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1.
Nat Commun ; 15(1): 7800, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39242511

RESUMO

Dynamic tracking of spinal instrumentation could facilitate real-time evaluation of hardware integrity and in so doing alert patients/clinicians of potential failure(s). Critically, no method yet exists to continually monitor the integrity of spinal hardware and by proxy the process of spinal arthrodesis; as such hardware failures are often not appreciated until clinical symptoms manifest. Accordingly, herein, we report on the development and engineering of a bio-adhesive metal detector array (BioMDA), a potential wearable solution for real-time, non-invasive positional analyses of osseous implants within the spine. The electromagnetic coupling mechanism and intimate interfacial adhesion enable the precise sensing of the metallic implants position without the use of radiation. The customized decoupling models developed facilitate the precise determination of the horizontal and vertical positions of the implants with incredible levels of accuracy (e.g., <0.5 mm). These data support the potential use of BioMDA in real-time/dynamic postoperative monitoring of spinal implants.


Assuntos
Metais , Próteses e Implantes , Coluna Vertebral , Dispositivos Eletrônicos Vestíveis , Humanos , Coluna Vertebral/cirurgia , Metais/química , Adesivos , Fusão Vertebral/instrumentação , Fusão Vertebral/métodos
2.
J Cancer ; 15(17): 5636-5642, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39308680

RESUMO

Actin, primarily a cytoplasmic cytoskeleton protein, is transported in and out of the nucleus with the help of actin-binding proteins (ABPs). Actin exists in two forms, i.e., monomeric globular (G-actin) and polymerized filamentous (F-actin). While G-actin promotes gene transcription by associating with RNA polymerases, F-actin can inhibit this effect in the nucleus. Unexpectedly, we found that lovastatin, an FDA-approved lipid-lowering drug, induces actin redistribution and its translocation into the nucleus in triple-negative breast cancer (TNBC) cancer stem cells. Lovastatin treatment also decreased levels of rRNAs and stemness markers, which are transcription products of RNA Pol I and Pol II, respectively. Bioinformatics analysis showed that actin genes were positively correlated with ABP genes involved in the translocation/polymerization and transcriptional regulation of nuclear actin in breast cancer. Similar correlations were found between actin genes and RNA Pol I genes and stemness-related genes. We propose a model to explain the roles of lovastatin in inducing nucleolar stress and inhibiting stemness in TNBC cancer stem cells. In our model, lovastatin induces translocation/accumulation of F-actin in the nucleus/nucleolus, which, in turn, induces nucleolar stress and stemness inhibition by suppressing the synthesis of rRNAs and decreasing the expression of stemness-related genes. Our model has opened up a new field of research on the roles of nuclear actin in cancer biology, offering potential therapeutic targets for the treatment of TNBC.

3.
bioRxiv ; 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39345413

RESUMO

Synthesizing perceivable artificial neural inputs independent of typical sensory channels remains a fundamental challenge in the development of next-generation brain-machine interfaces. Establishing a minimally invasive, wirelessly effective, and miniaturized platform with long-term stability is crucial for creating a clinically meaningful interface capable of mediating artificial perceptual feedback. In this study, we demonstrate a miniaturized fully implantable wireless transcranial optogenetic encoder designed to generate artificial perceptions through digitized optogenetic manipulation of large cortical ensembles. This platform enables the spatiotemporal orchestration of large-scale cortical activity for remote perception genesis via real-time wireless communication and control, with optimized device performance achieved by simulation-guided methods addressing light and heat propagation during operation. Cue discrimination during operant learning demonstrates the wireless genesis of artificial percepts sensed by mice, where spatial distance across large cortical networks and sequential order-based analyses of discrimination performance reveal principles that adhere to general perceptual rules. These conceptual and technical advancements expand our understanding of artificial neural syntax and its perception by the brain, guiding the evolution of next-generation brain-machine communication.

4.
Appl Environ Microbiol ; 90(8): e0012124, 2024 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-38980046

RESUMO

Naja atra, the Chinese cobra, is a major cause of snake envenomation in Asia, causing hundreds of thousands of clinical incidents annually. The current treatment, horse serum-derived antivenom, has unpredictable side effects and presents manufacturing challenges. This study focused on developing new-generation snake venom antidotes by using microbial phage display technology to derive nanobodies from an alpaca immunized with attenuated N. atra venom. Following confirmation of the immune response in the alpaca, we amplified VHH genes from isolated peripheral blood mononuclear cells and constructed a phage display VHH library of 1.0 × 107 transformants. After four rounds of biopanning, the enriched phages exhibited increased binding activity to N. atra venom. Four nanobody clones with high binding affinities were selected: aNAH1, aNAH6, aNAH7, and aNAH9. Specificity testing against venom from various snake species, including two Southeast Asian cobra species, revealed nanobodies specific to the genus Naja. An in vivo mouse venom neutralization assay demonstrated that all nanobodies prolonged mouse survival and aNAH6 protected 66.6% of the mice from the lethal dosage. These findings highlight the potential of phage display-derived nanobodies as valuable antidotes for N. atra venom, laying the groundwork for future applications in snakebite treatment.IMPORTANCEChinese cobra venom bites present a formidable medical challenge, and current serum treatments face unresolved issues. Our research applied microbial phage display technology to obtain a new, effective, and cost-efficient treatment approach. Despite interest among scientists in utilizing this technology to screen alpaca antibodies against toxins, the available literature is limited. This study makes a significant contribution by introducing neutralizing antibodies that are specifically tailored to Chinese cobra venom. We provide a comprehensive and unbiased account of the antibody construction process, accompanied by thorough testing of various nanobodies and an assessment of cross-reactivity with diverse snake venoms. These nanobodies represent a promising avenue for targeted antivenom development that bridges microbiology and biotechnology to address critical health needs.


Assuntos
Antivenenos , Camelídeos Americanos , Venenos Elapídicos , Anticorpos de Domínio Único , Mordeduras de Serpentes , Animais , Anticorpos de Domínio Único/imunologia , Camundongos , Mordeduras de Serpentes/terapia , Mordeduras de Serpentes/imunologia , Antivenenos/imunologia , Venenos Elapídicos/imunologia , Técnicas de Visualização da Superfície Celular , Naja naja , Biblioteca de Peptídeos
5.
Food Chem ; 460(Pt 1): 140473, 2024 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-39029366

RESUMO

Simple and rapid molecular detection technologies for authenticating animal species are urgently needed for food safety and authenticity. This study established a new direct-fast quantitative polymerase chain reaction (qPCR) detection technology for beef to achieve rapid and on-site nucleic acid detection in food. This technology can complete nucleic acid extraction in 4 min using a new type of food nucleic acid-releasing agent, followed by direct amplification of the DNA sample by fast qPCR in 25 min. The results indicated that direct-fast qPCR can specifically identify beef and can also identify 0.00001% of beef components in artificially simulated meat mixtures, with a detection precision variation coefficient of <4%. This method can be used to effectively identify beef in different food samples. As a simple, fast, and accurate molecular detection technology for beef, this method may provide a new tool for the on-site detection of beef components in food.


Assuntos
Contaminação de Alimentos , Reação em Cadeia da Polimerase em Tempo Real , Animais , Bovinos , Contaminação de Alimentos/análise , Reação em Cadeia da Polimerase em Tempo Real/métodos , Ácidos Nucleicos/análise , Carne/análise , Carne Vermelha/análise , DNA/análise
6.
Artigo em Inglês | MEDLINE | ID: mdl-38967079

RESUMO

BACKGROUND: Osteosarcoma is considered as the most prevalent form of primary malignant bone cancer, prompting a pressing need for novel therapeutic options. Arnicolide D, a sesquiterpene lactone derived from the traditional Chinese herbal medicine Centipeda minima (known as E Bu Shi Cao in Chinese), showed anticancer efficacy against several kinds of cancers. However, its effect on osteosarcoma remains unclear. OBJECTIVE: This study aimed to investigate the anticancer activity of arnicolide D and the underlying molecular mechanism of its action in osteosarcoma cells, MG63 and U2OS. METHODS: Cell viability and proliferation were evaluated through MTT assay and colony formation assay following 24 h and 48 h treatment with different concentrations of arnicolide D. Flow cytometry was employed to examine cell cycle progression and apoptosis after 24 h treatment of arnicolide D. Western blotting was performed to determine the expression of the PI3k, Akt and m-TOR and their phosphorylated forms. RESULTS: Our findings revealed that arnicolide D treatment resulted in a significant reduction in cell viability, the inhibition of proliferation, and the induction of apoptosis and cell cycle arrest in the G2/M phase. Furthermore, arnicolide D could inhibit the activation of PI3K/Akt/mTOR pathway in osteosarcoma cells. CONCLUSION: Based on our results, arnicolide D demonstrated significant anti-osteosarcoma activity and held the potential to be considered as a therapeutic candidate for osteosarcoma in the future.

7.
Global Spine J ; : 21925682241265878, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39030762

RESUMO

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: This study aimed to investigate the long-term outcomes of laminoplasty-alone (LP) and combined procedure (CP), consisting of laminoplasty and single-level anterior cervical discectomy and fusion, in comparable patients who had multilevel degenerative cervical myelopathy (MDCM) with concomitant anterior and posterior compression (CAPC). METHODS: Consecutive MDCM patients with CAPC underwent LP or CP between 2012 and 2015 from a same surgical group were enrolled and followed up for a minimum of 8 years. Preoperative demographic, radiological, and clinical variables were collected. Propensity score matching (PSM) analysis was performed to match patients with comparable conditions. The outcomes were evaluated by postoperative Japanese Orthopedic Association (JOA) score improvement, JOA recovery rate (JOARR) and complications. RESULTS: A total of 230 patients were included, of whom 146 underwent LP and 84 underwent CP. After PSM, 84 pairs of comparable patients were matched. The matched groups presented fair comparability in preoperative conditions. The CP group had significantly prolonged surgery time and greater blood loss. At the final follow-up, the postoperative JOA scores of LP and CP groups were 14.51 ± 1.79 and 15.47 ± 1.81 (P < 0.001) and the JOARR were 42.5% ± 53.3% and 68.5% ± 35.4%, respectively (P < 0.001). Three (3.6%) patients in the LP group underwent reoperations because of recurrent symptoms (P = 0.081). CONCLUSION: Both LP and CP demonstrated considerable long-term neurological recovery in patients with CAPC. The CP showed a significantly higher JOA improvement and JOARR. The combined decompression might be a safe and effective alternative in treating MDCM with CAPC in experienced hands.

8.
BMC Musculoskelet Disord ; 25(1): 445, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844933

RESUMO

BACKGROUND: T2-weighted increased signal intensity (ISI) is commonly recognized as a sign of more severe spinal cord lesions, usually accompanied by worse neurological deficits and possibly worse postoperative neurological recovery. The combined approach could achieve better decompression and better neurological recovery for multilevel degenerative cervical myelopathy (MDCM). The choice of surgical approach for MDCM with intramedullary T2-weighted ISI remains disputed. This study aimed to compare the neurological outcomes of posterior and one-stage combined posteroanterior approaches for MDCM with T2-weighted ISI. METHODS: A total of 83 consecutive MDCM patients with confirmed ISI with at least three intervertebral segments operated between 2012 and 2014 were retrospectively enrolled. Preoperative demographic, radiological and clinical condition variables were collected, and neurological conditions were evaluated by the Japanese Orthopedic Assessment score (JOA) and Neck Disability Index (NDI). Propensity score matching analysis was conducted to produce pairs of patients with comparable preoperative conditions from the posterior-alone and combined groups. Both short-term and mid-term surgical outcomes were evaluated, including the JOA recovery rate (JOARR), NDI improvements, complications, and reoperations. RESULTS: A total of 83 patients were enrolled, of which 38 and 45 patients underwent posterior surgery alone and one-stage posteroanterior surgery, respectively. After propensity score matching, 38 pairs of comparable patients from the posterior and combined groups were matched. The matched groups presented similar preoperative clinical and radiological features and the mean follow-up duration were 111.6 ± 8.9 months. The preoperative JOA scores of the posterior and combined groups were 11.5 ± 2.2 and 11.1 ± 2.3, respectively (p = 0.613). The combined group presented with prolonged surgery duration(108.8 ± 28.0 and 186.1 ± 47.3 min, p = 0.028) and greater blood loss(276.3 ± 139.1 and 382.1 ± 283.1 ml, p<0.001). At short-term follow-up, the combined group presented a higher JOARR than the posterior group (posterior group: 50.7%±46.6%, combined group: 70.4%±20.3%, p = 0.024), while no significant difference in JOARR was observed between the groups at long-term follow-up (posterior group: 49.2%±48.5%, combined group: 59.6%±47.6%, p = 0.136). No significant difference was found in the overall complication and reoperation rates. CONCLUSIONS: For MDCM patients with ISI, both posterior and one-stage posteroanterior approaches could achieve considerable neurological alleviations in short-term and long-term follow-up. With greater surgical trauma, the combined group presented better short-term JOARR but did not show higher efficacy in long-term neurological function preservation in patients with comparable preoperative conditions.


Assuntos
Vértebras Cervicais , Descompressão Cirúrgica , Pontuação de Propensão , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Vértebras Cervicais/cirurgia , Vértebras Cervicais/diagnóstico por imagem , Estudos Retrospectivos , Idoso , Seguimentos , Resultado do Tratamento , Descompressão Cirúrgica/métodos , Imageamento por Ressonância Magnética , Doenças da Medula Espinal/cirurgia , Doenças da Medula Espinal/diagnóstico por imagem , Recuperação de Função Fisiológica , Avaliação da Deficiência
9.
Front Pharmacol ; 15: 1367686, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38860175

RESUMO

Background: The therapeutic effects of vitamin D supplementation on Coronavirus disease 2019 (COVID-19) aggravation remain controversial and inconclusive. To probe into this contentious issue, we performed the present meta-analysis of randomized controlled trials (RCTs). Methods: Literature published up to June 2023 was retrieved from Cochrane Library, PubMed, Web of Science and Embase. RCTs assessing mortality, intensive care unit (ICU) admission, mechanical ventilation (MV), length of hospitalization (LOH), and inflammatory markers containing C-reactive protein (CRP), D-dimer, interleukin-6 (IL-6), lactate dehydrogenase (LDH) were included. 19 RCTs were involved in the analysis and were conducted subgroup analyses on the baseline COVID-19 severity and vitamin D administration. Results: In the severity subgroup, statistically significant effects in moderate to severe group were observed in ICU admission (OR 0.43, 95% CI 0.23, 0.80; p = 0.008), MV (OR 0.44, 95% CI 0.27, 0.72; p = 0.001) and LOH (SMD -0.49, 95% CI -0.92, -0.06; p = 0.027). In the administration subgroup, effects of ICU admission (OR 0.39, 95% CI 0.16, 0.97; p = 0.044), MV (OR 0.18, 95% CI 0.07, 0.46; p = 0.000) and LOH (SMD -0.50, 95% CI -0.96, -0.04; p = 0.034) were more pronounced in patients supplied with multiple-dose vitamin D than single-dose. Although the result of mortality showed no statistically significant effect, it indicated a reduced trend (OR 0.87, 95% CI 0.63, 1.12; p > 0.05). The results of inflammatory markers reached no statistical differences. Conclusion: This meta-analysis revealed that moderate to severe COVID-19 patients supplied with multiple doses of vitamin D were less apt to need ICU admission, mechanical ventilation and have shorter hospital stays.

10.
Int J Biol Sci ; 20(6): 2130-2148, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38617541

RESUMO

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with limited effective therapeutic options readily available. We have previously demonstrated that lovastatin, an FDA-approved lipid-lowering drug, selectively inhibits the stemness properties of TNBC. However, the intracellular targets of lovastatin in TNBC remain largely unknown. Here, we unexpectedly uncovered ribosome biogenesis as the predominant pathway targeted by lovastatin in TNBC. Lovastatin induced the translocation of ribosome biogenesis-related proteins including nucleophosmin (NPM), nucleolar and coiled-body phosphoprotein 1 (NOLC1), and the ribosomal protein RPL3. Lovastatin also suppressed the transcript levels of rRNAs and increased the nuclear protein level and transcriptional activity of p53, a master mediator of nucleolar stress. A prognostic model generated from 10 ribosome biogenesis-related genes showed outstanding performance in predicting the survival of TNBC patients. Mitochondrial ribosomal protein S27 (MRPS27), the top-ranked risky model gene, was highly expressed and correlated with tumor stage and lymph node involvement in TNBC. Mechanistically, MRPS27 knockdown inhibited the stemness properties and the malignant phenotypes of TNBC. Overexpression of MRPS27 attenuated the stemness-inhibitory effect of lovastatin in TNBC cells. Our findings reveal that dysregulated ribosome biogenesis is a targetable vulnerability and targeting MRPS27 could be a novel therapeutic strategy for TNBC patients.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Lovastatina/farmacologia , Lovastatina/uso terapêutico , Proteínas Ribossômicas/genética , Proteínas Nucleares , Ribossomos/genética , Proteínas Mitocondriais
11.
Gland Surg ; 13(1): 32-44, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38323231

RESUMO

Background: Functional parathyroid cysts (FPCs) are rare and difficult to diagnose with noninvasive methods. The aim of this study was to evaluate the diagnostic value of 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) single-photon emission computed tomography/computerized tomography (SPECT/CT) parathyroid imaging in the diagnosis of FPCs and to account for its performance. Methods: The data from 10 patients with suspected parathyroid cysts (PCs) who underwent 99mTc-MIBI SPECT/CT parathyroid imaging between 2012 and 2022 were retrospectively evaluated. The diagnostic value of 99mTc-MIBI SPECT/CT parathyroid imaging for FPCs was analyzed. Results: Surgical resection was performed in six cases and parathyroid puncture was performed in four cases. The sensitivity of 99mTc-MIBI SPECT/CT for FPCs was 100.0% (3/3), with a specificity of 100.0% (7/7) and an accuracy of 100.0% (10/10). The postoperative pathological findings in three cases of FPCs were parathyroid adenoma, parathyroid adenoma with hemorrhage, and parathyroid adenoma with cystic degeneration, respectively. The diagnostic accuracy of ultrasound and CT for PCs was only 22.22% (2/9) and 25.0% (1/4), respectively, and neither modality could indicate whether the cysts were functional or not. Conclusions: 99mTc-MIBI parathyroid SPECT/CT imaging has a high value in the diagnosis of FPCs in patients with suspected PCs, and an intense ring-shaped accumulation of radioactivity in the cyst wall on 99mTc-MIBI imaging suggests that the patient may have FPCs.

12.
JAMA Netw Open ; 7(2): e2354937, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38335001

RESUMO

Importance: Prehypertension increases the risk of developing hypertension and other cardiovascular diseases. Early and effective intervention for patients with prehypertension is highly important. Objective: To assess the efficacy of Tai Chi vs aerobic exercise in patients with prehypertension. Design, Setting, and Participants: This prospective, single-blinded randomized clinical trial was conducted between July 25, 2019, and January 24, 2022, at 2 tertiary public hospitals in China. Participants included 342 adults aged 18 to 65 years with prehypertension, defined as systolic blood pressure (SBP) of 120 to 139 mm Hg and/or diastolic BP (DBP) of 80 to 89 mm Hg. Interventions: Participants were randomized in a 1:1 ratio to a Tai Chi group (n = 173) or an aerobic exercise group (n = 169). Both groups performed four 60-minute supervised sessions per week for 12 months. Main Outcomes and Measures: The primary outcome was SBP at 12 months obtained in the office setting. Secondary outcomes included SBP at 6 months and DBP at 6 and 12 months obtained in the office setting and 24-hour ambulatory BP at 12 months. Results: Of the 1189 patients screened, 342 (mean [SD] age, 49.3 [11.9] years; 166 men [48.5%] and 176 women [51.5%]) were randomized to 1 of 2 intervention groups: 173 to Tai Chi and 169 to aerobic exercise. At 12 months, the change in office SBP was significantly different between groups by -2.40 (95% CI, -4.39 to -0.41) mm Hg (P = .02), with a mean (SD) change of -7.01 (10.12) mm Hg in the Tai Chi group vs -4.61 (8.47) mm Hg in the aerobic exercise group. The analysis of office SBP at 6 months yielded similar results (-2.31 [95% CI, -3.94 to -0.67] mm Hg; P = .006). Additionally, 24-hour ambulatory SBP (-2.16 [95% CI, -3.84 to -0.47] mm Hg; P = .01) and nighttime ambulatory SBP (-4.08 [95% CI, -6.59 to -1.57] mm Hg; P = .002) were significantly reduced in the Tai Chi group compared with the aerobic exercise group. Conclusions and Relevance: In this study including patients with prehypertension, a 12-month Tai Chi intervention was more effective than aerobic exercise in reducing SBP. These findings suggest that Tai Chi may help promote the prevention of cardiovascular disease in populations with prehypertension. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR1900024368.


Assuntos
Pré-Hipertensão , Tai Chi Chuan , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pressão Sanguínea , Exercício Físico , Pré-Hipertensão/terapia , Estudos Prospectivos , Adolescente , Adulto Jovem , Idoso
13.
Int Immunopharmacol ; 128: 111476, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38185035

RESUMO

Streptococcus pneumoniae is a clinically relevant pathogen notorious for causing pneumonia, meningitis, and otitis media in immunocompromised patients. Currently, antibiotic therapy is the most efficient treatment for fighting pneumococcal infections. However, an arise in antimicrobial resistance in S. pneumoniae has become a serious health issue globally. To resolve the problem, alternative and cost-effective strategies, such as monoclonal antibody-based targeted therapy, are needed for combating bacterial infection. S. pneumoniae alpha-enolase (spEno1), which is thought to be a great target, is a surface protein that binds and converts human plasminogen to plasmin, leading to accelerated bacterial infections. We first purified recombinant spEno1 protein for chicken immunization to generate specific IgY antibodies. We next constructed two single-chain variable fragments (scFv) antibody libraries by phage display technology, containing 7.2 × 107 and 4.8 × 107 transformants. After bio-panning, ten scFv antibodies were obtained, and their binding activities to spEno1 were evaluated on ELISA, Western blot and IFA. The epitopes of spEno1 were identified by these scFv antibodies, which binding affinities were determined by competitive ELISA. Moreover, inhibition assay displayed that the scFv antibodies effectively inhibit the binding between spEno1 and human plasminogen. Overall, the results suggested that these scFv antibodies have the potential to serve as an immunotherapeutic drug against S. pneumoniae infections.


Assuntos
Fosfopiruvato Hidratase , Anticorpos de Cadeia Única , Streptococcus pneumoniae , Animais , Humanos , Galinhas , Biblioteca de Peptídeos , Fosfopiruvato Hidratase/imunologia , Plasminogênio , Proteínas Recombinantes , Anticorpos de Cadeia Única/imunologia , Streptococcus pneumoniae/enzimologia , Streptococcus pneumoniae/imunologia
14.
Artigo em Inglês | MEDLINE | ID: mdl-38082730

RESUMO

Ingestible electronics are promising platforms for on-demand health monitoring and drug delivery. However, these devices and their actuators must operate in the gastrointestinal (GI) environment, which has a pH range of 1 to 8. Drug delivery systems using electrochemical dissolution of metal films are particularly susceptible to pH changes. Optimal operation in this dynamic environment stands to transform our capacity to help patients across a range of conditions. Here we present an energy-efficient ingestible electronic electrochemical drug delivery system to support subjects through operation in this dynamic environment. The proposed system consists of a drug reservoir sealed with an electrochemically dissolvable gold membrane and an electronic subsystem. An electronic subsystem controls the rate of gold dissolution by sensing and adapting to the pH of the GI environment and provides an option for energy-efficient drug delivery, reducing energy consumption by up to 42.8 %. Integrating the electronics with electrochemical drug delivery enables the proposed system to adapt to the dynamic physiological environments which makes it suitable for drug and/or therapeutic delivery at different locations in the GI tract.


Assuntos
Sistemas de Liberação de Medicamentos , Trato Gastrointestinal , Humanos , Trato Gastrointestinal/fisiologia , Preparações Farmacêuticas , Eletrônica , Ouro
15.
Am J Cancer Res ; 13(11): 5151-5173, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38058811

RESUMO

Although various HER2-targeted therapies have been approved clinically, drug resistance remains a considerable challenge. Studies have found that the cause of drug resistance is related to the expression of genes co-amplified with HER2 in breast cancer cells. Our study found that STARD3 was highly expressed in tumor tissues (n = 130, P < 0.001), especially in the HER2+ subtype (n = 35, P < 0.05), and correlated with poorer overall survival (HR = 1.47, P < 0.001). We discovered the interaction mechanism between STARD3 and HER2 proteins. We found that STARD3 overexpression increases HER2 levels by directly interacting with the HSP90 protein and inducing phosphorylated SRC, which may protect HER2 from degradation. Conversely, loss of STARD3 attenuates HER2 expression through lysosomal degradation. In addition, STARD3 overexpression induced cell cycle progression by inducing cyclin D1 and reducing p27. Therefore, the development of STARD3-specific targeted anti-cancer drugs would be helpful in the treatment of HER2+ patients. We further found that curcumin (15 µM) is a potent STARD3 inhibitor. STARD3-knockdown cells treated with curcumin (5 µM) showed a significant synergistic effect in inhibiting cancer cell growth and migration. The results suggest that targeting STARD3 would aid in treating HER2-positive breast cancer patients. This article uses curcumin as an example to prove that the targeted inhibition of STARD3 expression can be an option for the clinical treatment of HER2+ breast cancer patients.

16.
Quant Imaging Med Surg ; 13(12): 8669-8680, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38106262

RESUMO

Background: Exact preoperative localization is desirable to perform minimally invasive parathyroidectomy for hyperparathyroidism (HPT). This study aimed to evaluate the diagnostic values of 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) single photon emission computed tomography/computed tomography (SPECT/CT) of parathyroid glands by analyzing the relationship between lesion weight and false-negative (FN) results, as well as to explain the possible reason. Methods: The data from 314 patients with suspected HPT who underwent 99mTc-MIBI SPECT/CT parathyroid imaging between 2011 and 2022 were retrospectively evaluated. The sensitivity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of parathyroid 99mTc-MIBI SPECT/CT were calculated, and the false-positive (FP) and FN findings were analyzed. Results: Accurate localization by 99mTc-MIBI SPECT/CT was significantly associated with the parathyroid hormone (PTH) level. The 99mTc-MIBI SPECT/CT for diagnosis/lesion location reached a sensitivity of 84.6%/56.8%, a PPV of 97.3%/98.4%, an NPV of only 23.7%/4.18%, and an accuracy of 83.4%/57.1%, respectively. The largest diameter, shortest diameter, and lesion volume were lower in the FN group than in the TP group. A total of 7 FP cases were found, including 2 cases of thyroid nodules, 4 cases of thyroid tissue, and 1 case of hibernoma. A total of 45 FN patients, including 321 FN lesions, were confirmed, of which parathyroid hyperplasia accounted for 97.8%. Lesion weights greater than 20 µg were able to be detected, but lightweight lesions less than 100 mg were the principal source of FN results, accounting for approximately 39.3%. With lesion weights 0-100, 101-300, 301-1,000, and >1,000 mg, the FN rate was 70.8% (126/178), 51.8% (103/199), 34.6% (81/234), and 8.33% (11/132), respectively. Conclusions: 99mTc-MIBI SPECT/CT parathyroid imaging provides good sensitivity and high specificity in HPT location. Correct localization by 99mTc-MIBI SPECT/CT correlates positively with lesion weight and PTH levels. The smaller the lesion, the higher the FN rate in 99mTc-MIBI SPECT/CT parathyroid imaging, and lesions weighing less than 100 mg are the main source of FN results in 99mTc-MIBI SPECT/CT parathyroid imaging.

17.
Front Genet ; 14: 1266869, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37881804

RESUMO

Background: Multiple observational studies have discovered a substantial link between obstructive sleep apnea (OSA) and ventricular dysfunction. However, conventional observational studies are vulnerable to causal reversal and confounding, making it challenging to infer the causes of effects and their direction. Methods: With the help of a bidirectional, two-sample Mendelian randomization (MR) study, we assessed the potential causality between OSA and left and right ventricular (LV, RV) structure and function. We conducted our analysis utilizing summary data from genome-wide association studies of OSA (16,761 cases and 201,194 controls) in the FinnGen Study, as well as LV (36,041 participants) and RV (29,506 participants) in the UK Biobank cardiovascular magnetic resonance research. The inverse variance weighted (IVW) was selected as the main strategy, with the MR-Egger and weighted median methods serving as supplements. Other methods were employed as sensitivity analysis tools to look at heterogeneity and pleiotropy, including MR-Egger intercept, Cochran Q statistic, MR-PRESSO, and leave-one-out analysis. Results: In the primary IVW analysis, genetically predicted OSA was strongly causative on LV end-diastolic volume (ß = 0.114, 95% CI = 0.034-0.194, p = 0.006) and LV stroke volume (ß = 0.111, 95% CI = 0.031-0.191, p = 0.007), and genetically predicted LV ejection fraction was linked to an increased risk of OSA (OR = 1.161, 95% CI = 1.029-1.309, p = 0.015). However, there was no connection found between OSA and any RV parameters. Conclusion: Our genetic analysis raises a potential causative link between OSA and ventricular structure and function, which may improve the knowledge of OSA as a risk factor for cardiovascular disease by demonstrating a direct impact on cardiac structure and function.

18.
J Plast Reconstr Aesthet Surg ; 85: 26-33, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37454547

RESUMO

BACKGROUND: Although replantation of amputated facial segments remains challenging in reconstructive surgery, it offers excellent aesthetic and functional outcomes. METHODS: From May 2004 to October 2019, 12 patients underwent replantation of amputated facial tissues by supermicrosurgery. The case details, such as the rationale for replantation, the operation method, and postoperative therapy, are described. Four cases are discussed to demonstrate the replantation of different facial parts. RESULTS: Facial tissue replantation was successful in all 12 patients without secondary surgery. The cases included the nose (1 patient), ears (8 patients), lips (2 patients), and one of the soft tissue segments surrounding the lower jaw. Venous congestion occurred in three patients who received a solitary arterial repair and were treated with bloodletting. All patients expressed satisfaction with the cosmetic and functional results at the final follow-up. CONCLUSIONS: Supermicrosurgical facial tissue replantation is a promising and effective procedure for providing patients with the best aesthetic and functional outcomes.


Assuntos
Amputação Traumática , Procedimentos de Cirurgia Plástica , Humanos , Amputação Traumática/cirurgia , Microcirurgia/métodos , Reimplante/métodos , Nariz/cirurgia
19.
Front Immunol ; 14: 1175118, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37304305

RESUMO

Glioblastoma (GBM) is among the most fatal and recurring malignant solid tumors. It arises from the GBM stem cell population. Conventional neurosurgical resection, temozolomide (TMZ)-dependent chemotherapy and radiotherapy have rendered the prognosis of patients unsatisfactory. Radiotherapy and chemotherapy can frequently induce non-specific damage to healthy brain and other tissues, which can be extremely hazardous. There is therefore a pressing need for a more effective treatment strategy for GBM to complement or replace existing treatment options. Cell-based and cell-free immunotherapies are currently being investigated to develop new treatment modalities against cancer. These treatments have the potential to be both selective and successful in minimizing off-target collateral harm in the normal brain. In this review, several aspects of cell-based and cell-free immunotherapies related to GBM will be discussed.


Assuntos
Glioblastoma , Humanos , Glioblastoma/terapia , Imunoterapia , Encéfalo , Temozolomida/uso terapêutico , Nível de Saúde
20.
BMC Musculoskelet Disord ; 24(1): 526, 2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37370097

RESUMO

BACKGROUND: This study aimed to determine potential risk factors for post-laminoplasty kyphosis and the effect of postoperative kyphosis on neurologic function recovery. METHODS: A total of 266 patients with cervical spondylotic myelopathy (CSM) underwent traditional cervical laminoplasty with a minimum of a 12-month follow-up period. The patients were divided into non-kyphosis (NK group) and kyphosis (K group) groups based on the postoperative C2-7 Cobb angle. Clinical and radiological measurements were collected preoperatively and at the final follow-up. RESULTS: Of the 266 patients, 26 (9.77%) developed postoperative kyphosis at the final follow-up. The postoperative Japanese Orthopedic Association score did not differ significantly between the NK and K groups (P > 0.05). The postoperative numeric rating scale (NRS) also showed no significant difference between the NK and K groups; however, postoperative NRS improved better than the preoperative values in the NK group (P < 0.001). Multivariate analysis revealed that the preoperative C2-7 extension Cobb angle and C2-7 Cobb angle were independent predictors of post-laminoplasty kyphosis. Cut-off values for predicting postoperative kyphosis were a C2-7 extension Cobb angle of 18.00° and a C2-7 Cobb angle of 9.30°. CONCLUSIONS: Low preoperative C2-7 extension Cobb angle and C2-7 Cobb angle may be associated with post-laminoplasty kyphosis in CSM patients without preoperative kyphosis. The cut-off value of the C2-7 extension Cobb angle and C2-7 Cobb angle were 18.00° and 9.30°, respectively.


Assuntos
Cifose , Laminoplastia , Doenças da Medula Espinal , Espondilose , Humanos , Estudos Retrospectivos , Laminoplastia/efeitos adversos , Cifose/diagnóstico por imagem , Cifose/etiologia , Cifose/cirurgia , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Doenças da Medula Espinal/diagnóstico por imagem , Doenças da Medula Espinal/etiologia , Doenças da Medula Espinal/cirurgia , Resultado do Tratamento , Espondilose/complicações , Espondilose/diagnóstico por imagem , Espondilose/cirurgia
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