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.

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.

Background: Tooth infraocclusion is a process in which a completely or partially erupted tooth gradually moves away from the occlusal plane. Submerged teeth can lead to serious complications. Treating teeth with infraocclusion is very challenging. One of the procedures allowing for the replacement of a missing tooth is autotransplantation. The aim of this paper is to review the literature on teeth autotransplantation, supported by a case report involving the autotransplantation of a third mandibular molar into the site of an extracted infraoccluded first mandibular molar, as well as the utilization of advanced platelet-rich fibrin (A-PRF) alongside autogenous dentin grafts for bone tissue regeneration. Methods: A severely infraoccluded first permanent right mandibular molar was extracted and then ground to obtain the dentin graft. A-PRF clots (collected from the patient\'s peripheral blood) were added to the autogenous dentin graft, to create the A-PRF membrane. An atraumatic extraction of the lower left third molar was performed and then it was transplanted into the socket of tooth no. 46. Immediately after transplantation, tooth no. 38 was stabilized with orthodontic bracket splints for 3 months. The patient attended regular follow-up visits within 12 months. Results: After one year, the patient did not report any pain. In the clinical examination, the tooth and surrounding tissues did not show any signs of infection. However, radiographically, cervical inflammatory resorption, unchanged pulp canal dimensions, absent root growth, periapical radiolucency, and lack of apical and marginal healing were observed. Reconstruction of the bone defect was obtained and the alveolar ridge of the mandible was preserved. Due to poor stability of the tooth and severe resorption, the tooth needed to be extracted. Conclusions: This study is designed to critically evaluate the efficacy of autotransplantation, the application of growth factors, and the integration of autogenous dentin grafts in remedying dental deficiencies resulting from reinclusion. We aim to point out the possible causes of treatment failure.

Following nerve injury, growth factors (GFs) are transiently upregulated in injured neurons, proliferating Schwann cells, and denervated muscle and skin. They act on these same cells and tissues to promote nerve regeneration and end-organ reinnervation. Consequently, much attention has been focused on developing GF-based therapeutics. A major barrier to clinical translation of GFs is their short half-life. To provide sustained GF treatment to the affected nerve, muscle, and skin in a safe and practical manner, engineered drug delivery systems are needed. This review highlights recent advancements in GF-based therapeutics and discusses the remaining hurdles for clinical translation.

Recently, low human epidermal growth factor receptor 2 (HER2) protein expression has been proposed as a predictive biomarker for response to the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) in metastatic breast cancer. HER2 expression in non-small cell lung cancer (NSCLC) patients has never been carefully measured, and little is known about the frequency of cases with unamplified but detectable levels of the protein. Although some HER2-targeted therapies have been studied in NSCLC patients, they have been restricted to those with genomic ERBB2 gene alterations, which only represent relatively rare cases of NSCLC. Still, emerging investigations of T-DXd in NSCLC have shown promise in patients with unamplified HER2. Taken together, we hypothesize that there may be many cases of NSCLC with levels of HER2 protein expression comparable with levels seen in breast cancer that benefit from T-DXd. Here, we used a previously validated, analytic, quantitative immunofluorescence (QIF) assay that is more sensitive than legacy clinical HER2 immunohistochemistry assays. We measured HER2 protein levels in NSCLC cases to determine the proportion of cases with detectable HER2 expression. Using cell line calibration microarrays alongside our QIF method enabled us to convert HER2 signal into units of attomoles per mm2. We found that over 63% of the 741 analyzed NSCLC cases exhibited HER2 expression above the limit of detection, with more than 17% of them exceeding the lower limit of quantification. Although the threshold for response to T-DXd in breast cancer is still unknown, many cases of NSCLC have expression in a range comparable to breast cancer cases with immunohistochemistry scores of 1+ or 2+. Our assay could potentially select NSCLC cases with a detectable target (ie, HER2) that might benefit from HER2 antibody-drug conjugates, irrespective of ERBB2 genomic alterations.

Autologous or allogeneic bone tissue grafts remain the mainstay of treatment for clinical bone defects. However, the risk of infection and donor scarcity in bone grafting pose challenges to the process. Therefore, the development of excellent biomaterial grafts is of great clinical importance for the repair of bone defects. In this study, we used gas-assisted microfluidics to construct double-cross-linked hydrogel microspheres with good biological function based on the ionic cross-linking of Cu2+ with alginate and photo-cross-linking of gelatin methacryloylamide (GelMA) by loading vascular endothelial growth factor (VEGF) and His-tagged bone morphogenetic protein-2 (BMP2) (AGMP@VEGF&BMP2). The Cu2+ component in the microspheres showed good antibacterial and drug-release behavior, whereas VEGF and BMP2 effectively promoted angiogenesis and bone tissue repair. In in vitro and in vivo experiments, the dual cross-linked hydrogel microspheres showed good biological function and biocompatibility. These results demonstrate that AGMP@VEGF&BMP2 microspheres could be used as a bone defect graft substitute to promote effective healing of bone defects and may be applied to other tissue engineering studies.

Bioactive hydrogels are currently receiving significant attention. In this study, silk fibroin tyramine-modified gelatin hydrogels (SF-TG) with varying degrees of tyramine root substitution were explored. The physicochemical property and biocompatibility of low degree of substitution tyramine-modified gelatin hydrogel (SF-LTG) and high degree of substitution tyramine-modified gelatin hydrogel (SF-HTG) were compared. The results showed that SF-LTG possessed better mechanical property and higher biocompatibility. Thus, SF-LTG was selected as a bioactive matrix and loaded with basic fibroblast growth factor (bFGF); subsequently, curcumin-coupled chitosan rods (CCCRs-EGF) enriched with epidermal growth factor (EGF) were added to obtain SF-LTG-bFGF@CCCRs-EGF hydrogels. The results showed that SF-LTG-bFGF@CCCRs-EGF retained the basic structural and mechanical properties of the SF-LTG matrix gel material and underwent multiple loading and orderly release with different activities while displaying antioxidant, anti-inflammatory, antimicrobial, and pro-cellular proliferation activities and orderly regulation of activity during wound healing. Therefore, the SF-LTG-bFGF@CCCRs-EGF hydrogel is of great value in healing complex wounds.

OBJECTIVE: 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.
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.
CONCLUSIONS: VEGF-A is elevated in patients with POAG and can potentially have a prognostic ability for these patients.

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.

Titanium and titanium alloys are widely favored materials for orthopedic implants due to their exceptional mechanical properties and biological inertness. The additional benefit of sustained local release of bioactive substances further promotes bone tissue formation, thereby augmenting the osseointegration capacity of titanium implants and attracting increasing attention in bone tissue engineering. Among these bioactive substances, growth factors have shown remarkable osteogenic and angiogenic induction capabilities. Consequently, researchers have developed various physical, chemical, and biological loading techniques to incorporate growth factors into titanium implants, ensuring controlled release kinetics. In contrast to conventional treatment modalities, the localized release of growth factors from functionalized titanium implants not only enhances osseointegration but also reduces the risk of complications. This review provides a comprehensive examination of the types and mechanisms of growth factors, along with a detailed exploration of the methodologies used to load growth factors onto the surface of titanium implants. Moreover, it highlights recent advancements in the application of growth factors to the surface of titanium implants (Scheme 1). Finally, the review discusses current limitations and future prospects for growth factor-functionalized titanium implants. In summary, this paper presents cutting-edge design strategies aimed at enhancing the bone regenerative capacity of growth factor-functionalized titanium implants-a significant advancement in the field of enhanced bone regeneration.