Investigation of collagen reconstruction mechanism in skin wound through dual-beam laser welding: Insights from multi-spectroscopy, molecular dynamics simulation, and finite element multiphysics simulation.

Since the mechanism underlying real-time acquisition of mechanical strength during laser-induced skin wound fusion remains unclear, and collagen is the primary constituent of skin tissue, this study investigates the structural and mechanical alterations in collagen at temperatures ranging from 40 °C to 60 °C using various spectroscopic techniques and molecular dynamics calculations. The COMSOL Multiphysics coupling is employed to simulate the three-dimensional temperature field, stress-strain relationship, and light intensity distribution in the laser thermal affected zone of skin wounds during dual-beam laser welding process. Raman spectroscopy, synchronous fluorescence spectroscopy and circular dichroism measurement results confirm that laser energy activates biological activity in residues, leading to a transformation in the originally fractured structure of collagen protein for enhanced mechanical strength. Molecular dynamics simulations reveal that stable hydrogen bonds form at amino acid residues within the central region of collagen protein when the overall temperature peak around the wound reaches 60 °C, thereby providing stability to previously fractured skin incisions and imparting instantaneous strength. However, under a 55 °C system, Type I collagen ensures macrostructural stability while activating biological properties at amino acid bases to promote wound healing function; this finding aligns with experimental analysis results. The COMSOL simulation outcomes also correspond well with macroscopic morphology after laser welding samples, confirming that by maintaining temperatures between 55 °C-60 °C during laser welding of skin incisions not only can certain instantaneous mechanical strength be achieved but irreversible thermal damage can also be effectively controlled. It is anticipated that these findings will provide valuable insights into understanding the healing mechanism for laser-welded skin wounds.

Macrophages modulate fibrosis during newt lens regeneration.

BACKGROUND: Previous studies have suggested that macrophages are present during lens regeneration in newts, but their role in the process is yet to be elucidated. METHODS: Here we generated a transgenic reporter line using the newt, Pleurodeles waltl, that traces macrophages during lens regeneration. Furthermore, we assessed early changes in gene expression during lens regeneration using two newt species, Notophthalmus viridescens and Pleurodeles waltl. Finally, we used clodronate liposomes to deplete macrophages during lens regeneration in both species and tested the effect of a subsequent secondary injury after macrophage recovery. RESULTS: Macrophage depletion abrogated lens regeneration, induced the formation of scar-like tissue, led to inflammation, decreased iris pigment epithelial cell (iPEC) proliferation, and increased rates of apoptosis in the eye. Some of these phenotypes persisted throughout the last observation period of 100 days and could be attenuated by exogenous FGF2 administration. A distinct transcript profile encoding acute inflammatory effectors was established for the dorsal iris. Reinjury of the newt eye alleviated the effects of macrophage depletion, including the resolution of scar-like tissue, and re-initiated the regeneration process. CONCLUSIONS: Together, our findings highlight the importance of macrophages for facilitating a pro-regenerative environment in the newt eye by regulating fibrotic responses, modulating the overall inflammatory landscape, and maintaining the proper balance of early proliferation and late apoptosis of the iPECs.

Macrophage MCT4 inhibition activates reparative genes and protects from atherosclerosis by histone H3 lysine 18 lactylation.

Macrophage activation is a hallmark of atherosclerosis, accompanied by a switch in core metabolism from oxidative phosphorylation to glycolysis. The crosstalk between metabolic rewiring and histone modifications in macrophages is worthy of further investigation. Here, we find that lactate efflux-associated monocarboxylate transporter 4 (MCT4)-mediated histone lactylation is closely related to atherosclerosis. Histone H3 lysine 18 lactylation dependent on MCT4 deficiency activated the transcription of anti-inflammatory genes and tricarboxylic acid cycle genes, resulting in the initiation of local repair and homeostasis. Strikingly, histone lactylation is characteristically involved in the stage-specific local repair process during M1 to M2 transformation, whereas histone methylation and acetylation are not. Gene manipulation and protein hydrolysis-targeted chimerism technology are used to confirm that MCT4 deficiency favors ameliorating atherosclerosis. Therefore, our study shows that macrophage MCT4 deficiency, which links metabolic rewiring and histone modifications, plays a key role in training macrophages to become repair and homeostasis phenotypes.

Long-term costs of minimally-invasive sacral colpopexy compared to native tissue vaginal repair with concomitant hysterectomy.

STUDY OBJECTIVE: To determine the long-term costs of hysterectomy with minimally-invasive sacrocolpopexy (MISCP) versus uterosacral ligament suspension (USLS) for primary uterovaginal prolapse repair. STUDY DESIGN: A hospital-based decision analysis model was built using TreeAge Pro (TreeAge Software Inc, Williamstown, MA). Those with prolapse were modeled to undergo either vaginal hysterectomy with uterosacral ligament suspension (USLS) or minimally invasive total hysterectomy with sacrocolpopexy (MISCP). We modeled the chance of complications of the index procedure, prolapse recurrence with the option for surgical retreatment, complications of the salvage procedure, and possible second prolapse recurrence. The primary outcome was cost of the surgical strategy. The proportion of patients living with prolapse after treatment was the secondary outcome. SETTING: Tertiary center for urogynecology PATIENTS: Female patients undergoing surgical repair by the same team for primary uterovaginal prolapse INTERVENTIONS: Comparison analysis of estimated long-term costs was performed MEASUREMENTS AND MAIN RESULTS: Our primary outcome showed that a strategy of undergoing MISCP as the primary index procedure cost $19,935 and that undergoing USLS as the primary index procedure cost $15,457, a difference of $4,478. Furthermore, 21.1% of women in the USLS group will be living with recurrent prolapse compared to 6.2% of MISCP patients. Switching from USLS to MISCP to minimize recurrence risk would cost $30,054 per case of prolapse prevented. Additionally, a surgeon would have to perform 6.7 cases by MISCP instead of USLS in order to prevent 1 patient from having recurrent prolapse. CONCLUSION: The higher initial costs of MISCP compared to USLS persist in the long term after factoring in recurrence and complication rates, though more patients who undergo USLS live with prolapse recurrence.

Mid-term outcomes of laparoscopic vaginal stump?round (Kakinuma method) and stump?uterosacral (Shull method) ligament fixation for pelvic organ prolapse: a retrospective comparative study.

BACKGROUND: Laparoscopic sacrocolpopexy (LSC) and robot-assisted sacrocolpopexy (RSC) using mesh are popular approaches for treating pelvic organ prolapse (POP). However, it is not uncommon that native tissue repair (NTR) should be presented as an option to patients who are expected to have extensive intraperitoneal adhesion or patients for whom LSC or RSC is difficult owing to various risk factors. Laparoscopic vaginal stump-uterosacral ligament fixation (Shull method) has been introduced as a method for NTR in case of POP. However, effective repair using this surgical procedure may not be possible in severe POPs. To solve the problems of the Shull method, we devised the laparoscopic vaginal stump-round ligament fixation (Kakinuma method) in which the vaginal stump is fixed to the uterine round ligament, a histologically strong tissue positioned anatomically higher than the uterosacral ligament. This study aimed to retrospectively and clinically compare the two methods. METHODS: Of the 78 patients who underwent surgery for POP between January 2017 and June 2022 and postoperative follow-up for at least a year, 40 patients who underwent the Shull method (Shull group) and 38 who underwent the Kakinuma method (Kakinuma group) were retrospectively analyzed. RESULTS: No significant differences were observed between the two groups in patient background variables such as mean age, parity, body mass index, and POP-Q stage. The mean operative duration and mean blood loss in the Shull group were 140.5 ± 31.7 min and 91.3 ± 96.3 ml, respectively, whereas the respective values in the Kakinuma group were 112.2 ± 25.3 min and 31.4 ± 47.7 ml, respectively. Thus, compared with the Shull group, the operative duration was significantly shorter (P < 0.001) and blood loss was significantly less (P = 0.003) in the Kakinuma group. Recurrence was observed in six patients (15.0%) in the Shull group and two patients (5.3%) in the Kakinuma group. Hence, compared with the Shull group, recurrence was significantly less in the Kakinuma group (P = 0.015). No patients experienced perioperative complications in either group. CONCLUSIONS: The results suggest that the Kakinuma method can serve as a novel and viable NTR procedure for POP.

Roles of airway and intestinal epithelia in responding to pathogens and maintaining tissue homeostasis.

Epithelial cells form a resilient barrier and orchestrate defensive and reparative mechanisms to maintain tissue stability. This review focuses on gut and airway epithelia, which are positioned where the body interfaces with the outside world. We review the many signaling pathways and mechanisms by which epithelial cells at the interface respond to invading pathogens to mount an innate immune response and initiate adaptive immunity and communicate with other cells, including resident microbiota, to heal damaged tissue and maintain homeostasis. We compare and contrast how airway and gut epithelial cells detect pathogens, release antimicrobial effectors, collaborate with macrophages, Tregs and epithelial stem cells to mount an immune response and orchestrate tissue repair. We also describe advanced research models for studying epithelial communication and behaviors during inflammation, tissue injury and disease.

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.

Biomaterials-mediated radiation-induced diseases treatment and radiation protection.

In recent years, the intersection of the academic and medical domains has increasingly spotlighted the utilization of biomaterials in radioactive disease treatment and radiation protection. Biomaterials, distinguished from conventional molecular pharmaceuticals, offer a suite of advantages in addressing radiological conditions. These include their superior biological activity, chemical stability, exceptional histocompatibility, and targeted delivery capabilities. This review comprehensively delineates the therapeutic mechanisms employed by various biomaterials in treating radiological afflictions impacting the skin, lungs, gastrointestinal tract, and hematopoietic systems. Significantly, these nanomaterials function not only as efficient drug delivery vehicles but also as protective agents against radiation, mitigating its detrimental effects on the human body. Notably, the strategic amalgamation of specific biomaterials with particular pharmacological agents can lead to a synergistic therapeutic outcome, opening new avenues in the treatment of radiation- induced diseases. However, despite their broad potential applications, the biosafety and clinical efficacy of these biomaterials still require in-depth research and investigation. Ultimately, this review aims to not only bridge the current knowledge gaps in the application of biomaterials for radiation-induced diseases but also to inspire future innovations and research directions in this rapidly evolving field.

Precise healing of oral and maxillofacial wounds: tissue engineering strategies and their associated mechanisms.

Precise healing of wounds in the oral and maxillofacial regions is usually achieved by targeting the entire healing process. The rich blood circulation in the oral and maxillofacial regions promotes the rapid healing of wounds through the action of various growth factors. Correspondingly, their tissue engineering can aid in preventing wound infections, accelerate angiogenesis, and enhance the proliferation and migration of tissue cells during wound healing. Recent years, have witnessed an increase in the number of researchers focusing on tissue engineering, particularly for precise wound healing. In this context, hydrogels, which possess a soft viscoelastic nature and demonstrate exceptional biocompatibility and biodegradability, have emerged as the current research hotspot. Additionally, nanofibers, films, and foam sponges have been explored as some of the most viable materials for wound healing, with noted advantages and drawbacks. Accordingly, future research is highly likely to explore the application of these materials harboring enhanced mechanical properties, reduced susceptibility to external mechanical disturbances, and commendable water absorption and non-expansion attributes, for superior wound healing.

Impaired LAIR-1-mediated immune control due to collagen degradation in fibrosis.

Tissue repair is disturbed in fibrotic diseases like systemic sclerosis (SSc), where the deposition of large amounts of extracellular matrix components such as collagen interferes with organ function. LAIR-1 is an inhibitory collagen receptor highly expressed on tissue immune cells. We questioned whether in SSc, impaired LAIR-1-collagen interaction is contributing to the ongoing inflammation and fibrosis. We found that SSc patients do not have an intrinsic defect in LAIR-1 expression or function. Instead, fibroblasts from healthy controls and SSc patients stimulated by soluble factors that drive inflammation and fibrosis in SSc deposit disorganized collagen products in vitro, which are dysfunctional LAIR-1 ligands. This is dependent of matrix metalloproteinases and platelet-derived growth factor receptor signaling. In support of a non-redundant role of LAIR-1 in the control of fibrosis, we found that LAIR-1-deficient mice have increased skin fibrosis in response to repeated injury and in the bleomycin mouse model for SSc. Thus, LAIR-1 represents an essential control mechanism for tissue repair. In fibrotic disease, excessive collagen degradation may lead to a disturbed feedback loop. The presence of functional LAIR-1 in patients provides a therapeutic opportunity to reactivate this intrinsic negative feedback mechanism in fibrotic diseases.

Swim bladder-derived biomaterials: structures, compositions, properties, modifications, and biomedical applications.

Animal-derived biomaterials have been extensively employed in clinical practice owing to their compositional and structural similarities with those of human tissues and organs, exhibiting good mechanical properties and biocompatibility, and extensive sources. However, there is an associated risk of infection with pathogenic microorganisms after the implantation of tissues from pigs, cattle, and other mammals in humans. Therefore, researchers have begun to explore the development of non-mammalian regenerative biomaterials. Among these is the swim bladder, a fish-derived biomaterial that is rapidly used in various fields of biomedicine because of its high collagen, elastin, and polysaccharide content. However, relevant reviews on the biomedical applications of swim bladders as effective biomaterials are lacking. Therefore, based on our previous research and in-depth understanding of this field, this review describes the structures and compositions, properties, and modifications of the swim bladder, with their direct (including soft tissue repair, dural repair, cardiovascular repair, and edible and pharmaceutical fish maw) and indirect applications (including extracted collagen peptides with smaller molecular weights, and collagen or gelatin with higher molecular weights used for hydrogels, and biological adhesives or glues) in the field of biomedicine in recent years. This review provides insights into the use of swim bladders as source of biomaterial; hence, it can aid biomedicine scholars by providing directions for advancements in this field.

Hydrogel-based immunoregulation of macrophages for tissue repair and regeneration.

The rational design of hydrogel materials to modulate the immune microenvironment has emerged as a pivotal approach in expediting tissue repair and regeneration. Within the immune microenvironment, an array of immune cells exists, with macrophages gaining prominence in the field of tissue repair and regeneration due to their roles in cytokine regulation to promote regeneration, maintain tissue homeostasis, and facilitate repair. Macrophages can be categorized into two types: classically activated M1 (pro-inflammatory) and alternatively activated M2 (anti-inflammatory and pro-repair). By regulating the physical and chemical properties of hydrogels, the phenotypic transformation and cell behavior of macrophages can be effectively controlled, thereby promoting tissue regeneration and repair. A full understanding of the interaction between hydrogels and macrophages can provide new ideas and methods for future tissue engineering and clinical treatment. Therefore, this paper reviews the effects of hydrogel components, hardness, pore size, and surface morphology on cell behaviors such as macrophage proliferation, migration, and phenotypic polarization, and explores the application of hydrogels based on macrophage immune regulation in skin, bone, cartilage, and nerve tissue repair. Finally, the challenges and future prospects of macrophage-based immunomodulatory hydrogels are discussed.

Local Alpha1-Antitrypsin Accelerates the Healing of Tympanic Membrane Perforation in Mice.

BACKGROUND: Most tympanic membrane (TM) perforations heal spontaneously, but 10%-20% remain chronic and might lead to impaired hearing and recurrent middle ear infections. Alpha1-antitrypsin (AAT) is a circulating tissue-protective protein that is elevated under inflammatory conditions and is currently indicated for genetic AAT deficiency. Recently, AAT has been shown to promote tissue remodeling and inflammatory resolution. OBJECTIVE: This study aimed to examine the effects of local clinical-grade AAT treatment on tissue repair in a mouse model of acute traumatic TM perforation. METHODS: Wild-type mice underwent unilateral TM perforation and were either left untreated or treated locally with human AAT (9 × 10-3 mL at 20 mg/mL on days 0, 1, and 2; n = 15/group). The perforations were evaluated macroscopically on a serial basis. Mice were sacrificed on various days post-injury, and TMs were excised for gene analysis by RT-PCR. RESULTS: There were no adverse reactions in hAAT-treated ears throughout the study period. Compared with untreated animals, TM closure occurred earlier in the treated group (days until full closure, median: 4 and 9, respectively). According to gene expression analysis, VEGF, TGFß, and collagen-5A1 were induced earlier in AAT-treated mice (day 4-5 compared with day 9). Additionally, IL-10 expression levels were higher and IL-6 levels were lower in treated versus untreated mice. CONCLUSION: A local tissue environment rich in AAT promotes early tissue repair in a perforated TM model both macroscopically and molecularly. Studies are underway to examine TM functionality and recombinant AAT formulations for micro-dosing in the format of a single local application. LEVEL OF EVIDENCE: NA Laryngoscope, 2024.

Origins and functions of eosinophils in two non-mucosal tissues.

Eosinophils are a type of granulocyte named after the presence of their eosin-stained granules. Traditionally, eosinophils have been best known to play prominent roles in anti-parasitic responses and mediating allergic reactions. Knowledge of their behaviour has expanded with time, and they are now recognized to play integral parts in the homeostasis of gastrointestinal, respiratory, skeletal muscle, adipose, and connective tissue systems. As such, they are implicated in a myriad of pathologies, and have been the target of several medical therapies. This review focuses on the lifespan of eosinophils, from their origins in the bone marrow, to their tissue-resident role. In particular, we wish to highlight the functions of eosinophils in non-mucosal tissues with skeletal muscle and the adipose tissues as examples, and to discuss the current understanding of their participation in diseased states in these tissues.

To mesh or not mesh "apical prolapse," that is the question!

Surgical approaches for pelvic organ prolapse have evolved over the last 30 years and is a popular topic for debate, particularly when discussing apical prolapse. Transvaginal native tissue repairs remain the mainstay of POP surgeries, however, transabdominal approaches continue to evolve. Use of interposition material, such as synthetic polypropylene mesh, is the standard when performing an abdominal sacrocolpopexy, however, use of autologous fascia can be considered. This debate article provides an overview of this subject and highlights the value of different approaches to apical prolapse. The authors were asked to support their approach in various scenarios including:extremes of age, prior hysterectomy and intact uterus, desire to avoid mesh, sexual activity, and presence of comorbidities. In discussing common patient scenarios, ultimate decision making on specific POP surgeries is determined by patient preference and goals.

Success of Lesion Sterilization and Tissue Repair Therapy and Pulpectomy in the Management of Infected Primary Molars with Poor Prognosis.

Background and aim: To establish lesion sterilization and tissue repair (LSTR) therapy as an alternate treatment option in managing infected primary molars with poor prognosis that were indicated for extraction, thereby fulfilling the objective of retaining the primary tooth till its normal exfoliation in the dental arch. Materials and methods: A total of 84 children who met the inclusion criteria requiring extraction in 142 teeth involving primary molars were included in the study. The selected patients were allocated to two groups, that is, group I-LSTR therapy with 3Mix-MP paste and group II-pulpectomy with metapex. All the treated teeth were then clinically and radiographically evaluated after 1, 3, 6, 9, and 12 months, respectively, to determine the success between groups I and II. Pearson's Chi-squared test along with the z-test was used to compare the clinical and radiographic success of the two groups (p < 0.05). Results: Pain and tenderness were completely resolved within one month of follow-up in both groups. Abscesses were resolved completely at 1 month in the pulpectomy group and mobility was resolved at 6 months follow-up in both groups. Interradicular and periradicular radiolucency persisted even at 12 months of the follow-up period in both groups. The intergroup comparison revealed no statistical differences between LSTR and pulpectomy procedure and both were equally effective at all time intervals (p > 0.05). Conclusion: Both LSTR therapy with 3Mix-MP and pulpectomy with metapex showed 100% clinical success rates. Radiographically no changes were observed even at the 12-month follow-up period in both groups. LSTR therapy can be an alternative treatment option for pulpally involved primary teeth with poor prognosis and in cases where mechanical instrumentation could not be achieved due to physiologic root resorption. How to cite this article: Sefa I, Garg N, Pathivada L, et al. Success of Lesion Sterilization and Tissue Repair Therapy and Pulpectomy in the Management of Infected Primary Molars with Poor Prognosis. Int J Clin Pediatr Dent 2024;17(1):41-47.

Galectins in epithelial-mesenchymal transition: roles and mechanisms contributing to tissue repair, fibrosis and cancer metastasis.

Galectins are soluble glycan-binding proteins that interact with a wide range of glycoproteins and glycolipids and modulate a broad spectrum of physiological and pathological processes. The expression and subcellular localization of different galectins vary among tissues and cell types and change during processes of tissue repair, fibrosis and cancer where epithelial cells loss differentiation while acquiring migratory mesenchymal phenotypes. The epithelial-mesenchymal transition (EMT) that occurs in the context of these processes can include modifications of glycosylation patterns of glycolipids and glycoproteins affecting their interactions with galectins. Moreover, overexpression of certain galectins has been involved in the development and different outcomes of EMT. This review focuses on the roles and mechanisms of Galectin-1 (Gal-1), Gal-3, Gal-4, Gal-7 and Gal-8, which have been involved in physiologic and pathogenic EMT contexts.

The Role of SOX2 and SOX9 Transcription Factors in the Reactivation-Related Functional Properties of NT2/D1-Derived Astrocytes.

Astrocytes are the main homeostatic cells in the central nervous system, with the unique ability to transform from quiescent into a reactive state in response to pathological conditions by reacquiring some precursor properties. This process is known as reactive astrogliosis, a compensatory response that mediates tissue damage and recovery. Although it is well known that SOX transcription factors drive the expression of phenotype-specific genetic programs during neurodevelopment, their roles in mature astrocytes have not been studied extensively. We focused on the transcription factors SOX2 and SOX9, shown to be re-expressed in reactive astrocytes, in order to study the reactivation-related functional properties of astrocytes mediated by those proteins. We performed an initial screening of SOX2 and SOX9 expression after sensorimotor cortex ablation injury in rats and conducted gain-of-function studies in vitro using astrocytes derived from the human NT2/D1 cell line. Our results revealed the direct involvement of SOX2 in the reacquisition of proliferation in mature NT2/D1-derived astrocytes, while SOX9 overexpression increased migratory potential and glutamate uptake in these cells. Our results imply that modulation of SOX gene expression may change the functional properties of astrocytes, which holds promise for the discovery of potential therapeutic targets in the development of novel strategies for tissue regeneration and recovery.

How Old Is Too Old? Outcomes of Prolapse Native-Tissue Repair through Uterosacral Suspension in Octogenarians.

INTRODUCTION: Medical advancements are expected to lead to a substantial increase in the population of women aged 80 and older by 2050. Consequently, a significant number of individuals undergoing corrective prolapse surgery will fall into the elderly-patient category. The research indicates a notable rise in complications associated with prolapse surgery in patients older than 80, irrespective of frailty and other risk factors. Despite these challenges, the vaginal approach has been identified as the safest surgical method for pelvic organ prolapse (POP) repair in the elderly population. For this reason, we aimed to investigate the efficacy, complication rate, and functional outcomes associated with vaginal hysterectomy and an apical suspension/high uterosacral ligaments suspension as a primary technique for prolapse repair, both within a cohort of elderly patients. METHODS: We retrospectively analyzed patients who underwent transvaginal hysterectomy plus an apical suspension procedure for stage ≥ II and symptomatic genital prolapse between January 2006 and December 2013. Anatomical and functional outcomes were evaluated. The Patient Global Impression of Improvement (PGI-I) score was used to evaluate subjective satisfaction after surgery. RESULTS: Sixty-five patients were included in the analysis. The median age was 81.3 years. All individuals exhibited an anterior compartment prolapse stage II or higher, and the majority also a central prolapse stage II or higher. Notably, all participants reported symptoms of vaginal bulging. Over half of the population (58.6%) complained of incomplete bladder emptying. The intervention for all participants involved a vaginal hysterectomy with an apical suspension. Sixty-three patients (96.9%) and forty-four patients (67.6%) underwent a simultaneous anterior or posterior repair, respectively. Long-term complications (>30 days from surgery) were observed during follow-up, with a median duration of 23 ± 20 months. Seven (10.7%) anatomical recurrences were recorded, five (7.69%) concerning the anterior compartment, one (1.5%) the central, and three (4.6%) the posterior. Nevertheless, none of them necessitated further surgical intervention due to symptoms. Significant anatomical improvements for the anterior, central, and posterior compartments were noticed, compared to preoperative assessment (p < 0.001 for Aa and Ba, p < 0.001 for Ap and Bp, and p < 0.001 for C). PGI-I values established that 100% of patients were satisfied (PGI-I ≥ 2), with a median score of 1.12. Consequently, objective and subjective cure rates were 89.5% and 100%, respectively. CONCLUSION: Vaginal hysterectomy combined with apical suspension, particularly high uterosacral ligaments suspension, is a safe and effective primary surgical approach, even in elderly patients.

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.