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1.
Int J Mol Sci ; 25(20)2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39456866

RESUMO

Intermittent hypoxia (IH) has been extensively studied in recent years, demonstrating adverse and beneficial effects on several physiological systems. However, the precise mechanism underlying its cardiac effects on the heart remains unclear. This study aims to explore the effect of treatment on atrial fibrillation under IH conditions, providing data that can potentially be used in the treatment of heart disease. An atrial fibrillation (AF) model was induced by injecting monocrotaline (MCT, 60 mg/kg) into rats. The study included 32 rats divided into four groups: Control, Control + IH, AF, and AF + IH. We evaluated molecular changes associated with AF using ELISA and Western blot and performed electrophysiological experiments to evaluate AF. Arrhythmia-related calcium and fibrosis markers were investigated. Phosphorylation levels of CaMKII, Phospholamban, and RyR2 all increased in the AF group but decreased in the IH-exposed group. Additionally, fibrosis marker expressions such as SMA, MMP2, MMP9, and TGF-ß increased in the AF group but were significantly downregulated with IH treatment. Connexin 43 and AQP4 expression were restored in the IH-treated group. These findings suggest that IH may prevent AF by downregulating the expression of calcium-handling proteins and fibrosis-associated proteins in an AF-induced rat model.


Assuntos
Fibrilação Atrial , Hipóxia , Animais , Fibrilação Atrial/metabolismo , Fibrilação Atrial/etiologia , Ratos , Hipóxia/metabolismo , Masculino , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Conexina 43/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Modelos Animais de Doenças , Ratos Sprague-Dawley , Fibrose , Cálcio/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Fosforilação , Aquaporina 4
2.
J Trauma Inj ; 37(1): 20-27, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-39381145

RESUMO

Purpose: Severe abdominal injuries often require immediate clinical assessment and surgical intervention to prevent life-threatening complications. In Jeju Regional Trauma Center, we have instituted a protocol for emergency department (ED) laparotomy at the trauma bay. We investigated the mortality and time taken from admission to ED laparotomy. Methods: We reviewed the data recorded in our center's trauma database between January 2020 and December 2022 and identified patients who underwent laparotomy because of abdominal trauma. Laparotomies that were performed at the trauma bay or the ED were classified as ED laparotomy, whereas those performed in the operating room (OR) were referred to as OR laparotomy. In cases that required expeditious hemostasis, ED laparotomy was performed appropriately. Results: From January 2020 to December 2022, 105 trauma patients admitted to our hospital underwent emergency laparotomy. Of these patients, six (5.7%) underwent ED laparotomy. ED laparotomy was associated with a mortality rate of 66.7% (four of six patients), which was significantly higher than that of OR laparotomy (17.1%, 18 of 99 patients, P=0.006). All the patients who received ED laparotomy also underwent damage control laparotomy. The time between admission to the first laparotomy was significantly shorter in the ED laparotomy group (28.5 minutes; interquartile range [IQR], 14-59 minutes) when compared with the OR laparotomy group (104 minutes; IQR, 88-151 minutes; P<0.001). The two patients who survived after ED laparotomy had massive mesenteric bleeding, which was successfully ligated. The other four patients, who had liver laceration, kidney rupture, spleen injury, and pancreas avulsion, succumbed to the injuries. Conclusions: Although ED laparotomy was associated with a higher mortality rate, the time between admission and ED laparotomy was markedly shorter than for OR laparotomy. Notably, major mesenteric hemorrhages were effectively controlled through ED laparotomy.

3.
J Trauma Inj ; 37(1): 28-36, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-39381149

RESUMO

Purpose: Recent advancements in interventional radiology have made angioembolization an invaluable modality in trauma care. Angioembolization is typically performed by interventional radiologists. In this study, we aimed to investigate the safety and efficacy of emergency angioembolization performed by trauma surgeons. Methods: We identified trauma patients who underwent emergency angiography due to significant trauma-related hemorrhage between January 2020 and June 2023 at Jeju Regional Trauma Center. Until May 2022, two dedicated interventional radiologists performed emergency angiography at our center. However, since June 2022, a trauma surgeon with a background and experience in vascular surgery has performed emergency angiography for trauma-related bleeding. The indications for trauma surgeon-performed angiography included significant hemorrhage from liver injury, pelvic injury, splenic injury, or kidney injury. We assessed the angiography results according to the operator of the initial angiographic procedure. The term "failure of the first angioembolization" was defined as rebleeding from any cause, encompassing patients who underwent either re-embolization due to rebleeding or surgery due to rebleeding. Results: No significant differences were found between the interventional radiologists and the trauma surgeon in terms of re-embolization due to rebleeding, surgery due to rebleeding, or the overall failure rate of the first angioembolization. Mortality and morbidity rates were also similar between the two groups. In a multivariable logistic regression analysis evaluating failure after the first angioembolization, pelvic embolization emerged as the sole significant risk factor (adjusted odds ratio, 3.29; 95% confidence interval, 1.05-10.33; P=0.041). Trauma surgeon-performed angioembolization was not deemed a significant risk factor in the multivariable logistic regression model. Conclusions: Trauma surgeons, when equipped with the necessary endovascular skills and experience, can safely perform angioembolization. To further improve quality control, an enhanced training curriculum for trauma surgeons is warranted.

4.
Biomedicines ; 12(7)2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39062186

RESUMO

Stiffness and adhesions following rotator cuff tears (RCTs) are common complications that negatively affect surgical outcomes and impede healing, thereby increasing the risk of morbidity and failure of surgical interventions. Tissue engineering, particularly through the use of nanofiber scaffolds, has emerged as a promising regenerative medicine strategy to address these complications. This review critically assesses the efficacy and limitations of nanofiber-based methods in promoting rotator cuff (RC) regeneration and managing postrepair stiffness and adhesions. It also discusses the need for a multidisciplinary approach to advance this field and highlights important considerations for future clinical trials.

5.
Arch Orthop Trauma Surg ; 144(6): 2491-2500, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38698293

RESUMO

Rotator cuff tendon tears are a leading cause of shoulder pain. They are challenging to treat, and tendon-bone healing has a high failure rate despite successful surgery. Tendons connect the muscles and bones, which make them important for the body's overall mobility and stability. Metabolic diseases, including diabetes or high blood pressure, can affect the healing process after repair of a damaged tendon. With a global incidence of 9.3%, diabetes is considered as a significant risk factor for rotator cuff tendon healing because it causes structural, inflammatory, and vascular changes in the tendon. However, the mechanisms of how diabetes affects tendon healing remain unknown. Several factors have been suggested, including glycation product accumulation, adipokine dysregulation, increased levels of reactive oxygen species, apoptosis, inflammatory cytokines, imbalanced matrix-metalloproteinase-to-tissue-inhibitor ratio, and impaired angiogenesis and differentiation of the tendon sheath. Despite the effects of diabetes on tendon function and healing, few treatments are available to improve recovery in these patients. This review summarizes the current literature on the pathophysiological changes of the tendon in diabetes and hyperlipidemia. Preclinical and clinical evidence regarding the association between diabetes and tendon healing is presented. Moreover, current approaches to improve tendon healing in patients with diabetes are reviewed.


Assuntos
Lesões do Manguito Rotador , Tendinopatia , Cicatrização , Humanos , Lesões do Manguito Rotador/cirurgia , Lesões do Manguito Rotador/fisiopatologia , Lesões do Manguito Rotador/complicações , Cicatrização/fisiologia , Tendinopatia/etiologia , Tendinopatia/fisiopatologia , Manguito Rotador/cirurgia , Manguito Rotador/fisiopatologia , Diabetes Mellitus , Animais
6.
Nature ; 630(8016): 509-515, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38750366

RESUMO

Temperature profoundly affects macromolecular function, particularly in proteins with temperature sensitivity1,2. However, its impact is often overlooked in biophysical studies that are typically performed at non-physiological temperatures, potentially leading to inaccurate mechanistic and pharmacological insights. Here we demonstrate temperature-dependent changes in the structure and function of TRPM4, a temperature-sensitive Ca2+-activated ion channel3-7. By studying TRPM4 prepared at physiological temperature using single-particle cryo-electron microscopy, we identified a 'warm' conformation that is distinct from those observed at lower temperatures. This conformation is driven by a temperature-dependent Ca2+-binding site in the intracellular domain, and is essential for TRPM4 function in physiological contexts. We demonstrated that ligands, exemplified by decavanadate (a positive modulator)8 and ATP (an inhibitor)9, bind to different locations of TRPM4 at physiological temperatures than at lower temperatures10,11, and that these sites have bona fide functional relevance. We elucidated the TRPM4 gating mechanism by capturing structural snapshots of its different functional states at physiological temperatures, revealing the channel opening that is not observed at lower temperatures. Our study provides an example of temperature-dependent ligand recognition and modulation of an ion channel, underscoring the importance of studying macromolecules at physiological temperatures. It also provides a potential molecular framework for deciphering how thermosensitive TRPM channels perceive temperature changes.


Assuntos
Ativação do Canal Iônico , Canais de Cátion TRPM , Temperatura , Humanos , Trifosfato de Adenosina/metabolismo , Trifosfato de Adenosina/farmacologia , Sítios de Ligação , Cálcio/metabolismo , Microscopia Crioeletrônica , Células HEK293 , Ativação do Canal Iônico/efeitos dos fármacos , Ligantes , Modelos Moleculares , Ligação Proteica , Domínios Proteicos , Especificidade por Substrato , Canais de Cátion TRPM/agonistas , Canais de Cátion TRPM/antagonistas & inibidores , Canais de Cátion TRPM/química , Canais de Cátion TRPM/metabolismo , Vanadatos/química , Vanadatos/farmacologia , Vanadatos/metabolismo
7.
Nat Biomed Eng ; 8(9): 1124-1141, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38698155

RESUMO

The adenovirus-mediated somatic transfer of the embryonic T-box transcription factor 18 (TBX18) gene can convert chamber cardiomyocytes into induced pacemaker cells. However, the translation of therapeutic TBX18-induced cardiac pacing faces safety challenges. Here we show that the myocardial expression of synthetic TBX18 mRNA in animals generates de novo pacing and limits innate and inflammatory immune responses. In rats, intramyocardially injected mRNA remained localized, whereas direct myocardial injection of an adenovirus carrying a reporter gene resulted in diffuse expression and in substantial spillover to the liver, spleen and lungs. Transient expression of TBX18 mRNA in rats led to de novo automaticity and pacemaker properties and, compared with the injection of adenovirus, to substantial reductions in the expression of inflammatory genes and in activated macrophage populations. In rodent and clinically relevant porcine models of complete heart block, intramyocardially injected TBX18 mRNA provided rate-adaptive cardiac pacing for one month that strongly correlated with the animal's sinus rhythm and physical activity. TBX18 mRNA may aid the development of biological pacemakers.


Assuntos
Miocárdio , RNA Mensageiro , Proteínas com Domínio T , Animais , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Suínos , Miocárdio/metabolismo , Bloqueio Cardíaco/terapia , Bloqueio Cardíaco/genética , Adenoviridae/genética , Masculino , Estimulação Cardíaca Artificial/métodos , Miócitos Cardíacos/metabolismo , Feminino
8.
bioRxiv ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38617205

RESUMO

Precise connectivity between specific neurons is essential for the formation of the complex neural circuitry necessary for executing intricate motor behaviors and higher cognitive functions. While trans -interactions between synaptic membrane proteins have emerged as crucial elements in orchestrating the assembly of these neural circuits, the synaptic surface proteins involved in neuronal wiring remain largely unknown. Here, using unbiased single-cell transcriptomic and mouse genetic approaches, we uncover that the neurexin family of genes enables olfactory sensory neuron (OSNs) axons to form appropriate synaptic connections with their mitral and tufted (M/T) cell synaptic partners, within the mammalian olfactory system. Neurexin isoforms are differentially expressed within distinct populations of OSNs, resulting in unique pattern of neurexin expression that is specific to each OSN type, and synergistically cooperate to regulate axonal innervation, guiding OSN axons to their designated glomeruli. This process is facilitated through the interactions of neurexins with their postsynaptic partners, including neuroligins, which have distinct expression patterns in M/T cells. Our findings suggest a novel mechanism underpinning the precise assembly of olfactory neural circuits, driven by the trans -interaction between neurexins and their ligands.

9.
Nat Commun ; 15(1): 3360, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637611

RESUMO

The mammalian olfactory system detects and discriminates between millions of odorants to elicit appropriate behavioral responses. While much has been learned about how olfactory sensory neurons detect odorants and signal their presence, how specific innate, unlearned behaviors are initiated in response to ethologically relevant odors remains poorly understood. Here, we show that the 4-transmembrane protein CD20, also known as MS4A1, is expressed in a previously uncharacterized subpopulation of olfactory sensory neurons in the main olfactory epithelium of the murine nasal cavity and functions as a mammalian olfactory receptor that recognizes compounds produced by mouse predators. While wildtype mice avoid these predator odorants, mice genetically deleted of CD20 do not appropriately respond. Together, this work reveals a CD20-mediated odor-sensing mechanism in the mammalian olfactory system that triggers innate behaviors critical for organismal survival.


Assuntos
Neurônios Receptores Olfatórios , Receptores Odorantes , Animais , Camundongos , Aprendizagem/fisiologia , Mamíferos/metabolismo , Odorantes , Mucosa Olfatória/metabolismo , Neurônios Receptores Olfatórios/metabolismo , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Olfato/fisiologia , Antígenos CD20/metabolismo
10.
Heliyon ; 10(6): e28164, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38545191

RESUMO

Mollusca species shell such as oyster shell (OS) and snail shell (SS), are discarded after taking the meat, and the discarded shell causes the environmental problems. Therefore, recycling shell waste could potentially eliminate the environmental problems. This study aimed to evaluate the potential of OS and SS as natural calcium resources. The minerals, calcium, magnesium, potassium, phosphorus and sodium were analyzed in OS and SS extracts. Among them, the calcium content was the highest: 36.87 (%) and 33.42 (%) in the OS and SS extracts, respectively. Further, the content of ionized bioavailable form of calcium in OS and SS was higher than that of CaCO3 under simulated gastrointestinal digestion conditions. Additionally, OS and SS were added to kimchi, and their inhibitory effect on kimchi acidification was evaluated by assessing pH, titratable acidity and microbial analysis. As the results indicated that the addition of OS and SS had little effect on inhibiting the growth of lactic acid bacteria. However, it was confirmed that calcium neutralizes the organic acids produced during fermentation. Overall, the results of this study provide preliminary information on the re-use of OS and SS extracts as ionized natural calcium supplements and fermentation retardants.

11.
Hand Surg Rehabil ; 43(2): 101674, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38431044

RESUMO

OBJECTIVES: The relationship between volar fragment size and postoperative volar tilt loss in complete articular distal radius fracture is not well known. In this study, we measured precise radiological parameters to help identify other factors that might contribute to volar tilt loss. MATERIAL AND METHODS: We retrospectively reviewed the radiological examinations and charts of 256 patients with distal radial fracture who underwent volar locking plate fixation between March 2014 and July 2022. Radiological parameters were measured based on preoperative CT and immediate postoperative radiographs. Univariate and multivariate linear regression analysis was performed to identify relevant factors associated with volar tilt loss following volar locking plate fixation. The receiver operating characteristic curve was used to identify the cutoff value of the independent parameters. RESULTS: On univariate analysis, 2 radiologic parameters on preoperative CT (volar fragment length at the lunate fossa, and teardrop angle) and 4 on immediate postoperative X-ray (radial inclination, radial length, capitate shift, and volar tilt) were significantly associated with postoperative volar tilt loss. On multivariate linear regression analysis, the risk of volar tilt loss increased as the capitate moved toward the back of the radial shaft. The cut-off for anteroposterior length in the lunate fossa was 6.5 mm. CONCLUSIONS: AO/OTA type-C distal radius fractures with <6.5 mm anteroposterior length in the lunate fossa had significantly higher rates of malunion with dorsal deformity. In addition, preoperative teardrop angle <37.2 ° and immediate postoperative volar tilt <3.7º are also predictors of postoperative volar tilt loss.


Assuntos
Placas Ósseas , Fixação Interna de Fraturas , Fraturas do Rádio , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osso Semilunar/diagnóstico por imagem , Osso Semilunar/cirurgia , Complicações Pós-Operatórias/diagnóstico por imagem , Fraturas do Rádio/cirurgia , Fraturas do Rádio/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
12.
Nat Metab ; 6(2): 343-358, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38351124

RESUMO

The canonical biological function of selenium is in the production of selenocysteine residues of selenoproteins, and this forms the basis for its role as an essential antioxidant and cytoprotective micronutrient. Here we demonstrate that, via its metabolic intermediate hydrogen selenide, selenium reduces ubiquinone in the mitochondria through catalysis by sulfide quinone oxidoreductase. Through this mechanism, selenium rapidly protects against lipid peroxidation and ferroptosis in a timescale that precedes selenoprotein production, doing so even when selenoprotein production has been eliminated. Our findings identify a regulatory mechanism against ferroptosis that implicates sulfide quinone oxidoreductase and expands our understanding of selenium in biology.


Assuntos
Ferroptose , Selênio , Selênio/farmacologia , Selênio/metabolismo , Ubiquinona/farmacologia , Selenoproteínas/metabolismo , Sulfetos , Oxirredutases
13.
Heliyon ; 10(2): e24441, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38304807

RESUMO

The cultivar of red pepper used in kimchi contributes to spiciness, red color, and fermentation characteristics. Capsaicinoids are the main components of red pepper. Therefore, understanding changes in metabolites during kimchi fermentation according to capsaicinoid concentration is necessary to control the quality of kimchi. The purpose of this study was to investigate the effect of capsaicinoids on metabolites during kimchi fermentation. To profile the effect of capsaicinoid concentrations on kimchi fermentation, five kimchi samples were prepared using different concentrations of capsaicinoids (4, 12, 30.7, 40.9, and 50.3 mg/kg) and stored at 4 °C for 28 days. During kimchi fermentation, pH, titratable acidity, capsaicinoid concentration, total viable and lactic acid bacteria, free sugars, amino acids, and microbial community were evaluated. Each result was statistically analyzed for changes in capsaicin concentration and fermentation time. The capsaicinoid concentration did not change during kimchi fermentation but the growth of lactic acid bacteria changed. According to the growth of lactic acid bacteria, free sugar, amino acids, and microbial community changed with the capsaicinoid concentration. Overall, the results of this study provide preliminary information on the use of red pepper and capsaicinoids in the kimchi industry.

14.
Arthroscopy ; 40(8): 2174-2183, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38311267

RESUMO

PURPOSE: To determine the effects of topical tranexamic acid (TXA) administration on tendon adhesions, shoulder range of motion (ROM), and tendon healing in an acute rotator cuff repair rat model. METHODS: A total of 20 Sprague Dawley rats were used. Tendon adhesion, ROM, and biomechanical and histological analysis of tendon-bone healing was conducted at 3 and 6 weeks after surgery. The rats underwent rotator cuff repair surgery on both shoulders and were administered TXA via subacromial injections. The tendon adhesion was evaluated macroscopically and histologically. Biomechanical tendon healing was measured using a universal testing machine, and histological analysis was quantified by H&E, Masson's trichrome, and picrosirius red staining. RESULTS: At 3 weeks after surgery, the adhesion score was significantly lower in the TXA group (2.10 ± 0.32) than in the control group (2.70 ± 0.48) (P = .005), but there was no significant difference between the 2 groups at 6 weeks. Regarding ROM, compared with the control group, the TXA group showed significantly higher external rotation (36.35° ± 4.52° vs 28.42° ± 4.66°, P < .001) and internal rotation (45.35° ± 9.36° vs 38.94° ± 5.23°, P = .013) 3 weeks after surgery. However, at 6 weeks, there were no significant differences in external and internal rotation between the 2 groups. In the biomechanical analysis, no significant differences in gross examination (3 weeks, P = .175, 6 weeks, P = .295), load to failure (3 weeks, P = .117, 6 weeks, P = .295), or ultimate stress (3 weeks, P = .602, 6 weeks, P = .917) were noted between the 2 groups 3 and 6 weeks after surgery. In the histological analysis of tendon healing, no significant differences in the total score (3 weeks, P = .323, 6 weeks, P = .572) were found between the 2 groups 3 and 6 weeks after surgery. CONCLUSIONS: Topical TXA administration showed a beneficial effect in reducing tendon adhesions and improving ROM 3 weeks postoperatively and had no effect at 6 weeks. This suggests that additional intervention with TXA may be useful in achieving long-term improvement in shoulder stiffness. Additionally, TXA may increase tissue ground substance accumulation in the late postoperative period but does not adversely affect tendon-bone interface healing. CLINICAL RELEVANCE: The use of TXA after rotator cuff repair has no effect on tendon-bone interface healing in clinical practice and can improve shoulder stiffness in the early postoperative period. Additional research on the long-term effects is needed.


Assuntos
Antifibrinolíticos , Modelos Animais de Doenças , Amplitude de Movimento Articular , Ratos Sprague-Dawley , Lesões do Manguito Rotador , Ácido Tranexâmico , Cicatrização , Animais , Ácido Tranexâmico/uso terapêutico , Ácido Tranexâmico/administração & dosagem , Ácido Tranexâmico/farmacologia , Aderências Teciduais/prevenção & controle , Aderências Teciduais/etiologia , Lesões do Manguito Rotador/cirurgia , Lesões do Manguito Rotador/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Ratos , Antifibrinolíticos/uso terapêutico , Antifibrinolíticos/administração & dosagem , Antifibrinolíticos/farmacologia , Amplitude de Movimento Articular/efeitos dos fármacos , Manguito Rotador/cirurgia , Masculino , Fenômenos Biomecânicos , Administração Tópica
15.
Orthod Craniofac Res ; 27(1): 102-109, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37496461

RESUMO

OBJECTIVE: This finite element analysis (FEA) aimed to assess the stress distribution in the mandible and fixation system with various directions of the intermaxillary fixation (IMF) using mini-implants (MIs) and elastics following mandibular advancement with a bilateral sagittal split ramus osteotomy (BSSRO). MATERIALS AND METHODS: A total of nine mandibular advancement models were set according to the position of the MIs (1.6 mm in diameter, 8 mm in length) and direction of the IMF elastics (1/4 inch, 5 oz). Major and minor principal stresses in the cortical and cancellous bones, von Mises stresses in the fixation system (miniplate and monocortical screws), and bending angles of the miniplate were analysed. RESULTS: Compressive and tensile stress distributions in the mandible and von Mises stress distributions in the fixation system were greater in models with a Class III IMF elastic direction and a higher IMF elastic force than in models with a Class II IMF elastic direction and a lower IMF elastic force. The bending angle of the miniplate was negligible. CONCLUSIONS: Stress distributions in the bone and fixation system varied depending on the direction, amount of force, and position of IMF elastics and MIs. Conclusively, IMF elastics in the Class II direction with minimal load in the area close to the osteotomy site should be recommended.


Assuntos
Implantes Dentários , Avanço Mandibular , Procedimentos de Ancoragem Ortodôntica , Osteotomia Sagital do Ramo Mandibular , Análise de Elementos Finitos , Placas Ósseas , Parafusos Ósseos , Estresse Mecânico , Mandíbula/cirurgia
16.
Oncogene ; 43(5): 304-318, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38087050

RESUMO

Odorant receptors, traditionally associated with olfaction as chemoreceptors, have been increasingly recognized for their presence and diverse functions in various non-nasal tissues throughout the body. Beyond their roles in sensory perception, emerging evidence suggests a compelling interplay between odorant receptors and cancer progression as well. Alongside the canonical GPCR odorant receptors, dysregulation of non-canonical odorant receptors such as trace amine-associated receptors (TAARs), formyl peptide receptors (FPRs), and membrane-spanning 4A family (MS4As) has been observed in various cancer types, suggesting their contributions to cancer progression. The roles of these non-canonical chemoreceptors in cancer are complex, with some receptors promoting tumorigenesis and others acting as tumor-suppressing factors upon activation, depending on the cancer type. These findings shed light on the potential of non-canonical odorant receptors as therapeutic targets and prognostic markers in cancer, inviting further exploration to unravel their precise mechanisms of action and implications in cancer biology. In this review, we provide a comprehensive overview of the intricate relationships between these chemoreceptors and various types of cancer, potentially paving the way for innovative odor-based therapeutics. Ultimately, this review discusses the potential development of novel therapeutic strategies targeting these non-canonical chemoreceptors.


Assuntos
Neoplasias , Receptores Odorantes , Humanos , Receptores Odorantes/genética , Odorantes
17.
Small Methods ; 8(5): e2301428, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38161256

RESUMO

Mitigating sepsis-induced severe organ dysfunction with magnetic nanoparticles has shown remarkable advances in extracorporeal blood treatment. Nevertheless, treating large septic animals remains challenging due to insufficient magnetic separation at rapid blood flow rates (>6 L h-1) and limited incubation time in an extracorporeal circuit. Herein, superparamagnetic nanoclusters (SPNCs) coated with red blood cell (RBC) membranes are developed, which promptly capture and magnetically separate a wide range of pathogens at high blood flow rates in a swine sepsis model. The SPNCs exhibited an ultranarrow size distribution of clustered iron oxide nanocrystals and exceptionally high saturation magnetization (≈ 90 emu g-1) close to that of bulk magnetite. It is also revealed that CD47 on the RBCs allows the RBC-SPNCs to remain at a consistent concentration in the blood by evading innate immunity. The uniform size distribution of the RBC-SPNCs greatly enhances their effectiveness in eradicating various pathogenic materials in extracorporeal blood. The use of RBC-SPNCs for extracorporeal treatment of swine infected with multidrug-resistant E. coli is validated and found that severe bacteremic sepsis-induced organ dysfunction is significantly mitigated after 12 h. The findings highlight the potential application of RBC-SPNCs for extracorporeal therapy of severe sepsis in large animal models and potentially humans.


Assuntos
Nanopartículas de Magnetita , Sepse , Animais , Sepse/terapia , Suínos , Nanopartículas de Magnetita/química , Eritrócitos , Insuficiência de Múltiplos Órgãos/terapia , Insuficiência de Múltiplos Órgãos/prevenção & controle , Modelos Animais de Doenças , Infecções por Escherichia coli/terapia , Nanopartículas Magnéticas de Óxido de Ferro/química , Escherichia coli
18.
Clin Orthop Surg ; 15(6): 873-879, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38045588

RESUMO

Rotator cuff tears are a condition characterized by damage to the muscles and tendons that connect the scapula and humerus, which are responsible for shoulder rotation and arm lifting. Metabolic factors such as diabetes, thyroid disease, high cholesterol, vitamin D deficiency, obesity, and smoking have been associated with an increased risk of rotator cuff tears. Interestingly, patients with hyperlipidemia, a condition characterized by high levels of cholesterol and other fats in the blood, have been found to have a higher incidence of rotator cuff tears and breakdown of tendon matrix. As a result, statin therapy, which is commonly used to lower cholesterol levels in hyperlipidemia, has been explored as a potential treatment to improve clinical outcomes in rotator cuff tears. However, the results of preclinical and clinical studies on the effects of statins on tendon healing in rotator cuff tears are limited and not well-defined. Moreover, since hyperlipidemia and rotator cuff tears are more prevalent in older individuals, a literature review on the efficacy and safety of statin therapy in this population is needed.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Hiperlipidemias , Lesões do Manguito Rotador , Humanos , Idoso , Manguito Rotador , Lesões do Manguito Rotador/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Resultado do Tratamento , Colesterol , Hiperlipidemias/tratamento farmacológico
19.
ACS Synth Biol ; 12(11): 3406-3413, 2023 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-37864563

RESUMO

A small and efficient DNA mutation-inducing machine was constructed with an array of microplasma jet devices (7 × 1) that can be operated at atmospheric pressure for microbial mutagenesis. Using this machine, we report disruption of a plasmid DNA and generation of mutants of an oleaginous yeast Rhodosporidium toruloides. Specifically, a compact-sized microplasma channel (25 × 20 × 2 mm3) capable of generating an electron density of greater than 1013 cm-3 was constructed to produce reactive species (N2*, N2+, O, OH, and Hα) under helium atmospheric conditions to induce DNA mutagenesis. The length of microplasma channels in the device played a critical role in augmenting both the volume of plasma and the concentration of reactive species. First, we confirmed that microplasma treatment can linearize a plasmid by creating nicks in vitro. Second, we treated R. toruloides cells with a jet device containing 7 microchannels for 5 min; 94.8% of the treated cells were killed, and 0.44% of surviving cells showed different colony colors as compared to their parental colony. Microplasma-based DNA mutation is energy-efficient and can be a safe alternative for inducing mutations compared to conventional methods using toxic mutagens. This compact and scalable device is amenable for industrial strain improvement involving large-scale mutagenesis.


Assuntos
Rhodotorula , Mutagênese , Mutação/genética , Rhodotorula/genética , DNA
20.
Clin Orthop Surg ; 15(5): 809-817, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37811501

RESUMO

Background: Cage subsidence after oblique lumbar interbody fusion (OLIF) induces restenosis and adversely affects patient outcomes. Many studies have investigated the causes of subsidence, one of which is endplate fracture (EF). This study aimed to identify predictors of EF after OLIF. Methods: This retrospective study reviewed consecutive patients who underwent OLIF at a single institute between August 2019 and February 2022. A total of 104 patients were enrolled. The patients' demographic data and surgical details were collected through chart reviews. Radiographic variables were measured. Related variables were also analyzed using binomial logistic regression, dividing each group into those with versus without EF. Results: EF occurred at 30 of 164 levels (18.3%), and the binary logistic analysis revealed that sex (odds ratio [OR], 11.07), inferior endplate concave depth (OR, 1.95), disc wedge angle (OR, 1.22), lumbar lordosis (OR, 1.09), pelvic incidence (OR, 1.07), sagittal vertical axis (OR, 1.02), sacral slope (OR, 0.9), L3-4 level (OR, 0.005), and L4-5 level (OR, 0.004) were significantly related to EF. Conclusions: OLIF in older Asian patients should be performed carefully after recognizing the high possibility of EF and confirming the factors that should be considered preoperatively.


Assuntos
Fraturas Ósseas , Lordose , Fusão Vertebral , Humanos , Idoso , Estudos Retrospectivos , Resultado do Tratamento , Região Lombossacral , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Fusão Vertebral/efeitos adversos
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