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Iridocyclitis and the use of glucocorticoid medication have been widely studied as susceptibility factors for cataracts. However, the causal relationship between them remains unclear. This study aimed to investigate the causal relationship between the development of iridocyclitis and the genetic liability of glucocorticoid medication use on the risk of senile cataracts occurrence by performing Two-sample Mendelian randomization (MR) analyses. Instrumental variables (IVs) significantly associated with exposure factors (P < 5 × 10-8) were identified using published genome-wide association data from the FinnGen database and UK Biobank. Reliability analyses were conducted using five approaches, including inverse-variance weighted (IVW), MR-Egger regression, simple median, weighted median, and weighted mode. A sensitivity analysis using the leave-one-out method was also performed. Genetic susceptibility to glucocorticoid use was associated with an increased risk of developing senile cataracts (OR, 1.10; 95% CI, 1.02-1.17; P < 0.05). Moreover, iridocyclitis was significantly associated with a higher risk of developing senile cataracts (OR, 1.03; 95% CI, 1.01-1.05; P < 0.05). Nonetheless, some heterogeneity in the IVs was observed, but the MR results remained consistent after penalizing for outliers. The estimates were consistent in multivariate analyses by adjusting for body mass index (BMI) and diabetes mellitus type 2 (T2DM). This study provides new insights into the prevention and management of senile cataracts by highlighting the increased risk associated with iridocyclitis and the use of glucocorticoids.
Assuntos
Catarata , Glucocorticoides , Iridociclite , Análise da Randomização Mendeliana , Humanos , Catarata/genética , Catarata/epidemiologia , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Iridociclite/genética , Iridociclite/epidemiologia , Estudo de Associação Genômica Ampla , Predisposição Genética para Doença , Fatores de Risco , IdosoRESUMO
Sepsis is a systemic inflammatory response syndrome caused by infection, with high morbidity and mortality. Sepsis-induced liver injury(SILI) is one of the manifestations of sepsis-induced multiple organ syndrome. At present, there is no recommended pharmacological intervention for the treatment of SILI. traditional Chinese medicine(TCM), based on the holism and dialectical treatment concept, shows the therapeutic characteristics of multi-target and multi-pathway and can comprehensively prevent and treat SILI by interfering with inflammatory factors, inflammatory signaling pathways, and anti-oxidative stress and inhibiting apoptosis. This article reviewed the experimental studies on the treatment of SILI with TCM to clarify its pathogenic mechanism and therapeutic characteristics, so as to provide more ideas and directions for the development or preparation of new drugs.
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Doença Hepática Crônica Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas , Sepse , Humanos , Medicina Tradicional Chinesa , Doença Hepática Crônica Induzida por Substâncias e Drogas/tratamento farmacológico , Sepse/complicações , Sepse/tratamento farmacológico , Apoptose , Transdução de Sinais , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologiaRESUMO
BACKGROUND: Antithrombin III (AT3) deficiency, an autosomal dominant disease, increases the likelihood of an individual developing venous thromboembolism (VTE). Long-term anticoagulation treatment is required for those suffering from AT3 deficiency. CASE SUMMARY: A man aged 23, who had a history of deep venous thrombosis (DVT), experienced recurrent pain and swelling in his right lower extremity for three days following withdrawal of Rivaroxaban. He was diagnosed with DVT and antithrombin III deficiency as genetic testing revealed a single nucleotide variant in SERPINC1 (c.667T>C, p.S223P). The patient was advised to accept long-term anticoagulant therapy. CONCLUSION: Inherited AT3 deficiency due to SERPINC1 mutations results in recurrent VTE. Patients may benefit from long-term anticoagulant therapy.
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We developed a computational method to identify NAD- and FAD-binding sites in proteins. First, we extracted from the Protein Data Bank structures of proteins that bind to at least one of these ligands. NAD-/FAD-binding residue templates were then constructed by identifying binding residues through the ligand-binding database BioLiP. The fragment transformation method was used to identify structures within query proteins that resembled the ligand-binding templates. By comparing residue types and their relative spatial positions, potential binding sites were identified and a ligand-binding potential for each residue was calculated. Setting the false positive rate at 5%, our method predicted NAD- and FAD-binding sites at true positive rates of 67.1% and 68.4%, respectively. Our method provides excellent results for identifying FAD- and NAD-binding sites in proteins, and the most important is that the requirement of conservation of residue types and local structures in the FAD- and NAD-binding sites can be verified.
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Bioquímica/métodos , Flavina-Adenina Dinucleotídeo/metabolismo , NAD/metabolismo , Proteínas/química , Aminoácidos , Sítios de Ligação , Modelos Moleculares , Máquina de Vetores de SuporteRESUMO
5-Enolpyruvylshikimate-3-phosphate synthase (EPSPS), the target enzyme for glyphosate inhibition, catalyzes an essential step in the shikimate pathway for aromatic amino acid biosynthesis. The full-length cDNA of 1,751 nucleotides (CaEPSPS, Genbank accession number: EU698030) from Convolvulus arvensis was cloned and characterized. The CaEPSPS encodes a polypeptide of 520 amino acids with a calculated molecular weight of 55.5 kDa and an isoelectric point of 7.05. The results of homology analysis revealed that CaEPSPS showed highly homologous with EPSPS proteins from other plant species. Tissue expression pattern analysis indicated that CaEPSPS was constitutively expressed in stems, leaves and roots, with lower expression in roots. CaEPSPS expression level could increase significantly with glyphosate treatment, and reached its maximum at 24 h after glyphosate application. We fused CaEPSPS to the CaMV 35S promoter and introduced the chimeric gene into Arabidopsis. The resultant expression of CaEPSPS in transgenic Arabidopsis plants exhibited enhanced tolerance to glyphosate in comparison with control.
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3-Fosfoshikimato 1-Carboxiviniltransferase/genética , Clonagem Molecular , Convolvulus/genética , Regulação da Expressão Gênica de Plantas , 3-Fosfoshikimato 1-Carboxiviniltransferase/metabolismo , Sequência de Aminoácidos , Sequência de Bases , Convolvulus/classificação , Convolvulus/metabolismo , DNA Complementar/química , DNA Complementar/genética , Resistência a Medicamentos/genética , Ativação Enzimática , Perfilação da Expressão Gênica , Glicina/análogos & derivados , Glicina/farmacologia , Herbicidas/farmacologia , Dados de Sequência Molecular , Fenótipo , Filogenia , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas , Alinhamento de Sequência , GlifosatoRESUMO
BACKGROUND: The role of radiation therapy (RT) for ameloblastoma remains controversial and undetermined due to the rarity of the disease. METHODS: A case of repeatedly recurrent ameloblastoma with malignant transformation is presented. The clinical course and managements are described. RESULTS: The 63-year-old man had a recurrent ameloblastoma in the left mandible. Five years after the first surgical resection, he underwent 8 more rounds of surgical excision of the recurrent tumors. The malignant transformation occurred and the unresectable tumor invaded the masticator space, parapharyngeal space, and skull base. He received 3-dimensional conformal RT, at the dose of 66 Gray (Gy) in 33 fractions. The ulcerative exophytic mass had regressed gradually. After follow-up of 28 months, the tumor was well controlled. CONCLUSIONS: RT seems to be a feasible treatment option for recurrent ameloblastoma with malignant transformation.
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Ameloblastoma/patologia , Transformação Celular Neoplásica/patologia , Neoplasias Mandibulares/patologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Radioterapia Conformacional/métodos , Ameloblastoma/cirurgia , Biópsia por Agulha , Seguimentos , Humanos , Imuno-Histoquímica , Masculino , Neoplasias Mandibulares/cirurgia , Pessoa de Meia-Idade , Radiografia Panorâmica/métodos , Dosagem Radioterapêutica , Fatores de Tempo , Resultado do TratamentoRESUMO
The +1 order diffraction of polarization holographic gratings generated by two linear orthogonally polarized writing beams in dye-doped liquid-crystal films were increased by using two recording beams with unequal intensity. The maximum diffraction efficiency of the polarization holograms in our experimental sample can reach 23% when the intensity ratio of two recording beams is 7:1, and this value is almost triple that when the intensity ratio of two recording beams is 1:1.
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OBJECTIVE: Tuberculosis (TB) of the head and neck is currently a reemerging infectious disease and may be a diagnostic challenge for dental care providers. The aim of the present study was to retrospectively review the clinical features of patients diagnosed with TB of the head and neck during the past 16 years. MATERIALS AND METHODS: Thirteen male and 7 female patients with TB of the head and neck were histologically identified following surgical biopsy in our department between 1991 and 2007. The medical charts were reviewed. RESULTS: The age distribution was broad, with 11 patients (55%) older than 50 years and 4 (20%) younger than 10 years old. Thirteen patients had oral lesions and 2 had multiple lesions. The most common oral location was the buccal mucosa and/or vestibule (5 cases), followed by the alveolar mucosa (4 cases), palate (2 cases), lip (2 cases), and tongue (1 case). Seven patients had cervical TB. The predominant clinical manifestation was ulceration. Two patients were found to have coexistent metastatic squamous cell carcinoma. Four patients were identified with active pulmonary lesions and 1 patient with evidence of old pulmonary TB on the 14 chest radiographs available. CONCLUSION: Tuberculosis of the head and neck may not be as rare as once thought. We emphasize the importance of early diagnosis in such lesions, especially in slow-to-heal wounds and undiagnosed neck lumps.
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Tuberculose dos Linfonodos/patologia , Tuberculose Bucal/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: To analyze image artifact types and occurrence frequency when using a phosphor storage plate (PSP) digital radiographic system. STUDY DESIGN: A total of 15,912 scanned digital images were evaluated by 3 observers, and image artifacts were classified into: 1) operator errors; 2) scanning errors; 3) PSP plate defects. To avoid damage to the sensor plate, a modification technique innovated by Roberts and Mol was used where needed and 2 double-sided pieces of tape were placed around the sensor plate covering. RESULTS: A total of 643 image artifacts were identified. The main image artifact cause was operator error (n = 554), followed by defects of plate (n = 60) and scanning (n = 29). Scanning errors could generally be corrected by rescanning, but most other artifacts required image retaking. The use of a modified clinical technique greatly reduced artifacts caused by wearing of the sensor plate (20%). CONCLUSIONS: Modified methods to decrease the occurrence of image artifacts using PSP digital radiographic system are encouraged.
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Artefatos , Radiografia Dentária Digital/instrumentação , Humanos , Variações Dependentes do Observador , Ecrans Intensificadores para Raios XRESUMO
Defected mitochondrial respiratory chain (RC), in addition to causing a severe ATP deficiency, often augments reactive oxygen species (ROS) generation in mitochondria (mROS) which enhances pathological conditions and diseases. Previously, we demonstrated a potent endogenously RC defect-augmented mROS associated dose-dependently with a commonly seen large-scale deletion of 4977 base pairs of mitochondrial DNA (mtDNA), i.e. the common deletion (CD). As current treatments for CD-associated diseases are rather supplementary and ineffective, we investigated whether melatonin, a potential mitochondrial protector, provides beneficial protection for CD-augmented mitochondrial oxidative stress and apoptosis particularly upon the induction of a secondary oxidative stress. Detailed mechanistic investigations were performed by using laser scanning dual fluorescence imaging microscopy to provide precise spatial and temporal resolution of mitochondrial events at single cell level. We demonstrate, for the first time, that melatonin significantly prevents CD-augmented mROS formation under basal conditions as well as at early time-points upon secondary oxidative stress induced by H2O2 exposure. Thus, melatonin prevents mROS-mediated depolarization of mitochondrial membrane potential (DeltaPsim) and subsequent opening of the mitochondrial permeability transition pore (MPTP) and cytochrome c release. Moreover, melatonin prevents depletion of cardiolipin which appears to be crucial for postponing later MPTP opening, disruption of the mitochondrial membrane and apoptosis. Finally, the protection provided by melatonin is superior to those caused by the suppression of mitochondrial Ca2+ regulators including the mitochondrial Na+-Ca2) exchanger, the MPTP, and the mitochondrial Ca2+ uniporter and by antioxidants including vitamin E and mitochondria-targeted coenzyme Q, MitoQ. As RC defect-augmented endogenous mitochondrial oxidative stress is centrally involved in a variety of pathological conditions and diseases, melatonin thus may serve as a therapeutic drug to benefit many clinical conditions that involve malfunction of the mitochondria.
Assuntos
Apoptose/efeitos dos fármacos , DNA Mitocondrial/genética , Melatonina/farmacologia , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Cardiolipinas/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Transporte de Elétrons/efeitos dos fármacos , Células Híbridas , Peróxido de Hidrogênio/farmacologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Microscopia Confocal , Mitocôndrias/genética , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Deleção de SequênciaRESUMO
A simple and rapid MEKC method was developed for the simultaneous determination of myo-inositol, scyllo-inositol, and glucose. Prior to electrophoretic separation, the nonfluorescent inositols and glucose were derivatized by N-methylisatoic anhydride at 25 degrees C for 10 min so that they could be detected by a fluorescence detector during separation. The good separation with high efficiency by MEKC was achieved in 13 min with a glycine buffer containing SDS and PEG 4000. Several parameters affecting the separation were studied, including the pH of BGE, the concentrations of glycine, SDS, and PEG 4000, and the applied voltage. Using glycerol as an internal standard, the linear ranges of the method for myo-inositol, scyllo-inositol, and glucose were 0.03-10, 0.01-5, and 0.05-20 mM; the concentration LODs of myo-inositol, scyllo-inositol, and glucose were 0.020, 0.0078, and 0.026 mM, respectively. The method was applied to analyze extracellular myo-inositol and glucose in the microdialysates from rat brain cortex of ischemia animal model and intracellular myo-inositol and scyllo-inositol in the rat brain extract.