in senescent cells, while ouabain-resistant K fluxes remain unchanged.

Effects of IGFBP3 knockdown on human endometrial mesenchymal stromal cells stress-induced senescence.

Insulin-like growth factor binding protein 3 (IGFBP3) is known for its pleiotropic ability to regulate various cellular processes such as proliferation, apoptosis, differentiation etc. It has recently been shown that IGFBP3 is part of the secretome of senescent human endometrial mesenchymal stromal cells (MESCs) (Griukova et al., 2019) that takes part in paracrine propagation of senescence-like phenotype in MESCs (Vassilieva et al.

Outcomes of Deferoxamine Action on HO-Induced Growth Inhibition and Senescence Progression of Human Endometrial Stem Cells.

Mesenchymal stem cells (MSCs) are broadly applied in regenerative therapy to replace cells that are lost or impaired during disease. The low survival rate of MSCs after transplantation is one of the major limitations heavily influencing the success of the therapy. Unfavorable microenvironments with inflammation and oxidative stress in the damaged regions contribute to MSCs loss.

Chondrogenic differentiation followed IGFBP3 loss in human endometrial mesenchymal stem cells.

Insulin-like growth factor binding protein 3 (IGFBP3) is a multifunctional protein, able either to stimulate the cell growth or to promote apoptosis. In particular, IGFBP3 plays significant role in propagation of stress-induced senescence in human endometrium-derived mesenchymal stem cells (MESCs) (Vassilieva et al., 2020).

Paracrine senescence of human endometrial mesenchymal stem cells: a role for the insulin-like growth factor binding protein 3.

Stress-induced premature cell senescence is well recognized to be accompanied by emerging the senescence-associated secretory phenotype (SASP). Secreted SASP factors can promote the senescence of normal neighboring cells through autocrine/paracrine pathways and regulate the senescence response, as well. Regarding human endometrium-derived mesenchymal stem cells (MESCs), the SASP regulation mechanisms as well as paracrine activity of senescent cells have not been studied yet.

Vitiligo - New Treatment Approach.

Introduction: Vitiligo is one of the most common hypomelanoses. Current treatments include ultraviolet, topical corticosteroids, calcineurin inhibitors. Orally administered vitamins, acting as anti-oxidants and in combination with ultraviolet light have also demonstrated skin re-pigmentation.

Molecular basis of senescence transmitting in the population of human endometrial stromal cells.

Hormone-regulated proliferation and differentiation of endometrial stromal cells (ESCs) determine overall endometrial plasticity and receptivity to embryos. Previously we revealed that ESCs may undergo premature senescence, accompanied by proliferation loss and various intracellular alterations. Here we focused on whether and how senescence may be transmitted within the ESCs population.

Preclinical Development of the Anti-LAG-3 Antibody REGN3767: Characterization and Activity in Combination with the Anti-PD-1 Antibody Cemiplimab in Human -Knockin Mice.

In the tumor microenvironment, multiple inhibitory checkpoint receptors can suppress T-cell function, thereby enabling tumor immune evasion. Blockade of one of these checkpoint receptors, PD-1, with therapeutic antibodies has produced positive clinical responses in various cancers; however, the efficacy of this approach can be further improved. Simultaneously targeting multiple inhibitory checkpoint receptors has emerged as a promising therapeutic strategy.

Proliferation-related changes in K content in human mesenchymal stem cells.

Intracellular monovalent ions have been shown to be important for cell proliferation, however, mechanisms through which ions regulate cell proliferation is not well understood. Ion transporters may be implicated in the intracellular signaling: Na and Cl participate in regulation of intracellular pH, transmembrane potential, Ca homeostasis. Recently, it is has been suggested that K may be involved in "the pluripotency signaling network".

Russian traditional medicine in dermatology.

The use of herbal remedies for various medical issues is becoming increasingly commonplace in all fields of medicine, and dermatology is no exception. This review focuses on traditional dermatologic herbal remedies, commonly used in Russia, as the rich array of 11 different plant zones has resulted in a great variety of medicinal plants. Herbal remedies warrant deeper investigation and research, especially due to their active substance content, which may interfere with or reinforce the effect of modern medications, something that medical professionals should be aware of when prescribing treatments.

Senescence-messaging secretome factors trigger premature senescence in human endometrium-derived stem cells.

Accumulating evidence suggests that the senescence-messaging secretome (SMS) factors released by senescent cells play a key role in cellular senescence and physiological aging. Phenomenon of the senescence induction in human endometrium-derived mesenchymal stem cells (MESCs) in response to SMS factors has not yet been described. In present study, we examine a hypothesis whether the conditioned medium from senescent cells (CM-old) may promote premature senescence of young MESCs.

Benefit of Rare-Earth "Smart Doping" and Material Nanostructuring for the Next Generation of Er-Doped Fibers.

Erbium-doped fiber amplifiers (EDFAs) for harsh environments require to develop specific fabrication methods of Er -doped fibers (EDFs) so as to limit the impact of radiation-induced absorption. In this context, a compromise has to be found between the concentration of Erbium and the glass composition. On the one hand, high concentration of Er ions helps to reduce the length of the EDF and hence the cumulated attenuation but generally leads to luminescence quenching mechanisms that limit the performances.

Characterization of the Anti-PD-1 Antibody REGN2810 and Its Antitumor Activity in Human Knock-In Mice.

The Programmed Death-1 (PD-1) receptor delivers inhibitory checkpoint signals to activated T cells upon binding to its ligands PD-L1 and PD-L2 expressed on antigen-presenting cells and cancer cells, resulting in suppression of T-cell effector function and tumor immune evasion. Clinical antibodies blocking the interaction between PD-1 and PD-L1 restore the cytotoxic function of tumor antigen-specific T cells, yielding durable objective responses in multiple cancers. This report describes the preclinical characterization of REGN2810, a fully human hinge-stabilized IgG4(S228P) high-affinity anti-PD-1 antibody that potently blocks PD-1 interactions with PD-L1 and PD-L2.

Calcium alterations signal either to senescence or to autophagy induction in stem cells upon oxidative stress.

Intracellular calcium ([Ca]) has been reported to play an important role in autophagy, apoptosis and necrosis, however, a little is known about its impact in senescence. Here we investigated [Ca] contribution to oxidative stress-induced senescence of human endometrium-derived stem cells (hMESCs). In hMESCs sublethal HO-treatment resulted in a rapid calcium release from intracellular stores mediated by the activation of PLC/IP3/IP3R pathway.

FGFR3-TACC3 fusion proteins act as naturally occurring drivers of tumor resistance by functionally substituting for EGFR/ERK signaling.

The epidermal growth factor receptor (EGFR) is a clinically validated target in head and neck squamous cell carcinoma (HNSCC), where EGFR-blocking antibodies are approved for first-line treatment. However, as with other targeted therapies, intrinsic/acquired resistance mechanisms limit efficacy. In the FaDu HNSCC xenograft model, we show that combined blockade of EGFR and ERBB3 promotes rapid tumor regression, followed by the eventual outgrowth of resistant cells.

[OXIDATIVE STRESS-PROMOTED RESPONSES IN HUMAN ENDOMETRIAL STEM CELLS AND LUNG EMBRYONIC FIBROBLASTS].

Human mesenchymal stem cells are an attractive cell source for tissue engineering. During transplantation they may be subjected to oxidative stress due to unfavorable cellular microenvironment, which is characterized by increased levels of reactive oxygen species. Recently, we have demonstrated that oxidative stress responses of human mesenchymal stem cells derived from endometrium (hMESCs) depend upon the oxidizer concentration.

ROLE OF P38 MAP-KINASE IN THE STRESS-INDUCED SENESCENCE PROGRESSION OF HUMAN ENDOMETRIUM-DERIVED MESENCHYMAL STEM CELLS.

Our recent findings clearly demonstrate that human endometrium-derived mesenchymal stem cells (hMESCs) respond to the sublethal oxidative stress by the premature senescence induction via ÀÒÌ/Chk2/p53/ p21/Rb pathway. Furthermore, based on the application of the SB203580 (SB) we suggested p38 MAP-kinase involvement in senescence progression. However, there are several disadvantages concerning this inhibitor: 1) using SB would not be suitable for in vivo experiments due to toxicity issue; 2) the poor kinase selectivity profile of SB complicates interpretation of the obtained data.

Tetraploidization or autophagy: The ultimate fate of senescent human endometrial stem cells under ATM or p53 inhibition.

Previously we demonstrated that endometrium-derived human mesenchymal stem cells (hMESCs) via activation of the ATM/p53/p21/Rb pathway enter the premature senescence in response to oxidative stress. Down regulation effects of the key components of this signaling pathway, particularly ATM and p53, on a fate of stressed hMESCs have not yet been investigated. In the present study by using the specific inhibitors Ku55933 and Pifithrin-α, we confirmed implication of both ATM and p53 in H(2)O(2)-induced senescence of hMESCs.

Reactive Oxygen Species Are Required for Human Mesenchymal Stem Cells to Initiate Proliferation after the Quiescence Exit.

The present study focuses on the involvement of reactive oxygen species (ROS) in the process of mesenchymal stem cells "waking up" and entering the cell cycle after the quiescence. Using human endometrial mesenchymal stem cells (eMSCs), we showed that intracellular basal ROS level is positively correlated with the proliferative status of the cell cultures. Our experiments with the eMSCs synchronized in the G0 phase of the cell cycle revealed a transient increase in the ROS level upon the quiescence exit after stimulation of the cell proliferation.