Tissue Repair Processes Research Articles

P-799 Augmenting endometrial thickness and implantation rates: investigating the efficacy of autologous blood cell derivative - endosera in women struggling with thin endometrium and infertility

Abstract Study question Could autologous platelet derived growth factor based strategies promote endometrial growth in women with refractory thin endometrium resulting in sustained implantation and live births? Summary answer Autologous platelet derived growth factor based strategies remarkably promote endometrial thickness and receptivity in women with refractory thin endometrium and pregnancy outcomes What is known already Repeated implantation failure (RIF) attributed to thin endometrium poses significant challenge in reproductive medicine. In cases where conventional treatments prove ineffective, couples often contemplate stressful option of surrogacy. Regenerative strategies, such as platelet-rich plasma (PRP), exhibit promise by capitalizing on anti-inflammatory and pro-regenerative attributes of platelet-derived growth factors. Recognizing the imperative for anti-inflammatory microenvironment conducive to successful implantation, Endosera, a cell-free growth factors concentrate tailored for implantation has been formulated. This study seeks to evaluate the effectiveness of Endosera in augmenting endometrial thickness and implantation rates, offering potential remedies for RIF and thin endometrium. Study design, size, duration In this prospective self-controlled study 62 women (24-47 years) were enrolled spanning May 2021 to December 2023. Women experienced >2 failed IVF cycles and multiple cycle cancellations due to refractory thin endometrium with poor endometrial receptivity defined as endometrial thickness of < 7mm despite standard medical therapy, abnormal endometrial pattern and suboptimal endometrialvascularity, negative hysteroscopic screening for endometrial pathology, and negative bacteriologicscreening and despite multiple failed conventional therapies were selected to undergo Endosera treatment. Participants/materials, setting, methods After obtaining informed consent, patients underwent three intrauterine infusions of Endosera on menstrual cycle Day 7, Day 12, and 2 days before frozen embryo transfer (FET). Alongside standard hormone replacement therapy (HRT), 0.8 ml of Endosera was introduced into the uterine cavity. Pregnancy confirmation relied on a positive serum β-HCG test two weeks post-ET, while clinical pregnancy was established by detecting fetal heartbeat through transvaginal ultrasound four weeks post-ET. Main results and the role of chance In this study involving 62 patients facing multiple cancelled IVF cycles due to refractory thin endometrium, the administration of three doses of Endosera demonstrated significant positive outcomes. Average endometrial thickness notably increased from 6.2 ± 1.2 mm to 8.4 ± 1.2 mm (P < 0.0001) after the 2nd Endosera dose, reaching an optimal thickness of ≥ 8mm. Among the participants, 43 achieved positive pregnancy result (69.4%), with 26 (41.9%) delivering healthy babies and 7 (11.3%) uneventful ongoing pregnancies. Poor outcomes included for 2 (3.2%) patients cycle was cancelled due to no endometrial improvement 5(8.1%) miscarriages before 10 weeks, while 12 (19.4%) women didn’t conceive and for 4.8%(3) patients results awaited post ET. No adverse effects were reported, indicating safety of Endosera.Cumulative positive pregnancy outcomes recorded to be 53.2% (33). The formulation, standardized to contain 6-9 times higher growth factor levels than peripheral blood, emphasizes implantation-friendly and anti-inflammatory cytokines. This optimized composition aligns with cyclical requirements of the endometrial phases (proliferation, secretion, and implantation), creating an angiogenic and anti-inflammatory environment crucial for successful implantation. Endosera’s safety, reproducibility, and efficacy in mimicking natural tissue repair and regeneration processes position it as promising solution for refractory thin endometrium-related challenges. Limitations, reasons for caution This study, though demonstrating improved outcomes in refractory thin endometrium cases with Endosera treatment, acknowledges limitations such as a small sample size and absence of a randomized control group. To establish Endosera as a routine adjuvant in IVF, larger study with stringent inclusion criteria for refractory thin endometrium is recommended. Wider implications of the findings Endosera demonstrated notable success with significant improvement in implantation, pregnancy, and live birth rates for refractory thin endometrium patients prompts rigorous randomized controlled studies. These will include diverse populations, validating results and offering patients hope to reduce financial and psychological stress and challenges associated with cycle cancellations and surrogacy. Trial registration number Not Applicable

P-329 Evaluating Implansera, autologous platelet-derived growth factors, to improve clinical pregnancy and live birth rates in frozen embryo transfer for women with recurrent implantation failure

Abstract Study question Can Implansera, Autologous Platelet-Derived Growth Factors, serve as a promising adjuvant therapy in assisted reproductive techniques to enhance endometrial thickness and implantation rates? Summary answer Use of Implansera significantly increased clinical pregnancy and Live Birth Rate In Patients With repeated implantation failure during FET cycles. What is known already Insufficient endometrial thickness and receptivity contribute to Recurrent Implantation Failure (RIF), prompting consideration of surrogacy. Despite global rise in Frozen Embryo Transfer (FET), quest for an optimal implantation protocol persists. Recent research highlights platelet-rich plasma (PRP) as promising solution for thin endometrium and RIF cases, attributing positive outcomes to PRP’s high growth factor concentration. Recognizing the need for precise platelet and growth factor concentrations, Implansera—a specialized platelet-derived growth factor concentrate—was developed. This innovation addresses the challenge of unresponsive endometrium, offering tailored solution to maximize therapeutic efficacy and improve pregnancy outcomes for patients facing RIF issues. Study design, size, duration Conducted from May 2021 to December 2023, this prospective interventional self-controlled study focused on 21 women (aged 30-48) experiencing recurrent IVF failure due to stubborn thin endometrium. Selected after negative hysteroscopic and bacteriologic screenings, and unsuccessful pregnancies despite multiple immune therapy regimens, such as intralipid and granulocyte colony-stimulating factor infusions, steroids, and endometrial scratching. The subjects underwent Implansera treatment, aiming to address refractory thin endometrium and potentially enhance their chances of successful conception. Participants/materials, setting, methods After obtaining informed consent women with at least two previous unexplained RIF, who were candidates for frozen-thawed embryo transfer were treated with intrauterine infusion of 0.8 ml of Implansera was infused into uterine cavity in addition to standard HRT protocols 2 days before ET. Clinical pregnancy was determined by positive serum β-HCG, 2weeks after ET and presence of fetal heart beat in trans-vaginal ultrasound 5weeks after ET. Main results and the role of chance Among 21 women, 10 achieved pregnancy (47.6%), while 11 did not conceive (52.4%). Clinical outcomes varied: 1 woman (4.8%) experienced chemical pregnancy, 3 (14.3%) miscarried before 6-12 weeks, 3 (14.3%) delivered healthy full-term babies, and 3 (14.3%) are in the 24th week of uneventful gestation accounts for 28.6% cumulative successful pregnancy outcomes. Implansera treatment yielded no reported adverse effects.Implansera, prepared through a patented proprietary process, standardized to contain 6-9 times higher growth factors than peripheral blood, particularly implantation-friendly and anti-inflammatory cytokines, addresses the crucial angiogenic and anti-inflammatory requirements for successful implantation. Tailored for the cyclical demands of endometrial proliferation, secretion, and implantation phases, it efficiently restores impaired uterine environments.Beyond efficacy, Implansera’s safety, reproducibility, and effectiveness in emulating natural tissue repair and regeneration processes are noteworthy. Studies underscore the significance of creating an environment conducive to successful implantation, and Implansera’s composition aligns with these requirements. Its capacity to mimic natural processes positions it as a promising solution, offering a comprehensive approach to enhancing endometrial receptivity, thus optimizing conditions for successful pregnancies. Limitations, reasons for caution This self-controlled prospective study, albeit with small sample size and lacking randomized control group, aligns with published data in demonstrating Implansera’s benefits. Proposing larger studies, particularly with unexplained RIF, to establish Implansera as routine IVF adjuvant. Further investigations aim to identify active molecules influencing implantation and suggest targeted recommendations. Wider implications of the findings Implansera improved implantation, pregnancy, and live birth rates (LBR) in unexplained RIF patients which indicates clearly endometrial thickness and receptivity improvement and motivated us to plan randomized controlled studies to confirm the results and provide opportunity for women with unexplained RIF to conceive and deliver in lesser number of cycles. Trial registration number Not applicable

P-305 Enhancing endometrial thickness and implantation rates: a study on the effectiveness of autologous blood cell derivative - endosera in infertile women with thin endometrium

Abstract Study question Could personalized regenerative medicine based strategies promote endometrial growth and receptivity in women with refractory thin endometrium resulting in successful implantation and live births? Summary answer Personalized regenerative medicine based strategies remarkably promote endometrial growth and receptivity in women with refractory thin endometrium resulting in successful implantation and live births. What is known already Repeated implantation failure (RIF) due to thin endometrium is a formidable challenge in reproductive medicine, often steering couples toward the stressful option of surrogacy. Regenerative approaches like platelet-rich plasma (PRP) have shown promise, leveraging the anti-inflammatory and pro-regenerative properties of platelet-derived growth factors. Recognizing the need for an anti-inflammatory milieu for successful implantation, Endosera, a cell-free implantation-friendly growth factors concentrate, has been developed. This study at Bloom IVF Centre-Mumbai, India, aims to assess Endosera’s efficacy in enhancing endometrial thickness and implantation rates, providing potential solutions for RIF and thin endometrium. Study design, size, duration In this prospective self-controlled study 72 women (27-49 years) were enrolled spanning December 2022 to December 2023. Women experienced two or more failed IVF cycles and multiple cycle cancellations due to refractory thin endometrium, negative hysteroscopic screening for endometrial pathology, and negative bacteriologic screening and despite multiple failed conventional therapies were selected to undergo Endosera treatment. Participants/materials, setting, methods After obtaining informed consent, patients underwent three intrauterine infusions of Endosera on menstrual cycle Day 7, Day 12, and 2 days before frozen embryo transfer (FET). Alongside standard hormone replacement therapy (HRT), Endosera was introduced into the uterine cavity. Pregnancy confirmation relied on a positive serum β-HCG test two weeks post-ET, while clinical pregnancy was established by detecting fetal heartbeat through transvaginal ultrasound four weeks post-ET. Main results and the role of chance In this study involving 72 patients facing recurrent implantation failure due to refractory thin endometrium, the administration of three doses of Endosera demonstrated significant positive outcomes. The average endometrial thickness notably increased from 6.4 ± 1.1 mm to 8.7 ± 1.0 mm (P < 0.0001) after the 2nd Endosera dose, reaching an optimal thickness of ≥ 7mm. Among the participants, 34 achieved a positive pregnancy result (47.2%), with 6 (8.3%) delivering healthy babies and 23 (31.9%) experiencing ongoing clinical pregnancies. Adverse outcomes included 2 (2.8%) ectopic pregnancies and 3 (4.2%) miscarriages before 10 weeks, while 36 (50%) women returned negative HCG results. No adverse effects were reported, indicating the safety of Endosera. The formulation, standardized to contain 6-9 times higher growth factor levels than peripheral blood, emphasizes implantation-friendly and anti-inflammatory cytokines. This optimized composition aligns with the cyclical requirements of the endometrial phases (proliferation, secretion, and implantation), creating an angiogenic and anti-inflammatory environment crucial for successful implantation. Endosera’s safety, reproducibility, and efficacy in mimicking natural tissue repair and regeneration processes position it as a promising solution for refractory thin endometrium-related challenges. Limitations, reasons for caution This study, though demonstrating improved outcomes in refractory thin endometrium cases with Endosera treatment, acknowledges limitations such as small sample size and absence of a randomized control group. To establish Endosera as a routine adjuvant in IVF, a larger study with stringent inclusion criteria for refractory thin endometrium is recommended. Wider implications of the findings Endosera demonstrated notable success with significant improvement in implantation, pregnancy, and live birth rates for refractory thin endometrium patients prompts rigorous randomized controlled studies. These will include diverse populations, validating results and offering patients hope to reduce financial and psychological stress and challenges associated with cycle cancellations and surrogacy. Trial registration number Not applicable

Midkine: A Cancer Biomarker Candidate and Innovative Therapeutic Approaches.

Midkine (MDK) is a protein that contributes to both physiological and pathological processes. Several studies provide insight into the different roles of MDK in development, tissue repair, neural plasticity, and health and disease processes. This research further examined how MDK contributed to conditions, including neurological diseases, inflammation, and ischaemia. Furthermore, MDK overexpression has been reported in many kinds of cancer and MDK is recognized as a malignancy marker. MDK stimulates pro-tumor activity by regulating a number of signaling pathways, which increase cancer cell proliferation, survival, metastasis, and treatment resistance. However, studies have shown that MDK also functions as a molecule that regulates drug resistance. Several cancer therapy techniques have been suggested to modify MDK function, including antibody-based therapies, oligonucleotides, oncolytic viruses, and small compounds. Further research and experimentation will be required to establish the therapeutic relevance and efficacy of these treatments. This review focuses on the role of MDK in cancer biology, as well as its multiple different roles in health and disease processes.

Polymorphism in the matrix metallopeptidase genes is associated with coronary artery disease risk with concomitant metabolic syndrome

Background: Metabolic syndrome (MS) and its components are the reasons of the development and progression of cardiovascular diseases. Nowadays, the association between coronary artery disease and MS remains ambiguous. The central role of matrix metallopeptidases (MMP) in the metabolism of connective tissue proteins, cell matrix remodeling, tissue repair and other complex biochemical processes has been shown, which implies their involvement in the pathogenesis of cardiovascular diseases. The aim of the study: To study the associations of polymorphic variants in the MMP genes with the risk of stable coronary artery disease with concomitant metabolic syndrome. Materials and methods: 170 patients with stable coronary artery disease concomitant with a visceral type of obesity in combination with two or more pathological conditions (elevated serum blood glucose level, elevated serum blood cholesterol level, hypertension) were included in the case group. Conditionally healthy volunteers (n=182) were recruited in the control group. Genotyping of five polymorphic sites in the four genes MMP1 (rs514921), MMP3 (rs6796620 and rs626750), MMP9 (rs17576) and TIMP2 (rs2277698) was performed by real-time PCR. The serum blood level of MMP was measured by ELISA. Gene-gene interactions were analyzed using MDR v.3.0.2 software. Results: The frequency of heterozygous C/T genotype in the MMP3 gene (rs626750) was higher in the control group (37.90%) compared to the case group (23.20%), which indicates its protective effect on the risk of coronary artery disease with concomitant metabolic syndrome (OR=0.47, 95%CI 0.29-0.75). 2.6-fold increased risk of coronary artery disease with concomitant metabolic syndrome was demonstrated for carriers of the A/G genotype in the TIMP2 gene (rs2277698) according to the codominant inheritance model. We found no associations of polymorphic variants in the MMP1 (rs514921), MMP3 (rs626750), MMP9 (rs17576) and TIMP2 (rs2277698) genes with the serum blood level of MMP, as well as their inhibitors. Four-loci model of gene-gene interactions (MMP9 (rs17576) – MMP3 (rs626750) – MMP1 (rs514921) – TIMP2 (rs2277698)) characterized by high sensitivity, specificity and risk effect to the coronary artery disease with concomitant metabolic syndrome development was discovered. Conclusion: This study revealed the association of polymorphic variants in the MMP genes and their inhibitors with the risk of coronary artery disease with concomitant metabolic syndrome. In addition, a four-locus model of intergenic interactions with high sensitivity and specificity was obtained.

The Influence of Bioceramic Cements on the Activity of Macrophages of Different Lineages: A Laboratory Study

IntroductionThe repair process of periradicular tissues depends, among other factors, on the properties of endodontic cements. Macrophages are among the main cells involved in this process. Materials and MethodsMurine peritoneal macrophages obtained from C57BL/6 (MBL6) and BALB/c (MBalb) mice, respectively, were cultured with capillaries containing or not Endosequence BC Sealer (BC), Sealer Plus BC (MK), Bio-C Sealer (Ang), and mineral trioxide aggregate (MTA). Cell viability was measured by Trypan blue and MTT methods at 24, 48, and 72 hours. Cell adhesion, phagocytosis of Saccharomyces boulardii, production of reactive oxygen species (ROS), nitric oxide (NO), and the cytokines tumor necrosis factor-α and transforming growth factor (TGF)-β were also evaluated. The data were analyzed using the analysis of variance test (P < .05). ResultsCell viability was similar between bioceramic sealers and MTA (P > .05). There was no statistical difference between both macrophages when adherence and phagocytose were assayed. The presence of inflammation stimulus significantly altered the production of ROS by MBL6 macrophages in contact with the cements. The production of TGF-β was similar for both lineages of macrophages. ConclusionsThis study shows that the evaluated bioceramic cements do not interfere with MBL6 and MBalb macrophage adhesion, phagocytic capacity, or TGF-β production. The cements stimulated the production of ROS by MBL6 macrophages in response to induced inflammation, potentially favoring the elimination of residual pathogens.

The effects of fraxetin and monnieriside A on Cultured L929 fibroblasts

Skin lesions are considered a public health problem, compromising patients’ quality of life. This work aimed to evaluate the effects of fraxetin and monnieriside A on Cultured L929 Fibroblasts through the scratch assay. Supernatants and cells from the fibroblast culture treated with the compounds were used to evaluate essential markers of the tissue repair process (IGF-1, VEGF, IL-8, IL-10, FGF-2, COL1A2, COL4A, PDGF) using ELISA and qRT-PCR. The results showed that fraxetin and MOA were non-cytotoxic and could stimulate cellular migration. Fraxetin induced IGF-1, VEGF, IL-8, and IL-10 expression, while MOA induced FGF2, COL1A2, and IL-10 expression. Altogether, these results set provides evidence that fraxetin and MOA have healing potential for tissue repair, paving the way for in vivo studies and clinical trials to validate the in vitro results.

Modulation of macrophage polarization by secondary cross-linked hyaluronan-dopamine hydrogels

The inflammatory response plays a critical role in standard tissue repair processes, wherein active modulation of macrophage polarization is necessary for wound healing. Dopamine, a mussel-inspired bioactive material, is widely involved in wound healing, neural/bone/myocardial regeneration, and more. Recent studies indicated that dopamine-modified biomaterials can potentially alter macrophages polarization towards a pro-healing phenotype, thereby enhancing tissue regeneration. Nevertheless the immunoregulatory activity of dopamine on macrophage polarization remains unclear. This study introduces a novel interpenetrating hydrogel to bridge this research gap. The hydrogel, combining varying concentrations of oxidized dopamine with hyaluronic acid hydrogel, allows precise regulation of mechanical properties, antioxidant bioactivity, and biocompatibility. Surprisingly, both in vivo and in vitro outcomes demonstrated that dopamine concentration modulates macrophage polarization, but not linearly. Lower concentration (2 mg/mL) potentially decrease inflammation and facilitate M2 type macrophage polarization. In contrast, higher concentration (10 mg/mL) exhibited a pro-inflammatory tendency in the late stages of implantation. RNA-seq analysis revealed that lower dopamine concentrations induced the M1/M2 transition of macrophages by modulating the NF-κB signaling pathway. Collectively, this research offers valuable insights into the immunoregulation effects of dopamine-integrated biomaterials in tissue repair and regeneration.

Single-Atom-Based Nanoenzyme in Tissue Repair.

Since the discovery of ferromagnetic nanoparticles Fe3O4 that exhibit enzyme-like activity in 2007, the research on nanoenzymes has made significant progress. With the in-depth study of various nanoenzymes and the rapid development of related nanotechnology, nanoenzymes have emerged as a promising alternative to natural enzymes. Within nanozymes, there is a category of metal-based single-atom nanozymes that has been rapidly developed due to low cast, convenient preparation, long storage, less immunogenicity, and especially higher efficiency. More importantly, single-atom nanozymes possess the capacity to scavenge reactive oxygen species through various mechanisms, which is beneficial in the tissue repair process. Herein, this paper systemically highlights the types of metal single-atom nanozymes, their catalytic mechanisms, and their recent applications in tissue repair. The existing challenges are identified and the prospects of future research on nanozymes composed of metallic nanomaterials are proposed. We hope this review will illuminate the potential of single-atom nanozymes in tissue repair, encouraging their sequential clinical translation.

Angiogenesis and Microvascular Permeability.

Angiogenesis, the formation of new blood microvessels, is a necessary physiological process for tissue generation and repair. Sufficient blood supply to the tissue is dependent on microvascular density, while the material exchange between the circulating blood and the surrounding tissue is controlled by microvascular permeability. We thus begin this article by reviewing the key signaling factors, particularly vascular endothelial growth factor (VEGF), which regulates both angiogenesis and microvascular permeability. We then review the role of angiogenesis in tissue growth (bone regeneration) and wound healing. Finally, we review angiogenesis as a pathological process in tumorigenesis, intraplaque hemorrhage, cerebral microhemorrhage, pulmonary fibrosis, and hepatic fibrosis. Since the glycocalyx is important for both angiogenesis and microvascular permeability, we highlight the role of the glycocalyx in regulating the interaction between tumor cells and endothelial cells (ECs) and VEGF-containing exosome release and uptake by tumor-associated ECs, all of which contribute to tumorigenesis and metastasis.

Wide Use of Hyaluronic Acid in the Process of Wound Healing—A Rapid Review

Hyaluronic acid (HA), as one of the main components of the extracellular matrix (ECM), plays an important role in the process of wound-healing and tissue-repair processes due to its unique properties and different physiological functions. HA has an ability to maintain a moist environment that promotes healing, the stimulation of growth factors and cellular constituents, and the migration of various cells essential for healing. This paper offers a review of HA use in the process of wound healing, with emphasis on hard-to-heal wounds, and examines its various applications in ophthalmology and otorhinolaryngology. It proves HA to be a versatile agent which finds its use in various fields of medicine for its antioxidant, anti-inflammatory, antibacterial properties and accelerated wound healing.

Identifying transcriptomic profiles of iron–quercetin complex treated peripheral blood mononuclear cells from healthy volunteers and diabetic patients

Peripheral blood is an alternative source of stem/progenitor cells for regenerative medicine owing to its ease of retrieval and blood bank storage. Previous in vitro studies indicated that the conditioned medium derived from peripheral blood mononuclear cells (PBMCs) treated with the iron–quercetin complex (IronQ) contains potent angiogenesis and wound-healing properties. This study aims to unveil the intricate regulatory mechanisms governing the effects of IronQ on the transcriptome profiles of human PBMCs from healthy volunteers and those with diabetes mellitus (DM) using RNA sequencing analysis. Our findings revealed 3741 and 2204 differentially expressed genes (DEGs) when treating healthy and DM PBMCs with IronQ, respectively. Functional enrichment analyses underscored the biological processes shared by the DEGs in both conditions, including inflammatory responses, cell migration, cellular stress responses, and angiogenesis. A comprehensive exploration of these molecular alterations exposed a network of 20 hub genes essential in response to stimuli, cell migration, immune processes, and the mitogen-activated protein kinase (MAPK) pathway. The activation of these pathways enabled PBMCs to potentiate angiogenesis and tissue repair. Corroborating this, quantitative real-time polymerase chain reaction (qRT-PCR) and cell phenotyping confirmed the upregulation of candidate genes associated with anti-inflammatory, pro-angiogenesis, and tissue repair processes in IronQ-treated PBMCs. In summary, combining IronQ and PBMCs brings about substantial shifts in gene expression profiles and activates pathways that are crucial for tissue repair and immune response, which is promising for the enhancement of the therapeutic potential of PBMCs, especially in diabetic wound healing.

Taurine attenuates activation of hepatic stellate cells by inhibiting autophagy and inducing ferroptosis.

Liver fibrosis is a compensatory response during the tissue repair process in chronic liver injury, and finally leads to liver cirrhosis or even hepatocellular carcinoma. The pathogenesis of hepatic fibrosis is associated with the progressive accumulation of activated hepatic stellate cells (HSCs), which can transdifferentiate into myofibroblasts to produce an excess of the extracellular matrix (ECM). Myofibroblasts are the main source of the excessive ECM responsible for hepatic fibrosis. Therefore, activated hepatic stellate cells (aHSCs), the principal ECM producing cells in the injured liver, are a promising therapeutic target for the treatment of hepatic fibrosis. To explore the effect of taurine on aHSC proliferation and the mechanisms involved. Human HSCs (LX-2) were randomly divided into five groups: Normal control group, platelet-derived growth factor-BB (PDGF-BB) (20 ng/mL) treated group, and low, medium, and high dosage of taurine (10 mmol/L, 50 mmol/L, and 100 mmol/L, respectively) with PDGF-BB (20 ng/mL) treated group. Cell Counting Kit-8 method was performed to evaluate the effect of taurine on the viability of aHSCs. Enzyme-linked immunosorbent assay was used to estimate the effect of taurine on the levels of reactive oxygen species (ROS), malondialdehyde, glutathione, and iron concentration. Transmission electron microscopy was applied to observe the effect of taurine on the autophagosomes and ferroptosis features in aHSCs. Quantitative real-time polymerase chain reaction and Western blot analysis were performed to detect the effect of taurine on the expression of α-SMA, Collagen I, Fibronectin 1, LC3B, ATG5, Beclin 1, PTGS2, SLC7A11, and p62. Taurine promoted the death of aHSCs and reduced the deposition of the ECM. Treatment with taurine could alleviate autophagy in HSCs to inhibit their activation, by decreasing autophagosome formation, downregulating LC3B and Beclin 1 protein expression, and upregulating p62 protein expression. Meanwhile, treatment with taurine triggered ferroptosis and ferritinophagy to eliminate aHSCs characterized by iron overload, lipid ROS accumulation, glutathione depletion, and lipid peroxidation. Furthermore, bioinformatics analysis demonstrated that taurine had a direct targeting effect on nuclear receptor coactivator 4, exhibiting the best average binding affinity of -20.99 kcal/mol. Taurine exerts therapeutic effects on liver fibrosis via mechanisms that involve inhibition of autophagy and trigger of ferroptosis and ferritinophagy in HSCs to eliminate aHSCs.

Scaffold-Based Poly(Vinylidene Fluoride) and Its Copolymers: Materials, Fabrication Methods, Applications, and Perspectives.

Tissue engineering involves implanting grafts into damaged tissue sites to guide and stimulate the formation of new tissue, which is an important strategy in the field of tissue defect treatment. Scaffolds prepared in vitro meet this requirement and are able to provide a biochemical microenvironment for cell growth, adhesion, and tissue formation. Scaffolds made of piezoelectric materials can apply electrical stimulation to the tissue without an external power source, speeding up the tissue repair process. Among piezoelectric polymers, poly(vinylidene fluoride) (PVDF) and its copolymers have the largest piezoelectric coefficients and are widely used in biomedical fields, including implanted sensors, drug delivery, and tissue repair. This paper provides a comprehensive overview of PVDF and its copolymers and fillers for manufacturing scaffolds as well as the roles in improving piezoelectric output, bioactivity, and mechanical properties. Then, common fabrication methods are outlined such as 3D printing, electrospinning, solvent casting, and phase separation. In addition, the applications and mechanisms of scaffold-based PVDF in tissue engineering are introduced, such as bone, nerve, muscle, skin, and blood vessel. Finally, challenges, perspectives, and strategies of scaffold-based PVDF and its copolymers in the future are discussed.

The ins and outs of microglial cells in brain health and disease.

Microglia are the brain's resident macrophages that play pivotal roles in immune surveillance and maintaining homeostasis of the Central Nervous System (CNS). Microglia are functionally implicated in various cerebrovascular diseases, including stroke, aneurysm, and tumorigenesis as they regulate neuroinflammatory responses and tissue repair processes. Here, we review the manifold functions of microglia in the brain under physiological and pathological conditions, primarily focusing on the implication of microglia in glioma propagation and progression. We further review the current status of therapies targeting microglial cells, including their re-education, depletion, and re-population approaches as therapeutic options to improve patient outcomes for various neurological and neuroinflammatory disorders, including cancer.

Nanotechnological Research for Regenerative Medicine: The Role of Hyaluronic Acid.

Hyaluronic acid (HA) is a linear, anionic, non-sulfated glycosaminoglycan occurring in almost all body tissues and fluids of vertebrates including humans. It is a main component of the extracellular matrix and, thanks to its high water-holding capacity, plays a major role in tissue hydration and osmotic pressure maintenance, but it is also involved in cell proliferation, differentiation and migration, inflammation, immunomodulation, and angiogenesis. Based on multiple physiological effects on tissue repair and reconstruction processes, HA has found extensive application in regenerative medicine. In recent years, nanotechnological research has been applied to HA in order to improve its regenerative potential, developing nanomedical formulations containing HA as the main component of multifunctional hydrogels systems, or as core component or coating/functionalizing element of nanoconstructs. This review offers an overview of the various uses of HA in regenerative medicine aimed at designing innovative nanostructured devices to be applied in various fields such as orthopedics, dermatology, and neurology.

Progress of the study of pericytes and their potential research value in adenomyosis.

Pericytes (PCs) are versatile cells integral to the microcirculation wall, exhibiting specific stem cell traits. They are essential in modulating blood flow, ensuring vascular permeability, maintaining homeostasis, and aiding tissue repair process. Given their involvement in numerous disease-related pathological and physiological processes, the regulation of PCs has emerged as a focal point of research. Adenomyosis is characterized by the presence of active endometrial glands and stroma encased by an enlarged and proliferative myometrial layer, further accompanied by fibrosis and new blood vessel formation. This distinct pathological condition might be intricately linked with PCs. This article comprehensively reviews the markers associated with PCs, their contributions to angiogenesis, blood flow modulation, and fibrotic processes. Moreover, it provides a comprehensive overview of the current research on adenomyosis pathophysiology, emphasizing the potential correlation and future implications regarding PCs and the development of adenomyosis.

Organoids as a tool to study homeostatic and pathological immune-epithelial interactions in the gut.

The intestine hosts the largest immune cell compartment in the body as a result of its continuous exposure to exogenous antigens. The intestinal barrier is formed by a single layer of epithelial cells which separate immune cells from the gut lumen. Bidirectional interactions between the epithelium and the immune compartment are critical for maintaining intestinal homeostasis by limiting infection, preventing excessive immune activation, and promoting tissue repair processes. However, our understanding of epithelial-immune interactions incomplete as the complexity of in vivo models can hinder mechanistic studies, cell culture models lack the cellular heterogeneity of the intestine and when established from primary cell can be difficult to maintain. In the last decade, organoids have emerged as a reliable model of the intestine, recapitulating key cellular and architectural features of native tissues. Herein, we provide an overview of how intestinal organoids are being co-cultured with immune cells leading to substantial advances in our understanding of immune-epithelial interactions in the gut. This has enabled new discoveries of the immune contribution to epithelial maintenance and regeneration both in homeostasis and in disease such as chronic inflammation, infection and cancer. Organoids can additionally be used to generate immune cells with a tissue-specific phenotype and to investigate the impact of disease associated risk genes on the intestinal immune environment. Accordingly, this review demonstrates the multitude of applications for intestinal organoids in immunological research and their potential for translational approaches.

Role of regulatory T cells in mouse lung development.

Regulatory T cells (Tregs) constitute a specialized subset of T cells with dual immunoregulatory and modulatory functions. Recent studies have reported that Tregs mediate immune responses and regulate the development and repair processes in non-lymphoid tissues, including bone and cardiac muscle. Additionally, Tregs facilitate the repair and regeneration of damaged lung tissues. However, limited studies have examined the role of Tregs in pulmonary development. This study aimed to evaluate the role of Tregs in pulmonary development by investigating the dynamic alterations in Tregs and their hallmark cellular factor Forkhead box P3 (Foxp3) at various stages of murine lung development and establishing a murine model of anti-CD25 antibody-induced Treg depletion. During the early stages of murine lung development, especially the canalicular and saccular stages, the levels of Treg abundance and expression of Foxp3 and transforming growth factor-β (TGF-β) were upregulated. This coincided with the proliferation period of alveolar epithelial cells and vascular endothelial cells, indicating an adaptation to the dynamic lung developmental processes. Furthermore, the depletion of Tregs disrupted lung tissue morphology and downregulated lung development-related factors, such as surfactant protein C (SFTPC), vascular endothelial growth factor A (VEGFA) and platelet endothelial cell adhesion molecule-1 (PECAM1/CD31). These findings suggest that Tregs promote murine lung development.

Evolution and Function of the Notch Signaling Pathway: An Invertebrate Perspective.

The highly conserved Notch signaling pathway affects embryonic development, neurogenesis, homeostasis, tissue repair, immunity, and numerous other essential processes. Although previous studies have demonstrated the location and function of the core components of Notch signaling in various animal phyla, a more comprehensive summary of the Notch core components in lower organisms is still required. In this review, we objectively summarize the molecular features of the Notch signaling pathway constituents, their current expression profiles, and their functions in invertebrates, with emphasis on their effects on neurogenesis and regeneration. We also analyze the evolution and other facets of Notch signaling and hope that the contents of this review will be useful to interested researchers.