Transplantation of a pectoralis major flap for the repair of myiasis wounds

Myiasis is a disease caused by the invasion and colonization of human tissues and organs by the larvae of flies.This is manifested by the formation of necrotic tissue in the lesion,the colonization of fly eggs and the spread of fly larvae.This disease is mostly found in areas with poor sanitary conditions.Poor wound care,necrotic tissue formation,reduced immunity,and frequent contact with flies are risk factors for this disease.Myiasis can be divided into obligate and facultative parasitism,^([1])while some scholars have classified myiasis according to its location.^([2])In addition,some cases of myiasis are secondary to wound infection or poor surgical maintenance.^([3,4]).

The Oral Health Status of Person with Special Needs in Kumasi

Background: The most prevalent non-communicable disease worldwide is oral health-related disease, with dental caries and periodontal conditions being common. Oral health status significantly impacts overall health and quality of life. Barriers to dental care affect children with special needs. This study evaluates the oral health status and treatment requirements of people with special needs. Methodology: This descriptive cross-sectional study in Kumasi, Ghana examined oral health status among people, 121 children with special needs over two months, in June-July 2022. Dental caries, periodontal changes, malocclusion, and trauma were assessed. The data was analyzed using SPSS 20.0. Results: The oral health status among people with special needs in this study was generally moderate, with a range from very good to very poor. The prevalence of dental caries was 37%, with a mean DMFT score of 2.82. Periodontal health showed unsatisfactory indicators such as mobile teeth, poor gingival health, high plaque scores, and the presence of halitosis. Conclusion: This descriptive study aimed to provide baseline data on the oral health status of special needs students in Kumasi, addressing the lack of knowledge in this area. It highlighted the importance of dental care in maintaining good oral health and overall well-being in individuals with special needs. Coordinated efforts by dental professionals are needed to provide dental health education and preventive interventions for these children.

A novel saliva-based miRNA profile to diagnose and predict oral cancer

Oral cancer (OC) is the most common form of head and neck cancer. Despite the high incidence and unfavourable patient outcomes, currently, there are no biomarkers for the early detection of OC. This study aims to discover, develop, and validate a novel saliva-based microRNA signature for early diagnosis and prediction of OC risk in oral potentially malignant disorders (OPMD).The Cancer Genome Atlas (TCGA) miRNA sequencing data and small RNA sequencing data of saliva samples were used to discover differentially expressed miRNAs. Identified miRNAs were validated in saliva samples of OC (n=50), OPMD (n=52), and controls(n=60) using quantitative real-time PCR. Eight differentially expressed miRNAs (miR-7-5p, miR-10b-5p, miR-182-5p, miR-215-5p,miR-431-5p, miR-486-3p, miR-3614-5p, and miR-4707-3p) were identified in the discovery phase and were validated. The efficiency of our eight-miRNA signature to discriminate OC and controls was:area under curve (AUC):0.954, sensitivity:86%, specificity:90%,positive predictive value (PPV):87.8%and negative predictive value (NPV):88.5%whereas between OC and OPMD was:AUC:0.911,sensitivity:90%, specificity:82.7%, PPV:74.2%and NPV:89.6%. We have developed a risk probability score to predict the presence or risk of OC in OPMD patients. We established a salivary miRNA signature that can aid in diagnosing and predicting OC,revolutionising the management of patients with OPMD. Together, our results shed new light on the management of OC by salivary miRNAs to the clinical utility of using miRNAs derived from saliva samples.

Periodontal treatment and microbiome-targeted therapy in management of periodontitis-related nonalcoholic fatty liver disease with oral and gut dysbiosis

A growing body of evidence from multiple areas proposes that periodontal disease,accompanied by oral inflammation and pathological changes in the microbiome,induces gut dysbiosis and is involved in the pathogenesis of nonalcoholic fatty liver disease(NAFLD).A subgroup of NAFLD patients have a severely progressive form,namely nonalcoholic steatohepatitis(NASH),which is characterized by histological findings that include inflammatory cell infiltration and fibrosis.NASH has a high risk of further progression to cirrhosis and hepatocellular carcinoma.The oral microbiota may serve as an endogenous reservoir for gut microbiota,and transport of oral bacteria through the gastro-intestinal tract can set up a gut microbiome dysbiosis.Gut dysbiosis increases the production of potential hepatotoxins,including lipopolysaccharide,ethanol,and other volatile organic compounds such as acetone,phenol and cyclopentane.Moreover,gut dysbiosis increases intestinal permeability by disrupting tight junctions in the intestinal wall,leading to enhanced translocation of these hepatotoxins and enteric bacteria into the liver through the portal circulation.In particular,many animal studies support that oral administration of Porphyromonas gingivalis,a typical periodontopathic bacterium,induces disturbances in glycolipid metabolism and inflammation in the liver with gut dysbiosis.NAFLD,also known as the hepatic phenotype of metabolic syndrome,is strongly associated with metabolic complications,such as obesity and diabetes.Periodontal disease also has a bidirectional relationship with metabolic syndrome,and both diseases may induce oral and gut microbiome dysbiosis with insulin resistance and systemic chronic inflammation cooperatively.In this review,we will describe the link between periodontal disease and NAFLD with a focus on basic,epidemiological,and clinical studies,and discuss potential mechanisms linking the two diseases and possible therapeutic approaches focused on the microbiome.In conclusion,it is presumed that the pathogenesis of NAFLD involves a complex crosstalk between periodontal disease,gut microbiota,and metabolic syndrome.Thus,the conventional periodontal treatment and novel microbiome-targeted therapies that include probiotics,prebiotics and bacteriocins would hold great promise for preventing the onset and progression of NAFLD and subsequent complications in patients with periodontal disease.

Multidrug dissolvable microneedle patch for the treatment of recurrent oral ulcer

Recurrent oral ulcer is a painful oral mucosal disorder that affects 20%of the world’s population.The lack of a radical cure due to its unknown underlying cause calls for innovative symptomatic treatments.This work reports a hyaluronic acid-based dissolvablemicroneedle patch(ROUMNpatch,short for recurrent oral ulcer microneedle)loaded with dexamethasone acetate,vitamin C and tetracaine hydrochloride for the treatment of recurrent oral ulcers.The ROUMN patch shows enhancement in both the anti-inflammatory effect elicited by dexamethasone and the pro-proliferation effect of vitamin C.In vitro experiments show that ROUMN has a higher efficiency in suppressing lipopolysaccharide(LPS)-induced interleukin-6(IL-6)expression than dexamethasone alone.Cell proliferation and migrationwere also significantly promoted byROUMNcompared to vitamin C alone.The healing-promoting effect of ROUMN was also verified in vivo using an acetic acid-cauterized oral ulcer model in rats.ROUMN as a treatment accelerated the healing process of oral ulcers,shortening the total healing time to 5 days compared with the 7 days required by treatment using watermelon frost,a commonly used over-the-counter(OTC)drug for oral ulcers.The rapid dissolution of the hyaluronic acid-based microneedles and the superior healing-promoting effect of the drug combination could lead to a broad application prospect of the ROUMN patch in the treatment of recurrent oral ulcers.

Hybrid treatment of varied orthodontic appliances for a patient with skeletal class II and temporomandibular joint disorders:A case report and review of literature

BACKGROUND The relation between orthodontic treatment and temporomandibular disorders(TMDs)is under debate;the management of TMD during orthodontic treatment has always been a challenge.If TMD symptoms occur during orthodontic treatment,an immediate pause of orthodontic adjustments is recommended;the treatment can resume when the symptoms are managed and stabilized.CASE SUMMARY This case report presents a patient(26-year-old,female)with angle class I,skeletal class II and TMDs.The treatment was a hybrid of clear aligners,fixed appliances and temporary anchorage devices(TADs).After 3 mo resting and treatment on her TMD,the patient’s TMD symptom alleviated,but her anterior occlusion displayed deep overbite.Therefore,the fixed appliances with TAD were used to correct the anterior deep-bite and level maxillary and mandibular deep curves.After the levelling,the patient showed dual bite with centric relation and maximum intercuspation discrepancy on her occlusion.After careful examination of temporomandibular joints(TMJ)position,the stable bite splint and Invisible Mandibular Advancement appliance were used to reconstruct her occlusion.Eventually,the improved facial appearance and relatively stable occlusion were achieved.The 1-year follow-up records showed there was no obvious change in TMJ morphology,and her occlusion was stable.CONCLUSION TMD screening and monitoring is of great clinical importance in the TMD susceptible patients.Hybrid treatment with clear aligners and fixed appliances and TADs is an effective treatment modality for the complex cases.

Oral administration of Bifidobacterium breve improves anti-angiogenic drugs-derived oral mucosal wound healing impairment via upregulation of interleukin-10

Recent studies have suggested that long-term application of anti-angiogenic drugs may impair oral mucosal wound healing.This study investigated the effect of sunitinib on oral mucosal healing impairment in mice and the therapeutic potential of Bifidobacterium breve(B.breve).A mouse hard palate mucosal defect model was used to investigate the influence of sunitinib and/or zoledronate on wound healing.The volume and density of the bone under the mucosal defect were assessed by micro-computed tomography(micro-CT).Inflammatory factors were detected by protein microarray analysis and enzyme-linked immunosorbent assay(ELISA).The senescence and biological functions were tested in oral mucosal stem cells(OMSCs)treated with sunitinib.Ligated loop experiments were used to investigate the effect of oral B.breve.Neutralizing antibody for interleukin-10(IL-10)was used to prove the critical role of IL-10 in the pro-healing process derived from B.breve.Results showed that sunitinib caused oral mucosal wound healing impairment in mice.In vitro,sunitinib induced cellular senescence in OMSCs and affected biological functions such as proliferation,migration,and differentiation.Oral administration of B.breve reduced oral mucosal inflammation and promoted wound healing via intestinal dendritic cells(DCs)-derived IL-10.IL-10 reversed cellular senescence caused by sunitinib in OMSCs,and IL-10 neutralizing antibody blocked the ameliorative effect of B.breve on oral mucosal wound healing under sunitinib treatment conditions.In conclusion,sunitinib induces cellular senescence in OMSCs and causes oral mucosal wound healing impairment and oral administration of B.breve could improve wound healing impairment via intestinal DCs-derived IL-10.

Combination of Diclofenac Potassium and Propolis in the Therapy of Oral Aphthosis: A Randomized, Clinical, Double-Blind, Placebo-Controlled Study

Background: Oral aphthosis has a negative impact on oral health. This study aimed to assess the effectiveness of gel formulation including diclofenac and propolis in the treatment of oral ulcers. Methods: Participants included 100 normal individuals with aphthous, excluding those having allergies to any ingredient in the diclofenac formulation. Patients were randomly assigned into two groups: one group received treatment with a combination of diclofenac potassium 3% (10 mg/g, 60 g) and propolis 5% gel (Group II), and the other group received a placebo (Group 1). The patient was evaluated using standard digital photographs and chronic oral mucosal questionnaires on days 1, 3, 5, and 7 after healing. Utilizing the Mann-Whitney U test, the two groups were compared. Each group’s changes were examined using Friedman’s test. Results: There was a statistically dramatic change over time in Group II. After one day, the median total score dropped statistically significantly, and from one to three days with effect size (d) 2.485, Group II demonstrated 48% complete healing and 52% partial healing, while Group I demonstrated 4% partial healing and 96% no change. Effect size (V): 0.995. Conclusions: The combination of diclofenac and propolis provided instant relief and an affordable new regimen for treating oral aphthosis.

Single-cell transcriptomic analysis uncovers the origin and intratumoral heterogeneity of parotid pleomorphic adenoma

Pleomorphic adenoma(PA)is the most common benign tumour in the salivary gland and has high morphological complexity.However,the origin and intratumoral heterogeneity of PA are largely unknown.Here,we constructed a comprehensive atlas of PA at single-cell resolution and showed that PA exhibited five tumour subpopulations,three recapitulating the epithelial states of the normal parotid gland,and two PA-specific epithelial cell(PASE)populations unique to tumours.Then,six subgroups of PASE cells were identified,which varied in epithelium,bone,immune,metabolism,stemness and cell cycle signatures.Moreover,we revealed that CD36+myoepithelial cells were the tumour-initiating cells(TICs)in PA,and were dominated by the PI3K-AKT pathway.Targeting the PI3K-AKT pathway significantly inhibited CD36+myoepithelial cell-derived tumour spheres and the growth of PA organoids.Our results provide new insights into the diversity and origin of PA,offering an important clinical implication for targeting the PI3K-AKT signalling pathway in PA treatment.

POLE2 Regulates Apoptosis of Oral Squamous Cell Carcinoma Cells through the PI3K/AKT Signaling Pathway

Objective Oral squamous cell carcinoma(OSCC)is the most common malignant tumor of the head and neck,but its occurrence and progression mechanisms remain unclear.In addition-there is a lack of effective targeting drugs.The second major subunit of DNA polymerase(POLE2)catalyzes the prolongation of new strand replication and modifies exonuclease domain activity.Our previous study found that POLE2 was associated with OSCC progression,but the mechanism remains unclear.Methods The expression of POLE2 in OSCC tissues was detected using immunological assays.Mann-Whitney U analysis was used to investigate the relationship between POLE2 gene expression and tumor classification and prognosis of OSCC.POLE2 expression was inhibited in OSCC cells,and the effects of gene and protein expression were detected using RT-PCR and Western blotting.The POLE2 knockout model was constructed by transfecting a lentiviral vector.Cell proliferation,apoptosis,and migration were detected using various assays including colony formation,MTT,flow cytometry,wound healing assay,Transwell assay,and the Human Apoptosis Antibody Array.The animal model of OSCC was established by subcutaneous injection of transfected HN6 into 4-week-old female nude mice.After 30 days,tumors were removed under anesthesia and tumor weight and dimension were recorded.Tumor cell proliferation was analyzed using Ki67 staining.Results POLE2 gene levels were significantly higher in the OSCC tissues than in the normal tissues.In addition,POLE2 gene levels were statistically correlated with tumor classification and prognosis.Silencing POLE2 inhibited the proliferation of oral cancer cells and promoted apoptosis in vitro.Animal experiments also supported a positive correlation between POLE2 and OSCC tumor formation.We further demonstrated that POLE2 could upregulate the expression of apoptosis-related proteins such as caspase-3,CD40,CD40L,DR6,Fas,IGFBP-6,p21,and SMAC.In addition,POLE2 regulated OSCC development by inhibiting the PI3K/AKT signaling pathway.Conclusion POLE2 is closely related to the progression of OSCC.Thus,POLE2 may be a potential target for OSCC treatment.

Etiology, Prevalence, and Management of Oral and Maxillofacial Soft Tissue Injuries in Children at the Komfo Anokye Teaching Hospital, Kumasi-Ghana

Background: Maxillofacial injury may vary from simple soft tissue lacerations to complex fractures of the orofacial region. Soft tissue injuries, whether isolated or in combination with other injuries, form part of the frequent traumatic craniofacial injuries seen at the emergency department. The force of impact and the injury type is directly related to the severity of the injury sustained. This study aimed to analyze the etiological factors, prevalence, and management of oral and maxillofacial soft tissue injuries at the Komfo Anokye Teaching Hospital. Methods: This was a prospective study that involved children presenting with oral and maxillofacial injuries at the Accident and Emergency Department and the Oral and Maxillofacial Surgery unit of the Komfo Anokye Teaching Hospital in Kumasi between the period of April to October 2020 (6 months). Patient selection was by convenience sampling targeting all children with injuries who met the inclusion criteria. Inclusion criteria were children below the age of 18 years whose parents or caregivers consent to participation. Children with maxillofacial injuries as a result of burns were excluded from the study. Results: During the study period a total of 134 children were reviewed with oral and maxillofacial injuries at KATH. Of these, 107 (78.9%) were recorded cases of orofacial soft tissue injuries. There were 63 (58.9%) males and 44 (41.1%) females and the male-to-female ratio was 1.5:1. The age range of patients studied was 8 months – 17 years, with mean age ± SD being 9.5 ± 5.3 years. Road Traffic Crash (50.5%) was the most common etiology of which Motor cycle crash constituted 24.3% and Pedestrian knockdown was 19.6%. Falls (42.1%) were the next most common etiology. The lips (19.8%) and the forehead (18.5%) were the most frequently injured sites on the face whiles the tongue (3.3%) had the most injuries intraorally. Laceration (45.7%) was the most frequent injury reviewed, followed by abrasions (35.8%). Most of the soft tissue injuries underwent primary closure (56.3%). A complication rate of 21.2% was recorded in this study and hypertrophic scarring (11.3%) was the most observed.

Isolation and Identification Methods for Oral Klebsiella pneumoniae Involved in Onset of Inflammatory Bowel Disease

Purpose: Recently, it was reported that Klebsiella pneumoniae is related to the onset of inflammatory bowel disease including the Crohn disease. It was frequently reported that K. pneumoniae was detected in human oral cavities. Regrettably, it currently remains unclear whether K. pneumoniae is part of the normal oral flora. The aim of this study was to establish the isolation and identification methods for K. pneumoniae from human oral cavities, and investigate its transmission pattern. Methods: A selective medium, OKPSM, for the isolation of K. pneumoniae from oral cavities was developed in this study. Also, PCR primer for the identification and detection at subspecies level of K. pneumoniae was designed. Results: OKPSM and PCR method using the primers designed in this study were useful for the isolation and identification of K. pneumoniae from human oral cavities. K. pneumoniae subsp. pneumoniae was detected at 10.0% in 30 saliva samples. On the other hand, K. pneumoniae subsp. ozaenae and K. pneumoniae subsp. rhinoscleromatis were detected from no sample. Moreover, K. pneumoniae subsp. pneumoniae isolates from same subject at 0 month and after 3 months showed same genotypes on AP-PCR using OPA-07 primer. Conclusion: These results indicated that human oral cavities were not suitable for the habitat of K. pneumoniae.

Oral Health Management of Three Head and Neck Cancer Patients Performed by Dental Hygienists

Introduction: Oral health management is often difficult in patients after surgical tumor resection and/or radiotherapy due to defects, bulky flaps, limitation of tongue movement, and trismus. In addition, patients who have undergone radiotherapy have serious disabilities such as oral mucositis, mucosal weakening, soft tissue fibrosis, salivary gland disorder, and osteoradionecrosis. Dental hygienists must understand the characteristics of patients after surgical tumor resection and/or radiotherapy. In this report, the oral health management of three patients after maxillectomy, mandibulectomy, and radiotherapy was shown. Case Description: Case 1: A 53-year-old male patient visited our clinic after chemotherapy, radiotherapy, and partial maxillectomy for cancer of the right maxillary gingiva. Case 2: A 65-year-old male patient visited our clinic after radiotherapy for a right-sided tongue cancer, partial mandibulectomy of the right tongue to the oropharynx, a right-sided segmental mandibulectomy and a speech aid and a mandibular prosthesis were provided. Case 3: A 36-year-old female visited our clinic for radiotherapy for left-sided tongue cancer. Dental hygienists provided oral health management to the patients. In oral health management, it was suggested that intervention before cancer treatment, oral hygiene instructions tailored to patients’ symptoms, and frequent professional care are important. Conclusion: Oral health management by dental hygienists is extremely important for patients undergoing maxillofacial cancer treatment to maintain their quality of life in the long term.

Awareness and prevalence of stress induced oral ulcers among clinical medical and dental students in university of Benin:a cross-sectional study

Background:Awareness of clinical medical and dental students towards stress induced oral ulcer,to determine the most prevalent stress induced oral ulcers among the study population,and the relationship between perceived stress level and prevalence of stress induced oral ulcer.Methods:A descriptive cross-sectional study,involving clinical Medical and Dental students in College of Medical Sciences,University of Benin.Participants were in their 400,500,and 600 levels respectively with a sample size of 226 calculated using the Cochran formula for sample size determination.Data were collected using self-administered questionnaire.Results:Two hundred and twenty-six respondents were interviewed in this survey.The age of the participants varied from 21-30 years,with mean age of 25.5%.Majority of the respondents(66.4%)were aware of stress induced oral ulcer.The prevalence of stress induced oral ulcer in this study was 12.8% with recurrent aphthous ulcers accounting for a prevalence of 35.5% of all stress induced oral ulcers.Conclusion:Findings from this study shows about 66.4%of clinical Medical and Dental students were aware of stress induced oral ulcer.The prevalence of stress induced oral ulcer in this study was 12.8%and was seen more in males than females,with recurrent aphthous ulcer been the most prevalent stress induced oral ulcer among the study population with a prevalence of about 35.5%.

Pleomorphic adenoma(mixed tumor)of the upper lip:A case report

BACKGROUND Salivary gland tumors are relatively rare.Most minor salivary gland tumors are malignant with benign tumors accounting for 18%of the tumors.Pleomorphic adenoma(PA)is the most common salivary gland tumor.Lip PA is uncommon with 9.8%occurring in the upper lip.We are adding on the knowledge of the rare upper lip PA(benign mixed tumor).CASE SUMMARY We report an upper lip PA(benign mixed tumor)in a 28-year-old man.His complaint was a painless swelling on the upper lip.A painless,non-tender,well-circumscribed,slightly mobile,sessile,nodular,and rubbery(in consistency)tumor measuring 5.0 cm x 2.0 cm was noted on the left side of his upper lip.The overlying skin was not fixed and of normal color.There was no ulceration,and palpation did not elicit pain or bleeding.There was no history of trauma.Blunt dissection was used to completely excise the nodular,whitish,and encapsulated tumor.Microscopy showed a well-circumscribed and partly encapsulated biphasic lesion,with large lobules of myxo-chondroid stroma and intervening cellular nodules of basaloid cells,well-formed tubules containing eosinic secretion,and nests of myoepithelial cells.A diagnosis of PA(benign mixed tumor)was confirmed.CONCLUSION Blunt dissection is indicated to preserve the cosmesis and function of the upper lip.

Spatial transcriptomics reveals that metabolic characteristics define the tumor immunosuppression microenvironment via iCAF transformation in oral squamous cell carcinoma

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. Oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism,and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-βexpression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.

High quality repair of osteochondral defects in rats using the extracellular matrix of antler stem cells

BACKGROUND Cartilage defects are some of the most common causes of arthritis.Cartilage lesions caused by inflammation,trauma or degenerative disease normally result in osteochondral defects.Previous studies have shown that decellularized extracellular matrix(ECM)derived from autologous,allogenic,or xenogeneic mesenchymal stromal cells(MSCs)can effectively restore osteochondral integrity.AIM To determine whether the decellularized ECM of antler reserve mesenchymal cells(RMCs),a xenogeneic material from antler stem cells,is superior to the currently available treatments for osteochondral defects.METHODS We isolated the RMCs from a 60-d-old sika deer antler and cultured them in vitro to 70%confluence;50 mg/mL L-ascorbic acid was then added to the medium to stimulate ECM deposition.Decellularized sheets of adipocyte-derived MSCs(aMSCs)and antlerogenic periosteal cells(another type of antler stem cells)were used as the controls.Three weeks after ascorbic acid stimulation,the ECM sheets were harvested and applied to the osteochondral defects in rat knee joints.RESULTS The defects were successfully repaired by applying the ECM-sheets.The highest quality of repair was achieved in the RMC-ECM group both in vitro(including cell attachment and proliferation),and in vivo(including the simultaneous regeneration of well-vascularized subchondral bone and avascular articular hyaline cartilage integrated with surrounding native tissues).Notably,the antler-stem-cell-derived ECM(xenogeneic)performed better than the aMSC-ECM(allogenic),while the ECM of the active antler stem cells was superior to that of the quiescent antler stem cells.CONCLUSION Decellularized xenogeneic ECM derived from the antler stem cell,particularly the active form(RMC-ECM),can achieve high quality repair/reconstruction of osteochondral defects,suggesting that selection of decellularized ECM for such repair should be focused more on bioactivity rather than kinship.

A DNA tetrahedron-based ferroptosis-suppressing nanoparticle: superior delivery of curcumin and alleviation of diabetic osteoporosis

Diabetic osteoporosis(DOP)is a significant complication that poses continuous threat to the bone health of patients with diabetes;however,currently,there are no effective treatment strategies.In patients with diabetes,the increased levels of ferroptosis affect the osteogenic commitment and differentiation of bone mesenchymal stem cells(BMSCs),leading to significant skeletal changes.To address this issue,we aimed to target ferroptosis and propose a novel therapeutic approach for the treatment of DOP.We synthesized ferroptosis-suppressing nanoparticles,which could deliver curcumin,a natural compound,to the bone marrow using tetrahedral framework nucleic acid(tFNA).This delivery system demonstrated excellent curcumin bioavailability and stability,as well as synergistic properties with tFNA.Both in vitro and in vivo experiments revealed that nanoparticles could enhance mitochondrial function by activating the nuclear factor E2-related factor 2(NRF2)/glutathione peroxidase 4(GPX4)pathway,inhibiting ferroptosis,promoting the osteogenic differentiation of BMSCs in the diabetic microenvironment,reducing trabecular loss,and increasing bone formation.These findings suggest that curcumin-containing DNA tetrahedron-based ferroptosissuppressing nanoparticles have a promising potential for the treatment of DOP and other ferroptosis-related diseases.

Stromal thrombospondin 1 suppresses angiogenesis in oral submucous fibrosis

A decline in mucosal vascularity is a histological hallmark of oral submucous fibrosis (OSF), a premalignant disease that is largely induced by betel quid chewing. However, the lack of available models has challenged studies of angiogenesis in OSF. Here, we found that the expression of thrombospondin 1 (THBS1), an endogenous angiostatic protein, was elevated in the stroma of tissues with OSF. Using a fibroblast-attached organoid (FAO) model, the overexpression of THBS1 in OSF was stably recapitulated in vitro. In the FAO model,treatment with arecoline, a major pathogenic component in areca nuts, enhanced the secretion of transforming growth factor (TGF)-β1 by epithelial cells, which then promoted the expression of THBS1 in fibroblasts. Furthermore, human umbilical vein endothelial cells (HUVECs)were incorporated into the FAO to mimic the vascularized component. Overexpression of THBS1 in fibroblasts drastically suppressed the sprouting ability of endothelial cells in vascularized FAOs (v FAOs). Consistently, treatment with arecoline reduced the expression of CD31in v FAOs, and this effect was attenuated when the endothelial cells were preincubated with neutralizing antibody of CD36, a receptor of THBS1. Finally, in an arecoline-induced rat OSF model, THBS1 inhibition alleviated collagen deposition and the decline in vascularity in vivo. Overall, we exploited an assembled organoid model to study OSF pathogenesis and provide a rationale for targeting THBS1.