1.Role of caffeine and ethanol in modulating expression of Receptor Activator of Nuclear Factor κβ (RANK) and Osteoprotegerin (OPG) during orthodontic tooth movement: An in vivo study.
Ardiansyah S. PAWINRU ; Eka ERWANSYAH ; Eddy Heriyanto HABAR ; Abul FAUZI ; AMINULLAH ; Gita GAYATRI ; Yustisia PUSPITASARI ; Ita Purnama ALWI ; Andi Husnul HASANAH
Acta Medica Philippina 2026;60(8):115-122
BACKGROUND AND OBJECTIVES
Orthodontic tooth movement is driven by bone remodeling influenced by systemic factors, including caffeine and ethanol. This study aimed to investigate the effects of caffeine and ethanol on the expression of Receptor Activator of Nuclear Factor κβ (RANK) and Osteoprotegerin (OPG), key bone remodeling biomarkers, during orthodontic tooth movement.
METHODSA laboratory experimental study was conducted on 30 male Wistar rats divided into three groups: K1 (orthodontic force only), K2 (force + caffeine), and K3 (force + ethanol). Orthodontic force was applied using Ni-Ti coil springs. Caffeine and ethanol were administered orally daily. On days 7 and 14, maxillary tissues were collected and analyzed via immunohistochemistry for RANK and OPG expression. Data were analyzed using One-Way ANOVA and Independent Sample T-tests with significance at pRESULTS
Caffeine and ethanol administration increased RANK and OPG expression compared to controls; however, only the ethanol group showed a significant increase in RANK expression on day 14 (p = 0.044). OPG expression was significantly higher in treatment groups at both time points (pCONCLUSION
Caffeine and ethanol modulate bone remodeling marker expression during orthodontic force application, with ethanol significantly increasing RANK expression at later stages. Further studies are needed to clarify the clinical implications for orthodontic treatment.
Animals ; Tooth Movement Techniques ; Tooth Movement ; Osteoprotegerin ; Role ; Movement ; Ethanol ; Bone Remodeling ; Caffeine ; Immunohistochemistry
2.The role of crosslinked collagen-hydroxyapatite on the properties of tissue graft material.
Fitria Rahmitasari ; Widyasri Prananingrum ; Sularsih ; Moh Basroni Rizal ; Puguh Bayu Prabowo
Acta Medica Philippina 2026;60(6):99-106
OBJECTIVE
This review article aims to determine the properties, uses, toxicity, and other side effects of crosslinking agents in tissue scaffolds when applied in vitro and in vivo.
METHODSA literature search was performed using the PubMed-NCBI (MEDLINE) database (https://pubmed.ncbi.nlm. nih.gov/) with keywords: crosslinking reagent, collagen, hydroxyapatite, and bone regeneration. GRADE criteria were used to assess the quality of evidence.
RESULTSA total of six articles were included in the study. Improved mechanical properties of collagen-hydroxyapatite scaffolds with high porosity can be achieved by employing crosslinking methods, including physical dehydrothermal (DHT) treatment, chemical treatment with glutaraldehyde (GA), Microbial Transglutaminase (mTGase), 1‐ethyl‐3‐(3‐ dimethylaminopropyl) carbodiimide (EDAC), or a combination of both DHT and EDAC. Furthermore, the crosslinking of EDAC and DHT can lead to forming ester bonds between activated carboxyl groups and hydroxyl groups.
CONCLUSIONThe combination of DHT and EDAC crosslinking can increase mechanical strength, make the pore size appropriate, make the scaffold more stable, and support cell adhesion so that new cells can grow, and the process of osteogenesis can run more optimally.
Cross-linking Reagents ; Collagen ; Durapatite ; Hydroxyapatite ; Bone Regeneration
3.Role of caffeine and ethanol in modulating expression of Receptor Activator of Nuclear Factor κβ (RANK) and Osteoprotegerin (OPG) during orthodontic tooth movement: An in vivo study.
Ardiansyah S. PAWINRU ; Eka ERWANSYAH ; Eddy Heriyanto HABAR ; Abul FAUZI ; AMINULLAH ; Gita GAYATRI ; Yustisia PUSPITASARI ; Ita Purnama ALWI ; Andi Husnul HASANAH
Acta Medica Philippina 2026;60(8):115-122
BACKGROUND AND OBJECTIVES
Orthodontic tooth movement is driven by bone remodeling influenced by systemic factors, including caffeine and ethanol. This study aimed to investigate the effects of caffeine and ethanol on the expression of Receptor Activator of Nuclear Factor κβ (RANK) and Osteoprotegerin (OPG), key bone remodeling biomarkers, during orthodontic tooth movement.
METHODSA laboratory experimental study was conducted on 30 male Wistar rats divided into three groups: K1 (orthodontic force only), K2 (force + caffeine), and K3 (force + ethanol). Orthodontic force was applied using Ni-Ti coil springs. Caffeine and ethanol were administered orally daily. On days 7 and 14, maxillary tissues were collected and analyzed via immunohistochemistry for RANK and OPG expression. Data were analyzed using One-Way ANOVA and Independent Sample T-tests with significance at pRESULTS
Caffeine and ethanol administration increased RANK and OPG expression compared to controls; however, only the ethanol group showed a significant increase in RANK expression on day 14 (p = 0.044). OPG expression was significantly higher in treatment groups at both time points (pCONCLUSION
Caffeine and ethanol modulate bone remodeling marker expression during orthodontic force application, with ethanol significantly increasing RANK expression at later stages. Further studies are needed to clarify the clinical implications for orthodontic treatment.
Animals ; Tooth Movement Techniques ; Tooth Movement ; Osteoprotegerin ; Role ; Movement ; Ethanol ; Bone Remodeling ; Caffeine ; Immunohistochemistry
4.Comparison of the surgical outcomes of minimal incision and elliptical excision in treating epidermal inclusion cysts: A single-center, randomized controlled trial
John Michael A. Ramos ; Tetsuya Jumi B. Makino ; Charlene Marie U. Ang-tiu ; Maria Franchesca Quino-calayag
Journal of the Philippine Medical Association 2025;103(2):64-78
INTRODUCTION
Epidermal inclusion cysts require surgical intervention to prevent recurrence and symptoms. Elliptical excision is definitive but results in longer scar, while minimal incision techniques offer better cosmetic outcomes despite higher recurrence rates probably due to incomplete excision. To date, there are currently no local studies published.
METHODOLOGYA randomized controlled trial was conducted from October 2023 to May 2024 at a dermatology center in the Philippines. Patients were randomly assigned to minimal incision or elliptical excision techniques. Key metrics included operation time, scar length, post-operative complications, Hollander wound evaluation score (HWES), and histopathological completeness of excision.
RESULTSMedian operation duration was 31.86 minutes, with no significant difference between techniques (p = 0.5795). Post-operative scars were longer in the excision group (mean: 2.38 ± 0.66 cm) versus the minimal incision group (p < 0.001). Completeness of excision was higher in the excision group (83%) compared to the minimal incision group (27%) (p = 0.0123). Follow-up scar length was shorter in the minimal incision group (mean: 0.44 ± 0.21 cm) versus the excision group (mean: 2.1 ± 0.63 cm) (p < 0.001). HWES scores showed no significant difference in wound healing and aesthetic satisfaction.
CONCLUSIONMinimal incision technique results in shorter scars but lower completeness of excision compared to elliptical excision. Both techniques have similar long-term outcomes in wound healing and aesthetic satisfaction, with no recurrences or complications beyond two weeks. The choice should balance scar length and completeness of cyst removal, considering patient-specific factors.
Human ; Cicatrix ; Cysts ; Cosmetics
5.Core targets and immune regulatory mechanisms of Huoluo Xiaoling Pellet for promoting zebrafish fin regeneration.
Yan HUANG ; Xi CHEN ; Mengchen QIN ; Lei GAO
Journal of Southern Medical University 2025;45(3):494-505
OBJECTIVES:
To investigate the core targets and immunomodulatory mechanisms of Huoluo Xiaoling Pellet (HLXLP) for promoting tissue repair.
METHODS:
Network pharmacology and protein-protein interaction network were used to screen active components in HLXLP, the disease-related targets and the core targets, followed by GO and KEGG enrichment analyses and molecular docking to predict the pharmacological mechanisms. The toxicity of HLXLP was evaluated in zebrafish, and in a tissue regeneration model established in 3 dpf zebrafish larvae by amputating 95% of the tail fin, the effects of a formulated zebrafish embryo culture medium and 10, 20, and 40 μg/mL of aqueous extract of HLXLP on tissue regeneration was evaluated; RT-qPCR was performed to detect mRNA expressions of tissue regeneration marker genes and the core target genes. Transgenic zebrafish with fluorescently labeled macrophages and neutrophils were used to observe immune cell migration during tissue regeneration, and macrophage polarization at different stages was assessed with RT-qPCR.
RESULTS:
We identified a total of 149 intersected targets between HLXLP active components and tissue repair and 5 core targets (AKT1, IL-6, TNF-α, EGFR and STAT3). GO and KEGG analyses suggested that the effects of HLXLP were mediated primarily through the JAK-STAT pathway, adhesion junctions and positive regulation of cell migration. HLXLP was minimally toxic below 40 μg/mL and lethal at 320 μg/mL in zebrafish, and caused renal and pericardial edema and vascular defects above 80 μg/mL. In zebrafish with tail fin amputation, HLXLP significantly promoted tissue regeneration, reduced IL-6 and TNF-α and enhanced AKT1, EGFR and STAT3 mRNA expressions, modulated neutrophil and macrophage recruitment to the injury sites, and regulated M1/M2 macrophage polarization during tissue regeneration.
CONCLUSIONS
HLXLP promotes zebrafish tail fin regeneration through multiple active components, targets and pathways for immunomodulation of immune cell migration and macrophage polarization to suppress inflammation and accelerate healing.
Animals
;
Zebrafish/physiology*
;
Animal Fins/drug effects*
;
Drugs, Chinese Herbal/pharmacology*
;
Regeneration/drug effects*
;
Network Pharmacology
;
Signal Transduction
;
Macrophages
6.Polydopamine-modified phycocyanin nanoparticles with photothermal antimicrobial activity promote skin wound healing in mice.
Chen ZHANG ; Zhi XU ; Xiang LI ; Pengyixiang HE ; Kailin QU ; Qi NING ; Yile JIN ; Surui YANG ; Xu WU
Journal of Southern Medical University 2025;45(9):1959-1966
OBJECTIVES:
To evaluate the photothermal and antibacterial activities of polydopamine-modified phycocyanin nanoparticles (PDA@PC NPs) and their capacity for promoting wound healing.
METHODS:
PDA@PC NPs were synthesized from phycocyanin (C-PC) and dopamine hydrochloride using a one-pot method. The photothermal activity of the nanoparticles was assessed in vitro by 808 nm laser irradiation, their biocompatibility was evaluated using CCK-8 assay, and their photothermal antibacterial activity by plate colony counting. In adult male BALB/c mice, two symmetrical full-thickness skin wounds (1.0 cm ×1.0 cm) were created on both sides of the spine, and 200 μL of Staphylococcus aureus suspension was inoculated into the wounds. The mice were divided into control group, PDA@PC NPs group, and PDA@PC NPs with laser irradiation group, and wound healing rates and histomorphological changes in the wound tissues were evaluated on days 0, 7 and 14 after modeling.
RESULTS:
The synthesized PDA@PC NPs exhibited no obvious cytotoxicity up to a concentration of 500 μg/mL and showed strong photothermal and antibacterial activities in response to 808 nm laser irradiation. In the mouse models, the size of the infected skin wounds showed substantial reduction at 7 and 14 days in PDA@PC NPs group and PDA@PC NPs with laser irradiation group, and the mean wound healing rate was faster in the latter group. HE staining and Masson's trichrome staining revealed extensive granulation tissue formation and collagen deposition on the wound surfaces in both of the treatment groups, and these changes were more obvious in the PDA@PC NPs with laser irradiation group.
CONCLUSIONS
PDA@PC NPs possess excellent photothermal and antibacterial activities and can effectively promote wound healing in mice.
Animals
;
Indoles/chemistry*
;
Wound Healing/drug effects*
;
Mice
;
Mice, Inbred BALB C
;
Male
;
Nanoparticles
;
Polymers/chemistry*
;
Phycocyanin/chemistry*
;
Skin/injuries*
;
Staphylococcus aureus/drug effects*
;
Anti-Bacterial Agents/pharmacology*
7.Chitosan hydrogel loaded with human umbilical cord mesenchymal stem cell-derived exosomes promotes healing of chronic diabetic wounds in rats.
Xiaohui QIU ; Meng WANG ; Jiangjie TANG ; Jianda ZHOU ; Chen JIN
Journal of Southern Medical University 2025;45(10):2082-2091
OBJECTIVES:
To investigate the mechanism by which chitosan (CS) hydrogel loaded with human umbilical cord mesenchymal stem cell (HUVECs)-derived exosomes (hUCMSC-exos) (Exos@CS-Gel) improves diabetic wound healing.
METHODS:
hUCMSC-exos were extracted and Exos@CS-Gel was prepared. The effect of Exos@CS-Gel on proliferation and migration of HUVECs were evaluated using scratch wound assay and CCK-8 assay. Diabetic rat models with full-thickness skin wounds established by streptozotocin induction were randomized divided into 4 groups for treatment with Exos@CS-Gel (100 µg hUCMSC-exos dissolved in 100 µL 24% CS hydrogel), hUCMSC-exos (100 µg hUCMSC-exos dissolved in 100 µL PBS), CS hydrogel (100 µL 24% CS hydrogel), or PBS (control group). Wound healing and the therapeutic mechanisms were assessed using immunohistochemistry, HE staining, immunofluorescence, and qRT-PCR.
RESULTS:
In cultured HUVECs, Exos@CS-Gel treatment significantly promoted cell proliferation and migration. In the rat models of chronic diabetic wounds, the wound healing rate in Exos@CS-Gel group reached 92.7% on day 14, significantly higher than those in hUCMSC-exos group (9.12%), CS hydrogel group (16.28%), and control group (25.98%). Microvessel density and the expression levels of vascular endothelial growth factor and transforming growth factor β-1 were significantly increased in the Exos@CS-Gel group.
CONCLUSIONS
Exos@CS-Gel promotes survival capacity of hUCMSC-exos in vitro and accelerates diabetic wound healing in rats by promoting angiogenesis and cell proliferation.
Animals
;
Wound Healing
;
Humans
;
Chitosan
;
Exosomes
;
Mesenchymal Stem Cells/cytology*
;
Diabetes Mellitus, Experimental
;
Rats
;
Umbilical Cord/cytology*
;
Hydrogels
;
Human Umbilical Vein Endothelial Cells
;
Cell Proliferation
;
Rats, Sprague-Dawley
;
Male
8.YAP Signaling in Glia: Pivotal Roles in Neurological Development, Regeneration and Diseases.
Lin LIN ; Yinfeng YUAN ; Zhihui HUANG ; Yongjie WANG
Neuroscience Bulletin 2025;41(3):501-519
Yes-associated protein (YAP), the key transcriptional co-factor and downstream effector of the Hippo pathway, has emerged as one of the primary regulators of neural as well as glial cells. It has been detected in various glial cell types, including Schwann cells and olfactory ensheathing cells in the peripheral nervous system, as well as radial glial cells, ependymal cells, Bergmann glia, retinal Müller cells, astrocytes, oligodendrocytes, and microglia in the central nervous system. With the development of neuroscience, understanding the functions of YAP in the physiological or pathological processes of glia is advancing. In this review, we aim to summarize the roles and underlying mechanisms of YAP in glia and glia-related neurological diseases in an integrated perspective.
Humans
;
Animals
;
Neuroglia/metabolism*
;
Signal Transduction/physiology*
;
YAP-Signaling Proteins
;
Nerve Regeneration/physiology*
;
Nervous System Diseases/metabolism*
;
Adaptor Proteins, Signal Transducing/metabolism*
9.Reprogramming miR-146b-snphb Signaling Activates Axonal Mitochondrial Transport in the Zebrafish M-cell and Facilitates Axon Regeneration After Injury.
Xin-Liang WANG ; Zong-Yi WANG ; Xing-Han CHEN ; Yuan CAI ; Bing HU
Neuroscience Bulletin 2025;41(4):633-648
Acute mitochondrial damage and the energy crisis following axonal injury highlight mitochondrial transport as an important target for axonal regeneration. Syntaphilin (Snph), known for its potent mitochondrial anchoring action, has emerged as a significant inhibitor of both mitochondrial transport and axonal regeneration. Therefore, investigating the molecular mechanisms that influence the expression levels of the snph gene can provide a viable strategy to regulate mitochondrial trafficking and enhance axonal regeneration. Here, we reveal the inhibitory effect of microRNA-146b (miR-146b) on the expression of the homologous zebrafish gene syntaphilin b (snphb). Through CRISPR/Cas9 and single-cell electroporation, we elucidated the positive regulatory effect of the miR-146b-snphb axis on Mauthner cell (M-cell) axon regeneration at the global and single-cell levels. Through escape response tests, we show that miR-146b-snphb signaling positively regulates functional recovery after M-cell axon injury. In addition, continuous dynamic imaging in vivo showed that reprogramming miR-146b significantly promotes axonal mitochondrial trafficking in the pre-injury and early stages of regeneration. Our study reveals an intrinsic axonal regeneration regulatory axis that promotes axonal regeneration by reprogramming mitochondrial transport and anchoring. This regulation involves noncoding RNA, and mitochondria-associated genes may provide a potential opportunity for the repair of central nervous system injury.
Animals
;
Zebrafish
;
MicroRNAs/genetics*
;
Nerve Regeneration/physiology*
;
Mitochondria/metabolism*
;
Zebrafish Proteins/genetics*
;
Axons/metabolism*
;
Signal Transduction/physiology*
;
Axonal Transport/physiology*
;
Nerve Tissue Proteins/genetics*
10.The Dance Between Schwann Cells and Macrophages During the Repair of Peripheral Nerve Injury.
Wei LI ; Guixian LIU ; Jie LIANG ; Xiao WANG ; Meiying SONG ; Xiaoli LIU ; Luoyang WANG ; Zijie YANG ; Bei ZHANG
Neuroscience Bulletin 2025;41(8):1448-1462
Schwann cells and macrophages are the main immune cells involved in peripheral nerve injury. After injury, Schwann cells produce an inflammatory response and secrete various chemokines, inflammatory factors, and some other cytokines to promote the recruitment and M2 polarization of blood-derived macrophages, enhancing their phagocytotic ability, and thus play an important role in promoting nerve regeneration. Macrophages have also been found to promote vascular regeneration after injury, promote the migration and proliferation of Schwann cells along blood vessels, and facilitate myelination and axon regeneration. Therefore, there is a close interaction between Schwann cells and macrophages during peripheral nerve regeneration, but this has not been systematically summarized. In this review, the mechanisms of action of Schwann cells and macrophages in each other's migration and phenotypic transformation are reviewed from the perspective of each other, to provide directions for research on accelerating nerve injury repair.
Schwann Cells/metabolism*
;
Peripheral Nerve Injuries/physiopathology*
;
Animals
;
Macrophages/immunology*
;
Nerve Regeneration/physiology*
;
Humans
;
Cell Movement/physiology*


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