Proliferative Phase Research Articles

Chicken GLUT4 function via enhancing mitochondrial oxidative phosphorylation and inhibiting ribosome pathway in skeletal muscle satellite cells

Glucose Transporter 4 (GLUT4) is a crucial protein facilitating glucose uptake and metabolism across cell membranes in mammals. However, information on GLUT4 in birds has historically been limited. In this study, we investigated the dynamic expression profile of chicken GLUT4 using real-time quantitative PCR (RT-qPCR) and examined its potential effects and mechanisms via GLUT4 overexpression and RNA sequencing (RNA-seq) in chicken primary skeletal muscle satellite cells (CP-SMSCs). Our results demonstrated that chicken GLUT4 is differentially expressed across tissues, with predominant expression in skeletal muscles, and across developmental stages of CP-SMSCs, with notable upregulation during the phases of cell proliferation and early differentiation. Notably, 0.1 μM insulin for 60 min significantly elevated the expression of GLUT4 in CP-SMSCs (P < 0.05). GLUT4 overexpression in CP-SMSCs promoted cell proliferation, as evidenced by Cell Counting Kit-8 (CCK-8) (P < 0.05) and 5-Ethynyl-2'-Deoxyuridine (EDU) assays (P < 0.05), and enhanced glucose consumption following 0.1 μM insulin treatment (P < 0.05). However, it inhibited glucose consumption 12 h after the addition of 5 g/L glucose (P < 0.05). After overexpressing GLUT4, we identified 302 differentially expressed genes (DEGs) in CP-SMSCs, with 134 upregulated and 168 downregulated. These DEGs are primarily enriched in pathways such as oxidative phosphorylation, ribosome, cardiac muscle contraction, ATP metabolic processes, and mitochondrial protein complexes. Specifically, in the enriched oxidative phosphorylation pathway, the upregulated DEGs (12) encode mitochondrial proteins, while the downregulated DEGs (6) are nuclear genome-derived. The ribosomal pathway is predominantly inhibited, accompanying with the downregulation of the translocase of outer mitochondrial membrane 7 (TOMM7)/translocase of inner mitochondrial membrane 8 (TIMM8A) complex responsible for mitochondrial protein transport, and a reduction in 28S (LOC121106978) and 18S (LOC112533601) ribosomal rRNAs. In conclusion, chicken GLUT4 is dynamically modulated during development and acts as an insulin responder that significantly regulates cellular glucose uptake and cell proliferation. This regulation occurs mainly through enhancing the mitochondrial oxidative phosphorylation and inhibiting ribosomal pathway.

Stress-induced phosphoprotein 1 expression in the endometrium and myometrium of patients with adenomyosis

BACKGROUND: The study of stress-induced phosphoprotein 1 in the pathogenesis of adenomyosis is not only of theoretical interest, but this protein may be also considered as a potential biomarker of the disease. AIM: The aim of this study was to evaluate stress-induced phosphoprotein 1 expression in the endometrium and heterotopic foci in women with isolated adenomyosis and in combination with benign hyperproliferative diseases of the reproductive organs. MATERIALS AND METHODS: This study enrolled 66 women aged 21 to 47 years (34.9 ± 6.7 years), including 49 patients with adenomyosis and 17 women in the control group. The main group was divided into subgroups depending on the concomitant hyperproliferative disease such as isolated adenomyosis (n = 36), adenomyosis combined with uterine fibroids (n = 8), and adenomyosis combined with endometriosis (n = 5). The patients underwent endometrial biopsy and multifocal myometrial biopsy. Histological and immunohistochemical studies were performed to assess stress-induced phosphoprotein 1 expression in the glandular and stromal components of the endometrium and ectopic endometrial tissue within the uterine myometrium. RESULTS: We found increased stress-induced phosphoprotein 1 expression in the adenomyosis lesion compared to that in the myometrium of the control group, regardless of the phase of the menstrual cycle (p 0.001). When studying stress-induced phosphoprotein 1 expression in the endometrium of the main group in the proliferative phase of the menstrual cycle, an increase was found, but the differences were not significant. Stress-induced phosphoprotein 1 expression in the secretory phase of the menstrual cycle was higher in the glandular component of the endometrium of patients with adenomyosis compared to the levels in women in the control group (p 0.05). CONCLUSIONS: The increased expression of stress-induced phosphoprotein 1 in the glandular component of the adenomyosis lesion indicates a potential role of the protein in the pathogenesis of the disease. However, further research is needed to determine its practical significance.

8314 Masculinizing Hormone Therapy and Gynecological Neoplasm: a Single Institution Cohort

Abstract Disclosure: S. Korpaisarn: None. T. Ngaothepphurktharam: None. Y. Tingthanatikul: None. Background: Gynecological neoplasm/malignancy is one of the concerned areas among transgender men on masculinizing hormone therapy (MHT). Long-term MHT and gynecological neoplasm/malignancy remain unclear. Methods: A retrospective cohort chart review was done on all transgender men (TM) who underwent hysterectomy with or without oophorectomy between January 2014 and October 2022. Intraoperative findings and pathological results of genital organs, including the cervix, endometrium, myometrium, and fallopian tubes, were extracted. The pathological results were classified as benign, precancerous, and malignant. Descriptive statistical analysis was used to demonstrate the prevalence of gynecological neoplasm and malignancy. Results: A total of 30 TM underwent hysterectomy with oophorectomy. Twenty-eight (93%) had bilateral oophorectomy, and 7% had unilateral oophorectomy due to gynecological conditions. The mean age when TM underwent surgery was 32.1 ± 5.1 years, and the mean age of gender-affirming hormone initiation was 28.7± 5.1 years. The median duration of MHT before gynecological surgery was 32 months (IQR 22-59). Most TM (73%) used testosterone enanthate, 17% testosterone undecanoate, and 2 transgender men did not start MHT before genital surgery. All TM who used GHT became amenorrheic before surgery. The median preoperative testosterone level was 561.5 ng/dL (IQR 776-1189). Intraoperative findings revealed that most TM (86.7%) had unremarkable uterus size, and 13% showed enlarged uterus size. In the latter, all were from myoma uteri. Most intraoperative findings of ovaries showed 93% unremarkable. One TM had intraoperative polycystic ovarian morphology, and one showed a unilateral ovarian cyst. Cervical pathological reports showed unremarkable results in 67%. Five TM (17%) had chronic cervical inflammation. There was 1 TM (3%) who showed low-grade squamous intraepithelial lesion (LSIL) with squamous metaplasia. Regarding endometrial pathology, the mean endometrial thickness was 0.13 ± 0.08 cm. Most endometrial reports (66%) were in a proliferative phase, 27% were in an atrophic or inactive endometrium, and 7% were in the secretory phase. Regarding pathological reports of ovaries, 80% had cystic ovaries. None of the TM showed precancerous or malignant conditions of endometrium, ovaries, and fallopian tubes. PAP smear was available in 27 TM; all were negative for intraepithelial lesions or malignancy. Conclusion: Among a cohort of TM who received MHT for 32 months, there is no evidence of precancerous or malignant pathology of the endometrium, ovaries, and fallopian tubes. Most of them had thin endometrium with cystic ovaries. One TM showed LSIL with squamous metaplasia of the cervix. Healthcare providers should follow local gynecological cancer screening guidelines developed for cisgender women in their clinical practice. Presentation: 6/2/2024

The lncRNA SNHG26 drives the inflammatory-to-proliferative state transition of keratinocyte progenitor cells during wound healing

The cell transition from an inflammatory phase to a subsequent proliferative phase is crucial for wound healing, yet the driving mechanism remains unclear. By profiling lncRNA expression changes during human skin wound healing and screening lncRNA functions, we identify SNHG26 as a pivotal regulator in keratinocyte progenitors underpinning this phase transition. Snhg26-deficient mice exhibit impaired wound repair characterized by delayed re-epithelization accompanied by exacerbated inflammation. Single-cell transcriptome analysis combined with gain-of-function and loss-of-function of SNHG26 in vitro and ex vivo reveals its specific role in facilitating inflammatory-to-proliferative state transition of keratinocyte progenitors. A mechanistic study unravels that SNHG26 interacts with and relocates the transcription factor ILF2 from inflammatory genomic loci, such as JUN, IL6, IL8, and CCL20, to the genomic locus of LAMB3. Collectively, our findings suggest that lncRNAs play cardinal roles in expediting tissue repair and regeneration and may constitute an invaluable reservoir of therapeutic targets in reparative medicine.

Duramater Healing Following Decompression And Posterior Stabilization Using Platelet Rich Plasma And Platelet Rich Fibrin: A Systematic Review

Background: Platelet-rich plasma (PRP) applications have the potential to play adjunctive roles in a variety of regenerative medicine treatment plans. PRP therapy is based on the fact that platelet growth factors (PGFs) support the three phases of wound healing and repair cascade. This systematic review evaluates the efficacy of platelet-rich plasma (PRP) and platelet-rich fibrin (PRF) in enhancing duramater healing and reducing complications, particularly cerebrospinal fluid (CSF) leaks, following spinal surgeries. Incidental dural tears are a common complication in lumbar spine surgeries, leading to significant postoperative challenges. Methods: The review included randomized controlled trials comparing PRP and PRF with conventional treatments, sourced from databases such as PubMed, ScienceDirect, ProQuest, and Cochrane Library. Results: PRP and PRF are rich in growth factors such as platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and transforming growth factor-beta (TGF-β), all of which play crucial roles in wound healing. Conclusion: Both PRP and PRF significantly improve duramater healing, with PRF offering a more sustained release of growth factors, thereby enhancing watertight dura closure and reducing CSF leakage.

Adiponectin receptor 1 regulates endometrial receptivity via the adenosine monophosphate‑activated protein kinase/E‑cadherin pathway.

Endometrial receptivity is essential for successful embryo implantation and pregnancy initiation and is regulated via various signaling pathways. Adiponectin, an important adipokine, may be a potential regulator of reproductive system functions. The aim of the present study was to elucidate the regulatory role of adiponectin receptor 1 (ADIPOR1) in endometrial receptivity. The endometrial receptivity between RL95‑2 and AN3CA cell lines was confirmed using an in vitro JAr spheroid attachment model. 293T cells were transfected with control or short hairpin (sh)ADIPOR1 vectors and RL95‑2 cells were transduced with lentiviral particles targeting ADIPOR1. Reverse transcription‑quantitative PCR and immunoblot assays were also performed. ADIPOR1 was consistently upregulated in the endometrium during the mid‑secretory phase compared with that in the proliferative phase and in receptive RL95‑2 cells compared with that in non‑receptive AN3CA cells. Stable cell lines with diminished ADIPOR1 expression caused by shRNA showed reduced E‑cadherin expression and attenuated in vitro endometrial receptivity. ADIPOR1 regulated AMP‑activated protein kinase (AMPK) activity in endometrial epithelial cells. Regulation of AMPK activity via dorsomorphin and 5‑aminoimidazole‑4‑carboxamide ribonucleotide affected E‑cadherin expression and in vitro endometrial receptivity. The ADIPOR1/AMPK/E‑cadherin axis is vital to endometrial receptivity. These findings can help improve fertility treatments and outcomes.

Sex-specific divergences in the types and timing of infiltrating immune cells during the intervertebral disc acute injury response and their associations with degeneration

ObjectiveInadequate repair of the intervertebral disc (IVD) contributes to low back pain. Infiltrating immune cells into damaged tissues are critical mediators of repair, yet little is known about the identities, roles, and temporal regulation following IVD injury. By analyzing transcripts of immune cell markers, histopathologic analysis, immunofluorescence, and flow cytometry, we aimed to define the temporal cascade of infiltrating immune cells and their associations with IVD degeneration. MethodCaudal IVDs from 12-week old C57BL/6 mice were injured and monitored for 42-days post injury. Transcriptional markers identifying myeloid, B, and T immune cells, and angiogenic factors were measured in the IVDs every 2-3 days. Histopathologic degeneration of the IVD was measured throughout. Flow cytometry and immunofluorescence was used to identify and localize cells including the B, T, NKT, monocytes, neutrophils, macrophages, and dendritic cells. ResultsThe injured IVD revealed distinct phases of inflammation and proliferation. Robust temporal oscillation in the myeloid and T cell transcripts was observed in females. Cd3+ T cells were more abundant in females than in males. The Cd3+Cd4-Cd8- T cells that dominate the female cascade contain rare γδ T cells. Injury-mediated degeneration was prevalent in both sexes but more severe in males. ConclusionsThis study defines the coordinated infiltration of immune cells in the IVD following injury. We report the discovery of γδ T cells in the female IVD and this was associated with less severe degeneration. γδ T cells have potent anti-inflammatory roles and may suppress degeneration following IVD injury.

Expression Profiling of Coding and Noncoding RNAs in the Endometrium of Patients with Endometriosis.

The aim of this study was to identify differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) in the endometrium of individuals with and without endometriosis (EMS) during the proliferative (P) and secretory (S) phases of the menstrual cycle. Tissues were obtained from 18 control (CT; P-phase [pCT], n = 8; S-phase [sCT], n = 13) and 23 EMS patients (P-phase [pEMS], n = 13; S-phase [sEMS], n = 12). DElncRNAs and DEmRNAs were analyzed using total RNA-sequencing. In P-phase, expression of NONHSAG019742.2 and NONHSAT120701.2 was significantly higher in EMS than control patients, that of while NONHSAG048398.2 and NONHSAG016560.2 was lower in EMS patients. In S-phase, expression of NONHSAT000959.2, NONHSAT203423.1, and NONHSAG053769.2 was significantly increased in EMS patients, while that of NONHSAG012105.2 and NONHSAG020839.2 was lower. In addition, the expression of HSD11B2, THBS1, GPX3, and SHISA6 was similar to that of neighboring lncRNAs in both P- and S-phases. In contrast, ELP3 and NR4A1, respectively, were up- or downregulated in pEMS tissues. In sEMS, expression of LAMB3 and HIF1A was increased, while expression of PAM was reduced. Our findings on lncRNAs and mRNAs encourage not only exploration of the potential clinical applications of lncRNAs and mRNAs as prognostic or diagnostic biomarkers for EMS but also to gain valuable insights into its pathogenesis.

A retrospective multicenter cohort study of differences in clinical characteristics of Infantile Hemangiomas in preterm and term infants: Prematurity increases risk of permanent cutaneous sequelae

BackgroundWe observed many preterm infants with unexpectedly thick infantile hemangiomas (IH), a subtype known to be associated with increased risk of scarring. ObjectiveTo compare the clinical features of localized IH in preterm versus term infants. MethodsA retrospective study at three tertiary referral centers was conducted on 830 consecutive patients with localized IH. ResultsPreterm infants had a significantly higher incidence of superficial IH (75% in <33weeks, 57% in 33-<37 weeks, and 50% in term infants, p=0.007). Overall, their IH had thicker superficial components (p<0.001) and more stepped borders (p<0.001). These features correlated with the degree of prematurity. The average chronological age at presentation to the specialist was 5.6 (SD=6.2) months, with no difference between gestational age. LimitationsThe retrospective design and use of non-standardized clinical photographs. There may be biases introduced toward more severe IH types because the study sites were tertiary referral centers. ConclusionPreterm infants have features of IH that have obvious implication for systemic therapies. Most of these infants were seen beyond the typical proliferative phase when irreversible skin changes may have already occurred.

Bionic sulfated glycosaminoglycan-based hydrogel inspired by snail mucus promotes diabetic chronic wound healing via regulating macrophage polarization

The treatment of diabetic foot ulcers remains a significant challenge, as their morbidity is increasing while current therapies are expensive and often ineffective. The dried mucus from the snail Achatina fulica promotes diabetic wound healing. Herein, to develop a more controllable and stable wound dressing for diabetic wound treatment, the AFG/StarPEG hydrogel mimicking snail mucus was prepared by covalently coupling of sulfated glycosaminoglycan from A. fulica (AFG) with star-shaped polyethylene glycol (StarPEG) amine. The AFG/StarPEG hydrogel reduced excessive inflammation in wound tissues by decreasing pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) and increasing anti-inflammatory cytokines (IL-4 and IL-10). Moreover, it promoted the polarization of macrophages to M2 anti-inflammatory type in diabetic wound. By improving transition of diabetic chronic wound from inflammatory phase to proliferative phase, it promoted angiogenesis, collagen deposition and re-epithelialization, and thus tissue regeneration for wound healing. This work provides a convenient and effective dressing for treating chronic diabetic wound.

Quantitative Assessment of Polarization and Elastic Properties of Endometrial Tissue for Precancer/Cancer Diagnostics Using Multimodal Optical Coherence Tomography

Objectives: The most important phase in the endometrial pathologies diagnostics is the histological examination of tissue biopsies obtained under visual hysteroscopic control. However, the unclear visual diagnostics characteristics of subtle focal endometrial pathologies often lead to selection errors regarding suspicious endometrial lesions and to a subsequent false pathological diagnosis/underestimation of precancer or early-stage cancer. Methods: In this study, we investigate the potential of Multimodal Optical Coherence Tomography (MM OCT) to verify suspicious endometrial lesion regions before biopsy collection. We study the polarization (by cross-polarization OCT, CP OCT) and elastic (by compression OCT-elastography, C-OCE) properties of ex vivo endometrial tissue samples in normal conditions (proliferative and secretory phases to the menstrual cycle, atrophic endometrium) with endometrial hyperplasia (non-atypical and endometrial intraepithelial neoplasia) and endometrial cancer subtypes (low-grade, high-grade, clear cell and serous). Results: To the best of our knowledge, this is the first quantitative assessment of relevant OCT parameters (depth-resolved attenuation coefficient in co-[Att(co) values] and cross-[(Att(cross) values] polarizations and Young’s elastic modulus [stiffness values]) for the selection of the most objective criteria to identify the clinically significant endometrial pathologies: endometrial intraepithelial neoplasia and endometrial cancer. The study demonstrates the possibility of detecting endometrial pathologies and establishing optimal threshold values of MM OCT criteria for the identification of endometrial cancer using CP OCT (by Att(co) values = 3.69 mm−1, Sensitivity (Se) = 86.1%, Specificity (Sp) = 92.6%; by Att(cross) values = 2.27 mm−1, Se = 86.8%, Sp = 87.0%) and C-OCE (by stiffness values = 122 kPa, Se = 93.2%, Sp = 91.1%). The study also differentiates endometrial intraepithelial neoplasia from non-atypical endometrial hyperplasia and normal endometrium using C-OCE (by stiffness values = 95 kPa, Se = 87.2%, Sp = 90.1%). Conclusions: The results are indicative of the efficacy and potential of clinical implementation of in vivo hysteroscopic-like MM OCT in the diagnosis of endometrial pathologies.

Galectin-3/Gelatin Electrospun Scaffolds Modulate Collagen Synthesis in Skin Healing but Do Not Improve Wound Closure Kinetics.

Chronic wounds remain trapped in a pro-inflammatory state, with strategies targeted at inducing re-epithelialization and the proliferative phase of healing desirable. As a member of the lectin family, galectin-3 is implicated in the regulation of macrophage phenotype and epithelial migration. We investigated if local delivery of galectin-3 enhanced skin healing in a full-thickness excisional C57BL/6 mouse model. An electrospun gelatin scaffold loaded with galectin-3 was developed and compared to topical delivery of galectin-3. Electrospun gelatin/galectin-3 scaffolds had an average fiber diameter of 200 nm, with 83% scaffold porosity approximately and an average pore diameter of 1.15 μm. The developed scaffolds supported dermal fibroblast adhesion, matrix deposition, and proliferation in vitro. In vivo treatment of 6 mm full-thickness excisional wounds with gelatin/galectin-3 scaffolds did not influence wound closure, re-epithelialization, or macrophage phenotypes, but increased collagen synthesis. In comparison, topical delivery of galectin-3 [6.7 µg/mL] significantly increased arginase-I cell density at day 7 versus untreated and gelatin/galectin-3 scaffolds (p < 0.05). A preliminary assessment of increasing the concentration of topical galectin-3 demonstrated that at day 7, galectin-3 [12.5 µg/mL] significantly increased both epithelial migration and collagen content in a concentration-dependent manner. In conclusion, local delivery of galectin 3 shows potential efficacy in modulating skin healing in a concentration-dependent manner.

Enhanced wound healing effects of nanoscale lipid-diclofenac conjugates

Cold burn wounds have protracted and destructive effects on the body, like contracture, hypertrophic scars, and necrosis. Around 6.5 million people in the US are affected by chronic wounds every year. Different approaches have been utilized to cure this ailment, including cell-based therapy, drug based therapy, and temporary wound dressings, but no single treatment has been effective. Therefore, researchers are constantly searching for alternative therapeutic options. The present study evaluated the effects of nanoscale lipid-diclofenac conjugate (NLDCs) on cold-induced burn wounds. After NLDCs preparation and characterization, the therapeutic potential of them were evaluated. NLDCs exhibited better cell migration (in vitro), wound regeneration which in turn showed enhanced wound healing potential compared to diclofenac (positive control). Cell migration and wound closure in vitro was monitored by scratch assay. In vivo, a cold burn wound model was developed by direct exposure of the dorsal rat skin to liquid nitrogen. NLDCs were subcutaneously injected after 15 min of burn wound induction. The gross macroscopic examination of wound tissues was performed at days 1, 4, 8, and 16. Wound regeneration was observed in control (untreated) and treated groups (diclofenac and NLDCs). The wound regeneration was subsequently assessed by histological, gene expression, and immunohistochemical analyses at the early (day 8) and late (day 16) phases of wound healing. Scratch assay exhibited enhanced cell migration towards scratch area in the treated groups compared to the control. Macroscopic examination revealed early scab formations at day 8 in treated groups, while complete regeneration was only observed in the NLDCs group at day 16. Histological findings showed enhanced regeneration of skin layers along with hair follicles in the NLDCs treated group, while increased neovascularization was noted in both the treated groups. Gene expression profile of wound healing mediators showed downregulation of inflammatory (IL-1β, IL-6, and TNF-α) and Pain (COX-2, YKL-40, and Substance-7) markers and upregulation of angiogenic and remodeling (VEGF, TGFβ, FGF, PDGF, MMP-9, and EGF) markers at respective time points. In conclusion, NLDCs are potential anti-inflammatory, pain relieving, and wound healing agents. Prospects; We are optimistic that the NLDCs development and their scale-up production may pave the way towards clinical translation of nanomedicine in the management of pain, inflammation, and wound complications.

New perspectives on the role of platelet factors in enhancing wound regeneration

Aim. To analyze the use of biological factors in the stimulation of the wound healing process. In the course of the study, we analysed relevant domestic and foreign literature sources on the given topic.Methods. The literature was reviewed using the key query ‘the role of biological factors in wound healing stimulation’ through the eLIBRARY and PubMed databases.Results. Currently, the range of therapeutic approaches is broad and diverse, incorporating both traditional and experimental methods such as advanced dressings, tissue matrices, growth factors (GFs), cell therapy, and nanotechnology. The wound healing process is regulated by a complex interplay of intercellular, intracellular, and extracellular signalling mechanisms across various phases of healing.Conclusion. The application of platelet-based therapies in different medical fields has shown promising outcomes in certain conditions, such as acute and chronic injuries of bone and cartilage. However, platelet-based preparations have yet to gain widespread clinical use. Several studies have demonstrated the involvement of platelets and related products, such as platelet microparticles (PMPs) and exosomes, in multiple phases of wound healing. The presence of a substantial number of biologically active molecules within platelet granules—exhibiting anti-inflammatory, angiogenic, proliferative, and other properties—renders platelets particularly attractive for use in regenerative medicine, including the stimulation of wound healin

Radial Egg White Hydrogel Releasing Extracellular Vesicles for Cell Fate Guidance and Accelerated Diabetic Skin Regeneration.

Topology and bioactive molecules are crucial for stimulating cellular and tissue functions. To regulate the chronic wound microenvironment, mono-assembly technology is employed to fabricate a radial egg white hydrogel loaded with lyophilized adipose tissue-extracellular vesicles (radial EWH@L-EVs). The radial architecture not only significantly modified the gene expression of functional cells, but also achieved directional and controlled release kinetics of L-EVs. Through the synergy of topographical and inherent bioactive cues, radial EWH@L-EVs effectively reduced intracellular oxidative stressand promoted the polarization of macrophages toward an anti-inflammatory phenotype during the inflammatory phase. Afterward, radial EWH@L-EVs facilitated the centripetal migration and proliferation of fibroblasts and endothelial cells as the wound transitioned to the proliferative phase. During the latter remodeling phase, radial EWH@L-EVs accelerated the regeneration of granulation tissue, angiogenesis, and collagen deposition, thereby promoting the reorganization chronic wound. Compared with the gold standard collagen scaffold, radial EWH@L-EVs actively accommodated the microenvironment via various functions throughout all stages of diabetic wound healing. This can be attributed to the orientation of topological structures and bioactive molecules, which should be considered of utmost importance in tissue engineering.

Impact of nutrition on wound healing

Whether from an unintentional damage or surgical intervention, wounds require the cooperation of a complex network of blood cells, tissue types, cytokines, and growth hormones to heal. Increased cellular activity as a result leads to a higher metabolic need for nutrients. Inadequate nutrition can delay the healing process, and a number of nutrients needed for wound repair can speed up the healing process. Inflammatory, proliferative, remodelling, and wound closure are the four stages of wound healing. The wound must be cleaned and clot during the inflammatory period. Through tissue growth, the proliferative phase creates the wound bed. Collagen becomes more robust during the remodelling process. Nutritional integrity is essential at all times. Calcium, zinc, vitamins K, A, and E, and proteins are necessary during inflammation. Amino acids, B vitamins, fats, zinc, and iron all have a role in proliferation. However, this review highlights regarding possible roles for nutrition in wound healing.

In Vitro Wound-Healing Potential of Phenolic and Polysaccharide Extracts of Aloe vera Gel.

The present study aimed to conduct a comparative investigation of the biological properties of phenolic and polysaccharide extracts obtained using an ultrasound-assisted technique from Aloe vera gel and their effects on each stage of the wound healing process in in vitro experimental models. HPLC analysis showed that the phenolic extract contained aloin, ferulic, and caffeic acid, as well as quercetin dihydrate, as major compounds. Capillary zone electrophoresis indicated the prevalence of mannose and glucose in the polysaccharide extract. Cell culture testing revealed the anti-inflammatory properties of the phenolic extract at a concentration of 0.25 mg/mL through significant inhibition of pro-inflammatory cytokines-up to 28% TNF-α and 11% IL-8 secretion-in inflamed THP-1-derived macrophages, while a pro-inflammatory effect was observed at 0.5 mg/mL. The phenolic extract induced 18% stimulation of L929 fibroblast proliferation at a concentration of 0.5 mg/mL, enhanced the cell migration rate by 20%, and increased collagen type I synthesis by 18%. Moreover, the phenolic extract exhibited superior antioxidant properties by scavenging free DPPH (IC50 of 2.50 mg/mL) and ABTS (16.47 mM TE/g) radicals, and 46% inhibition of intracellular reactive oxygen species (ROS) production was achieved. The polysaccharide extract demonstrated a greater increase in collagen synthesis up to 25%, as well as antibacterial activity against Staphylococcus aureus with a bacteriostatic effect at 25 mg/mL and a bactericidal one at 50 mg/mL. All these findings indicate that the phenolic extract might be more beneficial in formulations intended for the initial phases of wound healing, such as inflammation and proliferation, while the polysaccharide extract could be more suitable for use during the remodeling stage. Moreover, they might be combined with other biomaterials, acting as efficient dressings with anti-inflammatory, antioxidant, and antibacterial properties for rapid recovery of chronic wounds.

Depositional Environment and Ecological Response of Bioconstructions: A Case Study of Southern China (Guizhou Province) in Moscovian-Gzhelian.

From the late Carboniferous to the early Permian, multiple pulses of glaciation and deglaciation have been caused by the LPIA. The Pennsylvanian period experienced phases of recovery, proliferation, and decline, ultimately forming a reef system distinctly different from that of the Mississippian period. During the late Bashkirian to Moscovian, the metazoan reef experienced a limited resurgence, with reef predominantly formed by chaetetid developing in the United States, northern China, and Japan. During the Kasimovian to Gzhelian, the phylloid algal reef dominated the global reef systems. In the late Pennsylvanian, bioconstruction cases and paleoenvironmental proxies in southern Guizhou Province were studied to investigate the composition, recovery, and evolutionary processes of the bioconstructions as well as their response to environmental variations during this period. Several bioconstructions have been reported in the Lumazhai section of Houchang Town, Guizhou Province, southern China, from the Moscovian to the Gzhelian. The upper Carboniferous strata are well-preserved and continuously exposed. The continuous strata, abundant fossils, and diverse bioconstructions provide excellent research materials for exploring the mutual constraints between organisms and their environment. This study identified ten microfacies, whose vertical evolution indicated significant changes in the depositional environment related to relative sea-level fluctuations. Skeletal grains are widely present in these facies. Among them, foraminifera, algae, bryozoans, crinoids, and Tubiphytes are the most common and exhibit distinct distribution characteristics in various environments. Quantitative statistics, CCA and theoretical ecospace have been utilized to examine and interpret environmental impact factors. Quantitative analysis of their relative abundance and distribution patterns provides insights into the complex interactions between organisms and environmental factors. The relative abundances of different organisms and factors controlling their bioconstructions are influenced by relative sea-level changes. CCA analysis reveal that hydrodynamic conditions are the primary influencing factor. Variation trends in average tiering and motility reveal the characteristics of biological communities during environmental changes in phylloid algae and microbial bioconstructions. These bioconstructions are not directly correlated with changes in environmental factors, and the biological communities in phylloid algae mounds and biostromes exhibit similar organism compositions and ecological niches across different environments.

Blood-responsive mussel-inspired hydrogels for hemostasis, antibacterial action, and wound healing

Rapid hemostasis, potent antimicrobial activity, and efficient wound management are critical factors in enhancing the survival of trauma patients. Chitosan, as a green and sustainable biomaterial with low cost, degradability and biocompatibility, is widely used in the biomedical field. However, chitosan dissolves in an acidic environment, which is not conducive to wound healing. In this study, chitosan was chemically modified to address this limitation. A mussel-inspired hydrogel composed of caffeic acid-grafted chitosan, gallic acid-grafted chitosan, and oxidized microcrystalline cellulose (CHI-C/CSG/OMCC) was designed. This hydrogel exhibits blood-responsive gelation behavior and offers a synergistic combination of tissue adhesion, antimicrobial properties, and tissue repair capabilities. The carboxyl, hydroxyl, phenolic hydroxyl and aldehyde groups within the hydrogel system endowed the hydrogel with excellent adhesion properties (53.1 kPa adhesion strength to porcine skin-adherent tissues), biocompatibility, and excellent antimicrobial properties. Surprisingly, this hydrogel not only achieved rapid and effective hemostasis, but also effectively promoted wound healing in a mouse skin injury model. In addition, its remarkable efficacy in stopping bleeding within approximately 2 min without rebleeding was demonstrated in a porcine model of acute gastrointestinal hemorrhage in the esophagus, stomach, and intestines. This blood-responsive ternary hydrogel offers a promising alternative to wound management materials due to its excellent overall performance and superior efficacy in all phases of wound healing.

CD26 Is Differentially Expressed throughout the Life Cycle of Infantile Hemangiomas and Characterizes the Proliferative Phase.

Infantile hemangiomas (IHs) are benign vascular neoplasms of childhood (prevalence 5-10%) due to the abnormal proliferation of endothelial cells. IHs are characterized by a peculiar natural life cycle enclosing three phases: proliferative (≤12 months), involuting (≥13 months), and involuted (up to 4-7 years). The mechanisms underlying this neoplastic disease still remain uncovered. Twenty-seven IH tissue specimens (15 proliferative and 12 involuting) were subjected to hematoxylin and eosin staining and a panel of diagnostic markers by immunohistochemistry. WT1, nestin, CD133, and CD26 were also analyzed. Moreover, CD31pos/CD26pos proliferative hemangioma-derived endothelial cells (Hem-ECs) were freshly isolated, exposed to vildagliptin (a DPP-IV/CD26 inhibitor), and tested for cell survival and proliferation by MTT assay, FACS analysis, and Western blot assay. All IHs displayed positive CD31, GLUT1, WT1, and nestin immunostaining but were negative for D2-40. Increased endothelial cell proliferation in IH samples was documented by ki67 labeling. All endothelia of proliferative IHs were positive for CD26 (100%), while only 10 expressed CD133 (66.6%). Surprisingly, seven involuting IH samples (58.3%) exhibited coexisting proliferative and involuting aspects in the same hemangiomatous lesion. Importantly, proliferative areas were characterized by CD26 immunolabeling, at variance from involuting sites that were always CD26 negative. Finally, in vitro DPP-IV pharmacological inhibition by vildagliptin significantly reduced Hem-ECs proliferation through the modulation of ki67 and induced cell cycle arrest associated with the upregulation of p21 protein expression. Taken together, our findings suggest that CD26 might represent a reliable biomarker to detect proliferative sites and unveil non-regressive IHs after a 12-month life cycle.