Proliferative Stage Research Articles

The Effect of Long-Term Passage on Porcine SMCs' Function and the Improvement of TGF-β1 on Porcine SMCs' Secretory Function in Late Passage.

Cultured meat is one of the meat substitutes produced through tissue engineering and other technologies. Large-scale cell culture is the key for cultured meat products to enter the market. Therefore, this study is aimed to explore the effect of long-term passage in vitro on smooth muscle cells (SMCs) and the effect of transforming growth factor-β1 (TGF-β1) on SMCs in the late passage. Multiple passages lead to the decline of the proliferation rate of SMCs in the proliferation stage and the differentiation ability in the differentiation stage. Transcriptome results showed that the ECM pathway and aging-related signaling pathways were significantly up-regulated in the late passage period. TGF-β1 did not promote SMCs of late passage proliferation at the proliferation stage but promoted the gene and protein expression of collagen as the main protein of the extracellular matrix proteins at the differentiation stage. In addition, proteomic analysis revealed that TGF-β1 promoted the expression of cell adhesion molecules which activate the Hippo signaling pathway and the HIF-1 signaling pathway and further promoted the production of collagen-containing extracellular matrix proteins. This could provide ideas for large-scale production of cultured meat products using SMCs.

Evaluation of serum levels of soluble (s)L- and (s)P-selectins in endometrial cancer.

A number of reports on the role of selectin in the process of carcinogenesis, at the stage of proliferation and metastasis, have been available. The aim of the study was to analyze (s)P- and (s)L-selectin serum concentrations in women with EC and to compare these concentrations to clinical/pathological parameters and disease progression using surgical-pathological staging data. A total of 46 patients with EC and 50 healthy controls were included in the study. Serum concentrations of sL- and sP-selectins were measured in all participants. The oncologic protocol was implemented in all women from the study group. Significantly higher serum concentrations were found in EC women as compared to controls. No statistically significant differences were found between the concentrations of the soluble forms of selectins and the following parameters: histologic type of EC, histologic tumor differentiation, depth of myometrial infiltration, cervical involvement, distant metastases, vascular space invasion, and disease advancement. Slightly higher (s)P-selectin concentrations were observed in serous carcinoma, in women with cervical involvement, in the sera of women with vascular space invasion and with advanced stages of the disease. Slightly higher mean (s)P-selectin concentrations correlated with lower differentiation of the tumor. Slightly higher mean (s)P-selectin concentration was detected in the sera of women with lymph node metastases and with the serosal and/or adnexal involvement. The results were statistically insignificant, but they almost reached statistical significance. L- and P-selectins play a role in the biology of EC. The absence of an unambiguous relationship between differences in (s)L- and (s)P-selectin levels and disease advancement suggests that they do not play a vital role in tumor progression in endometrial cancer.

A systematic review of transcriptomic studies of the human endometrium reveals inconsistently reported differentially expressed genes.

Genome-wide analysis of gene expression has been widely applied to study the endometrium, although to our knowledge no systematic reviews have been performed. Here, we identified 74 studies that described transcriptomes from whole (unprocessed) endometrium samples and found that these fitted into three broad investigative categories; endometrium across the menstrual cycle, endometrium in pathology, and endometrium during hormone treatment. Notably, key participant information such as menstrual cycle length and body mass index was often not reported. Fertility status was frequently not defined and fertility-related pathologies, such as recurrent implantation failure (RIF) and recurrent pregnancy loss, were variably defined, while hormone treatments differed between almost every study. A range of 1307-3637 reported differentially expressed genes (DEG) were compared in 4-7 studies in five sub-categories; (i) secretory vs proliferative stage endometrium, (ii) mid-secretory vs early secretory stage endometrium, (iii) mid-secretory endometrium from ovarian stimulation-treated participants vs controls, (iv) mid-secretory endometrium from RIF patients vs controls, and (v) mid-secretory eutopic endometrium from endometriosis patients vs controls. Only the first two sub-categories yielded consistently reported DEG between ≥3 studies, albeit in small numbers (<40), and these were enriched in developmental process and immune response annotations. This systematic review, though not PROSPERO registered, reveals that limited demographic detail, variable fertility definitions and differing hormone treatments in endometrial transcriptomic studies hinders their comparison, and that the large majority of reported DEG do not advance the identification of underlying biological mechanisms. Future studies should apply network biology approaches and experimental validation to establish causal gene expression signatures.

A Study of Parasympathetic Autonomic Function in Different Phases of the Menstrual Cycle among Young Adult Females

Background: The sex hormones, estrogen, and progesterone, as well as the gonadotropins, luteinizing hormone, and follicle-stimulating hormone produced from the anterior pituitary, govern the three stages of the menstrual cycle: menstrual, follicular, and luteal. Hormone fluctuations cause changes in autonomic function. There have been relatively few studies that show autonomic function modification throughout various periods of the menstrual cycle. Aim and Objectives: The current study was undertaken to investigate the difference in mean parasympathetic autonomic characteristics between the proliferative and secretory stages of the menstrual cycle. Materials and Methods: A total of 120 healthy young adult female volunteers were recruited among Kalinga Institute of Medical Sciences, Kalinga Institute of Nursing Sciences, and Kalinga Institute of Dental Sciences students. The study eliminated 20 students who were in the bleeding phase of their cycle. The electrocardiogram was captured, and parasympathetic parameters were determined using the fully automated CANWin instrument in the Department of Physiology. The data of the abovementioned parameters were compiled, tabulated, and entered into Microsoft Excel 2013 and statistically analyzed using STATA software 15.1. Results: The subjects’ mean ages, heights, and weights were 18.9 ± 0.70 years, 156.6 ± 5.25 cm, and 53.7 ± 8.63 kg, respectively. The mean resting heart rate in the secretory phase was substantially greater than in the proliferative phase, indicating sympathetic dominance. The 30:15 ratio between proliferative and secretory stages. The mean E: I ratio calculated from the slow deep breathing maneuver reveals a statistically significant difference between the proliferative and secretory phases. Conclusion: During the secretory phase, there is a considerable rise in parasympathetic activity among the individuals in the current study. Changes in parasympathetic activity throughout the follicular and secretory stages of the menstrual cycle may be caused by fluctuations in estrogen and progesterone levels.

Multi-layer-structured bioactive glass nanopowder for multistage-stimulated hemostasis and wound repair.

Current treatments for full-thickness skin injuries are still unsatisfactory due to the lack of hierarchically stimulated dressings that can integrate the rapid hemostasis, inflammation regulation, and skin tissue remodeling into the one system instead of single-stage boosting. In this work, a multilayer-structured bioactive glass nanopowder (BGN@PTE) is developed by coating the poly-tannic acid and ε-polylysine onto the BGN via facile layer-by-layer assembly as an integrative and multilevel dressing for the sequential management of wounds. In comparison to BGN and poly-tannic acid coated BGN, BGN@PTE exhibited the better hemostatic performance because of its multiple dependent approaches to induce the platelet adhesion/activation, red blood cells (RBCs) aggregation and fibrin network formation. Simultaneously, the bioactive ions from BGN facilitate the regulation of the inflammatory response while the poly-tannic acid and antibacterial ε-polylysine prevent the wound infection, promoting the wound healing during the inflammatory stage. In addition, BGN@PTE can serve as a reactive oxygen species scavenger, alleviate the oxidation stress in wound injury, induce the cell migration and angiogenesis, and promote the proliferation stage of wound repair. Therefore, BGN@PTE demonstrated the significantly higher wound repair capacity than the commercial bioglass dressing Dermlin™. This multifunctional BGN@PTE is a potentially valuable dressing for full-thickness wound management and may be expected to extend to the other wounds therapy.

Pyogenic granuloma — hypotheses of etiopathogenesis, clinical forms and features, modern diagnostic methods and choice of rational treatment tactics

Objective — to analyze modern hypotheses of etiopathogenesis and clinical features of pyogenic granulomas (PG) and to determine the importance of ultrasound of these neoplasms for the choice of individualized tactics of their treatment, taking into account the stage of tumor proliferation. Materials and methods. During 2020—2022, 94 patients with a diagnosis of «pyogenic granuloma» (PG) underwent outpatient treatment under our supervision at Dr. Bogomolets Institute of Dermatology and Cosmetology (Kyiv). The largest number of patients with PG examined by us was aged from 1 to 12 years (72 %), which correlates with the data of scientific research by other authors on the relevant problem. Anamnesis was collected in all examined patients (according to the patients and their parents) regarding the possible causes of neoplasms and the nature of their development. All the patients underwent a complex diagnostic instrumental examination of PG (dermoscopy, ultrasound, histopathology). The choice of treatment tactics was carried out individually in each specific clinical case, taking into account the results of the examination and the stage of tumor proliferation (radio wave removal or treatment with a 595­nm pulsed dye laser was carried out). Results and discussion. A total of 94 patients with PG were examined and treated on an outpatient basis. By age, children from 1 to 8 years old (48 %) and from 8 to 12 years old (24 %) prevailed among the examined. There were 6 % of teenagers and young adults (12—18 years old), 22 % over 18 years old. In 45 patients, neoplasms were localized on the skin of the face, in 7 — on the neck, in 9 — on the upper limbs, in 6 — on the lower limbs, in 27 — on the skin of the trunk. In 87 clinical cases, radio wave removal of neoplasms with their subsequent pathohistological diagnosis was carried out taking into account the results of a comprehensive examination of patients with PG, including the data of ultrasound of the skin in the areas affected by PG, which makes it possible to determine the depth of tumor invasion together with the exophytic part. In 6 clinical cases, PG removal therapy was selected and performed using a pulsed vascular dye laser with a wavelength of 595 nm. In one clinical case, taking into account the sufficiently large size of the tumor (more than 2 cm) and the significant vascularization of the neoplasm revealed by ultrasound, a diagnostic excisional biopsy was performed within healthy tissues. Recurrences of PG after treatment were observed after 2 months in 2 of 94 patients, in particular, after pulsed vascular laser therapy. Subsequently, in these two patients, PG was removed using the radio wave method. No recurrences of the disease were registered. Conclusions. The analysis of modern literature on the problem of PG and the results of own clinical observation and treatment of patients with the corresponding neoplasms indicate that ultrasound of these skin tumors is a sufficiently informative and promising diagnostic method that allows identifying the stage of proliferation and choosing the rational individualized treatment tactics. Considering that the use of ultrasound of skin tumors is a relatively new methods in dermatology, further research in the relevant direction is appropriate, which will increase its diagnostic informativeness.

P-321 increased expression of TGF-β1 contributes to the downregulation of progesterone receptor expression in the eutopic endometrium of infertile women with minimal/mild endometriosis

Abstract Study question Do immune cells regulate progesterone resistance and endometrial receptivity of eutopic endometrial stromal cells (ESCs) by transforming growth factor-β1 (TGF-β1)? Summary answer By activating TGF-β/Smad signaling in eutopic ESCs, elevated TGF-β1 from CD45+ immune cells could attenuate expression of progesterone receptor (PR), and further decrease endometrial receptivity. What is known already Endometriosis is a hormone-dependent disease related to impaired immunoregulation. We characterized the trascriptomic transformation of eutopic endometrium from patients with minimal/mild endometriosis and controls across the menstrual cycle. However, the regulatory mechanism of altered immune microenvironment on eutopic ESCs remains unclear. Study design, size, duration Single-cell RNA transcriptomes were profiled using 10x Genomics platform. Primary culture of eutopic ESCs was performed to explore the effects of TGF-β1 on the expression of Smad / PR, and the in vitro decidualization. Additionally, co-immunoprecipitation (Co-IP) was used to explore the direct interaction between Smad and PR. Participants/materials, setting, methods Endometrial tissue samples were obtained from twenty-four women who were laparoscopically confirmed minimal/mild endometriosis according to the revised American Fertility Society classification. Additionally, four patients who were laparoscopically endometriosis-free were enrolled as controls. All samples were collected in DMEM/F12 medium and processed in one of two ways, either for single-cell sequencing (n = 10) or primary cell culture (n = 14). Main results and the role of chance The results of single-cell RNA sequencing revealed that the percentage of CD45+ cells in eutopic endometrium was increase in both proliferative (26% vs 24.1%) and secretory (19.3% vs 8.3%) stages. Overexpression of TGF-β1 of CD45+ cells was observed in eutopic endometrium of endometriosis in both proliferative and secretory stages. We found attenuate expression of PRB (p = 0.026) and PRA (p = 0.678) after using TGF-β1 in eutopic ESCs by western blot. Similarly, qRT-PCR results showed that the mRNA level of PR (p＜0.001), PRB (p = 0.003) and HOXA10 (p＜0.001) decreased significantly after TGF-β1 treatment, but that increased (p＜0.01) after SB431542 treatment in the eutopic ESCs. Moreover, TGF-β1 has a negative effect on the in vitro decidualization of eutopic ESCs (p = 0.003). And the group with treatment of both TGF-β1 and SB435142 in eutopic ESCs showed significant decidual-like changes with increased prolactin level (p = 0.01). Co-IP showed no physical interaction between the PR and p-Smad3/Smad3 proteins. Limitations, reasons for caution This study focused on CD45+ immune cells and the cytokine, TGF-β1. Further in vivo and in vitro studies are needed to elucidate the specific types of immune cell and the mechanisms that behind endometrial receptivity decrease in endometriosis. Wider implications of the findings Our results demonstrate abnormal activation of CD45+ cells in eutopic endometrium with minimal/mild endometriosis. And overexpression of TGF-β1 was found by CD45+ cells. We found that TGF-β1 suppresses PR expression and decidualization in eutpoic ESCs. These results provide a novel insight into the mechanisms behind progesterone resistance in endometriosis. Trial registration number not applicable

Deep learning for automated detection of neovascular leakage on ultra-widefield fluorescein angiography in diabetic retinopathy

Diabetic retinopathy is a leading cause of blindness in working-age adults worldwide. Neovascular leakage on fluorescein angiography indicates progression to the proliferative stage of diabetic retinopathy, which is an important distinction that requires timely ophthalmic intervention with laser or intravitreal injection treatment to reduce the risk of severe, permanent vision loss. In this study, we developed a deep learning algorithm to detect neovascular leakage on ultra-widefield fluorescein angiography images obtained from patients with diabetic retinopathy. The algorithm, an ensemble of three convolutional neural networks, was able to accurately classify neovascular leakage and distinguish this disease marker from other angiographic disease features. With additional real-world validation and testing, our algorithm could facilitate identification of neovascular leakage in the clinical setting, allowing timely intervention to reduce the burden of blinding diabetic eye disease.

Effects of Red LED Irradiation in Enhancing the Mineralization of Human Dental Pulp Cells In Vitro.

Dentin regeneration is the preferred method used to preserve dental pulp vitality after pulp exposure due to caries. Red light-emitting diode irradiation (LEDI), which is based on photobiomodulation (PBM), has been used to promote hard-tissue regeneration. However, the underlying mechanism still needs elucidation. This study aimed to explore the mechanism involved in red LEDI affecting dentin regeneration. Alizarin red S (ARS) staining revealed that red LEDI induced mineralization of human dental pulp cells (HDPCs) in vitro. We further distinguished the cell proliferation (0-6 d), differentiation (6-12 d), and mineralization (12-18 d) of HDPCs in vitro and treated cells either with or without red LEDI in each stage. The results showed that red LEDI treatment in the mineralization stage, but not the proliferation or differentiation stages, increased mineralized nodule formation around HDPCs. Western blot also indicated that red LEDI treatment in the mineralization stage, but not the proliferation or differentiation stages, upregulated the expression of dentin matrix marker proteins (dentin sialophosphoprotein, DSPP; dentin matrix protein 1, DMP1; osteopontin, OPN) and an intracellular secretory vesicle marker protein (lysosomal-associated membrane protein 1, LAMP1). Therefore, the red LEDI might enhance the matrix vesicle secretion of HDPCs. On the molecular level, red LEDI enhanced mineralization by activating the mitogen-activated protein kinase (MAPK) signaling pathways (ERK and P38). ERK and P38 inhibition reduced mineralized nodule formation and the expression of relevant marker proteins. In summary, red LEDI enhanced the mineralization of HDPCs by functioning to produce a positive effect in the mineralization stage in vitro.

RXR agonist bexarotene modulates the cell‐fate and migration abilities of adult neural stem cells in vitro

AbstractBackgroundTargeting the nuclear RXR receptors has been associated with brain‐specific roles with striking therapeutic potential for Alzheimer’s Disease (AD), with similar observations to its dimerization partners such as LXR and PPAR whose responses are also under influence of RXR activation. Treatment with bexarotene, a selective RXR agonist, leads to significant recovery of cognitive loss in variable mice AD‐like models ‐ and also activates neurodevelopment and plasticity pathways in adult mice brains. Our hypothesis is that neural stem cells (NSC) residing in the adult brain directly respond to bexarotene, leading to improved neurogenesis and other effects compatible with brain recovery.MethodWe employed an in vitro strategy using NSCs isolated from the subventricular zone of adult rats’ brains. Adult NCSs were treated with bexarotene from neurosphere proliferative stage to differentiated states, and the cell‐fate consequences were evaluated through morphometric analysis and immunofluorescence of cell markers.ResultIn proliferative stages, bexarotene‐treated adult NSCs exhibited increased cell outgrowth from neurospheres. Bexarotene treatment also led to changes in the cell fate of differentiating cells, with a marked increase in GFAP staining after differentiation. Relatively to newborn neurons, we found a decrease in DCX positive staining of neuroblasts after bexarotene treatment. However, Tuj1 staining of neurons was preserved. Neurite number, length, and bifurcations in differentiated neurons were unaffected by bexarotene.ConclusionAdult NSCs respond to bexarotene by increasing migration abilities and generating more GFAP+ cells. Results indicate that RXR activation by bexarotene in adult NSCs preserves, but does not activate, neuronal differentiation and neurite complexity. The significance of the increased GFAP+ glial cell population, as well as the decreased DCX+ young neurons, remains to be unrevealed. Finally, we did not observe clear bexarotene‐induced changes in neurosphere proliferation, but the effect of RXR activation over pluripotency in these cells needs further investigation. These findings address a gap in our knowledge regarding the brain effects of bexarotene, substantiating the search and possible application of RXR‐based approaches to AD.

Study of hydrosalpinx on endometrial growth and expression of HOXA10mRNA and related factors

ObjectiveThe objective of the study is to extract the patient's endometrium at the time of proliferative stage using hydrosalpinx in order to culture the cells and decidualization induction in vitro. Further, the study is also intended at identifying the expression of HOXA10mRNA and related factors and understand the hydrosalpinx's impact upon the working mechanism of endometrial cells. MethodsOnce the extraction of the primary cells is over, the cells are cultured and other activities are performed such as the cell identification, CCK8 assay, cell decidua induction and HE staining. The researchers assessed the expression levels of HOXA10, IGFBP1 and avβ3 in either proliferation or secretion of the endometrium. This was accomplished using Western blot assay and real-time fluorescence quantitative PCR. ResultsThe results confirmed that at the time of endometrial proliferation, there was a decline in the expression of HOXA10 as a result of HS influence. This affected its expression in the secretory stage i.e., corresponding function. Further, a significant decline was observed in the levels of HOXA10mRNA of endometrial cells that were subjected to continuous HS, post decidualization. It was found that during decidualization, if the HS is removed, it is possible to restore the expression of HOXA10mRNA to a certain extent, though it is not possible to reach the general endometrial level. So, in terms of clinical aspects, the expression of HOXA10mRNA by the endometrial cells decreases significantly when blocking the hydrosalpinx. ConclusionsAmong hydrosalpinx patients, one of the major mechanisms that damage the endometrium was found to be the abnormal expression of HOXA10 followed by IGFBP1 and avβ3, its downstream genes. This further results in the implantation of the embryo as well. Though it is possible to gradually repair the damage after the removal of hydrosalpinx, the recovery is a time-consuming process.

Влияние степени адгезии внутренней пограничной мембраны на результаты хирургии тракционного диабетического макулярного отека

Internal limiting membrane (ILM) peeling is a technically complex manipulation that is performed during macular surgery. Experts'opinions vary on its necessity. Visual inspection during surgery does not always make it possible to assess the degree of ILM adhesion to the retina. The aimof the study was to evaluate the morphofunctional parameters of the macular zone after ILM peeling with different degree of adhesion in the long-term postoperative period. Material and methods. A study was conducted that included 119 patients with type 1 (65 (55%) and type 2 (54 (45%) diabetes mellitus with proliferative stage of diabetic retinopathy (PDR) and tractional diabetic macular edema (tDME). All patients underwent a standard three-port 25G vitrectomy with the use of an additional endo-luminaire «chandelier» and bimanual membrane peeling technique. During ILM peeling, all patients underwent intraoperative optical coherence tomography (I-OCT) in order to assess the degree of ILM adhesion to the retina. Before, 1 and 12 months after the operation, the determination of the maximum corrected visual acuity (MCVA), OCT of the macular zone with the measurement of the central retinal thickness (CRT) was performed. Results and discussion. 3 degrees of adhesion of ILM to the retina were identified with I-OCT during ILM peeling. The degree of ILM adhesion in fovea significantly correlated with the development of a retinal defect in its central area. The development of retinal central zone atrophy showed a significant correlation with a decrease in MCVA 12 months after surgery and with the degree of ILM adhesion to the retina in patients with both types of DM. Conclusions. According to the results of this study, a significant correlation was shown between the degree of ILM adhesion to the retina determined by I-OCT and the risk of macular atrophy, which in turn is associated with low visual functions of patients after tDME surgery with ILM peeling. The resulting principle can be used in surgery of other vitreomacular interface pathologies. Keywords: vitreomacular interface, epiretinal membrane, diabetic macular edema, tractional diabetic macular edema, intraoperative optical coherence tomography, vitreoretinal surgery, proliferative diabetic retinopathy

A Hybrid Technique for Diabetic Retinopathy Detection Based on Ensemble-Optimized CNN and Texture Features.

One of the most prevalent chronic conditions that can result in permanent vision loss is diabetic retinopathy (DR). Diabetic retinopathy occurs in five stages: no DR, and mild, moderate, severe, and proliferative DR. The early detection of DR is essential for preventing vision loss in diabetic patients. In this paper, we propose a method for the detection and classification of DR stages to determine whether patients are in any of the non-proliferative stages or in the proliferative stage. The hybrid approach based on image preprocessing and ensemble features is the foundation of the proposed classification method. We created a convolutional neural network (CNN) model from scratch for this study. Combining Local Binary Patterns (LBP) and deep learning features resulted in the creation of the ensemble features vector, which was then optimized using the Binary Dragonfly Algorithm (BDA) and the Sine Cosine Algorithm (SCA). Moreover, this optimized feature vector was fed to the machine learning classifiers. The SVM classifier achieved the highest classification accuracy of 98.85% on a publicly available dataset, i.e., Kaggle EyePACS. Rigorous testing and comparisons with state-of-the-art approaches in the literature indicate the effectiveness of the proposed methodology.

Repetitive transcranial magnetic stimulation and fluoxetine reverse depressive-like behavior but with differential effects on Olig2-positive cells in chronically stressed mice

Depression is a mood disorder coursing with several behavioral, cellular, and neurochemical alterations. The negative impact of chronic stress may precipitate this neuropsychiatric disorder. Interestingly, downregulation of oligodendrocyte-related genes, abnormal myelin structure, and reduced numbers and density of oligodendrocytes in the limbic system have been identified in patients diagnosed with depression, but also in rodents exposed to chronic mild stress (CMS). Several reports have emphasized the importance of pharmacological or stimulation-related strategies in influencing oligodendrocytes in the hippocampal neurogenic niche. Repetitive transcranial magnetic stimulation (rTMS) has gained attention as an intervention to revert depression. Here, we hypothesized that 5 Hz (Hz) of rTMS or Fluoxetine (Flx) would revert depressive-like behaviors by influencing oligodendrocytes and revert neurogenic alterations caused by CMS in female Swiss Webster mice. Our results showed that 5 Hz rTMS or Flx revert depressive-like behavior. Only rTMS influenced oligodendrocytes by increasing the number of Olig2-positive cells in the hilus of the dentate gyrus and the prefrontal cortex. However, both strategies exerted effects on some events of the hippocampal neurogenic processes, such as cell proliferation (Ki67-positive cells), survival (CldU-positive cells), and intermediate stages (doublecortin-positive cells) along the dorsal-ventral axis of this region.Interestingly, the combination of rTMS-Flx exerted antidepressant-like effects, but the increased number of Olig2-positive cells observed in mice treated only with rTMS was canceled. However, rTMS-Flx exerted a synergistic effect by increasing the number of Ki67-positive cells. It also increased the number of CldU- and doublecortin-positive cells in the dentate gyrus.Our results demonstrate that 5 Hz rTMS has beneficial effects, as it reverted depressive-like behavior by increasing the number of Olig2-positive cells and reverting the decrement in hippocampal neurogenesis in CMS-exposed mice. Nevertheless, the effects of rTMS on other glial cells require further investigation.

Bioactive Glasses for Soft and Hard Tissue Healing Applications—A Short Review

Bioactive glasses have developed into a variety of items that are used in order to treat a wide range of medical problems. Apart from being mostly applied in the healing processes of hard tissues, bioactive glasses are becoming very popular materials in soft tissues healing. Bioactive glasses have exhibited the ability to accelerate skin regeneration by enhancing angiogenesis and collagen deposition in the proliferation stage, as well as positive effects on all the other important stages of wound healing. They can adhere to hard tissues such as bone and aid in the regeneration of those tissues by forming a calcium–phosphate-like layer on their surfaces. The formation of this apatite layer results in a linkage between the hard tissue and the glass, which further leads to bone healing. This short review summarizes the dynamic process of wound healing along with the basic concepts of bioactive glasses applied in this domain. We aimed to explore constructs which aid different phases of wound healing. Moreover, several research studies dedicated to bioactive glass thin films are briefly discussed.

A neo-functionalized homolog of host transmembrane protein controls localization of bacterial endosymbionts in the trypanosomatid Novymonas esmeraldas

The stability of endosymbiotic associations between eukaryotes and bacteria depends on a reliable mechanism ensuring vertical inheritance of the latter. Here, we demonstrate that a host-encoded protein, located at the interface between the endoplasmic reticulum of the trypanosomatid Novymonas esmeraldas and its endosymbiotic bacterium Ca. Pandoraea novymonadis, regulates such a process. This protein, named TMP18e, is a product of duplication and neo-functionalization of the ubiquitous transmembrane protein 18 (TMEM18). Its expression level is increased at the proliferative stage of the host life cycle correlating with the confinement of bacteria to the nuclear vicinity. This is important for the proper segregation of bacteria into the daughter host cells as evidenced from the TMP18e ablation, which disrupts the nucleus-endosymbiont association and leads to greater variability of bacterial cell numbers, including an elevated proportion of aposymbiotic cells. Thus, we conclude that TMP18e is necessary for the reliable vertical inheritance of endosymbionts.

Adipose-derived Stem Cells Improving Inflammatory and Proliferative Responses in an Infected and Ischemic Ulcer Model in Type 1 Diabetic Rats: Insights Into Bacterial Count, Stereological Parameters, microRNA-21, and FGF2 Regulation

Background: Adipose-derived stem cells (ADSCs) have been shown to enhance wound healing in rats with type 1 diabetes (DM1). Objectives: This experimental study aimed to explore how ADSC administration affects bacterial count, wound size, biomechanical and stereological parameters, and the expression of microRNA-21 and FGF2 in a rat model of infected, ischemic, and delayed wound healing in DM1. Methods: Twenty-four male adult Wistar rats weighing less than 250 g were randomly assigned to four groups (n = 6 per group). Type 1 diabetes was induced in all animals, resulting in the development of a delayed, ischemic, and infected wound model. The CGday4 and CGday8 groups served as controls. In the AGday4 group, the animals received allograft h-ADSs and were euthanized on day four after surgery. Similarly, in the AGday8 group, the animals received h-ADSs and were euthanized on day eight after surgery. Microbial colony counts, wound size, stereological parameters, and the expression of microRNA-21 and FGF2 were evaluated in this study during the inflammation (day 4) and proliferation (day 8) stages of wound healing. Results: We demonstrated that h-ADSs significantly reduced microbiological counts compared to the control group on days 4 and 8. Moreover, in the AGday8 group compared to the AGday4 group, this decline in microbiological counts was even more pronounced. Moreover, we observed that the stereological characteristics in the AGday4 and AGday8 groups were significantly superior to those in the CG groups. Additionally, the AGday4 and AGday8 groups exhibited smaller ulcer area sizes compared to the CG groups. Furthermore, the AGday4 and AGday8 groups demonstrated higher expression levels of FGF2 and microRNA-21 than the CG groups on days 4 and 8. Notably, on day 8, the AGday8 group’s outcomes surpassed those of the AGday4 group (P &lt; 0.01). Conclusions: Through lowering microbial counts, modifying stereological parameters, microRNA-21, and FGF2 expression, the administration of hADS dramatically speeds up the healing of MARS-infected and ischemic ulcers in DM1 rats.

Effect of Melatonin on the Content of CD3low and CD3hi T Cells in the Thymus of Mice with Functional Pinealectomy.

Continuous lighting for 14 days (functional pinealectomy model) leads to a decrease in the relative number of CD3low and CD3hi T lymphocytes and the CD3low/CD3hi ratio in the thymus of C57BL/6 mice. Intragastric administration of melatonin in physiological doses (1 mg/kg body weight, 14 days) against the background of functional pinealectomy restores the percentage of CD3low and CD3hi thymocytes and CD3low/CD3hi ratio to the control values. Hence, prolonged continuous illumination inhibits the differentiation and maturation of young thymocytes into mature forms, while melatonin treatment helps to compensate the effects of functional pinealectomy triggering cell proliferation in the thymus from the earliest stages of proliferation and differentiation of T cells. Thus, melatonin has immunotropic properties and can be used for correction of the consequences of functional pinealectomy.

Snail-inspired AFG/GelMA hydrogel accelerates diabetic wound healing via inflammatory cytokines suppression and macrophage polarization

Diabetic foot ulcers (DFUs) are a severe and rapidly growing diabetic complication, but treating DFUs remains a challenge for the existing therapies are expensive and highly non-responsive. Recently, we discovered that a natural adhesive from snail mucus can promote skin wound healing. Herein, inspired by the finding, we developed a double-network hydrogel biomaterial that composed of snail glycosaminoglycan (AFG) and methacrylated gelatin (GelMA), in which AFG is the main bioactive component of snail mucus and GelMA provides a scaffold mimicking the proteins in snail mucus. The biomimetic hydrogel exhibited strong tissue adhesion, potent anti-inflammatory activity, and excellent biocompatibility. The biodegradable AFG/GelMA hydrogel markedly promoted chronic wound healing in both STZ-induced type 1 diabetic rat and db/db mouse models after a single treatment. Further mechanistic research showed that the hydrogel significantly attenuated inflammation by sequestrating pro-inflammatory cytokines, as well as downregulated their expression by inhibiting NF-ĸB signaling pathway, and it can also promote macrophage polarization to M2 phenotype. Taken together, the bioinspired hydrogel can effectively promote the transition of chronic wounds from inflammation to proliferation stage. These data suggest that the AFG/GelMA hydrogel is a promising therapeutic biomaterial for the treatment of chronic diabetic wounds.

Spiky surface topography of heterostructured nanoparticles for programmable acceleration of multistage wound healing

Wound healing is a complex and orchestrated physiological process that involves multiple stages, including hemostasis, inflammation, proliferation, and remodeling stages. Various nanomaterials have been developed to improve the wound healing; however, most of them can only promote an individual stage of this intricate process, lacking hierarchical acceleration for multiple stages. In the present study, spiky gold-palladium heterostructured nanoparticles (AuPd SHs) were designed to possess topographical architectures on the surface of nanoparticles, capable of promoting multistage wound healing in a programmable manner. First, the spiky surface topography of AuPd SHs exhibited the potent nanobridge effect for rapid wound closure, promoting the hemostasis stage. Second, the heterostructures of AuPd SHs realized visible-light-mediated hot electron excitation and electron–hole spatial separation between Au cores and Pd spikes to efficiently generate reactive oxygen species, beneficial for the inflammation stage. Third, the spiky surface topography of AuPd SHs triggered macrophage polarization from M1 to M2 phenotype, promoting the proliferation and maturation stages. Spiky AuPd SHs with simple composition and compact structures exhibit hierarchical acceleration on multiple stages of wound healing.