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1.
J Clin Med ; 13(16)2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39200981

RESUMO

Background/Objectives: Self-recognition of recurrent myocardial infarction (re-MI) may be essential for reducing prehospital time contrast to awareness of re-MI symptoms. However, data on the current status and clinical impact of self-recognition of re-MI are limited in the contemporary period. Thus, this study aimed to increase this body of knowledge. Methods: We enrolled 1018 patients with re-MI using data from the Korean Registry of Acute Myocardial Infarction for Regional Cardiocerebrovascular Centres. The patients were classified into self-recognised MI and unrecognised MI groups, and the differences between them were compared. Results: The rate of self-recognition among the patients with previous experience of MI was only 52.4%. Among the patients with re-MI, factors associated with self-recognition included recent first MI within 3 years, prior dyslipidaemia, two or more MI symptoms, and the male gender (p < 0.05). Factors associated with a lack of recognition were older age (≥70 years), prior stroke, and cancer history (p < 0.05). The proportion of symptoms-to-emergency room arrival time within 90 min among the patients with ST-elevation MI was significantly higher in the self-recognised group than in the unrecognised group (52.6% vs. 31.6%, p < 0.001). The self-recognised group showed a lower in-hospital mortality rate (1.5% vs. 6.2%, p < 0.001), and this benefit was maintained even after 1 year (hazard ratio: 0.53; p < 0.001). Conclusions: Only half of the patients who previously experienced a MI recognised a re-MI when it occurred. This recognition reduced prehospital delay and led to higher survival rates, which highlights the importance of patient education as well as objective monitoring devices, irrespective of individual recognition ability for immediate response.

2.
Genes Genomics ; 46(10): 1165-1174, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39153155

RESUMO

BACKGROUND: Heparan sulfate 2-O-sulfotransferase 1 (HS2ST1) catalyzes the sulfation of glucuronic acid residues in heparan sulfate proteoglycans, enabling these proteoglycans to interact with numerous ligands within tumor microenvironments. However, the prognostic role of HS2ST1 expression in cancer remains unclear. OBJECTIVE: This investigated HS2ST1 expression levels and their prognostic significance in various cancer types, demonstrated the prognostic value of HS2ST1 expression in hepatocellular carcinoma (HCC) patients, and identified molecular signatures associated with HS2ST1 expression. METHODS: HS2ST1 expression and patient survival data from The Cancer Genome Atlas (TCGA) datasets were analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA) portal. We obtained gene expression and clinicopathological information on HCC patients from the TCGA and the Japan and France International Cancer Genome Consortium (ICGC) databases and performed survival analyses. We also examined relevant protein networks, differentially expressed genes, gene set enrichments, and tumor immune microenvironment features associated with HS2ST1 expression. RESULTS: HS2ST1 exhibited higher expression in eight tumor types compared with normal tissues and was associated with poor prognoses in five tumors, including HCC. HS2ST1 status correlated with poor prognosis in two ICGC HCC cohorts. Elevated HS2ST1 expression in HCC tumors was associated with signaling pathways involved in cell cycle progression, protein secretion, and mTORC1 signaling. Moreover, HS2ST1 expression levels were inversely correlated with immune cell infiltration in the tumor microenvironment. CONCLUSION: Our study elucidates the prognostic significance of HS2ST1 expression in HCC patients and provides insights into the potential roles of HS2ST1 in signaling pathways and the tumor microenvironment.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Sulfotransferases , Microambiente Tumoral , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Sulfotransferases/genética , Sulfotransferases/metabolismo , Prognóstico , Microambiente Tumoral/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Masculino , Feminino
3.
Neurosurg Focus ; 56(5): E9, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38691864

RESUMO

OBJECTIVE: Chordomas are rare tumors of the skull base and spine believed to arise from the vestiges of the embryonic notochord. These tumors are locally aggressive and frequently recur following resection and adjuvant radiotherapy. Proton therapy has been introduced as a tissue-sparing option because of the higher level of precision that proton-beam techniques offer compared with traditional photon radiotherapy. This study aimed to compare recurrence in patients with chordomas receiving proton versus photon radiotherapy following resection by applying tree-based machine learning models. METHODS: The clinical records of all patients treated with resection followed by adjuvant proton or photon radiotherapy for chordoma at Mayo Clinic were reviewed. Patient demographics, type of surgery and radiotherapy, tumor recurrence, and other variables were extracted. Decision tree classifiers were trained and tested to predict long-term recurrence based on unseen data using an 80/20 split. RESULTS: Fifty-three patients with a mean ± SD age of 55.2 ± 13.4 years receiving surgery and adjuvant proton or photon therapy to treat chordoma were identified; most patients were male. Gross-total resection was achieved in 54.7% of cases. Proton therapy was the most common adjuvant radiotherapy (84.9%), followed by conventional or external-beam radiation therapy (9.4%) and stereotactic radiosurgery (5.7%). Patients receiving proton therapy exhibited a 40% likelihood of having recurrence, significantly lower than the 88% likelihood observed in those treated with nonproton therapy. This was confirmed on logistic regression analysis adjusted for extent of tumor resection and tumor location, which revealed that proton adjuvant radiotherapy was associated with a decreased risk of recurrence (OR 0.1, 95% CI 0.01-0.71; p = 0.047) compared with photon therapy. The decision tree algorithm predicted recurrence with an accuracy of 90% (95% CI 55.5%-99.8%), with the lowest risk of recurrence observed in patients receiving gross-total resection with adjuvant proton therapy (23%). CONCLUSIONS: Following resection, adjuvant proton therapy was associated with a lower risk of chordoma recurrence compared with photon therapy. The described machine learning models were able to predict tumor progression based on the extent of tumor resection and adjuvant radiotherapy modality used.


Assuntos
Cordoma , Recidiva Local de Neoplasia , Fótons , Terapia com Prótons , Neoplasias da Coluna Vertebral , Humanos , Cordoma/radioterapia , Cordoma/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/radioterapia , Terapia com Prótons/métodos , Radioterapia Adjuvante/métodos , Adulto , Idoso , Neoplasias da Coluna Vertebral/radioterapia , Neoplasias da Coluna Vertebral/cirurgia , Fótons/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
5.
Int J Mol Sci ; 25(4)2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38396988

RESUMO

Alzheimer's disease (AD) is a representative cause of dementia and is caused by neuronal loss, leading to the accumulation of aberrant neuritic plaques and the formation of neurofibrillary tangles. Oxidative stress is involved in the impaired clearance of amyloid beta (Aß), and Aß-induced oxidative stress causes AD by inducing the formation of neurofibrillary tangles. Hwangryunhaedok-tang (HHT, Kracie K-09®), a traditional herbal medicine prescription, has shown therapeutic effects on various diseases. However, the studies of HHT as a potential treatment for AD are insufficient. Therefore, our study identified the neurological effects and mechanisms of HHT and its key bioactive compounds against Alzheimer's disease in vivo and in vitro. In a 5xFAD mouse model, our study confirmed that HHT attenuated cognitive impairments in the Morris water maze (MWM) test and passive avoidance (PA) test. In addition, the prevention of neuron impairment, reduction in the protein levels of Aß, and inhibition of cell apoptosis were confirmed with brain tissue staining. In HT-22 cells, HHT attenuates tBHP-induced cytotoxicity, ROS generation, and mitochondrial dysfunction. It was verified that HHT exerts a neuroprotective effect by activating signaling pathways interacting with Nrf2, such as MAPK/ERK, PI3K/Akt, and LKB1/AMPK. Among the components, baicalein, a bioavailable compound of HHT, exhibited neuroprotective properties and activated the Akt, AMPK, and Nrf2/HO-1 pathways. Our findings indicate a mechanism for HHT and its major bioavailable compounds to treat and prevent AD and suggest its potential.


Assuntos
Doença de Alzheimer , Antioxidantes , Extratos Vegetais , Animais , Camundongos , Doença de Alzheimer/tratamento farmacológico , Proteínas Quinases Ativadas por AMP/metabolismo , Peptídeos beta-Amiloides/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Fosfatidilinositol 3-Quinases/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
6.
Maxillofac Plast Reconstr Surg ; 46(1): 4, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38233722

RESUMO

BACKGROUND: Frontal sinus injuries are relatively rare among facial bone traumas. Without proper treatment, they can lead to fatal intracranial complications, including meningitis or brain abscesses, as well as aesthetic and functional sequelae. The management of frontal sinus injuries remains controversial, with various treatment methods and outcomes being reported. This article describes the clinical characteristics, surgical methods, and outcomes among 17 patients who underwent surgery for frontal sinus injury and related complications. CASE PRESENTATION: We retrospectively included 17 patients who underwent surgery for frontal sinus injury and its related complications at the Kangwon National University Hospital between July 2010 and September 2021. Among them, six underwent simple open reduction and fixation of the anterior wall, eight underwent sinus obliteration, and three underwent cranialization. Two patients who underwent sinus obliteration died due to infection-related complications. The patient who underwent cranialization reported experiencing chronic headache and expressed dissatisfaction regarding the esthetic outcomes of the forehead. Except for these three patients, the other patients achieved satisfactory esthetic and functional recovery. CONCLUSION: Active surgical management of frontal sinus injuries is often required owing to the various complications caused by these injuries; however, several factors, including the fracture type, clinical presentation, related craniomaxillofacial injury, and medical history, should be considered while formulating the treatment plan. Surgical treatment through the opening of the frontal sinus should be actively considered in patients with severely damaged posterior wall fractures and those at risk of developing infection.

7.
World J Clin Cases ; 11(35): 8399-8403, 2023 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-38130620

RESUMO

BACKGROUND: In bow hunter's syndrome (BHS), also known as rotational vertebral artery (VA) syndrome, there is dynamic/rotational compression of the VA producing vertebrobasilar insufficiency. Most occurrences involve atlantoaxial rather than mid-cervical VA compromise, the latter being rarely reported. Herein, we detail successful VA decompression at mid-cervical spine, given a departure from its usual course. CASE SUMMARY: The patient, a 45-year-old man, presented to our hospital with occipital headache and vertigo. Computed tomography angiography showed anomalous C4 entry of right VA, with compression upon head rotation to that side. Thyroid cartilage and anterior tubercle of C5 transverse process were visibly at fault. We opted for surgery, using an anterior cervical approach to remove the anterior tubercle. Patient recovery was uneventful and brought resolution of all preoperative symptoms. CONCLUSION: BHS is an important consideration where aberrant coursing of VA and neurologic symptoms coexist.

8.
Clin Spine Surg ; 2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37684726

RESUMO

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: To perform a systematic review of the clinical symptoms, radiographic findings, and outcomes after spinal decompression in B-cell lymphoma. SUMMARY OF BACKGROUND DATA: B-cell lymphoma is a potential cause of spinal cord compression that presents ambiguously with nonspecific symptoms and variable imaging findings. Surgical decompression is a mainstay for both diagnosis and management, especially in patients with acute neurological deficits; however, the efficacy of surgical intervention compared with nonoperative management is still unclear. METHODS: The databases of Medline, PubMed, and the Cochrane Database of Systemic Reviews were queried for all articles reporting spinal B-cell lymphoma. Data on presenting symptoms, treatments, survival outcomes, and histologic markers were extracted. Using the R software "survival" package, we generated bivariate and multivariate Cox survival regression models and Kaplan-Meier curves. RESULTS: In total, 65 studies were included with 72 patients diagnosed with spinal B-cell lymphoma. The mean age was 56.22 (interquartile range: 45.00-70.25) with 68% of patients being males and 4.2% of patients being immunocompromised. Back pain was the most common symptom (74%), whereas B symptoms and cauda equina symptoms were present in 6% and 29%, respectively. The average duration of symptoms before presentation was 3.81 months (interquartile range: 0.45-3.25). The most common location was the thoracic spine (53%), with most lesions being hyperintense (28%) on T2 magnetic resonance imaging. Surgical resection was performed in 83% of patients. Symptoms improved in 91% of patients after surgery and in 80% of patients treated nonoperatively. For all 72 patients, the overall survival at 1 and 5 years was 85% (95% CI: 0.749-0.953; n = 72) and 66% (95% CI: 0.512-0.847; n = 72), respectively. CONCLUSION: Although surgery is usually offered in patients with acute spinal cord compression from B-cell lymphoma, chemotherapy and radiation alone offer a hopeful alternative to achieve symptomatic relief, particularly in patients who are unable to undergo surgery.

9.
World Neurosurg ; 176: 35-42, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37059357

RESUMO

INTRODUCTION: Spine surgery has undergone significant changes in approach and technique. With the adoption of intraoperative navigation, minimally invasive spinal surgery (MISS) has arguably become the gold standard. Augmented reality (AR) has now emerged as a front-runner in anatomical visualization and narrower operative corridors. In effect, AR is poised to revolutionize surgical training and operative outcomes. Our study examines the current literature on AR-assisted MISS, synthesizes findings, and creates a narrative highlighting the history and future of AR in spine surgery. MATERIAL AND METHODS: Relevant literature was gathered using the PubMed (Medline) database from 1975 to 2023. Pedicle screw placement models were the primary intervention in AR. These were compared to the outcomes of traditional MISS RESULTS: We found that AR devices on the market show promising clinical outcomes in preoperative training and intraoperative use. Three prominent systems were as follows: XVision, HoloLens, and ImmersiveTouch. In the studies, surgeons, residents, and medical students had opportunities to operate AR systems, showcasing their educational potential across each phase of learning. Specifically, one facet described training with cadaver models to gauge accuracy in pedicle screw placement. AR-MISS exceeded free-hand methods without unique complications or contraindications. CONCLUSIONS: While still in its infancy, AR has already proven beneficial for educational training and intraoperative MISS applications. We believe that with continued research and advancement of this technology, AR is poised to become a dominant player within the fundamentals of surgical education and MISS operative technique.


Assuntos
Realidade Aumentada , Parafusos Pediculares , Cirurgia Assistida por Computador , Humanos , Vértebras Lombares/cirurgia , Cirurgia Assistida por Computador/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos
10.
Clin Shoulder Elb ; 26(1): 71-81, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36919510

RESUMO

BACKGROUND: This study evaluated the clinical and radiologic outcomes of onlay patch augmentation in rotator cuff repair for moderate-to-large tears in elderly patients. METHODS: We reviewed 24 patients who underwent onlay augmentation with dermal allograft after arthroscopic rotator cuff repair from January 2017 to March 2020. Inclusion criteria were patients aged >65 years with tears >2.5 cm, who were followed for >12 months after surgery, and patients who could raise their arms above 90° preoperatively. American Shoulder and Elbow Surgeons (ASES) score, Constant-Murley score, pain visual analog scale (VAS), and VAS for satisfaction were used as clinical outcomes. For the evaluation of cuff integrity, magnetic resonance imaging scans were performed every 3 months after surgery. The results were compared before and after surgery in all patients and between the retear and intact groups. RESULTS: The average follow-up period was 16.38 months, and the mean age of patients was 71.05 years. All patients showed significant improvement in ASES score, Constant-Murley score, and pain VAS at the last evaluation. The average value of satisfaction VAS was 7.27/10. The retear rate was 25% (6/24) if Sugaya type 3 was categorized in the retear group, otherwise 16.7% (4/24), if Sugaya type 3 was categorized into the intact group. Irrespective of Sugaya type 3 being included in the retear group, there was no significant difference in outcome variables between the intact and retear groups during follow-up. CONCLUSIONS: In moderate-to-large rotator cuff tear in elderly patients, onlay patch augmentation improved clinical outcomes. Retear did not adversely affect clinical outcomes.

11.
J Ginseng Res ; 47(2): 283-290, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36160270

RESUMO

Hypercoagulability is frequently observed in patients with severe coronavirus disease-2019 (COVID-19). Platelets are a favorable target for effectively treating hypercoagulability in COVID-19 patients as platelet hyperactivity has also been observed. It is difficult to develop a treatment for COVID-19 that will be effective against all variants and the use of antivirals may not be fully effective against COVID-19 as activated platelets have been detected in patients with COVID-19. Therefore, patients with less severe side effects often turn toward natural remedies. Numerous phytochemicals are being investigated for their potential to treat a variety of illnesses, including cancer and bacterial and viral infections. Natural products have been used to alleviate COVID-19 symptoms. Panax ginseng has potential for managing cardiovascular diseases and could be a treatment for COVID-19 by targeting the coagulation cascade and platelet activation. Using molecular docking, we analyzed the interactions of bioactive chemicals in P. ginseng with important proteins and receptors involved in platelet activation. Furthermore, the SwissADME online tool was used to calculate the pharmacokinetics and drug-likeness properties of the lead compounds of P. ginseng. Dianthramine, deoxyharrtingtonine, and suchilactone were determined to have favorable pharmacokinetic profiles.

12.
Medicine (Baltimore) ; 101(45): e31718, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36397418

RESUMO

RATIONALE: Neurofibromatosis type 1 (NF-1) can manifest with various neurological symptoms. However, sensory ataxia has not been reported. PATIENT CONCERNS: A 44-year-old man with NF-1 presented with several weeks of unsteady gait. He was diagnosed with gastric neuroendocrine tumor with multiple hepatic metastases 6 years ago and received palliative chemotherapy. Neurological examination revealed ataxia veering to the right side with no motor weakness. DIAGNOSES: Clinical manifestations and electrodiagnostic studies suggested the dysfunction of the thoracic dorsal column (DC). Initial magnetic resonance imaging showed a lateral thoracic meningocele (LTM) located in the right paravertebral area at the T3-T4 vertebral level, but the spinal cord was unremarkable. Gait disturbance worsened after 9 months, and follow-up magnetic resonance imaging showed high signal intensity involving the right DC at the level adjacent to the LTM and spinal cord atrophy distal to the DC lesion. Tests for well-characterized paraneoplastic antibodies were negative. Ultimately, the patient was assumed to have sensory neuronopathy due to compressive damage to the dorsal root ganglia within the intervertebral foramina by LTM. INTERVENTIONS: Empirical treatment with vitamin B12 supplementation and corticosteroids failed to improve his condition. The patient underwent decompressive laminectomy and excision of the meningocele with dura repair. OUTCOMES: The patient temporarily improved to walk with assistance postoperatively. However, he developed dyspnea and hypotension 5 weeks later. Carcinoid heart disease confined the patient to the bed. The patient died of pneumonia 3 months after the operation. LESSONS: This case with NF-1 shows asymmetric sensory ataxia of subacute progression. LTM may contribute to the development of sensory neuronopathy by damaging sensory neurons of the dorsal root ganglia. The comorbidities of the patient, including gastric neuroendocrine tumor and LTM, made it challenging to investigate the pathomechanism.


Assuntos
Meningocele , Tumores Neuroendócrinos , Neurofibromatose 1 , Masculino , Humanos , Adulto , Neurofibromatose 1/complicações , Neurofibromatose 1/diagnóstico , Medula Espinal , Ataxia
13.
Ecotoxicol Environ Saf ; 246: 114141, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36206637

RESUMO

The kidney proximal tubule is responsible for reabsorbing water and NaCl to maintain the homeostasis of the body fluids, electrolytes, and nutrients. Thus, abnormal functioning of the renal proximal tubule can lead to life-threatening imbalances. Bisphenol A (BPA) has been used for decades as a representative chemical in household plastic products, but studies on its effects on the kidney proximal tubule are insufficient. In this study, immunocytochemical and cytotoxicity tests were performed using two- and three-dimensional human renal proximal tubular epithelial cell (hRPTEC) cultures to investigate the impact of low-dose BPA (1-10 µM) exposure. BPA was found to interfere with straight tubule formation as observed by low filamentous actin formation and reduced Na+/K+-ATPase expression in the tubules of hRPTEC 3D cultures. Similar results were observed in rat pup kidneys following oral administration of 250 mg/kg BPA. Moreover, the expression of HO-1 and 8-OHdG, key markers for oxidative stress, was increased in vitro and in vivo following BPA administration, whereas that of OAT1 and OAT, important transporters of the renal proximal tubules, was not altered. Overall, no-observed-adverse-effect-level (NOAEL)-dose BPA exposure can decrease renal function by promoting abnormal tubular formation both in vitro and in vivo. Therefore, we propose that although it does not exhibit life-threatening toxicity, exposure to low levels of BPA can negatively affect homeostasis in the body by means of long-term deterioration of renal proximal tubular function in humans.


Assuntos
Actinas , ATPase Trocadora de Sódio-Potássio , Ratos , Animais , Humanos , Actinas/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Túbulos Renais/metabolismo , Rim/metabolismo , Sódio/metabolismo
14.
Stem Cell Res Ther ; 13(1): 404, 2022 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-35932085

RESUMO

BACKGROUND: Smokers directly inhale mainstream cigarette smoke, which contains numerous known and potential toxic substances, and thus, smoking is expected to have broad harmful effects that cause tissue injury and dysfunction. Interestingly, many studies have suggested that the recent decline in female fertility and increased rate of spontaneous abortion could be associated with increased smoking rates. Indeed, women that smoked for 10 years or more were reported to have a ~ 20% higher infertility rate than women that had never smoked. However, the reasons for the underlying harmful aspects of smoking on female fertility remain a matter of debate. Importantly, a previous study revealed that resident endometrial stem cell deficiency significantly limits the cyclic regeneration potential of endometrium, which, in turn, decreases successful pregnancy outcomes. In this context, we postulated that exposure to mainstream cigarette smoke extracts might decrease female fertility by inhibiting the functions of resident endometrial stem cells. METHODS: We investigated whether cigarette mainstream smoke exposure directly inhibits various tissue regeneration-associated functions of endometrial stem cells, such as self-renewal, migration, pluripotency, and differentiation capacity in vitro. Next, we determined whether SERPINB2 mediates cigarette smoke-induced suppressive effects on various tissue regeneration-associated functions by depleting SERPINB2 expression with specific shRNA targeting SERPINB2. Mice were injected intraperitoneally with low (0.5 mg/kg) or high (1 mg/kg) doses of cigarette smoke extract (10 times for two weeks), and endometrial stem cells were then isolated from mice uterine tissues. RESULTS: We found that exposure to cigarette smoke extracts remarkably suppressed various tissue regeneration-associated functions of endometrial stem cells, such as self-renewal, migration, multilineage differentiation ability, and pluripotency in vitro and in vivo by activating the SERPINB2 gene. Indeed, cigarette smoke-induced inhibitory effects on various endometrial stem cell functions were significantly abolished by SERPINB2 knockdown. CONCLUSIONS: These findings provide valuable information on the harmful effects of cigarette smoking on resident endometrial stem cells and hopefully will facilitate the developments of promising therapeutic strategies for subfertile or infertile women that smoke cigarettes.


Assuntos
Infertilidade Feminina , Animais , Diferenciação Celular/genética , Endométrio , Feminino , Humanos , Infertilidade Feminina/metabolismo , Camundongos , Gravidez , Fumar/efeitos adversos , Fumar/genética , Células-Tronco
15.
J Toxicol Sci ; 47(8): 317-326, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35908932

RESUMO

Testicular Leydig cells produce testosterone through the participation of steroidogenic proteins. The CYP1B1 enzyme has been shown to catalyze 7,12-dimethylbenzanthracene (DMBA), a representative polycyclic aromatic hydrocarbon. We hypothesized that exposure to DMBA causes Leydig cell cytotoxicity through activation of CYP1B1. Leydig cells were exposed to various concentrations of DMBA for the induction of CYP1B1 expression and activity. The status of CYP1B1 function was monitored by evaluation of cytotoxicity-mediated cell death. Our data show that exposure to DMBA causes cytotoxicity in Leydig cells by CYP1B1 activation. DMBA evoked a significant increase in the generation of reactive oxygen species (ROS) by which the depolarization of mitochondrial membrane potential (MMP) is initiated and caspase-3 activation is augmented. The knockdown of CYP1B1 expression resulted in the suppression of DMBA-induced apoptosis via reduced p53 activation and caspase-3 activation, suggesting that a final metabolite of DMBA (i.e., DMBA-DE) bioactivated by CYP1B1 induces p53 activation by binding to DNA and subsequently causing apoptosis via caspase-3 activation. This finding provides evidence for constitutive expression of CYP1B1 in Leydig cells, which is a trait that only requires an initiating signal for its activity. Further research on CYP1B1 activation-provoked steroid metabolism in Leydig cells may provide decisive clues for elucidating its innate function.


Assuntos
9,10-Dimetil-1,2-benzantraceno , Células Intersticiais do Testículo , 9,10-Dimetil-1,2-benzantraceno/metabolismo , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Apoptose/genética , Caspase 3/genética , Caspase 3/metabolismo , Citocromo P-450 CYP1B1/genética , Citocromo P-450 CYP1B1/metabolismo , Humanos , Células Intersticiais do Testículo/metabolismo , Masculino , Proteína Supressora de Tumor p53/genética
16.
Chin Med ; 17(1): 70, 2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35701790

RESUMO

BACKGROUND: Recent years, a soaring number of marketed Trifolium pratense (red clover) extract products have denoted that a rising number of consumers are turning to natural alternatives to manage postmenopausal symptoms. T. pratense ethanolic extract (TPEE) showed immense potential for their uses in the treatment of menopause complications including osteoporosis and hormone dependent diseases. Early diagnosis of osteoporosis can increase the chance of efficient treatment and reduce fracture risks. Currently, the most common diagnosis of osteoporosis is performed by using dual-energy x-ray absorptiometry (DXA). However, the major limitation of DXA is that it is inaccessible and expensive in rural areas to be used for primary care inspection. Hence, serum biomarkers can serve as a meaningful and accessible data for osteoporosis diagnosis. METHODS: The present study systematically elucidated the anti-osteoporosis and estrogenic activities of TPEE in ovariectomized (OVX) rats by evaluating the bone microstructure, uterus index, serum and bone biomarkers, and osteoblastic and osteoclastic gene expression. Leverage on a pool of serum biomarkers obtained from this study, recursive feature elimination with a cross-validation method (RFECV) was used to select useful biomarkers for osteoporosis prediction. Then, using the key features extracted, we employed five classification algorithms: extreme gradient boosting (XGBoost), random forest, support vector machine, artificial neural network, and decision tree to predict the bone quality in terms of T-score. RESULTS: TPEE treatments down-regulated nuclear factor kappa-B ligand, alkaline phosphatase, and up-regulated estrogen receptor ß gene expression. Additionally, reduced serum C-terminal telopeptides of type 1 collagen level and improvement in the estrogen dependent characteristics of the uterus on the lining of the lumen were observed in the TPEE intervention group. Among the tested classifiers, XGBoost stood out as the best performing classification model with the highest F1-score and lowest standard deviation. CONCLUSIONS: The present study demonstrates that TPEE treatment showed therapeutic benefits in the prevention of osteoporosis at the transcriptional level and maintained the estrogen dependent characteristics of the uterus. Our study revealed that, in the case of limited number of features, RFECV paired with XGBoost model could serve as a powerful tool to readily evaluate and diagnose postmenopausal osteoporosis.

17.
Epilepsia ; 63(7): 1607-1618, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35451066

RESUMO

Drug-resistant epilepsy (DRE) is characterized by recurrent seizures despite appropriate treatment with antiseizure medication (ASM). Due to their regenerative and immunomodulatory potential, therapies with biologics such as mesenchymal stem cells (MSCs) offer a potential therapeutic benefit for structural causes of epilepsy, such as hippocampal sclerosis. In this article, we report a systematic review of the literature evaluating the preclinical and clinical studies of MSCs for DRE. Medline, Ovid EMBASE, Scopus, and the Cochrane Databases were searched electronically from their dates of inception to November 2021 using the following keywords: (("mesenchymal") AND ("stem cell")) AND (("epilepsy") OR ("convulsion") OR ("seizures")). This review followed Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) guidelines. The initial query identified 488 studies representing 323 unique manuscripts. After application of selection criteria, 15 studies were included in this systematic review; 11 were preclinical studies and 4 were clinical studies. All preclinical studies were performed in rodents and all clinical studies were phase 1 trials. Thus far, therapy with MSCs appears to be safe for use in humans, as no severe adverse events related directly to the therapy were reported. Furthermore, MSC therapy appears to provide a statistically significant clinical benefit by reducing the seizure burden of patients, reducing the electrophysiological biomarkers of epilepsy, and improving their comorbidities, such as depression and anxiety. In addition, animal studies reveal that the therapy exerts its effect by reducing aberrant mossy fiber sprouting (reduce excitatory pathways) and increasing γ-aminobutyric acid (GABA)ergic interneurons (increase inhibitory pathways). Both preclinical and clinical studies have shown MSC therapy to be safe and preliminary effective, thus warranting further studies to investigate its therapeutic potential.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsias Parciais , Epilepsia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Animais , Epilepsia Resistente a Medicamentos/etiologia , Epilepsias Parciais/etiologia , Epilepsias Parciais/terapia , Epilepsia/etiologia , Epilepsia/terapia , Humanos , Transplante de Células-Tronco Mesenquimais/efeitos adversos
18.
World Neurosurg ; 164: 367-373, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35351646

RESUMO

OBJECTIVE: Posterior costotransversectomy in the thoracic spine is commonly used for degenerative diseases, tumors, trauma, and other operative indications. It involves resection of the rib head after the ligamentous complexes have been disconnected from the transverse process and lateral vertebral body. The current literature provides only vague descriptions of the steps involved in rib disconnection with respect to posterior costotransversectomy. METHODS AND RESULTS: Through cadaveric studies and in vivo application, a stepwise method for rib disconnection is described. CONCLUSIONS: This manuscript is the first to outline an anatomical method for rib disconnection during costotransversectomy.


Assuntos
Procedimentos Ortopédicos , Parede Torácica , Humanos , Costelas/cirurgia , Vértebras Torácicas/cirurgia , Parede Torácica/cirurgia
19.
Eur J Hum Genet ; 30(6): 687-694, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35246666

RESUMO

Alexander disease (AxD) is a neurodegenerative astrogliopathy caused by mutation in the glial fibrillary acidic protein (GFAP) gene. A 42-year-old Korean man presented with temporary gait disturbance and psychiatric regression after a minor head trauma in the absence of bulbar symptoms and signs. Magnetic resonance images of the brain and spinal cord showed significant atrophy of the medulla oblongata and the entire spinal cord as well as contrast-enhanced T2 hypointensity in the basal ganglia. DNA sequencing revealed a novel 33-bp in-frame deletion mutation (p.Glu138_Leu148del) within the 1B rod domain of GFAP, which was predicted to be deleterious by PROVEAN analysis. To test whether the deletion mutant is disease-causing, we performed in vitro GFAP assembly and sedimentation assays, and GFAP aggregation assays in human adrenal carcinoma SW13 (Vim-) cells and rat primary astrocytes. All the assays revealed that GFAP p.Glu138_Leu148del is aggregation prone. Based on these findings, we diagnosed the patient with Type II AxD. This is a report that demonstrates the pathogenicity of InDel mutation of GFAP through functional studies. This patient's atypical presentation as well as the discrepancy between clinical symptoms and radiologic findings may extend the scope of AxD.


Assuntos
Doença de Alexander , Doença de Alexander/diagnóstico , Doença de Alexander/genética , Doença de Alexander/patologia , Animais , Encéfalo/metabolismo , Proteína Glial Fibrilar Ácida/genética , Humanos , Mutação , Fenótipo , Ratos
20.
J Clin Med ; 11(4)2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35207299

RESUMO

We investigated the complications and frequency of hook plate fixation in patients with shoulder trauma. We reviewed 216 cases of hook plate fixation use at our hospital between January 2010 and May 2020. Finally, we included 76 cases of acute distal clavicle fracture (DCF) and 84 cases of acute acromioclavicular joint dislocation (ACD). We investigated all complications after hook plate use, bony union in the DCF group, and reduction loss in the ACD group. We defined painful shoulder stiffness (PSS) as aggravating resting pain with stiff shoulder, and pain on shoulder elevation (PSE) as continued shoulder pain on elevation without PSS before plate removal. PSS was managed with intra-articular steroid injections or manipulation with or without arthroscopic capsular release (ACR). PSS occurred in 36 and 33 cases of DCF and ACD, respectively. PSE occurred in 17 of 76 fractures and 13 of 84 dislocations. However, no iatrogenic rotator cuff injury was verified by magnetic resonance imaging in patients with PSS or PSE. Subacromial erosion in patients with hook plate fixation should be considered a sequela and not a complication because it is unavoidable in surgery with an AO-type hook plate. The most common complication was PSS, followed by PSE.

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