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Objective: The predictability and long-term success of periodontal regeneration begins with oral hygiene education, disease management, and an individually tailored periodontal maintenance protocol. The treatment outcomes could be enhanced when biologics and bone grafts are combined. The aim of this report was to describe the outcome of two complex infrabony defects in the same patient treated with recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and freeze-dried bone allograft (FDBA) over 10 years. Case presentation: Two complex infrabony defects were treated following guided tissue regeneration principles and procedures. Fullthickness flaps were raised to allow visualization of the defects. The areas were debrided, and exposed root surfaces were planed. FDBA and rhPDGF-BB were combined to fill both defects. A collagen membrane was used over the bone graft in one case. The flaps were reapproximated to achieve primary closure. The patient was seen for regular periodontal maintenance visits and clinical and radiographic follow-ups over 10 years. Throughout the examination periods, the probing depths improved without bleeding on probing, and there was radiographic evidence of bone regeneration. Conclusion: The growth factorinfused bone graft was successfully utilized for periodontal regeneration in complex bony defects. [ABSTRACT FROM AUTHOR]

To achieve non-destructive and efficient identification of juvenile trees, the binocular measurement method of sapling parameters was studied using 3-year-old juvenile Erythrophleum fordii trees as the research object. Side image pairs of 52 E. fordii were obtained using a RealSense D415 binocular camera. The images were preprocessed using gamma correction and limited contrast histogram equalization (CLAHE) algorithm. Then, the left and right views were matched using an improved semi-global block matching (SGBM) algorithm. The pixels were spatially mapped according to the triangulation principle to generate three-dimensional point cloud data. By extracting the coordinate information of the key points in the point cloud, the height, crown width, and ground diameter of E. fordii were measured. The results show that the image’ s contrast was significantly enhanced after preprocessing. The transition of different gray areas is smoother, which makes the disparity calculation more accurate and the matching accuracy improved. The improved SGBM algorithm had a better matching effect than the traditional SGBM algorithm. The obtained disparity map was smoother and the disparity continuity was stronger. The obtained point cloud density was higher and there was less noise. The measurement error from tree height, crown width, and ground diameter was smaller. The mean relative errors (Emr) were1. 981%, 2. 459%, and 2. 942%, respectively. The mean absolute errors (Ema) were 1.492 cm, 1.567 cm, and 0. 044 cm, respectively. The root mean square errors (Erms) were 1.843 cm, 1.914 cm, and 0. 060 cm, respectively. In general, the binocular measurement method based on the improved SGBM algorithm significantly improved the measurement accuracy of juvenile E. fordii parameters, providing technical support for the precise cultivation and management of juvenile trees. [ABSTRACT FROM AUTHOR]

The formation of an oroantral communication (OAC) or fistula (OAF) is a rare complication resulting from the presence of processes in the lateral parts of the maxilla or for iatrogenic reasons. The most common causes of OAC or OAF are tooth extraction with periapical lesions. The aims of this systematic review were to assess the use of platelet-derived preparations rich in growth factors in the treatment of OAC or OAF, to determine the success of treating the communication or fistula, as well as impact on postoperative complications and the course of healing. The study was performed following PRISMA guidelines (PROSPERO: CRD42024570758). The inclusion criteria were as follows: at least ten patients, the presence of oroantral communication or oroantral fistula, treatment with platelet-derived preparations rich in growth factors, and information regarding the response to treatment. In order to find relevant studies, international databases, including PubMed, Google Scholar, Web of Science Core Collection, MDPI, Wiley, and Cochrane Library were searched. The last search was performed on 31 August 2024. Seven articles were included in the systematic review. In total, platelet-derived preparations rich in growth factors were used in 164 patients. Only studies in which OAC was treated and with platelet-rich fibrin (PRF) met the inclusion criteria. Only PRF was used as the sole treatment method in three studies. When OAC is greater than 5 mm, platelet-derived preparations rich in growth factors should be considered adjuncts to treatment, not the sole treatment method. The success rate of OAC treatment was 90–100%. The use of blood products to close OAC may be an effective therapeutic alternative. Proper patient qualification and the use of an appropriate protocol are crucial. There is a need for future well-designed case-control or cohort studies as well as randomized controlled trials to provide the required level of evidence. [ABSTRACT FROM AUTHOR]

Bronchopulmonary dysplasia (BPD) is the predominant chronic lung disease in preterm infants, linked with various adverse long-term outcomes. Multiple prenatal and postnatal risk factors can impede lung development, leading to BPD. Current management of BPD relies heavily on pharmacotherapies and alterations in ventilatory strategies. However, these interventions only mitigate BPD symptoms without addressing underlying alveolar, vascular, structural, and functional deficiencies. Given the retarded lung development in infants with BPD and the limitations of existing modalities, new therapeutic approaches are imperative. The induced differentiation of stem/progenitor cells and the spatiotemporal expression patterns of growth factors associated with lung developmental processes are critical for lung development reactivation in BPD, which focuses on stimulating pulmonary vasculogenesis and alveolarization. This review summarizes the process of lung development and offers a comprehensive overview of advancements in therapies designed to reinitiate lung development in BPD. Furthermore, we assessed the potential of these therapies for maintaining lung homeostasis and effectively restoring pulmonary structure and function through stem/progenitor cells and growth factors, which have been widely researched. [ABSTRACT FROM AUTHOR]

Growth-factor-induced cell signaling plays a crucial role in development; however, negative regulation of this signaling pathway is important for sustaining homeostasis and preventing diseases. SPROUTY2 (SPRY2) is a potent negative regulator of receptor tyrosine kinase (RTK) signaling that binds to GRB2 during RTK activation and inhibits the GRB2-SOS complex, which inhibits RAS activation and attenuates the downstream RAS/ERK signaling cascade. SPRY was formerly discovered in Drosophila but was later discovered in higher eukaryotes and was found to be connected to many developmental abnormalities. In several experimental scenarios, increased SPRY2 protein levels have been observed to be involved in both peripheral and central nervous system neuronal regeneration and degeneration. SPRY2 is a desirable pharmaceutical target for improving intracellular signaling activity, particularly in the RAS/ERK pathway, in targeted cells because of its increased expression under pathological conditions. However, the role of SPRY2 in brain-derived neurotrophic factor (BDNF) signaling, a major signaling pathway involved in nervous system development, has not been well studied yet. Recent research using a variety of small-animal models suggests that SPRY2 has substantial therapeutic promise for treating a range of neurological conditions. This is explained by its function as an intracellular ERK signaling pathway inhibitor, which is connected to a variety of neuronal activities. By modifying this route, SPRY2 may open the door to novel therapeutic approaches for these difficult-to-treat illnesses. This review integrates an in-depth analysis of the structure of SPRY2, the role of its major interactive partners in RTK signaling cascades, and their possible mechanisms of action. Furthermore, this review highlights the possible role of SPRY2 in neurodevelopmental disorders, as well as its future therapeutic implications. [ABSTRACT FROM AUTHOR]

Membrane ruffles are cell actin-based membrane protrusions that have distinct structural characteristics. Linear ruffles with columnar spike-like and veil-like structures assemble at the leading edge of cell membranes. Circular dorsal ruffles (CDRs) have no supporting columnar structures but their veil-like structures, connecting from end to end, present an enclosed ring-shaped circular outline. Membrane ruffles are involved in multiple cell functions such as cell motility, macropinocytosis, receptor internalization, fluid viscosity sensing in a two-dimensional culture environment, and protecting cells from death in response to physiologically compressive loads. Herein, we review the state-of-the-art knowledge on membrane ruffle structure and function, the growth factor-induced membrane ruffling process, and the growth factor-independent ruffling mode triggered by calcium and other stimulating factors, together with the respective underlying mechanisms. We also summarize the inhibitors used in ruffle formation studies and their specificity. In the last part, an overview is given of the various techniques in which the membrane ruffles have been visualized up to now. [ABSTRACT FROM AUTHOR]

OBJECTIVES Tracheal regeneration is challenging owing to its unique anatomy and low blood supply. Most tracheal regeneration applications require scaffolds. Herein, we developed bio-three-dimensional-printed scaffold-free artificial tracheas. METHODS We fabricated bio-three-dimensional-printed artificial tracheas. Their anterior surface comprised hyaline cartilage differentiated from mesenchymal stem cells, and their posterior surface comprised smooth muscle. Human bone marrow-derived mesenchymal stem cells were cultured and differentiated into chondrocytes using fibroblast growth factor-2 and transforming growth factor-beta-3. Initially, horseshoe-shaped spheroids were printed to cover the anterior surface of the artificial trachea, followed by the application of human bronchial smooth muscle cells for the posterior surface. After a 3-week maturing process, the artificial trachea was subjected to histological and immunohistochemical analyses. RESULTS The anterior surface of the artificial trachea comprised well-differentiated hyaline cartilage from human bone marrow-derived mesenchymal stem cells. Immunohistochemistry revealed that the smooth muscle expressed α-smooth muscle actin and smooth muscle myosin heavy chain 11. CONCLUSIONS A bio-three-dimensional-printed scaffold-free artificial trachea comprising different tissues at the front and back was successfully fabricated. [ABSTRACT FROM AUTHOR]

Conventional treatments for degenerative disc disease have limitations in regenerating the intervertebral disc because of its anatomical characteristics. Hence, researchers are investigating biological therapies for degenerative disc disease. The advances in genetic engineering and fields, such as tissue engineering, are accelerating the development of biological treatments for degenerative discs. Biological treatments for degenerative discs focus on inhibiting cell apoptosis and maintaining cell populations within the disc. Current biological therapies studied include gene therapy, cell therapy, and growth factor therapy. Gene therapy involves the use of RiboNucleic Acid (RNA) interference, such as small interfering RNA (siRNA), to inhibit genes related to cell apoptosis and to explore therapeutic targets. Cell therapy, which involves a direct injection of stem cells into the disc, has attracted considerable attention. Mesenchymal stem cells and notochordal cells are commonly used, with mesenchymal stromal/stem cells (MSCs) being preferred because of their ease of production and anti-inflammatory effects. Several clinical trials using MSCs have reported favorable clinical outcomes, such as alleviating lower back pain, but disc height was not restored. These results were not from randomized trials, and double-blind clinical trials using MSCs are currently underway. Research is ongoing to promote anabolic processes within the nucleus pulposus by injecting growth factors into the disc. Preclinical studies have shown that a biglycan fragment targeting transforming growth factor (TGF)-β can inhibit degenerative changes in the disc, and clinical trials using growth/differentiation factor (GDF)-5 are currently in progress. Research on biological treatments for degenerative discs is being conducted in three main areas: gene therapy, cell-based therapy, and growth factor-based therapy. Although cell therapy using MSCs has shown symptomatic improvement in clinical trials, a double-blind clinical trial is still needed to confirm the therapeutic effects. [ABSTRACT FROM AUTHOR]

Growth factor holds great promise for bone regeneration, and spatiotemporal control of their expressing through site-specific reactions is crucial but challenging for on-demand therapy. In this study, we present the development of a novel unnatural amino acids (UAAs)-triggered therapeutic switch (UATS) system, composed of an orthogonal aminoacyl-tRNA-synthase (aaRS)-tRNA pair and a bone morphogenetic protein 2 (BMP2) gene harboring premature stop codon, which enable in situ and on-demand initiation of the expression of BMP2. The resulting UATS system allowed specifically control of base expressing on the BMP2 mRNA that switched to the BMP2 protein with complete structure and function to facilitate bone regeneration. Our investigations showed that the UATS system exhibits remarkable attributes of rapid, sensitive, reversible, and sustained BMP2 expression both in vitro and in vivo settings. Moreover, the implantation of microencapsulated cells with UATS system is applied to a mouse femur defect model, demonstrating high effciency in controlled expressing of BMP2 protein and substantial repair of bone defect following oral administration of UAAs. Therefore, our findings underscore the great potential of UATS system for on-demand awakening of functional growth factor, thus offering promising prospects in the realm of regenerative medicine. [Display omitted] • We present a new unnatural amino acids-triggered therapeutic switch (UATS) system. • UATS system enables on-demand expression of bone morphogenetic protein 2 (BMP2). • UATS system could control BMP2 expression via site-specific biorthogonal reaction. • UATS system enhances bone regeneration effectively in a mouse femoral defect model. [ABSTRACT FROM AUTHOR]

[Display omitted] Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by type 2 inflammation in the United States, but the actual roles that eosinophils play in CRSwNP remain largely unclear. To reveal the roles and heterogeneity of eosinophils in nasal polyp (NP) tissue, we performed single cell RNA sequencing (scRNA-Seq) analysis of NP tissue. Sinonasal tissues (NP and control sinus tissue) and patient matched peripheral blood (PB) samples were obtained from 5 control patients and 5 patients with CRSwNP. Eosinophils were enriched before processing for scRNA-Seq. The gene expression profiles in eosinophils were determined by microwell-based scRNA-Seq technology (BD Rhapsody platform). We predicted the overall function of NP eosinophils by Gene Ontology (geneontology.org) enrichment and pathway analyses and confirmed expression of selected genes by flow cytometry. After filtering out contaminating cells, we detected 5,542 eosinophils from control PB, 3,883 eosinophils from CRSwNP PB, 101 eosinophils from control sinus tissues (not included in further analyses), and 9,727 eosinophils from NPs by scRNA-Seq. We found that 204 genes were downregulated and 354 genes upregulated in NP eosinophils compared to all PB eosinophils (>1.5-fold, P adj <.05). Upregulated genes in NP eosinophils were associated with activation, cytokine-mediated signaling, growth factor activity, NF-κB signaling, and antiapoptotic molecules. NP eosinophils displayed 4 clusters revealing potential heterogeneity of eosinophils in NP tissue. Elevated eosinophils in NP tissue appear to exist in several subtypes that may play important pathogenic roles in CRSwNP, in part by controlling inflammation and hyperproliferation of other cells. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) bioprinting has emerged as a promising strategy for fabricating complex tissue analogs with intricate architectures, such as vascular networks. Achieving this necessitates bioink formulations that possess highly printable properties and provide a cell-friendly microenvironment mimicking the native extracellular matrix. Rapid advancements in printing techniques continue to expand the capabilities of researchers, enabling them to overcome existing biological barriers. This review offers a comprehensive examination of ultraviolet-based 3D bioprinting, renowned for its exceptional precision compared to other techniques, and explores its applications in inducing angiogenesis across diverse tissue models related to hypoxia. The high-precision and rapid photocuring capabilities of 3D bioprinting are essential for accurately replicating the intricate complexity of vascular networks and extending the diffusion limits for nutrients and gases. Addressing the lack of vascular structure is crucial in hypoxia-related diseases, as it can significantly improve oxygen delivery and overall tissue health. Consequently, high-resolution 3D bioprinting facilitates the creation of vascular structures within three-dimensional engineered tissues, offering a potential solution for addressing hypoxia-related diseases. Emphasis is placed on fundamental components essential for successful 3D bioprinting, including cell types, bioink compositions, and growth factors highlighted in recent studies. The insights provided in this review underscore the promising prospects of leveraging 3D printing technologies for addressing hypoxia-related diseases through the stimulation of angiogenesis, complementing the therapeutic efficacy of cell therapy. [ABSTRACT FROM AUTHOR]

Objective To investigate the clinical effect of vacuum sealing drainage (VSD) combined with human epidermal growth factor in the treatment of diabetic foot ulcers. Methods A total of 62 patients diagnosed with diabetic foot ulcer (wagner grade 2～4) hospitalized in the first department of General Surgery and Vascular Surgery of Harbin 242 Hospital from January 2022 to January 2024 were selected as the study subjects. All patients were given standard systemic basic treatments such as controlling blood pressure, blood sugar, blood lipids, antiinfection, and thorough debridement of ulcer wounds. The patients were randomly divided into control group (n = 30) and experimental group (n = 32) by using random number table. The control group received a routine treatment plan of hydropathic compress and dressing change for ulcer wounds, while the experimental group accepted VSD combined with growth factors. Compared with the effective rate, wound area, duration of antibiotic use, wound healing time, and adverse reactions of foot ulcer wounds between two groups of patients after 6 weeks of treatment. Results The effective rate (χ² = 4.26, P = 0.031) in the experimental group were significantly higher than that in the control group. The wound area in the experimental group was smaller than that in the control group after treatment(P < 0.05), the duration of antibiotic use (t = 6.145, P < 0.001) and wound healing time (t = 9.486, P < 0.001) in the experimental group were significantly lower than these in control group. There were no obvious adverse reactions in two groups. Conclusion VSD combined with growth factor has a significant effect in the treatment of DFUs, which can enhance the treatment efficiency, reduce the duration of antibiotic use, shorten the wound healing time, safely and reliable as well. [ABSTRACT FROM AUTHOR]

GMCSF, discovered in 1977, was one of the first growth factors for myelopoiesis. However, over time, it has been found to be redundant for basal myelopoiesis. Rather, its important function seems to be its effect on mature myeloid cells and the immune system. It is produced by a variety of cells, including macrophages, endothelial cells, T-cells etc. and works on the GMCSF receptor, which is mainly expressed by mature myeloid cells such as neutrophils, monocytes and macrophages. It has been found to be an important mediator of at least two autoimmune diseases: rheumatoid arthritis and multiple sclerosis. Animal models prove that GMCSF produced from T-cells play a crucial role in their pathogenesis of both these autoimmune diseases. This has led to the development of therapeutics which target GMCSF or its receptor. Clinical trials have been carried out in rheumatoid arthritis, which have shown modest efficacy. In addition, anti-GMCSF therapy has shown promise in giant cell arteritis. [ABSTRACT FROM AUTHOR]

Platelet-rich plasma (PRP) shows promise as a regenerative modality for mild-to-moderate erectile dysfunction (ED). However, its efficacy in treating severe ED remains unknown. Blood samples from 8-week-old male rats were used to prepare PRP through a two-step centrifugation procedure, followed by chitosan activation and freeze thaw cycle. A hyperhomocysteinemia (HHcy)-related ED model was established using a methionine-enriched diet, and an apomorphine (APO) test was conducted during the 4th week. APO-negative rats were divided into two groups and were injected with PRP or saline every 2 weeks. Erectile function and histological analyses of the corpus cavernosum were performed during the 16th week. The results revealed that erectile function was significantly impaired in rats with HHcy-related ED compared to that in age-matched rats but was improved by repeated PRP injections. Immunofluorescence staining revealed a reduction in reactive oxygen species and additional benefits on the recovery of structures within the corpus cavernosum in rats that received PRP treatment compared to those in the saline-injected control group. Therefore, PRP could enhance functional and structural recovery in a severe HHcy-related ED model. A notable strength of the present study lies in the use of a repeated intracavernous injection method, mirroring protocols used in human studies, which offers more reliable results for translating the findings to humans.

Abstract Bronchopulmonary dysplasia (BPD) is the predominant chronic lung disease in preterm infants, linked with various adverse long-term outcomes. Multiple prenatal and postnatal risk factors can impede lung development, leading to BPD. Current management of BPD relies heavily on pharmacotherapies and alterations in ventilatory strategies. However, these interventions only mitigate BPD symptoms without addressing underlying alveolar, vascular, structural, and functional deficiencies. Given the retarded lung development in infants with BPD and the limitations of existing modalities, new therapeutic approaches are imperative. The induced differentiation of stem/progenitor cells and the spatiotemporal expression patterns of growth factors associated with lung developmental processes are critical for lung development reactivation in BPD, which focuses on stimulating pulmonary vasculogenesis and alveolarization. This review summarizes the process of lung development and offers a comprehensive overview of advancements in therapies designed to reinitiate lung development in BPD. Furthermore, we assessed the potential of these therapies for maintaining lung homeostasis and effectively restoring pulmonary structure and function through stem/progenitor cells and growth factors, which have been widely researched.

Introduction: In recent years, biotherapy in orthopedics has become widespread, and platelet-rich plasma (PRP) has been readily used to treat sports injuries and osteoarthritis. Production of freeze-dried PRP (PRP-FD) results in PRP that is in powder form, allowing it to be stored for long periods at room temperature. Using this technology, we have developed Valuable Platelet-Derived Factor Concentrate Freeze Dry (VFD). However, whether VFD contains sufficient levels of bioactive substances (BS) remains unknown and retains the same levels of BS during long-term storage. In this study, we examined whether VFD contains sufficient amounts of BS and whether they retain these BS levels during long-term storage. Methods: Peripheral blood was collected from 10 healthy men (mean ± SD: 46.5 ± 15 years old) and various BS, including transforming growth factor β (TGF-β), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), tissue inhibitors of metalloproteinases-1 (TIMP-1), interleukin-1 receptor antagonist (IL-1ra), matrix metallopeptidase-9 (MMP-9), and interleukin-6 (IL-6), were compared between VFD and normal PRP samples, including both leukocyte-rich PRP (LR-PRP) and leukocyte-poor PRP (LP-PRP). VFD was prepared using two rounds of centrifugation. LP-PRP and LR-PRP were activated by freezing and thawing before measurement. To evaluate the effects of long-term storage, the BS of VFD purified from five professional football players was compared between baseline and 1 year after storage. Results: In terms of the growth factors, the TGF-β and EGF levels were higher in LR-PRP than in VFD and LP-PRP (p

The use of stem cell-based treatment systems is prevalent in regenerative medicine. To enhance the regenerative capabilities of stem cells, growth factors are typically incorporated into the treatment system. Nonetheless, traditional hydrogel-encapsulated or heparinized scaffolds that bind factors have limitations. In this study, we prepared a biomaterial strategy using uniform poly(lactic-co-glycolic) acid (PLGA) microspheres (uPLGA-Ms) fabricated by microfluidic to sustain delivery of insulin-like growth factor 1 (IGF-1), a critical protein for hMSCs biological functions. The uPLGA-Ms loaded IGF-1 were highly monodispersed through precise manipulation of the flow rate of the two-phase of the flow-focusing microchannle. The results showed that the uPLGA-Ms stabilize IGF-1 and provide a more efficient sustained delivery and cost-effective of growth factor. Gene expression analysis demonstrated the uPLGA delivery of IGF-1 results in a (enhanced) supported hMSCs expansion, survival, stemness, and secretion abilities comparable with the conventional soluble IGF-1 group. In summary, this material-based strategy to stabilize and sustain delivery of growth factor has broad potential to regeneration of various tissues and organs.

BACKGROUND: The formation of postoperative abdominal adhesions is a complicated process, and the prevention of postoperative adhesions is an urgent problem in clinic. OBJECTIVE: To analyze the mechanism of adhesion at cellular and molecular levels, and to provide theoretical basis for the prevention and treatment of adhesion by mesenchymal stem cell exosomes. METHODS: “Abdominal adhesion, pelvic adhesion, postoperative adhesion, epithelial mesenchymal transformation, mesenchymal stem cells, stem cell exosomes, mesenchymal stem cell exosomes” were selected as Chinese and English search terms. We searched PubMed, CNKI, and Chinese biomedical literature and screened relevant articles on postoperative abdominal adhesion and mesenchymal stem cell exosomal intervention published from inception to August 2023. After systematic analysis, 54 articles were finally included for the review. RESULTS AND CONCLUSION: (1) Any pathological factors such as peritoneal inflammation, mechanical injury, tissue ischemia, and foreign body implantation cause peritoneal surface injury, resulting in postoperative abdominal adhesion. The formation process of adhesion includes the interaction of peritoneal mesothelial cell repair, inflammatory response, fibrinolytic system, coagulation pathway and other processes, involving a variety of cytokines and signaling pathways. Wnt/β-catenin pathway can induce fibrosis and angiogenesis, and cooperate with transforming growth factor-β/Smads signaling pathway to stimulate fibroblast proliferation and cause peritoneal fibrosis. Meanwhile, nuclear factor-κB signaling pathway up-regulates the expression of cellular inflammatory factors, promotes fibroblast proliferation, and plays a key role in the process of tissue fibrosis. (2) The paracrine function of stem cells is an important direction of molecular intervention in abdominal adhesions based on regenerative medicine. It can participate in a variety of complex cytokines and signaling pathways involved in abdominal adhesions. (3) Compared with traditional methods for treating abdominal adhesions, mesenchymal stem cell exosome has biological activity and is safe to use. Mesenchymal stem cell exosomes without special culture and expansion have lower immunogenicity, longer stability and other advantages, can guide a normal repair and healing through a variety of ways. (4) Mesenchymal stem cell exosome has been proven to be involved in regulating the above processes of adhesion formation in previous studies, showing potential application prospects in clinical studies. However, further clinical studies are needed to explore appropriate treatment options for mesenchymal stem cell exosomes to address the problem of clinical translation. [ABSTRACT FROM AUTHOR]

Abstract The growth factor Neuregulin-1 (NRG1) has pleiotropic roles in proliferation and differentiation of the stem cell niche in different tissues. It has been implicated in gut, brain and muscle development and repair. Six isoform classes of NRG1 and over 28 protein isoforms have been previously described. Here we report a new class of NRG1, designated NRG1-VII to denote that these NRG1 isoforms arise from a myeloid-specific transcriptional start site (TSS) previously uncharacterized. Long-read sequencing was used to identify eight high-confidence NRG1-VII transcripts. These transcripts presented major structural differences from one another, through the use of cassette exons and alternative stop codons. Expression of NRG1-VII was confirmed in primary human monocytes and tissue resident macrophages and induced pluripotent stem cell-derived macrophages (iPSC-derived macrophages). Isoform switching via cassette exon usage and alternate polyadenylation was apparent during monocyte maturation and macrophage differentiation. NRG1-VII is the major class expressed by the myeloid lineage, including tissue-resident macrophages. Analysis of public gene expression data indicates that monocytes and macrophages are a primary source of NRG1. The size and structure of class VII isoforms suggests that they may be more diffusible through tissues than other NRG1 classes. However, the specific roles of class VII variants in tissue homeostasis and repair have not yet been determined.

Objective(s): Early effective treatment and appropriate coverage are vital for full-thickness wounds. Amnion membrane-derived products have recently emerged in tissue engineering. However, the optimal concentration, carrier for controlled release, and handling have remained challenges. This study aims to develop and optimize an in situ forming, amniotic-based hydrogel for wound healing.Materials and Methods: Here, a composite matrix was fabricated with gelatin hydrogel modified with methacrylate functional group conjugated (GelMA) and keratose (wt.1%), loaded with mesenchymal stem cells (MSCs, 1×105 cell/ml) and optimized soluble amniotic membrane (SAM, 0.5 mg/ml). The physicochemical properties of the final subject were evaluated in vitro and in vivo environments. Results: The results of the in vitro assay demonstrated that conjugation of the methacryloyl group with gelatin resulted in the formation of GelMA hydrogel (26.7±1.2 kPa) with higher mechanical stability. Modification of GelMA with a glycosaminoglycan sulfate (Keratose) increased controlled delivery of SAM (47.3% vs. 84.3%). Metabolic activity (93%) and proliferation (21.2 ± 1.5 µg/ml) of MSCs encapsulated in hydrogel improved by incorporation of SAM (0.5 mg/ml). Furthermore, the migration of fibroblasts was facilitated in the scratched assay by SAM (0.5 mg/ml)/MSCs (1×105 cell/ml) conditioned medium. The GelMA hydrogel groupes revealed regeneration of full-thickness skin defects in rats after 3 weeks due to the high angiogenesis (6.3 ± 0.3), cell migration, and epithelialization. Conclusion: The results indicated in situ forming and tunable GelMA hydrogels containing SAM and MSCs could be used as efficient substrates for full-thickness wound regeneration.

Microorganisms, physical factors such as temperature or mechanical injury, and chemical factors such as free monomers from composite resin are the main causes of dental pulp diseases. Current clinical treatment methods for pulp diseases include the root canal therapy, vital pulp therapy and regenerative endodontic therapy. Regenerative endodontic therapy serves the purpose of inducing the regeneration of new functional pulp tissues through autologous revascularization or pulp tissue engineering. This article first discusses the current clinical methods and reviews strategies as well as the research outcomes regarding the pulp regeneration. Then the in vivo models, the prospects and challenges for regenerative endodontic therapy were further discussed.

Sensitivity and uncertainty analysis serves as a tool for modeling physical phenomenon and evaluating the model validity. It finds applications in simulating the dynamical behavior of aerosols in different contexts. Hygroscopic growth of aerosol particles is one such domain where it can optimize the accuracy of model output greatly. Accurate prediction of hygroscopic growth characteristics depends on the intrinsic parameters and the size-dependent evolution of growth factors. In reactor accident scenarios, growth characteristics of fission/activation product aerosols play a significant role in determining the airborne or deposited fraction. Köhler theory is fundamentally used to predict the growth behavior of aerosols with a detailed physical explanation of critical size and supersaturation characteristics. Alternative approaches including modified Köhler theories and semi-empirical models rely on the linkage of physical and chemical composition-based parameters. The variation of involved parameters and the choice of working range influence the outcome of the theory greatly. This study is focused on sensitivity analysis of the modified Köhler theory given by Brechtel and Kreidenweis and the evaluation of sensitivity and associated uncertainty in the parameters. Monte Carlo approach has been employed, and sensitivity indices were obtained. Identified sensitive parameters were dry particle diameter, solute density, molecular weight, and chemical composition dependent factor (b0). These parameters require careful attention while designing experimental measurements and/or preprocessing model inputs. All sensitive parameters were subjected to uncertainty analysis and the overall output of the aerosol growth code thus obtained has been observed to follow log-normal law with median size at 335.2 nm with a geometric standard deviation of 1.54. This finds applications in the case of studies aiming to predict the growth of aerosols in the reactor component systems during accident conditions. In such conditions, there lies no choice of selection of input parameters and one cannot be sure about their variation range. This provides a conservative estimate for such a random scenario as uncertainty analysis performed in this study covers all the random combinations of input parameters and the overall most probable grown droplet size is estimated.

ABSTRACT: Surgery of the nose involves a series of operations that are directed at restoring the nasal anatomy and physiology. The extent or degree of reconstruction needed is dependent on the appearance-based requirement of the patients and the procedure exploited for the correction such that nasal airflow is preserved. Standard surgical approach includes the use of autologous tissue or implantation alloplastic bio or synthetic/fabricated construct materials to correct the defects. Over the years, tissue engineering has been proven to be a promising technique for reconstructing tissue and organ defects, including the nose. Recently, there has been keen interest in fabricating new tissues and organ scaffolds using 3D printing technology with good control over the micro-architecture and excellent interior architecture suitable for cell seeding. Unviability of the tissue and harvest-associated complications have increased the need for the investigation of tissue engineering based methods for nasal reconstruction using biomaterials, stem cells, and growth factors combined with 3D bioprinting. However, there are only a handful of studies vis-à-vis the application of cartilage tissue engineering, stem cells, and growth factors for the purpose. This review provides highlights about the available studies based on the application of stem cells, biomaterials, and growth factors for nasal reconstruction surgery, as there is limited recent information on the use of these entities in nasal surgeries.

The growth factor Neuregulin-1 (NRG1) has pleiotropic roles in proliferation and differentiation of the stem cell niche in different tissues. It has been implicated in gut, brain and muscle development and repair. Six isoform classes of NRG1 and over 28 protein isoforms have been previously described. Here we report a new class of NRG1, designated NRG1-VII to denote that these NRG1 isoforms arise from a myeloid-specific transcriptional start site (TSS) previously uncharacterized. Long-read sequencing was used to identify eight high-confidence NRG1-VII transcripts. These transcripts presented major structural differences from one another, through the use of cassette exons and alternative stop codons. Expression of NRG1-VII was confirmed in primary human monocytes and tissue resident macrophages and induced pluripotent stem cell-derived macrophages (iPSC-derived macrophages). Isoform switching via cassette exon usage and alternate polyadenylation was apparent during monocyte maturation and macrophage differentiation. NRG1-VII is the major class expressed by the myeloid lineage, including tissue-resident macrophages. Analysis of public gene expression data indicates that monocytes and macrophages are a primary source of NRG1. The size and structure of class VII isoforms suggests that they may be more diffusible through tissues than other NRG1 classes. However, the specific roles of class VII variants in tissue homeostasis and repair have not yet been determined. [ABSTRACT FROM AUTHOR]

BACKGROUND: Warm-needling moxibustion can effectively treat knee osteoarthritis. Degeneration, injury and fracture of the anterior cruciate ligament can affect the local stability of the knee joint, and then induce the formation of knee osteoarthritis. Whether warm-needling moxibustion can repair the injured cruciate ligament and the mechanism of action are still unclear. OBJECTIVE: To observe the effects of warm-needling moxibustion on the morphology of the anterior cruciate ligament and the expression of insulin growth factor-1 and transforming growth factor-β in rabbits with knee osteoarthritis and to clarify the mechanism of anterior cruciate ligament repair by warmneedling moxibustion. METHODS: Thirty New Zealand rabbits were randomly divided into blank group, model group and warm-needling moxibustion group, with 10 rabbits in each group. Knee osteoarthritis model was established by plaster cast immobilization. The blank group was not intervened. Rabbits in the model group rabbits were fixed in a rabbit holder for 15 minutes every day. The warm-needling moxibustion group was treated with warm acupuncture, once a day, 7 days as a course of treatment, a total of two courses. After treatment, the imaging changes of the anterior cruciate ligament were observed by MRI and MRI grading statistics were performed. Morphological changes of the anterior cruciate ligament were observed by transmission electron microscope and hematoxylin-eosin staining. mRNA and protein expressions of insulin growth factor-1 and transforming growth factor-β were detected by RT-PCR and western blot, respectively. RESULTS AND CONCLUSION: MRI examination: Compared with the blank control group, the anterior cruciate ligament in the model group was thickened, edematous, and partially torn, and the difference in grading statistics was statistically significant (P < 0.05). Compared with the model group, the anterior cruciate ligament in the warm-needling moxibustion group was slightly thickened, with mild edema and no tearing, and the difference in grading statistics was statistically significant (P < 0.05). General observation: In the model group, the surface of the anterior cruciate ligament was glossy and faded, with the edge being covered with flocculent periosteum and obvious tissue necrosis; in the warm-needling moxibustion group, the surface of the ligament was glossy, and the ligament was in a normal helical shape. Hematoxylin-eosin staining: In the model group, there was obvious tissue necrosis in the anterior cruciate ligament, a large number of new capillaries, loosely arranged fibroblasts and collagen fibers. In the warm-needling moxibustion group, there was a small amount of tissue necrosis and few new vessels in the anterior cruciate ligament, and the cells and collagen fibers were loosely and irregularly arranged. Transmission electron microscopy: In the model group, the fibers in the anterior cruciate ligament were arranged in a disordered way with uneven thickness and distribution, and there are more fibroblasts that were irregular in morphology; in the warm acupuncture group, the fibers were basically arranged longitudinally, with uneven thickness and distribution, and a small number of oval-shaped fibroblasts were observed. RT-PCR and western blot assay: mRNA and protein expressions of insulin growth factor-1 and transforming growth factor-β were significantly decreased in the model group compared with the blank control group (P < 0.05), but significant increased after treatment with warm-needling moxibustion (P < 0.05). To conclude, warm-needling moxibustion can alleviate anterior cruciate ligament injury and regulate the expression of insulin growth factor-1 and transforming growth factor-β to treat knee osteoarthritis. [ABSTRACT FROM AUTHOR]

Objective To investigate the impact of co-injection of deoxyribonuclease 1 (Dnase1) and platelet-rich plasma (PRP) on wound healing in diabetic rats after degradation of neutrophil extracellular traps (NETs) by Dnase1 injection. Methods Four ulcer wound models were established in diabetic rats from May 2022 to July 2022, Huazhong University of Science and Technology Union Shenzhen Hospital Animal Laboratory in collaboration with Topu Biological Experimental Center and randomly divided into 4 groups: Group A (Dnase+PRP): Dnase1 and PRP were sequentially injected subcutaneously at the edge of the wound. Group B (PRP): PRP was injected subcutaneously at the edge of the wound. Group C (Dnase): Dnase1 was injected subcutaneously at the edge of the wound. Group D (Control): Normal saline was injected subcutaneously at the edge of the wound. Twelve rats from each group were selected on the 5th and 14th days to observe wound healing and granulation tissue growth. Wound tissues were collected, and histological examination using HE staining and immunohistochemistry was conducted to observe tissue growth. Tissue growth factors, inflammatory factors, and NETs-related indicators were detected and compared. Results After 5 days of treatment, there was no significant change in wound healing rate in each group. However, after 14 days of treatment, Group A showed the highest wound healing rate. The concentrations of vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1) in wound tissues of Group A and B were higher than those in the other two groups (P<0.05). The production of myeloperoxidase (MPO) and neutrophil elastase (NE) in wound tissues of Group A and C was lower than that in the other two groups (P<0.05). Conclusion Co-injection of Dnase1 and PRP can reduce the level of NETs in diabetic rat wounds, promote cell proliferation, angiogenesis, and thereby facilitate wound healing [ABSTRACT FROM AUTHOR]

Background/Objectives: Various biological response modifiers play important roles in the immunopathogenesis of chronic hepatitis C (CHC). While serum levels of cytokines and growth factors change with the disease severity and treatment responses, the impact of concomitant liver steatosis on systemic inflammatory response is largely unknown. The aim of this study was to analyze the characteristics and kinetics of serum profiles of interleukins and growth factors in CHC patients with steatotic liver disease (SLD). Methods: Serum concentrations of 12 cytokines (IL-5, IL-13, IL-2, IL-6, IL-9, IL-10, IFN-γ, TNF-α, IL-17A, IL-17F, IL-4 and IL-22) and 6 growth factors (Angiopoietin-2, EGF, EPO, HGF, SCF, VEGF) were analyzed in 56 CHC patients at four time points (baseline, week 4, week 8 and SVR12) with bead-based flow cytometry assay. Results: At baseline, patients with SLD had significantly lower IL-9, IL-10, IL-13 and IL-22 and higher serum concentrations of EGF, VEGF and ANG. In a subgroup of patients with advanced liver fibrosis, SLD was linked with lower serum concentrations of IL-4, IL-5, IL-9, IL-10, IL-13 and IL-22 and higher concentrations of HGH and VEGF. Distinct cytokine kinetics during DAA treatment was observed, and SLD was identified as the main source of variation for IL-5, IL-9, IL-10, IL-13, IL-17A, IL-22, EGF, VEGF and ANG. Patients with SLD at SVR12 had significantly higher VEGF and HGF serum concentrations. Conclusions: SLD is associated with distinct cytokine and growth factor profiles and kinetics during CHC treatment, which might be associated with disease severity and the capacity for liver regeneration and contribute to fibrosis persistence. [ABSTRACT FROM AUTHOR]

Bile acid-induced hepatotoxicity is inevitable in Cholestasis pathogenesis and L-Glutamine (L-Gln) has been reported to prevent total parenteral nutrition (TPN)-induced cholestasis in premature neonates. While mechanisms remain unknown, we hypothesize that bile acids impair growth factor (GF) function in hepatocytes which L-glutamine prevents through NAPDH oxidase (NOX) modulation. Glycochenodeoxycholic acid (GCDC, 0–100 µM) when added to primary hepatocyte cultures significantly (p < 0.01) decreased the FBS-induced BrdU incorporation, however inhibition of Fibroblast Growth factor (FGF)- or Hepatocyte growth factor (HGF)-induced DNA synthesis was more pronounced (p < 0.001). L-Gln markedly attenuated GCDC-mediated inhibition of DNA synthesis in both FBS and GF-treated cells. GCDC significantly increased the NADPH oxidase activity and NOX-1 protein expression that were markedly reduced by L-Gln and protein kinase c (PKC) inhibitor, LY-333531. Apocynin (APCN) and diphenyliodonium (DPI) significantly blocked the GCDC-mediated inhibition of GF-induced DNA synthesis. This study demonstrates that bile acid-induced hepatotoxicity involves dysfunction of certain growth factors via protein kinase c (PKC)- mediated NOX modulation which can be corrected, at least partly, by L-glutamine. [ABSTRACT FROM AUTHOR]

Objective(s): Early effective treatment and appropriate coverage are vital for full-thickness wounds. Amnion membrane-derived products have recently emerged in tissue engineering. However, the optimal concentration, carrier for controlled release, and handling have remained challenges. This study aims to develop and optimize an in situ forming, amniotic-based hydrogel for wound healing. Materials and Methods: Here, a composite matrix was fabricated with gelatin hydrogel modified with methacrylate functional group conjugated (GelMA) and keratose (wt.1%), loaded with mesenchymal stem cells (MSCs, 1×105 cell/ml) and optimized soluble amniotic membrane (SAM, 0.5 mg/ml). The physicochemical properties of the final subject were evaluated in vitro and in vivo environments. Results: The results of the in vitro assay demonstrated that conjugation of the methacryloyl group with gelatin resulted in the formation of GelMA hydrogel (26.7±1.2 kPa) with higher mechanical stability. Modification of GelMA with a glycosaminoglycan sulfate (Keratose) increased controlled delivery of SAM (47.3% vs. 84.3%). Metabolic activity (93%) and proliferation (21.2 ± 1.5 µg/ml) of MSCs encapsulated in hydrogel improved by incorporation of SAM (0.5 mg/ml). Furthermore, the migration of fibroblasts was facilitated in the scratched assay by SAM (0.5 mg/ml)/MSCs (1×105 cell/ml) conditioned medium. The GelMA hydrogel groupes revealed regeneration of full-thickness skin defects in rats after 3 weeks due to the high angiogenesis (6.3 ± 0.3), cell migration, and epithelialization. Conclusion: The results indicated in situ forming and tunable GelMA hydrogels containing SAM and MSCs could be used as efficient substrates for full-thickness wound regeneration. [ABSTRACT FROM AUTHOR]

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, TGFβ, 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, 134:3802–3806, 2024 [ABSTRACT FROM AUTHOR]

Gaussian elimination (GE) is the most used dense linear solver. Error analysis of GE with selected pivoting strategies on well-conditioned systems can focus on studying the behavior of growth factors. Although exponential growth is possible with GE with partial pivoting (GEPP), growth tends to stay much smaller in practice. Support for this behavior was provided recently by Huang and Tikhomirov's average-case analysis of GEPP, which showed GEPP growth factors for Gaussian matrices stay at most polynomial with very high probability. GE with complete pivoting (GECP) has also seen a lot of recent interest, with improvements to both lower and upper bounds on worst-case GECP growth provided by Bisain, Edelman, and Urschel in 2023. We are interested in studying how GEPP and GECP behave on the same linear systems as well as studying large growth on particular subclasses of matrices, including orthogonal matrices. Moreover, as a means to better address the question of why large growth is rarely encountered, we further study matrices with a large difference in growth between using GEPP and GECP, and we explore how the smaller growth strategy dominates behavior in a small neighborhood of the initial matrix. [ABSTRACT FROM AUTHOR]

Over several decades, agricultural policies have undergone changes considering societal dynamics. The development of land policy changes is divided into three periods: Landreform (1963-1965), National Agrarian Reform Program (PPAN) (2007-2014), and Agrarian Reform (2017-2019). The dynamics of land policies are fundamental for shaping more inclusive and comprehensive policies in the future, as land policies encompass many aspects of social and economic life. The purpose of this research is to describe the development of land policies in Indonesia from 1945 to 2022. The research method used is qualitative with a normative legal approach, exploring principles or standards of positive law. The research findings highlight the agricultural dynamics from the period of President Sukarno to Joko Widodo, focusing significantly on Agrarian Reform, which heavily influences every natural resource. During Sukarno's period, initial national agrarian arrangements were made. Since Soeharto took office, the issue of Agrarian Reform nearly disappeared and was not implemented. President Habibie revived Agrarian Reform. During the leadership of Gus Dur, Megawati, and SBY, they were pioneers of reform after Habibie. During their governance, the issue of Agrarian Reform continued to strengthen, alongside the growth of food resources and attention to imported food products and farmers. During President Jokowi's tenure, the concept of Agrarian Reform strengthened further and was demonstrated to the public, successfully enacting implementation regulations. Political considerations related to agrarian issues should at least result in legal order and harmonization of different legal systems. The political connection with national agricultural laws should ideally have beneficial effects in the future. [ABSTRACT FROM AUTHOR]

Growth differentiation factor 15 (GDF-15) is a multifunctional cytokine that belongs to the transforming growth factor-beta (TGF-β) superfamily. GDF-15 is involved in immune tolerance and is elevated in several acute and chronic stress conditions, often correlating with disease severity and patient prognosis in cancer172 and metabolic and cardiovascular disorders. Despite these clinical associations, the molecular mechanisms orchestrating its effects remain to be elucidated. The effects of GDF-15 are pleiotropic but cell-specific and dependent on the microenvironment. While GDF-15 expression can be stimulated by inflammatory mediators, its predominant effects were reported as anti-inflammatory and pro-fibrotic. The role of GDF-15 in the macrophage system has been increasingly investigated in recent years. Macrophages produce high levels of GDF-15 during oxidative and lysosomal stress, which can lead to fibrogenesis and angiogenesis at the tissue level. At the same time, macrophages can respond to GDF-15 by switching their phenotype to a tolerogenic one. Several GDF-15-based therapies are under development, including GDF-15 analogs/mimetics and GDF-15-targeting monoclonal antibodies. In this review, we summarize the major physiological and pathological contexts in which GDF-15 interacts with macrophages. We also discuss the major challenges and future perspectives in the therapeutic translation of GDF-15. [ABSTRACT FROM AUTHOR]

This study is focused on fractionation of insulin-like growth factor I (IGF-I) and transforming growth factor-β2 (TGF-β2) using a new electro-based membrane process calledelectrodialysis with filtration membranes (EDFM). Before EDFM, different pretreatments were tested, and four pH conditions (4.25, 3.85, 3.45, and 3.05) were used during EDFM. It was demonstrated that a 1:1 dilution of defatted colostrum with deionized water to decrease mineral content followed by the preconcentration of GFs by UF is necessary and allow for these compounds to migrate to the recovery compartment during EDFM. MS analyses confirmed the migration, in low quantity, of only α-lactalbumin (α-la) and β-lactoglobulin (β-lg) from serocolostrum to the recovery compartment during EDFM. Consequently, the ratio of GFs to total protein in recovery compartment compared to that of feed serocolostrum solution was 60× higher at pH value 3.05, the optimal pH favoring the migration of IGF-I and TGF-β2. Finally, these optimal conditions were tested on acid whey to also demonstrate the feasibility of the proposed process on one of the main by-products of the cheese industry; the ratio of GFs to total protein was 2.7× higher in recovery compartment than in feed acid whey solution, and only α-la migrated. The technology of GF enrichment for different dairy solutions by combining ultrafiltration and electrodialysis technologies was proposed for the first time. [ABSTRACT FROM AUTHOR]

Background/Aim: The purpose of the current study was to compare the vascular endothelial growth factor-A (VEGF-A) levels in the aqueous humor of patients with primary open angle glaucoma (POAG) and non-glaucomatous eyes and reveal any potential statistically significant correlations. Patients and Methods: This was an observational cross-sectional study. Aqueous humor samples (50-100 µl) were collected under aseptic conditions, from the anterior chamber at the start of glaucoma or cataract surgery. The levels of VEGF-A were measured using a multiplex bead-based immunoassay. Results: Aqueous humor samples were obtained from 76 participants: 39 with POAG and 36 with age-related cataracts as controls. VEGF-A levels were significantly elevated in the POAG group (166.37±110.04 pg/ml, p=0.011) compared to the control group (119.02±49.09 pg/ml). The receiver operating characteristic (ROC) analysis showed that VEGF-A had significant prognostic ability for POAG (AUC=0.67; p=0.006). An optimal cut-off for VEGF-A was found to be 148.5 pg/ml with a sensitivity of 54%, specificity of 81.1%, positive prognostic value (PPV) of 75% and negative prognostic value (NPV) of 62.5%. Logistic regression analysis showed that after adjusting for sex and age, patients with VEGF-A higher than 148.5 pg/ml had almost 10 times greater likelihood for POAG. Conclusion: VEGF-A is elevated in patients with POAG and can potentially have a prognostic ability for these patients. [ABSTRACT FROM AUTHOR]

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Impaired insulin and growth factor functions are thought to drive many alterations in neurodegenerative diseases like dementia and seem to contribute to oxidative stress and inflammatory responses. Recent studies revealed that nasal growth factor therapy could induce neuronal and oligodendroglia protection in rodent brain damage induction models. Impairment of several growth factors signaling was reported in neurodegenerative diseases. So, in the present study, we examined the effects of intranasal co-treatment of insulin and a pool of growth factor-rich serum (GFRS) which separated from activated platelets on memory, and behavioral defects induced by intracerebroventricular streptozotocin (icv-STZ) rat model also investigated changes in the hippocampal oxidative-nitrosative state and histology. We found that icv-STZ injection (3 mg/kg bilaterally) impairs spatial learning and memory in Morris Water Maze, leads to anxiogenic-like behavior in the open field arena, and induces oxidative-nitrosative stress, neuroinflammation, and neuronal/oligodendroglia death in the hippocampus. GFRS (1µl/kg, each other day, 9 doses) and regular insulin (4 U/40 µl, daily, 18 doses) treatments improved learning, memory, and anxiogenic behaviors. The present study showed that co-treatment (GFRS + insulin with respective dose) has more robust protection against hippocampal oxidative-nitrosative stress, neuroinflammation, and neuronal/oligodendroglia survival in comparison with the single therapy. Memory and behavioral improvements in the co-treatment of insulin and GFRS could be attributed to their effects on neuronal/oligodendroglia survival and reduction of neuroinflammation in the hippocampus. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether there is a correlation between the inflammatory state and the pathogenesis and clinical features of sudden hearing loss (SHL) by studying the expression of inflammation‐related cytokines in the peripheral blood of patients with SHL. Methods: In this work, we analyzed the cytokine profiles of 48 analytes in 38 patients with SHL compared to 38 healthy donors using a multiplex immunoassay. This study used appropriate statistical methods to screen for inflammatory cytokines associated with the pathogenesis of SHL, to analyze their network correlation, and to analyze the relationship between clinical features of SHL and inflammatory cytokines. Results: Several cytokines, including CTACK, Eotaxin, HGF, INF‐α2, IFN‐β, IL‐1β, IL‐1ra, IL‐2Rα, IL‐4, IL‐7, IL‐8, IL‐9, IL‐10, IL‐12(p40), IL‐13, MIG, β‐NGF, SCF, and TNF‐α, exhibited significantly higher levels in the peripheral blood of the SHL group compared to the control group. An inflammatory network composed of multiple cytokines, including IL‐1β, is a risk factor for the development of SHL. Conclusion: This study identified several inflammatory cytokines with elevated expression, which may be linked with the onset of SHL. The results of this study also provide a basis for the theoretical hypothesis of inflammation in SHL. Level of Evidence: 3 Laryngoscope, 134:3293–3301, 2024 [ABSTRACT FROM AUTHOR]

Diabetes is a diverse metabolic disease that is caused by increased levels of blood glucose, which also leads to the generation of several other complications. The formation of wounds and their delayed healing are among the main areas of concern. Wound repair is a process, which replaces damaged cells with healthy cells; it generally occurs in four steps – haemostasis, inflammation, proliferation and remodelling. This review covers the causes of diabetes mellitus, its prevalence, its impact on wound healing, different types of wounds and their management. Diabetes mellitus impairs wound healing through several mechanisms such as impaired angiogenesis, altered collagen production, etc. [ABSTRACT FROM AUTHOR]

BACKGROUND: The key to preventing the recurrence of intrauterine adhesions is to reconstruct the endometrium with normal function. The latest breakthrough in the treatment of recurrent intrauterine adhesions in and outside China is the use of degradable materials to prepare hydrogels to prevent the recurrence of adhesions. OBJECTIVE: To review the research advance in hydrogel-promoted endometrial repair in intrauterine adhesions. METHODS: PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and WanFang databases were searched systematically, with the keywords “intrauterine adhesions, endometrial injury, endometrium regeneration, hydrogel” in Chinese and English. Relevant articles published in each database from January 1990 to March 2023 were collected. RESULTS AND CONCLUSION: In recent years, research on hydrogel-promoted endometrial repair in uterine adhesions in and outside China has made some progress and plays an important role in the prevention and treatment of intrauterine adhesions and the promotion of endometrial repair: (1) As an important carrier in tissue engineering, hydrogel itself has excellent biocompatibility, biodegradability and three-dimensional network structure, which can be better applied in the treatment of intrauterine adhesions. (2) The hydrogel-based carrier system can promote the proliferation and differentiation of endometrial epithelial cells by transporting drugs/biologics/stem cells, and restore normal uterine morphology to prevent adhesion recurrence. (3) Hyaluronic acid hydrogels can not only meet good biocompatibility, but also promote the proliferation and differentiation of endometrial epithelial cells, and will be hydrolyzed by corresponding enzymes in utero, without affecting the normal metabolism of the body. They are currently commonly used uterine anti-adhesion agents in the clinic and are also the most commonly used hydrogel carriers in tissue engineering research. (4) Poloxamer hydrogel with excellent temperature-sensitive properties can rapidly gelate into the body, quickly form a physical barrier, and can play a slow-release effect on carrying substances and provide a platform for cell growth/adhesion. (5) There are broad prospects for the preparation of therapeutic hydrogels using materials with different characteristics, such as temperature-sensitive hydrogels, pH-responsive hydrogels and photosensitive hydrogels, but there are still many problems to be solved, such as the safety of the hydrogel system, whether the degradation products cause immune reactions, and whether they have an impact on the normal body’s menstrual period. A large number of animal experiments and clinical trials are needed to verify its safety and efficacy, and continuously improve the treatment strategy. [ABSTRACT FROM AUTHOR]

Heparan sulfate proteoglycans are highly glycosylated proteins in which heparan sulfate, a glycosaminoglycan sugar chain, is an acidic sugar chain consisting of a repeating disaccharide structure of glucuronic acid and N-acetylglucosamine is locally sulfated. Syndecan, one of the transmembrane HSPGs, functions as a receptor that transmits signals from the extracellular microenvironment to the inside of the cell. In the vascular system, heparan sulfate proteoglycans, a major component of the glycocalyx, enable the binding of various plasma-derived molecules due to their diversity, epimerization of glycosaminoglycans chains, long chains, and sulfation. Heparan sulfate proteoglycans present in the extracellular matrix serve as a reservoir for bioactive molecules such as chemokines, cytokines, and growth factors. Aberrant expression of heparan sulfate proteoglycans, heparanase, and sulfatase is observed in many pathological conditions. Therefore, it can be applied to therapeutic strategies for a wide range of fields including Alzheimer's disease, heart failure, cancer, organ transplants, diabetes, chronic inflammation, aging, and autoimmune diseases. [ABSTRACT FROM AUTHOR]

Introductionβ-TCP ceramics are bone replacement materials that have recently been tested as a drug delivery system that can potentially be applied to endogenous substances like growth factors found in blood platelets to facilitate positive attributes.MethodsIn this work, we used flow chamber loading to load β-TCP dowels with blood suspensions of platelet-rich plasma (PRP), platelet-poor plasma (PPP), or buffy coat (BC) character. PRP and BC platelet counts were adjusted to the same level by dilution. Concentrations of TGF-β1, PDGF-AB, and IGF-1 from dowel-surrounding culture medium were subsequently determined using ELISA over 5 days. The influence of alginate was additionally tested to modify the release.ResultsConcentrations of TGF-β1 and PDGF-AB increased and conclusively showed a release from platelets in PRP and BC compared to PPP. The alginate coating reduced the PDGF-AB release but did not reduce TGF-β1 and instead even increased TGF-β1 in the BC samples. IGF-1 concentrations were highest in PPP, suggesting circulating levels rather than platelet release as the driving factor. Alginate samples tended to have lower IGF-1 concentrations, but the difference was not shown to be significant.DiscussionThe release of growth factors from different blood suspensions was successfully demonstrated for β-TCP as a drug delivery system with release patterns that correspond to PRP activation after Ca2+-triggered activation. The release pattern was partially modified by alginate coating.

Objective(s): Polycystic ovary syndrome (PCOS) causes a developmental arrest of antral follicles and disrupts oocyte maturation. Retinoic acid (RA) and Fibroblast Growth Factor-2 (FGF2) are effective in follicle growth, thus their effects on histopathology and in vitro fertility of oocytes were investigated in PCOS-induced mice.Materials and Methods: Eighty female NMRI mice were randomly divided into 8 groups including 1-Normal mice, 2-PCOS mice without any treatment, 3-Normal mice treated with RA, 4-Normal mice treated with FGF2, 5-PCOS mice treated with RA, 6- PCOS mice treated with FGF2, 7- PCOS mice treated with RA and FGF2, and 8- Normal mice treated with RA and FGF2. Following PCOS induction, the mice were treated with intraperitoneal RA and FGF2 as a treatment. Then ovarian stimulation, for preparing the oocyte and embryo microscopic examinations was performed. After oocyte morphometry, through in vitro fertilization, the embryo formation was assessed. Data was analyzed by one-way ANOVA and Tukey tests.Results: The results showed simultaneous injection of RA and FGF2 into PCOS-induced mice increases antral follicles and corpus luteum, but decreases cystic follicles. Simultaneous injection of these two substances into healthy mice increases the pre-antral follicles and corpus luteum. Simultaneous injection of RA and FGF2 increases the number of embryos in both control and intervention groups. Conclusion: It can be concluded that RA and FGF2 increase the maturity of ovarian follicles, the number of two-celled embryos, and the number of grade-A embryos in mice with PCOS, which is more effective when these two substances are injected simultaneously.

Aim: In routine dental care, various dental luting cements are utilized to cement the dental prosthesis. Thus, the aim of the current study was to assess the Cytotoxic effect of three different dental luting cements on human gingival mesenchymal stem cell and evaluation of cytokines and growth factors release. Settings and Design: Cytotoxicity of glass ionomer cement (GIC), resin modified glass ionomer cement (RMGIC) and resin cement (RC) on the human gingival mesenchymal stem cells (HGMSCs) was evaluated. Amongst the cements tested, least cytotoxic cement was further tested for the release of cytokines and growth factors. Materials and Methods: MTT test was used to evaluate the cytotoxicity of the dental luting cements at 1 h, 24 h, and 48 h on HGMSCs. Cytokines such as interleukin (IL) 1α & IL 8 and growth factors such as platelet derived growth factor & transforming growth factor beta release from the least cytotoxic RC was evaluated using flow cytometry analysis. Statistical Analysis Used: The mean absorbance values by MTT assay and cell viability at various time intervals between four groups were compared using a one way analysis of variance test and Tukey's post hoc test. The least cytotoxic RC group and the control group's mean levels of cytokines and growth factors were compared using the Mann–Whitney test. Result: As exposure time increased, the dental luting cement examined in this study were cytotoxic. RC was the least cytotoxic, RMGIC was moderate and glass ionomer cement showed the highest cytotoxic effect. Concomitantly, a significant positive biological response of gingival mesenchymal stem cells with the release of ILs when exposed to the RC was observed. Conclusion: For a fixed dental prosthesis to be clinically successful over the long term, it is imperative that the biocompatibility of the luting cement be taken into account in order to maintain a healthy periodontium surrounding the restoration.

Abstract Narrow clawed crayfish, Pontastacus (Astacus) leptodactylus, represents an ecologically and economically valuable freshwater species. Despite the high importance of artificial breeding for conservation purpose and aquaculture potential, hatching protocols have not been developed so far in this species. Further, limited knowledge exists regarding the artificial egg incubation, the temperature effect on embryonic development, hatching synchronization and hatching rate. In the present study we investigated the temperature increase (from 17 oC to 22oC) effects in two different embryonic developmental stages of P. leptodactylus. Furthermore, two primer pairs for the Fibroblast Growth Factor Receptor 4 (FGFR4) gene cDNA amplification were successfully designed, characterising for the first time the FGFR4 gene in P. leptodactylus in relation to different developmental stages and temperatures. Apart from the FGFR4 gene, the Na+/K+-ATPase α-subunit expression was also explored. Both the FGFR4 and Na+/K+-ATPase α-subunit expression levels were higher in embryos closer to hatching. Egg incubation at 22oC for seven days led to significant increase of FGFR4 expression in embryos from earlier developmental stages. Nevertheless, temperature increase did not affect FGFR4 expression in eggs from latter developmental stages and Na+/K+-ATPase α-subunit expression in all developmental stages. Temperature increase represents therefore probably a promising strategy for accelerating hatching in freshwater crayfish particularly in early developmental stages. Specifically, our results indicate that FGFR4 expression increased in embryonic stages closer to hatching and that temperature influences significantly its expression in embryos from earlier developmental stages. Overall, these findings can provide a better understanding of artificial egg incubation of P. leptodactylus, and therefore can be employed for the effective management of this species, both for economic and biodiversity retention reasons.

Classical knowledge about the pathogenesis of diabetes and its complications in recent years has been supplemented by ideas about the role of chronic inflammation. It has been established that inflammatory reactions play a role in the beta cell dysfunction, the formation of insulin resistance and remodeling of the vascular wall. Cytokines, soluble low molecular weight proteins and peptides that perform informational and regulatory functions, play central role in the development of inflammation. A wide range of biological activity and involvement in many aspects of pathogenesis make it possible to consider cytokines as promising molecules for diagnosing and predicting the complications. In this review, we summarize data from studies that assessed the role of cytokines as diagnostic and prognostic markers for the development of microvascular diabetic complications. Current data indicate that angiogenic and pro-inflammatory cytokines (VEGF, TNF-α, IL-6, IL-8, IL-15, IL-17, MCP-1, IP-10, INF-γ, PEDF, etc.) are promising biomarkers for proliferative diabetic retinopathy, especially when their local production is assessed (in vitreous, aqueous humor and tears). The role of these molecules as biomarkers of non-proliferative diabetic retinopathy and diabetic macular edema needs further research. Serum proinflammatory and fibrogenic cytokines (primarily MCP-1, IL-6, TNF-α, YKL-40, TGF-β and bFGF) and cytokine receptors (sTNFR1, sTNFR2) are considered as promising diagnostic and prognostic markers of diabetic kidney disease. Urinary excretion of IL-6 and MCP-1 turned out to be a predictor of the progression of diabetic nephropathy. Multi-bead assay and mass spectrometry make it possible to study cytokine panels in small samples of biological material. Combined biomarkers, including several cytokines, may increase the reliability of the prognosis of diabetic complications.

Heparan sulfate proteoglycans are highly glycosylated proteins in which heparan sulfate, a glycosaminoglycan sugar chain, is an acidic sugar chain consisting of a repeating disaccharide structure of glucuronic acid and N-acetylglucosamine is locally sulfated. Syndecan, one of the transmembrane HSPGs, functions as a receptor that transmits signals from the extracellular microenvironment to the inside of the cell. In the vascular system, heparan sulfate proteoglycans, a major component of the glycocalyx, enable the binding of various plasma-derived molecules due to their diversity, epimerization of glycosaminoglycans chains, long chains, and sulfation. Heparan sulfate proteoglycans present in the extracellular matrix serve as a reservoir for bioactive molecules such as chemokines, cytokines, and growth factors. Aberrant expression of heparan sulfate proteoglycans, heparanase, and sulfatase is observed in many pathological conditions. Therefore, it can be applied to therapeutic strategies for a wide range of fields including Alzheimer’s disease, heart failure, cancer, organ transplants, diabetes, chronic inflammation, aging, and autoimmune diseases.