Telocytes (TCs) are a brand-new cell type frequently observed in the interstitial space of many organs (see www.telocytes.com). TCs are defined by very long (tens of micrometers) and slender prolongations named telopodes. At their level, dilations—called podoms (~300 nm), alternate with podomers (80–100 nm). TCs were identified in a myometrial interstitial cell culture based on morphological criteria and by CD34 and PDGF receptor alpha (PDGFRα) immunopositivity. However, the mechanism(s) of telopodes formation and/or elongation and ramification is not known. We report here the low-level laser stimulation (LLLS) using a 1,064-nm neodymium-doped yttrium aluminum garnet (Nd:YAG) laser (with an output power of 60 mW) of the telopodal lateral extension (TLE) growth in cell culture. LLLS of TCs determines a higher growth rate of TLE in pregnant myometrium primary cultures (10.3 ± 1.0 μm/min) compared to nonpregnant ones (6.6 ± 0.9 μm/min). Acute exposure (30 min) of TCs from pregnant myometrium to 1 μM mibefradil, a selective inhibitor of T-type calcium channels, determines a significant reduction in the LLLS TLE growth rate (5.7 ± 0.8 μm/min) compared to LLLS per se in same type of samples. Meanwhile, chronic exposure (24 h) completely abolishes the LLLS TLE growth in both nonpregnant and pregnant myometria. The initial direction of TLE growth was modified by LLLS, the angle of deviation being more accentuated in TCs from human pregnant myometrium than in TCs from nonpregnant myometrium. In conclusion, TCs from pregnant myometrium are more susceptible of reacting to LLLS than those from nonpregnant myometrium. Therefore, some implications are emerging for low-level laser therapy (LLLT) in uterine regenerative medicine.

Bacterial cellulose (BC) is a unique microbial biopolymer with a huge number of significant applications in the biomedical field, including bone tissue engineering. The present study proposes to obtain and characterize BC hybrid composites with calcium phosphate as biocompatible and bioactive membranes for bone tissue engineering. BC precursor membranes were obtained in static culture fermentation, and after purification, were oxidized to obtain 2,3-dialdehyde bacterial cellulose (DABC). Calcium phosphate-BC oxidized membranes were produced by successive immersion in precursor solutions under ultrasonic irradiation. The samples were characterized for their physicochemical properties using scanning electron microscopy (SEM) coupled with energy-dispersive X-ray spectroscopy, attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy grazing incidence X-ray diffraction (GI-XRD), solid-state ¹³C nuclear magnetic resonance (CP/MAS ¹³C NMR), and complex thermal analysis. In vitro cell studies were also performed to evaluate the influence of modified morphological characteristics on cell adhesion and proliferation. The results showed an increase in porosity and biodegradability for DABC hybrid composites compared with BC. In vitro cell studies have revealed that both hybrid composites favor cell adhesion to the surface. The new BC and DABC hybrid composites with calcium phosphate could be considered promising materials for bone tissue regeneration.

Voltage-gated calcium channels and estrogen receptors are essential players in uterine physiology, and their association with different calcium signaling pathways contributes to healthy and pathological conditions of the uterine myometrium. Among the properties of the various cell subtypes present in human uterine myometrium, there is increasing evidence that calcium oscillations in telocytes (TCs) contribute to contractile activity and pregnancy. Our study aimed to evaluate the effects of beta-estradiol on voltage-gated calcium channels and estrogen receptors in TCs from human uterine myometrium and to understand their role in pregnancy. For this purpose, we employed patch-clamp recordings, ratiometric Fura-2-based calcium imaging analysis, and qRT-PCR techniques for the analysis of cultured human myometrial TCs derived from pregnant and non-pregnant uterine samples. In human myometrial TCs from both non-pregnant and pregnant uterus, we evidenced by qRT-PCR the presence of genes encoding for voltage-gated calcium channels (Cav3.1, Ca3.2, Cav3.3, Cav2.1), estrogen receptors (ESR1, ESR2, GPR30), and nuclear receptor coactivator 3 (NCOA3). Pregnancy significantly upregulated Cav3.1 and downregulated Cav3.2, Cav3.3, ESR1, ESR2, and NCOA3, compared to the non-pregnant condition. Beta-estradiol treatment (24 h, 10, 100, 1000 nM) downregulated Cav3.2, Cav3.3, Cav1.2, ESR1, ESR2, GRP30, and NCOA3 in TCs from human pregnant uterine myometrium. We also confirmed the functional expression of voltage-gated calcium channels by patch-clamp recordings and calcium imaging analysis of TCs from pregnant human myometrium by perfusing with BAY K8644, which induced calcium influx through these channels. Additionally, we demonstrated that beta-estradiol (1000 nM) antagonized the effect of BAY K8644 (2.5 or 5 µM) in the same preparations. In conclusion, we evidenced the presence of voltage-gated calcium channels and estrogen receptors in TCs from non-pregnant and pregnant human uterine myometrium and their gene expression regulation by beta-estradiol in pregnant conditions. Further exploration of the calcium signaling in TCs and its modulation by estrogen hormones will contribute to the understanding of labor and pregnancy mechanisms and to the development of effective strategies to reduce the risk of premature birth.

In this review, we describe the current knowledge on calcium signaling pathways in interstitial cells with a special focus on interstitial cells of Cajal (ICCs), interstitial Cajal-like cells (ICLCs), and telocytes. In detail, we present the generation of Ca²⁺ oscillations, the inositol triphosphate (IP₃)/Ca²⁺ signaling pathway and modulation exerted by cytokines and vasoactive agents on calcium signaling in interstitial cells. We discuss the physiology and alterations of calcium signaling in interstitial cells, and in particular in telocytes. We describe the physiological contribution of calcium signaling in interstitial cells to the pacemaking activity (e.g., intestinal, urinary, uterine or vascular pacemaking activity) and to the reproductive function. We also present the pathological contribution of calcium signaling in interstitial cells to the aortic valve calcification or intestinal inflammation. Moreover, we summarize the current knowledge of the role played by calcium signaling in telocytes in the uterine, cardiac and urinary physiology, and also in various pathologies, including immune response, uterine and cardiac pathologies.

Background: Faecal microbiota transplant (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection (rCDI) with cure rates ranging between 85 and 92%. The FMT role for primary Clostridioides difficile infection (CDI) has yet to be settled because of limited data and small-sample studies presented in the current literature. Our study goals were to report the risk factors and the risk of recurrence after FMT for each CDI episode (first, second, and third) and to explore if there is a role of FMT in primary severe CDI. Methods: We conducted a retrospective study to analyze the clinical characteristics and the outcomes of 96 FMT patients with a prior 10 day course of antibiotic treatment in the medical records, of which 71 patients with recurrent CDI and 25 patients with a primary CDI. Results: The overall primary cure rate in our study was 88.5% and the primary cure rate for the severe forms was 85.7%. The data analysis revealed 5.25%, 15.15%, and 27.3% FMT recurrence rates for primary, secondary, and tertiary severe CDI. The risk of recurrence was significantly associated with FMT after the second and the third CDI severe episodes (p < 0.05), but not with FMT after the first severe CDI episode. Conclusions: This study brings new data in supporting the FMT role in CDI treatment, including the primary severe CDI, however, further prospective and controlled studies on larger cohorts should be performed in this respect.

The skin is a complex and selective system from the perspective of permeability to substances from the external environment. Microemulsion systems have demonstrated a high performance in encapsulating, protecting and transporting active substances through the skin. Due to the low viscosity of microemulsion systems and the importance of a texture that is easy to apply in the cosmetic and pharmaceutical fields, gel microemulsions are increasingly gaining more interest. The aim of this study was to develop new microemulsion systems for topical use; to identify a suitable water-soluble polymer in order to obtain gel microemulsions; and to study the efficacy of the developed microemulsion and gel microemulsion systems in the delivery of a model active ingredient, namely curcumin, into the skin. A pseudo-ternary phase diagram was developed using AKYPO^® SOFT 100 BVC, PLANTACARE^® 2000 UP Solution and ethanol as a surfactant mix; caprylic/capric triglycerides, obtained from coconut oil, as the oily phase; and distilled water. To obtain gel microemulsions, sodium hyaluronate salt was used. All these ingredients are safe for the skin and are biodegradable. The selected microemulsions and gel microemulsions were physicochemically characterized by means of dynamic light scattering, electrical conductivity, polarized microscopy and rheometric measurements. To evaluate the efficiency of the selected microemulsion and gel microemulsion to deliver the encapsulated curcumin, an in vitro permeation study was performed.