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

BACKGROUND

Rabies remains to be a neglected tropical disease in the Philippines, with the country reporting a higher number of cases compared to its counterparts in Asia.

OBJECTIVE

To describe the demographics, animal bite characteristics, and post-exposure prophylaxis of animal bite patients coming in for care at the Research Institute for Tropical Medicine (RITM), a large government referral center for infectious diseases, and animal bites.

METHODS

Electronic patient records from January 1, 2018 to December 31, 2019 were obtained from the National Rabies Information System (NaRIS) database of the Department of Health, and summarized using applicable descriptive statistics.

RESULTS

A total of 14,614 patients were included over the two-year study period, and more than third of the patients were children below 15 years old, while more than half were adult males. Lower extremities were the most frequently affected area, while with children, more than a third of exposures were in the head and neck areas. Intradermal route was mostly used for the post-exposure prophylaxis, while WHO prequalified vaccines were utilized in more than 90% of the patients. Only 55.7% of patients completed the prophylaxis regimen at RITM.

CONCLUSION

These findings reflect the significant exposure of children from animal bites, and the non-compliance of patients to the prescribed post-exposure prophylaxis.

Human ; Animals ; Rabies ; Post-exposure Prophylaxis ; Rabies Vaccines

OBJECTIVE: To explore the mechanism by which ω-3 polyunsaturated fatty acids (hereinafter referred to as "ω-3") exert antioxidant stress protection and promote osteogenic differentiation in MC3T3-E1 cells, and to reveal the relationship between ω-3 and the key antioxidant stress pathway involving nuclear factor E2-related factor 2 (Nrf2) and NAD (P) H quinone oxidoreductase 1 (NQO1) in MC3T3-E1 cells. METHODS: The optimal concentration of H ₂O ₂ (used to establish the oxidative stress model of MC3T3-E1 cells in vitro) and the optimal intervention concentrations of ω-3 were screened by cell counting kit 8. MC3T3-E1 cells were divided into blank control group, oxidative stress group (H ₂O ₂), low-dose ω-3 group (H ₂O ₂+low-dose ω-3), and high-dose ω-3 group (H ₂O ₂+high-dose ω-3). After osteoblastic differentiation for 7 or 14 days, the intracellular reactive oxygen species (ROS) level was measured by fluorescence staining and flow cytometry, and the mitochondrial morphological changes were observed by biological transmission electron microscope; the expression levels of Nrf2, NQO1, heme oxygenase 1 (HO-1), Mitofusin 1 (Mfn1), and Mfn2 were detected by Western blot to evaluate the cells' antioxidant stress capacity; the expression levels of Runt-related transcription factor 2 (RUNX2) and osteocalcin (OCN) were detected by immunofluorescence staining and Western blot; osteogenic potential of MC3T3-E1 cells was evaluated by alkaline phosphatase (ALP) staining and alizarin red staining. RESULTS: Compared with the oxidative stress group, the content of ROS in the low and high dose ω-3 groups significantly decreased, and the protein expressions of Nrf2, NQO1, and HO-1 significantly increased ( P<0.05). At the same time, the mitochondrial morphology of MC3T3-E1 cells improved, and the expressions of mitochondrial morphology-related proteins Mfn1 and Mfn2 significantly increased ( P<0.05). ALP staining and alizarin red staining showed that the low-dose and high-dose ω-3 groups showed stronger osteogenic ability, and the expressions of osteogenesis-related proteins RUNX2 and OCN significantly increased ( P<0.05). And the above results showed a dose-dependence in the two ω-3 treatment groups ( P<0.05). CONCLUSION ω-3 can enhance the antioxidant capacity of MC3T3-E1 cells under oxidative stress conditions and upregulate their osteogenic activity, possibly through the Nrf2/NQO1 signaling pathway.
Oxidative Stress/drug effects* ; NF-E2-Related Factor 2/metabolism* ; NAD(P)H Dehydrogenase (Quinone)/metabolism* ; Animals ; Mice ; Osteogenesis/drug effects* ; Cell Differentiation/drug effects* ; Fatty Acids, Omega-3/pharmacology* ; Signal Transduction/drug effects* ; Osteoblasts/drug effects* ; Reactive Oxygen Species/metabolism* ; Cell Line ; Hydrogen Peroxide/pharmacology* ; Core Binding Factor Alpha 1 Subunit/metabolism* ; Antioxidants/pharmacology* ; Heme Oxygenase-1/metabolism*

OBJECTIVE: To investigate the effect of mild hypothermia on neurological function in rats with spinal cord injury (SCI) based on the adenosine monophosphate activated protein kinase (AMPK)/Nod-like receptor protein 3 (NLRP3) pathway. METHODS: Fifty 7-8 weeks old SPF male Sprague Dawley rats were used to establish rat model of SCI by Allen's method. Among them, 48 successfully modeled rats were randomly divided into SCI group, mild hypothermia group (SCI+mild hypothermia treatment), and Compound C group (SCI+mild hypothermia+intraperitoneal injection of 20 mg/kg AMPK/NLRP3 pathway inhibitor Compound C), with 16 rats in each group. Another 16 normal rats with laminectomy were selected as sham-operation group. Basso-Beattie-Bresnahan (BBB) score was used to evaluate the motor ability of rats at 1, 3, 7, 14 days after treatment. After 14 days, the rats were sacrificed, and the spinal cord histopathological morphology was observed by HE staining, the neuronal apoptosis in spinal cord tissue was detected by TUNEL assay, and the serum levels of interleukin 2 (IL-2), IL-6, transforming growth factor β ₁ (TGF-β ₁), malondialdehyde (MDA), and superoxide dismutase (SOD) were detected by ELISA. The expressions of AMPK/NLRP3 pathway proteins in spinal cord tissue, including B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and cleaved-Caspase-9 were detected by Western blot. RESULTS: At 1 day after treatment, the rats in SCI group, mild hypothermia group, and Compound C group did not recover their motor ability. With the prolongation of time, the motor function of rats in each group gradually recovered. Among them, the BBB score of SCI group was significantly lower than that of sham-operation group and mild hypothermia group ( P<0.05), and the BBB score of Compound C group was significantly lower than that of mild hypothermia group ( P<0.05). Compared with the sham-operation group, the SCI group displayed obvious pathological changes in the spinal cord tissue, with disordered tissue architecture, inflammatory infiltration, and blurred interstitial boundaries. The neuronal apoptosis rate, Bax/Bcl-2 ratio, cleaved Caspase-9 expression, NLRP3 protein expression, serum IL-2, IL-6, and MDA levels were elevated, whereas serum TGF-β ₁, SOD levels, and spinal cord phosphorylation AMPK/AMPK protein expression significantly decreased ( P<0.05). Compared with the SCI group, the above phenomena significantly improved in the mild hypothermia group ( P<0.05), while the Compound C group showed the opposite trend of change compared to the mild hypothermia group ( P<0.05). CONCLUSION Mild hypothermia can attenuate neurological dysfunction after SCI in rats, potentially by activating the AMPK/NLRP3 pathway.
Animals ; Spinal Cord Injuries/physiopathology* ; Rats, Sprague-Dawley ; Male ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; AMP-Activated Protein Kinases/metabolism* ; Hypothermia, Induced ; Signal Transduction ; Spinal Cord/pathology* ; Apoptosis ; Interleukin-6/metabolism* ; Disease Models, Animal ; bcl-2-Associated X Protein/metabolism* ; Superoxide Dismutase/metabolism* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Caspase 9/metabolism*

OBJECTIVE: To summarize recent research progress in hydrogel-based growth factors for treatment of intervertebral disc degeneration (IDD). METHODS: The relevant literature on hydrogel-based growth factors for IDD treatment at home and abroad was extensively reviewed, and their advantages and therapeutic effects in repairing IDD were analyzed and summarized. RESULTS: Hydrogels exhibit high hydration, biocompatibility, and biodegradability, enabling targeted delivery and sustained release of growth factors such as growth differentiation factors and transforming growth factors. This facilitates enhanced efficacy in promoting cell proliferation, extracellular matrix synthesis, and reducing inflammatory responses. Consequently, hydrogels demonstrate broad application prospects in the repair of IDD. CONCLUSION Research on hydrogel-based growth factors for treating IDD demonstrates advantages such as avoiding disc damage caused by repeated injections and controlling growth factor release concentrations. However, drawbacks include the limited variety of loaded growth factors and the need to verify the long-term stability and biocompatibility of hydrogels. Therefore, further research is required on aspects such as the types of loaded growth factors and the long-term stability and biocompatibility of hydrogels to establish an experimental foundation for their clinical application.
Intervertebral Disc Degeneration/therapy* ; Hydrogels/chemistry* ; Humans ; Intercellular Signaling Peptides and Proteins/administration & dosage* ; Biocompatible Materials/chemistry* ; Animals ; Tissue Engineering/methods* ; Cell Proliferation/drug effects* ; Drug Delivery Systems

OBJECTIVE: To review the recent advances in the application of exosome-hydrogel system for wound healing. METHODS: A wide range of recent domestic and international studies were reviewed to systematically outline the roles and mechanisms of exosomes, hydrogels, and their composite system in promoting wound repair. RESULTS: Wound healing is a complex and finely regulated process. Traditional therapies lack targeted regulation of key mechanisms such as inflammation control, angiogenesis, collagen remodeling, and re-epithelialization. The exosome-hydrogel system enhances wound repair through targeted modulation of these mechanisms and provides effective protection against bacterial infection, hypoxia, excessive oxidative stress, and hyperglycemic microenvironments. CONCLUSION The exosome-hydrogel system represents an emerging approach for chronic wound repair and skin regeneration, potentially overcoming the inherent limitations of traditional therapies. Nevertheless, the lack of standardized preparation methods and dosing protocols calls for further optimization.
Wound Healing ; Humans ; Hydrogels ; Exosomes ; Skin/injuries* ; Animals ; Re-Epithelialization

OBJECTIVE: To investigate the effects of bone density, plate bending degree and proximal screw type on the stress fracture of clavicle hook. METHODS: Three sows weighing between 45 and 50 kg were selected, from which a total of 40 rivs were collected. The 15 ribs of sows were divided into 3 groups according to bone density and bone hardness with 5 rivs in each group. And then the 3 groups were fixed with 6-hole collarbone hook plates and 3 locking screws. Measure the maximum torsion force when the ribs were fractured by force. The same size 15 rids were divided into 3 groups, named forward bending group, 0° group(the angle between the plate surface and the rib surface) and reverse bending group. All fixed with 6-hole collarbone hook plates and locking screws to measure the maximum torsion force of rib stress fracture. Then the same size 10 rids were divided into 2 groups, the normal screw group and the locking screw group with 5 ribs in each group. Both groups were fixed with 6-hole collarbone hook plates and screws. The normal screw group was a normal screw, fixed in proximal end, and two locking screws. The locking screw group was fixed by locking screws. Measure the maximum torsion force of the two groups when the ribs fracture by force. RESULTS: In the bone density experiment, the torque force of hard bone group (104.51±6.27) N was greater than the normal bone group (75.04±3.81) N(t=8.979, P<0.05). The force of normal bone group was greater than the osteoporosis group (49.99±2.12) N(t=12.832, P<0.05). In the bending collarbone hook experiment, the order of the torque force generated by each group as follow:the forward bending group (343.59±6.18) N greater than the 0° group (106.01±5.29) N(t=65.279, P<0.05) greater than the reverse bending group (95.82±4.12) N(t=3.398, P<0.05). The force of the normal screw group (98.68±0.70) N was greater than the locking screw group (50.20±0.95) N(t=91.484, P<0.05). The data comparisons of each group were statistically significant. CONCLUSION Bone density, plate bending degree and proximal screw type had an impact on stress fracture of clavicle hook plate. Higher bone density, forward bending of the steel plate, and ordinary screws in proximal end can reduce the rates of stress fractures of clavicle hooks.
Animals ; Bone Plates ; Clavicle/surgery* ; Swine ; Fractures, Stress/etiology* ; Female ; Risk Factors ; Fracture Fixation, Internal/instrumentation* ; Bone Screws ; Biomechanical Phenomena ; Bone Density