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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]

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]

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]

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]

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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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]

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]

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.

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.

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]

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.

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.

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]

BACKGROUND: Due to the sudden release and the rapid removal by proteases, platelet-rich plasma hydrogel leads to shorter residence times of growth factors at the wound site. In recent years, researchers have focused on the use of hydrogels to encapsulate platelet-rich plasma in order to improve the deficiency of platelet-rich plasma hydrogels. OBJECTIVE: To prepare self-assembled polypeptide-platelet-rich plasma hydrogel and to explore its effects on the release of bioactive factors of platelet-rich plasma. METHODS: The self-assembled polypeptide was synthesized by the solid-phase synthesis method, and the solution was prepared by D-PBS. Hydrogels were prepared by mixing different volumes of polypeptide solutions with platelet-rich plasma and calcium chloride/thrombin solutions, so that the final mass fraction of polypeptides in the system was 0.1%, 0.3%, and 0.5%, respectively. The hydrogel state was observed, and the release of growth factors in platelet-rich plasma was detected in vitro. The polypeptide self-assembly was stimulated by mixing 1% polypeptide solution with 1% human serum albumin solution, so that the final mass fraction of the polypeptide was 0.1%, 0.3%, and 0.5%, respectively. The flow state of the liquid was observed, and the rheological mechanical properties of the self-assembled polypeptide were tested. The microstructure of polypeptide (mass fraction of 0.1% and 0.001%) -human serum albumin solution was observed by scanning electron microscope and transmission electron microscope. RESULTS AND CONCLUSION: (1) Hydrogels could be formed between different volumes of polypeptide solution and platelet-rich plasma. Compared with platelet-rich plasma hydrogels, 0.1% and 0.3% polypeptide-platelet-rich plasma hydrogels could alleviate the sudden release of epidermal growth factor and vascular endothelial growth factor, and extend the release time to 48 hours. (2) After the addition of human serum albumin, the 0.1% polypeptide group still exhibited a flowing liquid, the 0.3% polypeptide group was semi-liquid, and the 0.5% polypeptide group stimulated self-assembly to form hydrogel. It was determined that human serum albumin in platelet-rich plasma could stimulate the self-assembly of polypeptides. With the increase of the mass fraction of the polypeptide, the higher the storage modulus of the self-assembled polypeptide, the easier it was to form glue. (3) Transmission electron microscopy exhibited that the polypeptide nanofibers were short and disordered before the addition of human serum albumin. After the addition of human serum albumin, the polypeptide nanofibers became significantly longer and cross-linked into bundles, forming a dense fiber network structure. Under a scanning electron microscope, the polypeptides displayed a disordered lamellar structure before adding human serum albumin. After the addition of human serum albumin, the polypeptides self-assembled into cross-linked and densely arranged porous structures. (4) In conclusion, the novel polypeptide can self-assemble triggered by platelet-rich plasma and the self-assembly effect can be accurately adjusted according to the ratio of human serum albumin to polypeptide. This polypeptide has a sustained release effect on the growth factors of platelet-rich plasma, which can be used as a new biomaterial for tissue repair. [ABSTRACT FROM AUTHOR]

BACKGROUND: Tendinopathy is a musculoskeletal disorder characterized by pain and decreased mobility, with pathological changes of disturbed collagen and hyperplasia of the vasculature. Tendinopathy tends to occur in athletes, physical workers, and the elderly. One of the mechanisms of tendinopathy is the “failed healing response”, and part of what causes the failed healing response is the erroneous differentiation of tendon stem/progenitor cells. OBJECTIVE: By reviewing the relevant literature, we introduce the characteristics of tendon stem/progenitor cells, summarize the factors that affect the differentiation of tendon stem/progenitor cells to tendon cells and those that lead to mis-differentiation of tendon stem/progenitor cells (differentiation to adipocytes, osteocytes and chondrocytes), and also describe the limitations of tendon stem/progenitor cells in clinical applications. METHODS: PubMed and Web of Science databases were searched for the terms “tendon stem/progenitor cells, tendinopathy, tendon injury, differentiation”. The relevant literature was screened by reading and 109 articles were included for the analysis of the results. RESULTS AND CONCLUSION: (1) Tendon stem/progenitor cells are a type of stem cells that can spontaneously differentiate into tendons and have the ability to self-renew, clone, and multi-differentiate. Various external conditions acting on tendon stem/progenitor cells can lead them to differentiate in diverse directions. The specific factors that regulate the fate of tendon stem/progenitor cells are not known with certainty. When stem cell renewal and differentiation in tendons becomes abnormal, it can lead to failure of tendon healing and consequently to tendinopathy. (2) Aging, changes in extracellular matrix composition, excessive mechanical stimulation, prostaglandin E2 and interleukin-6 as well as interleukin-10 and some systemic diseases may be important in regulating the mis-differentiation of tendon stem/progenitor cells. (3) Possible favorable factors that promote the differentiation of tendon stem/progenitor cells to tenocytes are: some growth factors and cytokines, moderate mechanical stimulation and topography of the extracellular matrix, low oxygen tension, drugs, and several transcriptional genes and proteins. (4) The most desirable therapeutic tools are the regulation of endogenous tendon stem/progenitor cells or the stimulation of endogenous tendon stem/progenitor cell proliferation and differentiation by exogenous tendon stem/progenitor cells. (5) Understanding the factors that regulate mis-differentiation of tendon stem/progenitor cells may provide insight into the pathogenesis of tendinopathy and identify therapeutic targets. Elaborating on the induction of tendon stem/progenitor cell differentiation into tendons could facilitate their use in tissue engineering. [ABSTRACT FROM AUTHOR]

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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. [ABSTRACT FROM AUTHOR]

Mammalian melanin is produced in melanocytes and accumulated in melanosomes. Melanogenesis is supported by many factors derived from the surrounding tissue environment, such as the epidermis, dermis, and subcutaneous tissue, in addition to numerous melanogenesis-related genes. The roles of these genes have been fully investigated and the molecular analysis has been performed. Moreover, the role of paracrine factors derived from epidermis has also been studied. However, the role of dermis has not been fully studied. Thus, in this review, dermis-derived factors including soluble and insoluble components were overviewed and discussed in normal and abnormal circumstances. Dermal factors play an important role in the regulation of melanogenesis in the normal and abnormal mammalian skin. [ABSTRACT FROM AUTHOR]

Chronic odontogenic maxillary sinusitis (COMS), a prolonged inflammation of the maxillary sinus lasting over 12 weeks, is often a result of periapical lesions, marginal periodontitis, and complications like oro-antral communication (OAC) and fistula (OAF). OAC, commonly emerging post-teeth extraction in the lateral maxilla, lacks documented treatments using advanced platelet-rich fibrin (A-PRF). This study evaluates A-PRF's efficacy in treating COMS and immediately sealing extensive OAC. A case of a 28-year-old male with COMS linked to a periapical lesion and supernumerary molars is presented. Treatment involved extracting specific teeth while preserving adjacent ones and using A-PRF for immediate OAC closure. A-PRF, enriched with growth factors, was pivotal in healing, showcasing enhanced tissue regeneration, pain reduction, and faster recovery. The findings suggest A-PRF as an effective adjunct in treating extensive OAC and COMS, proposing its inclusion in standard treatment protocols. This study underscores A-PRF's potential in improving outcomes for patients with COMS and related complications. [ABSTRACT FROM AUTHOR]

BACKGROUND: Recently, regenerative endodontic therapy is a promising alternative to the maturation of tissue engineering. Inflammatory microenvironment plays a key role in regulating pulp regeneration. OBJECTIVE: To focus on the change in the inflammatory pulp microenvironment, the balance between inflammation and regeneration, and the research advances in tissue-engineered regenerative endodontic therapy within the context of the inflammatory microenvironment to provide a reference for future investigations into regenerative endodontic therapy. METHODS: We conducted a literature search on PubMed and CNKI using search terms “pulp regeneration, inflammation, regenerative endodontic therapy, tissue engineering” in Chinese and English for articles published between 2013 and 2023. The review finally included 61 relevant articles. RESULTS AND CONCLUSION: (1) The changes in the microenvironment of pulpitis involve a complex interplay of cellular and molecular reactions, which, as inflammation progresses, ultimately the microenvironment hinders tissue repair more than facilitates it. (2) Inflammation can promote dental pulp regeneration through stem cell recruitment and activate the complement system, but it can also hinder the regenerative process through immunosuppression and fibrosis. (3) Tissue engineering’s three components (stem cells, growth factors, scaffold materials) collaborate to balance inflammation and regeneration, for example, by using interleukin-6 to regulate dental pulp stem cells and foster a regenerative environment. (4) Current research has been largely silent on infection and inflammation issues. The mechanisms underlying changes in the microenvironment of pulpitis are still not fully understood. One promising avenue for improving the clinical applicability of regenerative dental pulp therapy is to achieve precise regulation of the inflammatory-regeneration balance and create a regenerative microenvironment by synergistically leveraging the three elements of tissue engineering. However, this field of investigation still exhibits significant gaps in understanding, necessitating further exploration into innovative strategies for facilitating dental pulp regeneration under inflammation. As such, additional animal experimentation and randomized clinical trials are required to establish a robust foundation for the clinical practice of tissue engineeringbased regenerative dental pulp therapy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Simple Summary: Tamoxifen is prescribed to premenopausal patients with estrogen-receptor-positive breast cancers for a period of 5–10 years after cancer diagnosis. This prolonged treatment regimen, though effective at preventing cancer recurrence, is often associated with unwanted cognitive and affective symptoms. To understand the clinical side effects of tamoxifen, animal studies investigating the effect of tamoxifen on the brain must model the chronic nature of tamoxifen therapy. This study describes a novel method of tamoxifen administration in female rats conducive to long-term administration of tamoxifen. Blood samples from treated rats showed levels of tamoxifen similar to levels in humans. Brain samples revealed tamoxifen-induced changes of a neurotrophic factor in the hippocampus, a structure critical to cognitive and affective processing. This study, therefore, suggests a potential mechanism that may underlie the cognitive side effects reported in patients. Tamoxifen, a selective estrogen receptor modulator (SERM), is commonly used as an adjuvant drug therapy for estrogen-receptor-positive breast cancers. Though effective at reducing the rate of cancer recurrence, patients often report unwanted cognitive and affective side effects. Despite this, the impacts of chronic tamoxifen exposure on the brain are poorly understood, and rodent models of tamoxifen exposure do not replicate the chronic oral administration seen in patients. We, therefore, used long-term ad lib consumption of medicated food pellets to model chronic tamoxifen exposure in a clinically relevant way. Adult female Long-Evans Hooded rats consumed tamoxifen-medicated food pellets for approximately 12 weeks, while control animals received standard chow. At the conclusion of the experiment, blood and brain samples were collected for analyses. Blood tamoxifen levels were measured using a novel ultra-performance liquid chromatography–tandem mass spectrometry assay, which found that this administration paradigm produced serum levels of tamoxifen similar to those in human patients. In the brain, brain-derived neurotrophic factor (BDNF) was visualized in the hippocampus using immunohistochemistry. Chronic oral tamoxifen treatment resulted in a decrease in BDNF expression across several regions of the hippocampus. These findings provide a novel method of modeling and measuring chronic oral tamoxifen exposure and suggest a putative mechanism by which tamoxifen may cause cognitive and behavioral changes reported by patients. [ABSTRACT FROM AUTHOR]

This paper combines modern numerical computation with theoretical results to improve our understanding of the growth factor problem for Gaussian elimination. On the computational side we obtain lower bounds for the maximum growth for complete pivoting for n = 1:75 and n = 100 using the Julia JuMP optimization package. At n = 100 we obtain a growth factor bigger than 3n. The numerical evidence suggests that the maximum growth factor is bigger than n if and only if n≥ 11. We also present a number of theoretical results. We show that the maximum growth factor over matrices with entries restricted to a subset of the reals is nearly equal to the maximum growth factor over all real matrices. We also show that the growth factors under floating point arithmetic and exact arithmetic are nearly identical. Finally, through numerical search, and stability and extrapolation results, we provide improved lower bounds for the maximum growth factor. Specifically, we find that the largest growth factor is bigger than 1.0045n for n > 10, and the lim sup of the ratio with n is greater than or equal to 3.317. In contrast to the old conjecture that growth might never be bigger than n, it seems likely that the maximum growth divided by n goes to infinity as n→∞. [ABSTRACT FROM AUTHOR]

Silk fibroin (SF) has been utilized in various applications, including as, in bone, cartilage, nerve, skin regeneration, owing to its biocompatibility, controllable biodegradability, minimal inflammation, and tunable mechanical properties. Excellent neovascularization of silk matrices is prerequisite for the success of promoting wound healing in different tissues. Neovascularization of SF can provide a nutrient supply to the newly developed granulation tissue at the wound site and accelerate vessel formation and remodeling. In this review, we summarize the neovascularization of SF in different forms and dissolution by recombining different composites, modifying active peptides, and adding growth factors in the treatment of various wound healing processes. [ABSTRACT FROM AUTHOR]

Gastrointestinal cancer represents one of the most encountered oncologic pathologies and research studies are performed thoroughly in order to identify the exact causes and possible novel therapies. Obesity is a complex manifestation associated with numerous physiological and primarily molecular changes capable of tackling the behavior of tumoral cells and the nearby or faraway microenvironment. Adipose tissue has been once considered to have limited physiological roles, but in recent years it has been recognized as an active endocrine organ, secreting substances such as growth factors and adipokines. From an epidemiological perspective, obesity -- particularly morbid obesity -- is linked to an unfavorable progression of cancer. A key mechanism that may elucidate the association between obesity and cancer involves the insulin and insulin-like growth factor (IGF-1) pathway, sex hormones, and adipokines. [ABSTRACT FROM AUTHOR]

The precise delivery of growth factors (GFs) in regenerative medicine is crucial for effective tissue regeneration and wound repair. However, challenges in achieving controlled release, such as limited half-life, potential overdosing risks, and delivery control complexities, currently hinder their clinical implementation. Despite the plethora of studies endeavoring to accomplish effective loading and gradual release of GFs through diverse delivery methods, the nuanced control of spatial and temporal delivery still needs to be elucidated. In response to this pressing clinical imperative, our review predominantly focuses on explaining the prevalent strategies employed for spatiotemporal delivery of GFs over the past five years. This review will systematically summarize critical aspects of spatiotemporal GFs delivery, including judicious bio-scaffold selection, innovative loading techniques, optimization of GFs activity retention, and stimulating responsive release mechanisms. It aims to identify the persisting challenges in spatiotemporal GFs delivery strategies and offer an insightful outlook on their future development. The ultimate objective is to provide an invaluable reference for advancing regenerative medicine and tissue engineering applications. [Display omitted] • The spatiotemporal delivery of growth factors is pivotal in tissue regeneration engineering. • This review emphasized key factors for achieving spatiotemporal delivery of growth factors. • Various approaches for growth factor delivery in recent 5 years have been summarized in this review. [ABSTRACT FROM AUTHOR]

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) 1a & 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 FROM AUTHOR]