The doublecortin (DCX) gene encodes DCX, a microtubule-associated protein that plays a crucial role in brain development. DCX variants can disrupt microtubule binding and stabilization, interfere with intracellular transport, and affect post-translational modifications. A correlation exists between variant types and clinical severity. Animal models and induced pluripotent stem cell (iPSC) models simulating DCX deficiency revealed the dynamic progression of the disease, which has provided a powerful tool for investigating disease mechanisms and screening therapeutic agents. Currently there is no cure for DCX variants, with treatment primarily relying on anti-epileptic drugs and symptom management. Basic research is now offering new avenues for future therapeutic approaches. This article has summarized the potential pathogenic mechanisms and therapeutic strategies for the DCX variants, with an aim to provide insights for clinical treatment.
Humans ; Doublecortin Protein ; Doublecortin Domain Proteins ; Animals ; Neuropeptides/metabolism* ; Microtubule-Associated Proteins/metabolism* ; Mutation

The pathogenesis of Parkinson's disease is closely related to genetic factors. This article has systematically reviewed the research progress of molecular genetic mechanism on Parkinson's disease by focusing on the role of six high-penetrance pathogenic genes (SNCA, LRRK2, PRKN, PINK1, PARK7, and VPS35) and some risk genes (such as GBA1). These genetic variants eventually converge in three core pathogenic biological pathways, including lysosomal-autophagy pathway disorder, mitochondrial quality control disorder and α-synuclein metabolic abnormality. In-depth understanding of these molecular mechanisms is of great significance for the development of targeted therapy and realization of precision medicine for this disease.
Humans ; Parkinson Disease/metabolism* ; alpha-Synuclein/genetics* ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics* ; Genetic Predisposition to Disease ; Protein Kinases/genetics* ; Animals ; Glucosylceramidase/genetics* ; Ubiquitin-Protein Ligases/genetics*

BACKGROUND

Myiasis is a parasitic infestation of humans caused by dipteran flies' larvae, which feed on the host's tissue. It affects various body parts, including the skin, eyes, ears, nose, mouth, and gastrointestinal tract. Cutaneous myiasis is the most common clinical form, while wound myiasis is the main manifestation. Myiasis can be caused by various fly families, including blowflies, flesh flies, and botflies, with different types depending on the site and infestation type. A rare occurrence rarely reported in medical literature, Sarcophaga species infestation within a tracheostomy tube in a patient with laryngeal carcinoma, is presented in this case. Given that the airway is protected and has built-in barriers against external contamination, the presence of flesh flies (Sarcophaga spp.) at a tracheostomy site is extremely uncommon. By showing how weakened respiratory structures, along with particular environmental and patient factors, may make people more susceptible to this uncommon parasitic complication, this report adds to our understanding of the condition. Recognizing such atypical infestations is crucial for clinicians in early diagnosis, prevention, and effective management of similar cases.

CASE PRESENTATION

The study details a rare instance of Sarcophaga species myiasis in a tracheostomy tube in a patient who Had laryngeal carcinoma after radiation therapy. The 71-year-old farmer patient first complained of pruritus, localized warmth, and tightness in his neck. Prior tracheostomy excision and cobalt therapy were part of his medical history. After being treated for pneumonia, the patient experienced severe bleeding at the tracheostomy site, which led to additional testing. Many larvae were seen emerging from necrotic tissues during clinical examination, which raised the possibility of myiasis. Sarcophaga spp., a rare discovery in respiratory structures, were confirmed to be present by species identification. More than 100 larvae were removed during the emergency surgical procedure, which also involved replacing the compromised tracheostomy tube and cutting and draining necrotic areas. Following surgery, there were no more bleeding or reinfestation episodes, and the patient showed signs of stable recovery.

CONCLUSION

The parasitic infestation known as myiasis, which is brought on by dipteran fly larvae, is usually linked to exposed wounds and weakened tissue. Flesh flies, or Sarcophaga species, are drawn to recently opened, exudative wounds, which makes them more likely to infest susceptible people. Although myiasis commonly occurs in cutaneous wounds, ocular, and nasopharyngeal sites, it is extremely uncommon to occur in tracheostomy incisions, especially in tropical areas like the Philippines. The need for increased clinical awareness of this uncommon complication is highlighted by this case, which shows an unusual manifestation of Sarcophaga species myiasis within a tracheostomy tube of a patient who had laryngeal carcinoma following radiation therapy. Prioritizing preventive measures, such as thorough wound hygiene, efficient fly control techniques, and ongoing postoperative monitoring, is necessary due to the grave consequences of tracheostomy-associated myiasis. Parasitic infestations are more likely to occur in patients recuperating from head and neck surgery, especially those who have had extended wound exposure. Patient outcomes can be improved and morbidity can be considerably decreased by teaching family members and caregivers about wound surveillance, early detection, and prompt intervention. To reduce the chance of infestation, preventive measures like appropriate wound dressing, environmental sanitation, and fly management must be strengthened. In order to develop more focused preventive measures, more research is necessary to identify the endemic distribution of rare myiasis-causing species and to characterize them. Clinicians can establish more efficient management procedures by identifying particular environmental factors and patient vulnerabilities that contribute to atypical myiasis cases. The knowledge gathered from this report adds to the body of knowledge on tracheostomy-associated myiasis and is a useful
guide for early detection and treatment of similar cases.

Human ; Animals ; Male ; Female ; Aged: 65-79 Yrs Old ; Research Report ; Patients ; Carcinoma ; Sarcophagidae ; Tracheostomy

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.

METHODS

A 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

OBJECTIVES: Ovarian cancer is a common gynecologic malignancy, with poor prognosis in advanced stages. This study aimed to identify differentially expressed long noncoding RNA (lncRNA) associated with ovarian cancer prognosis and to explore the effects of lncRNA RP11-499E18.1 on the malignant biological behavior of ovarian cancer cells. METHODS: Ovarian cancer-related lncRNA datasets were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed and prognostically relevant tumor-suppressive lncRNAs were screened using lncRNA sequencing combined with clinical data. Reverse transcription PCR (RT-PCR) was used to detect the expression of lncRNA RP11-499E18.1 in ovarian cancer tissues, adjacent normal tissues, the IOSE80 normal ovarian epithelial cell line, and various ovarian cancer cell lines. Fluorescence in situ hybridization (FISH) was performed to determine its subcellular localization. Ovarian cancer cell lines CaOV3 and SKOV3 were divided into 3 groups: a negative control (NC) group, a knockdown (si-RP11-499E18.1) group, and a overexpression (pcDNA-RP11-499E18.1) group. Methyl thiazolyl tetrazolium (MTT) and Transwell assays were used to assess the effects of lncRNA RP11-499E18.1 on cell proliferation and migration. Western blotting was used to evaluate its effect on epithelial-mesenchymal transition (EMT)-related molecules. BALB/c nude mice were injected with CaOV3 cells transfected with pcDNA-RP11-499E18.1 (experimental group) or empty vector (control group), and tumor growth was monitored. Immunohistochemistry was used to assess the expression of Caspase 3 and Ki67 in tumor tissues. RESULTS: LncRNA sequencing identified RP11-499E18.1 as a differentially expressed and associated with prognosis. GEO data analysis showed that low RP11-499E18.1 expression was correlated with shorter overall and progression-free survival (both P<0.05). Its expression was significantly lower in ovarian cancer tissues and cell lines compared to normal controls (P<0.05 or P<0.001), and it was localized in both the nucleus and cytoplasm. In CaOV3 and SKOV3 cells, proliferation rates increased significantly in the si-RP11-499E18.1 group and decreased in the pcDNA-RP11-499E18.1 group (P<0.05 or P<0.001). Cell migration was enhanced in the si-RP11-499E18.1 group and suppressed in the pcDNA-RP11-499E18.1 group. Overexpression increased E-cadherin and decreased vimentin expression, while knockdown had the opposite effect. Tumor volume in the mouse model was significantly smaller in the experimental group (P<0.001), with increased Caspase 3 and decreased Ki67 expression in tumor tissues (both P<0.05). CONCLUSIONS LncRNA RP11-499E18.1 inhibits proliferation, migration, and EMT of ovarian cancer cells, and its low expression is associated with poor prognosis.
Female ; Humans ; RNA, Long Noncoding/physiology* ; Ovarian Neoplasms/pathology* ; Cell Line, Tumor ; Animals ; Mice ; Mice, Nude ; Cell Proliferation ; Prognosis ; Mice, Inbred BALB C ; Gene Expression Regulation, Neoplastic ; Cell Movement ; Epithelial-Mesenchymal Transition

OBJECTIVES: Wild-caught Microtus fortis (M. fortis) at the age of 9-15 months can develop epithelial ovarian cancers similar to human epithelial ovarian cancers under natural conditions during experimental animal breeding, but its pathological types and biological characteristics remain unclear. This study aims to analyze the biological characteristics of spontaneous ovarian cancer in M. fortis, intending to develop M. fortis as an animal model for human epithelial ovarian cancer. METHODS: The female M. fortis (9-15 months old) with spontaneous ovarian cancer were selected as the experimental group, and healthy M. fortis from the same litter were selected as the control group. The ovarian pathological changes of the two groups were observed by dissection. Blood routine and biochemical indicators were measured by biochemical analysis. Hematoxylin and eosin (HE) staining was performed to observe the pathological changes in the ovarian cancer tissue of M. fortis. Immunohistochemical staining was used to detect the protein expression of common ovarian cancer markers, and real-time RT-PCR was used to analyze the transcription levels of ovarian cancer-related genes. RESULTS: Spontaneous ovarian cancer in M. fortis mainly affects both ovaries, with tumors appearing solid or cystic. HE staining and histopathological analysis confirmed that the ovarian tumors originated from ovarian surface epithelium. Compared to the control group, the experimental group showed significantly decreased hemoglobin (P<0.01), hematocrit (P<0.05), albumin (P<0.05), and blood glucose levels (P<0.01), while lymphocyte percentage (P<0.05), monocyte percentage (P<0.05), cholesterol (P<0.01), and progesterone (P<0.01) levels were significantly increased. Expression of ovarian cancer-related genes, including ID3, CDC42, RHOA, RB1CC1, NF1, PIN1, MIB1, PDS5A, MCM7, and MLH1, was significantly downregulated (all P<0.05), while PAX8 gene expression was significantly upregulated (P<0.05). Immunohistochemical results showed that Wilms' tumor gene 1 (WT1) protein was mainly distributed throughout the cell, with significantly higher expression in ovarian cancer M. fortis. Tumor protein 53 (TP53) was expressed in both healthy and ovarian cancer M. fortis and was distributed throughout the cell. Hepatocyte nuclear factor 1 beta (HNF1B) and progesterone receptor (PR) protein were highly expressed in the ovarian tissue of healthy M. fortis but were significantly reduced in the ovarian cancer M. fortis, though both were located in the cytoplasm. CONCLUSIONS Spontaneous ovarian cancer in M. fortis is serous ovarian cancer. Compared to healthy M. fortis, significant differences were observed in ovarian tissue morphology, biochemical indicators, ovarian cancer-related gene expression, and protein expression, which show similarity to the biological characteristics of human serous ovarian cancer. This suggests that M. fortis could be an ideal animal model for studying human serous ovarian cancer.
Female ; Ovarian Neoplasms/metabolism* ; Animals ; Carcinoma, Ovarian Epithelial ; Disease Models, Animal ; Humans ; Neoplasms, Glandular and Epithelial/metabolism* ; Ovary/pathology*

OBJECTIVES: Hypoxia/reoxygenation (H/R) injury is a critical pathological process during liver transplantation. Kazinol B has known anti-inflammatory, anti-apoptotic, and metabolic regulatory properties, but its protective mechanism in H/R-induced liver injury remains unclear. This study aims to investigate the protective effects and underlying mechanisms of Kazinol B in H/R-induced hepatocyte injury. METHODS: An ischemia-reperfusion model was established in healthy adult male Sprague-Dawley rats, and an in vitro H/R model was created using cultured hepatocytes. Hepatocytes were treated with Kazinol B (0-100 μmol/L) to assess cytotoxicity and protective effects. Cell viability was evaluated using the cell counting kit-8 (CCK-8) and lactate dehydrogenase (LDH) release assays. Expression of apoptosis-related proteins, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated death promoter (Bad), and cleaved caspase-3, was detected by Western blotting. Reactive oxygen species (ROS) levels were assessed via fluorescence probes, and inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured using enzyme-linked immunosorbent assay (ELISA). TdT-mediated nick end labeling (TUNEL) staining was performed to assess DNA damage and apoptosis. RESULTS: Kazinol B had no significant effect on hepatocyte viability at 0-50 μmol/L, but showed cytotoxicity at 100 μmol/L (P<0.05). At 0.1-20 μmol/L, Kazinol B significantly improved cell survival, reduced LDH release, decreased apoptosis, and attenuated DNA damage (all P<0.001). At 10 μmol/L, Kazinol B markedly down-regulated Bad and cleaved caspase-3 (both P<0.05), and up-regulated Bcl-2 (P<0.01). It also dose-dependently reduced ROS levels and inflammatory cytokines TNF-α and IL-1β (all P<0.01). Both in vitro and in vivo, Kazinol B inhibited activation of the c-Jun N-terminal kinase (JNK) pathway without affecting extracellular regulated protein kinase (ERK) signaling (P>0.05). TUNEL staining showed that the protective effect of Kazinol B against apoptosis was partially reversed by the JNK agonist anisomycin (P<0.01). CONCLUSIONS Kazinol B mitigates hepatocyte injury induced by H/R by inhibiting the JNK signaling pathway. Its protective effect is associated with suppression of oxidative stress and inflammation, indicating its potential as a hepatoprotective agent.
Animals ; Hepatocytes/pathology* ; Rats, Sprague-Dawley ; Male ; Rats ; Reperfusion Injury/prevention & control* ; Apoptosis/drug effects* ; Reactive Oxygen Species/metabolism* ; MAP Kinase Signaling System/drug effects* ; Cell Survival/drug effects* ; Cell Hypoxia ; Cells, Cultured

Exosomes are small vesicles commonly found in bodily fluids such as blood, urine, ascites, and breast milk. As essential mediators of intercellular communication, exosomes play pivotal roles in physiological and pathological processes including material transport, signal transduction, homeostasis regulation, immune response, and angiogenesis. They are promising biomarkers for disease diagnosis and key carriers for therapeutic drug delivery. Longitudinal tracking of exosome biodistribution, elucidating their migratory routes and homing effects, determining optimal delivery routes and therapeutic dosages, and evaluating implantation in target tissues are crucial for better understanding their mechanisms of action and guiding clinical applications. Magnetic resonance imaging (MRI), as a non-invasive and repeatable imaging technique, offers an ideal approach for exosome tracking. By labeling exosomes with specific contrast agents or tracers and detecting them via MRI, researchers can trace exosomes in vivo. This facilitates advancements in exosome-based nanomedicine and accelerates the clinical translation of exosome diagnostics and therapeutics.
Exosomes/metabolism* ; Humans ; Magnetic Resonance Imaging/methods* ; Contrast Media ; Animals ; Tissue Distribution

OBJECTIVES: Psoriasis is associated with lipid metabolism disorders, but the underlying mechanisms remain unclear. This study aims to investigate the role of trimethylamine N-oxide (TMAO) in lipid metabolism dysregulation in psoriasis. METHODS: An imiquimod (IMQ)-induced psoriasis-like mouse model was used to assess lipid metabolism parameters, TMAO levels, and liver flavin monooxygenase 3 (FMO3) mRNA expression. Blood samples from healthy individuals and psoriatic patients were collected to measure serum TMAO levels and lipid profiles. To clarify the role of TMAO in the lipid metabolism disorder of mice with psoriasis model, exogenous TMAO, choline, or 3,3-dimethyl-1-butanol (DMB) were administered via intraperitoneal injections or diet in IMQ-treated mice. Liver tissues from the mouse models were subjected to RNA sequencing to identify TMAO-regulated signaling pathways. RESULTS: IMQ-induced psoriatic mice exhibited abnormal glucose, insulin, and lipid levels. IMQ treatment also downregulated the hepatic mRNA expression of glucose transporter 2 (Glut2) and silence information regulator 1 (Sirt1), while upregulating glucose transporter 4 (Glut4) and peroxisome proliferator-activated receptor gamma (PPARγ). Elevated serum TMAO levels were observed in both psoriatic patients and IMQ-treated mice. Additionally, liver FMO3 mRNA expression was increased in the psoriatic mouse model. In patients, TMAO levels positively correlated with Psoriasis Area and Severity Index (PASI) scores, serum triglyceride (TG), and total cholesterol (TC) levels. The intraperitoneal injection of TMAO exacerbated lipid dysregulation in IMQ-treated mice. A choline-rich diet further aggravated lipid abnormalities and liver injury in psoriatic mice, whereas DMB treatment alleviated these effects. RNA-Seq analysis demonstrated that TMAO upregulated hepatic microRNA-122 (miR-122), which may suppress the expression of gremlin 2 (GREM2), thus contributing to lipid metabolism disorder. CONCLUSIONS TMAO may promote lipid metabolism dysregulation in psoriasis by modulating the hepatic miR-122/GREM2 pathway.
Animals ; Methylamines/blood* ; Mice ; Psoriasis/chemically induced* ; Lipid Metabolism/drug effects* ; Humans ; Male ; Liver/metabolism* ; Female ; Oxygenases/genetics* ; Disease Models, Animal ; Lipid Metabolism Disorders/etiology* ; Adult ; Mice, Inbred C57BL

OBJECTIVES: Psoriasis is a chronic inflammatory skin disease often accompanied by comorbidities such as hyperglycemia, insulin resistance, and obesity. Acitretin, as a second-generation retinoid, is used in the treatment of psoriasis. This study aims to explore the role of acitretin on glucose and lipid metabolism in psoriasis. METHODS: HepG2 cells were treated with acitretin under high- or low-glucose conditions. mRNA and protein expression levels of glucose transport-related genes were evaluated using real-time reverse transcription PCR (real-time RT-PCR) and Western blotting. Glucose uptake was analyzed by flow cytometry, and intracellular lipid droplet formation was assessed via Oil Red O staining. Healthy adult female BALB/C mice were randomly divided into 3 groups: a control group, an imiquimod (IMQ)-induced psoriasis model group (IMQ group), and an acitretin treatment group. Skin lesions and inflammatory markers were examined, along with changes in body weight, plasma glucose/lipid levels, and transcription of metabolic genes. Islets were isolated from normal and psoriasis-induced mice, and the effect of acitretin on insulin secretion was evaluated in vitro. RESULTS: Acitretin treatment increased glucose uptake and lipid droplet synthesis of HepG2 in high-glucose environment, with elevated transcription levels of glucose transport-related genes GLUT1 and GLUT4. Transcription of gluconeogenesis-related gene G6pase decreased, while transcription levels of glycogen synthesis-related genes AKT1 and GSY2 increased (all P<0.05), while acitretin inhibits glucose uptake and promotes gluconeogenesis in low-glucose environment. In vivo experiments revealed that compared with the control group, the blood glucose level in the IMQ group was significantly decreased (P<0.05), while acitretin treatment partially restored glucose homeostasis and alleviated weight loss. Ex vivo culture of islets from psoriatic mice revealed that acitretin reduced elevated insulin secretion and downregulated PDX-1 expression, while upregulating glucose homeostasis gene SIRT1 and insulin sensitivity gene PPARγ (all P<0.05). These findings suggest that acitretin plays a critical role in improving islet function and restoring islet homeostasis. CONCLUSIONS Acitretin helps maintain the balance between hepatic glycogenesis and gluconeogenesis, enhances insulin sensitivity, and improves pancreatic islet function, thereby promoting systemic and cellular glucose homeostasis.
Acitretin/therapeutic use* ; Psoriasis/drug therapy* ; Animals ; Imiquimod ; Humans ; Glucose/metabolism* ; Homeostasis/drug effects* ; Mice ; Lipid Metabolism/drug effects* ; Mice, Inbred BALB C ; Female ; Hep G2 Cells ; Disease Models, Animal