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1.
Sci Rep ; 14(1): 22110, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39333226

RESUMO

This study aims to develop a theoretical model for predicting the permeability of concrete in underground structures using compressive elastic waves. This research is motivated by the necessity of monitoring the permeability of concrete used in critical underground infrastructure, such as tunnels and radioactive waste disposal sites, to ensure their long-term safety. Increased permeability owing to crack generation can lead to groundwater inflow, undermining the structural integrity of these facilities. Traditional methods for permeability monitoring face challenges at depths of 500 m-1 km owing to high temperatures, high pressures, and limited space conditions. To address these issues, Biot's model, which correlates the P-wave characteristics with the properties of porous media, was applied in this study. The P-wave velocity and attenuation were studied according to the permeability of concrete based on Biot's model. Subsequently, concrete specimens were prepared to measure the permeability, P-wave velocity, and attenuation. The permeability results from the experiment were compared with those obtained from the model for validation. The findings indicate that the modified Biot's model can effectively monitor permeability through elastic wave characteristics, offering a non-destructive and reliable method for assessing the condition of concrete structures in underground environments. This approach is expected to enhance the safety of underground infrastructure through accurate permeability monitoring.

2.
Cancer Med ; 13(16): e70104, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39171503

RESUMO

OBJECTIVES: We aimed to identify predictive markers for metachronous gastric cancer (MGC) in early gastric cancer (EGC) patients curatively treated with endoscopic submucosal dissection (ESD). MATERIALS AND METHODS: From EGC patients who underwent ESD, bulk RNA sequencing was performed on non-cancerous gastric mucosa samples at the time of initial EGC diagnosis. This included 23 patients who developed MGC, and 23 control patients without additional gastric neoplasms for over 3 years (1:1 matched by age, sex, and Helicobacter pylori infection state). Candidate differentially-expressed genes were identified, from which biomarkers were selected using real-time quantitative polymerase chain reaction and cell viability assays using gastric cell lines. An independent validation cohort of 55 MGC patients and 125 controls was used for marker validation. We also examined the severity of gastric intestinal metaplasia, a known premalignant condition, at initial diagnosis. RESULTS: From the discovery cohort, 86 candidate genes were identified of which KDF1 and CDK1 were selected as markers for MGC, which were confirmed in the validation cohort. CERB5 and AKT2 isoform were identified as markers related to intestinal metaplasia and were also highly expressed in MGC patients compared to controls (p < 0.01). Combining these markers with clinical data (age, sex, H. pylori and severity of intestinal metaplasia) yielded an area under the curve (AUC) of 0.91 (95% CI, 0.85-0.97) for MGC prediction. CONCLUSION: Assessing biomarkers in non-cancerous gastric mucosa may be a useful method for predicting MGC in EGC patients and identifying patients with a higher risk of developing MGC, who can benefit from rigorous surveillance.


Assuntos
Biomarcadores Tumorais , Segunda Neoplasia Primária , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/genética , Masculino , Feminino , Biomarcadores Tumorais/genética , Pessoa de Meia-Idade , Idoso , Segunda Neoplasia Primária/genética , Segunda Neoplasia Primária/patologia , Ressecção Endoscópica de Mucosa , Proteína Quinase CDC2/genética , Proteína Quinase CDC2/metabolismo , Mucosa Gástrica/patologia , Mucosa Gástrica/cirurgia , Mucosa Gástrica/microbiologia , Mucosa Gástrica/metabolismo , Infecções por Helicobacter/complicações , Infecções por Helicobacter/genética , Gastroscopia , Regulação Neoplásica da Expressão Gênica , Metaplasia/genética , Metaplasia/patologia , Helicobacter pylori/isolamento & purificação , Estudos de Casos e Controles
3.
BMC Geriatr ; 24(1): 579, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965464

RESUMO

BACKGROUND: With an increasing proportion of older adults and the associated risk of Alzheimer's Disease and Related Dementias (ADRD) around the globe, there is an urgent need to engage in ADRD risk reduction efforts. African American (AA) older adults in the U.S. are disproportionally impacted by ADRD compared to other races and ethnicities. Mindful walking integrates two potentially protective factors of ADRD by elevating mindfulness and physical activity (i.e., walking), resulting in a synergistic behavioral strategy that is feasible and safe for older adults. However, the efficacy of applying this intervention for cognitive health outcomes has not been evaluated using experimental designs. METHODS: This paper documents the goal and protocol of a community-based, mindful walking randomized controlled trial to examine the short- and longer-term efficacy on cognitive and other health-related outcomes in ADRD at-risk AA older adults. The study outcomes include various brain health determinants, including cognitive function, quality of life, psychological well-being, physical activity, mindfulness, sleep, and overall health status. In addition, the estimated costs of program implementation are also collected throughout the study period. This study will recruit 114 older adults (ages 60+ years) with elevated ADRD risk from the Midlands region of South Carolina. Older adults are randomly assigned to participate in 24 sessions of outdoor mindful walking over three months or a delayed mindful walking group (n=57 in each group). Participants in both groups follow identical measurement protocols at baseline, after 12 weeks, after 18 weeks, and after 24 weeks from baseline. The outcome measures are administered in the lab and in everyday settings. Costs per participant are calculated using micro-costing methods. The eliciting participant costs for mindful walking engagement with expected results are reported using the payer and the societal perspectives. DISCUSSION: This study will generate evidence regarding the efficacy of mindful walking on sustaining cognitive health in vulnerable older adults. The results can inform future large-scale effectiveness trials to support our study findings. If successful, this mindful walking program can be scaled up as a low-cost and viable lifestyle strategy to promote healthy cognitive aging in diverse older adult populations, including those at greatest risk. TRIAL REGISTRATION: ClinicalTrials.gov number NCT06085196 (retrospectively registered on 10/08/2023).


Assuntos
Negro ou Afro-Americano , Demência , Atenção Plena , Caminhada , Humanos , Idoso , Caminhada/fisiologia , Negro ou Afro-Americano/psicologia , Demência/etnologia , Demência/prevenção & controle , Demência/psicologia , Masculino , Atenção Plena/métodos , Feminino , Cognição/fisiologia , Pessoa de Meia-Idade
4.
Ann Surg Oncol ; 31(10): 6774-6785, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38969851

RESUMO

BACKGROUND: Current guidelines recommend against the use of routine imaging tests to detect distant metastasis in asymptomatic breast cancer patients. However, recent advancements in effective therapeutics and diagnostic accuracy have raised the need to reassess the clinical efficacy of intensive metastasis surveillance. We report the results of a multicenter retrospective study to investigate the association between intensive imaging studies and survival outcomes. PATIENTS AND METHODS: We retrospectively reviewed the data of 4130 patients who underwent surgery from 11 hospitals in Korea between January 2010 and December 2011. Patients were divided into two groups on the basis of the intensity of metastasis imaging studies during their disease-free period. The types and intervals of the imaging studies were based on each physician's decisions. RESULTS: High-intensive screening showed a shorter distant metastasis-free survival [p < 0.001, hazard ratio (HR) 1.62; 95% confidence interval (CI) 1.29-2.04], especially for patients in whom bone or lung was the first site of metastasis. With a median follow-up period of 110.0 months, the 5-year breast cancer-specific survival (BCSS) rate was 96.5%. The high-intensity screening group showed significantly poorer BCSS compared with the low-intensity screening group (p < 0.001, HR 3.13; 95% CI 2.32-4.21). However, both multivariable analysis and propensity score matching analysis showed no significant association between the screening intensity and BCSS. CONCLUSIONS: Frequent imaging studies to detect distant metastasis were associated with earlier detection of distant metastasis, especially for lung and bone metastasis. However, intensive surveillance showed no apparent association with BCSS despite the use of currently available treatments.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Neoplasias da Mama/mortalidade , Estudos Retrospectivos , Pessoa de Meia-Idade , Taxa de Sobrevida , República da Coreia/epidemiologia , Seguimentos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/terapia , Prognóstico , Neoplasias Ósseas/secundário , Neoplasias Ósseas/terapia , Idoso , Adulto , Sobreviventes de Câncer/estatística & dados numéricos
5.
Light Sci Appl ; 13(1): 169, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39019860

RESUMO

Nonlinear intersubband polaritonic metasurfaces, which integrate giant nonlinear responses derived from intersubband transitions of multiple quantum wells (MQWs) with plasmonic nanoresonators, not only facilitate efficient frequency conversion at pump intensities on the order of few tens of kW cm-2 but also enable electrical modulation of nonlinear responses at the individual meta-atom level and dynamic beam manipulation. The electrical modulation characteristics of the magnitude and phase of the nonlinear optical response are realized through Stark tuning of the resonant intersubband nonlinearity. In this study, we report, for the first time, experimental implementations of electrical modulation characteristics of mid-infrared third-harmonic generation (THG) using an intersubband polaritonic metasurface based on MQW with electrically tunable third-order nonlinear response. Experimentally, we achieved a 450% modulation depth of the THG signal, 86% suppression of zero-order THG diffraction tuning based on local phase tuning exceeding 180 degrees, and THG beam steering using phase gradients. Our work proposes a new route for electrically tunable flat nonlinear optical elements with versatile functionalities.

6.
ACS Sens ; 9(8): 4028-4036, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39054598

RESUMO

Owing to the biological significance of Cl- in cells, several chemical fluorescent probes and biosensors have been constructed to monitor this anion in the cytosol and subcellular organelles. However, a fluorescent probe for the selective detection of nuclear Cl- has not been described thus far. In the current study, we developed the first nuclear Cl--selective biosensor, Cl-YFP-NLS, whose fluorescence was effectively quenched by this anion, and demonstrated that it is an efficient and powerful tool for determining the levels of nuclear Cl-. The results of cell studies using Cl-YFP-NLS as the probe suggested that the level of Cl- in the nucleus is lower than that in the cytosol. In addition, Cl-YFP-NLS along with lysosomal (Lyso-MQAE) and mitochondrial Cl--selective fluorescent probes (Mito-MQAE) were utilized to determine the effects of various substances on the levels of Cl- in subcellular organelles. The results showed that lysosomotropic agents decrease the lysosomal Cl- concentration and increase the levels of mitochondrial and nuclear Cl-. Also, observations suggested that substances capable of inducing mitochondrial outer membrane permeabilization without inducing lysosomal membrane permeabilization increase mitochondrial and nuclear Cl- concentrations but they do not affect the level of lysosomal Cl-. Moreover, a substance directly disrupting nuclear pore complexes increased the level of nuclear Cl- and did not change the levels of lysosomal and mitochondrial Cl-. Finally, nucleus-affecting substances that cause deoxyribonucleic acid damage and activate p53 and Bax increased the levels of mitochondrial and nuclear Cl- without influencing the level of lysosomal Cl-.


Assuntos
Núcleo Celular , Cloretos , Corantes Fluorescentes , Corantes Fluorescentes/química , Humanos , Núcleo Celular/metabolismo , Cloretos/química , Cloretos/análise , Células HeLa , Lisossomos/química , Lisossomos/metabolismo , Mitocôndrias/metabolismo , Técnicas Biossensoriais/métodos
7.
ACS Nano ; 18(25): 16297-16311, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38867457

RESUMO

While mesalamine, a 5-aminosalicylic acid (5-ASA), is pivotal in the management of inflammatory bowel disease (IBD) through both step-up and top-down approaches in clinical settings, its widespread utilization is limited by low bioavailability at the desired site of action due to rapid and extensive absorption in the upper gastrointestinal (GI) tract. Addressing mesalamine's pharmacokinetic challenges, here, we introduce nanoassemblies composed exclusively of a mesalamine prodrug that pairs 5-ASA with a mucoadhesive and cathepsin B-cleavable peptide. In an IBD model, orally administered nanoassemblies demonstrate enhanced accumulation and sustained retention in the GI tract due to their mucoadhesive properties and the epithelial enhanced permeability and retention (eEPR) effect. This retention enables the efficient uptake by intestinal pro-inflammatory macrophages expressing high cathepsin B, triggering a burst release of the 5-ASA. This cascade fosters the polarization toward an M2 macrophage phenotype, diminishes inflammatory responses, and simultaneously facilitates the delivery of active agents to adjacent epithelial cells. Therefore, the nanoassemblies show outstanding therapeutic efficacy in inhibiting local inflammation and contribute to suppressing systemic inflammation by restoring damaged intestinal barriers. Collectively, this study highlights the promising role of the prodrug nanoassemblies in enhancing targeted drug delivery, potentially broadening the use of mesalamine in managing IBD.


Assuntos
Doenças Inflamatórias Intestinais , Macrófagos , Mesalamina , Pró-Fármacos , Mesalamina/química , Mesalamina/farmacologia , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Doenças Inflamatórias Intestinais/tratamento farmacológico , Animais , Camundongos , Humanos , Nanopartículas/química , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/administração & dosagem
8.
Biosens Bioelectron ; 260: 116436, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38824701

RESUMO

A mid-infrared label-free immunoassay-based biosensor is an effective device to help identify and quantify biomolecules. This biosensor employs a surface-enhanced infrared absorption spectroscopy, which is a highly potent sensing technique for detecting minute quantities of analytes. In this study, a biosensor was constructed using a metamaterial absorber, which facilitated strong coupling effects. For maximum coupling effect, it is necessary to enhance the near-field intensity and the spatial and spectral overlap between the optical cavity resonance and the vibrational mode of the analyte. Due to significant peak splitting, conventional baseline correction methods fail to adequately analyze such a coupling system. Therefore, we employed a coupled harmonic oscillation model to analyze the spectral distortion resulting from the peak splitting induced by the strong coupling effect. The proposed biosensor with a thrombin-binding aptamer-based immunoassay could achieve a limit of detection of 267.4 pM, paving the way for more efficient protein detection in clinical practice.


Assuntos
Técnicas Biossensoriais , Limite de Detecção , Técnicas Biossensoriais/métodos , Imunoensaio/métodos , Imunoensaio/instrumentação , Humanos , Aptâmeros de Nucleotídeos/química , Desenho de Equipamento , Espectrofotometria Infravermelho , Proteínas/análise , Trombina/análise
9.
Orthop J Sports Med ; 12(6): 23259671241252421, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38840789

RESUMO

Background: The effect of local corticosteroid (CS) injections on rotator cuff muscles remains poorly defined, despite the significance of muscle quality as a crucial prognostic factor for patients with rotator cuff tears (RCTs). Purpose: To compare alterations in gene and protein expression patterns in the rotator cuff muscles of patients with RCTs who received frequent joint CS injections with alterations in those without a history of CS injections. Study Design: Controlled laboratory study. Methods: A total of 24 rotator cuff muscle samples with medium-sized tears from 12 patients with a frequent joint CS injection history (steroid group; 7 men and 5 women who had received ≥5 injections with at least 1 within the previous 3 months; mean age, 63.0 ± 7.2 years) and 12 age- and sex-matched control patients without a history of CS injections (no-steroid group) were acquired. Alterations in the expression of genes and proteins associated with adipogenesis, myogenesis, inflammation, and muscle fibrosis were compared between the groups using quantitative reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemistry. Statistical analysis included comparison of group means using the Mann-Whitney U test, chi-square test, or Fisher exact test and logistic regression for multivariate analysis. Results: In the steroid group, the mRNA expression levels of adipogenic CCAAT/enhancer-binding protein alpha (C/EBPα; P = .008) and muscle atrophy-related genes (atrogin; P = .019) were significantly higher, and those of myogenic differentiation 1 (MyoD; P = .035), inflammatory interleukin 6 (IL-6; P = .035), and high mobility group box 1 (P = .003) were significantly lower compared with the no-steroid group. In addition, MyoD (P = .041) and IL-6 (P = .026) expression were decreased in the steroid versus no-steroid group. Immunohistochemistry revealed increased expression of C/EBPα and atrogin and decreased expression of MyoD and IL-6 in the steroid versus no-steroid group. Conclusion: Patients with RCTs and a history of frequent CS injections exhibited an upregulation of adipogenic and muscle atrophy-related genes and proteins within the rotator cuff muscles and a downregulation in the expression of myogenic and inflammatory genes and proteins in the same muscles. Clinical Relevance: These altered gene and protein expressions by frequent local CS injections may cause poor outcomes in patients with RCTs.

10.
J Int Med Res ; 52(6): 3000605241260540, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38902205

RESUMO

Immunoglobulin G4-related disease (IgG4-RD) is a fibroinflammatory condition characterized by chronic activation of the immune system and a tendency to form tumorous lesions. IgG4-RD is frequently characterized by the presence of tumor-like masses affecting multiple organs and is easily mistaken for a malignant neoplasm. However, IgG4-RD affecting the appendix is extremely rare, with only seven cases reported previously. We report the case of a woman in her early 60s who presented with insidious abdominal pain and radiological findings mimicking appendiceal neoplasms. After diagnosing appendiceal neoplasms, surgery was performed. The patient had a serum IgG4 concentration of <1.35 g/L, which did not satisfy one of the three revised comprehensive diagnostic criteria for IgG4-RD. A pathological examination was conducted, and the patient was diagnosed with appendiceal IgG4-RD. To the best of our knowledge, there have been no previously reported cases of IgG4-RD affecting the appendix in patients with low serum IgG4 concentrations. This report may prove beneficial for the future understanding of IgG4-RD and for the revision of diagnostic and treatment strategies.


Assuntos
Neoplasias do Apêndice , Doença Relacionada a Imunoglobulina G4 , Imunoglobulina G , Humanos , Feminino , Neoplasias do Apêndice/diagnóstico , Neoplasias do Apêndice/patologia , Doença Relacionada a Imunoglobulina G4/diagnóstico , Diagnóstico Diferencial , Pessoa de Meia-Idade , Imunoglobulina G/sangue , Tomografia Computadorizada por Raios X , Apêndice/patologia , Apêndice/diagnóstico por imagem , Apêndice/cirurgia
11.
Breast Cancer Res ; 26(1): 49, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38515107

RESUMO

BACKGROUND: Patient-derived xenograft (PDX) models serve as a valuable tool for the preclinical evaluation of novel therapies. They closely replicate the genetic, phenotypic, and histopathological characteristics of primary breast tumors. Despite their promise, the rate of successful PDX engraftment is various in the literature. This study aimed to identify the key factors associated with successful PDX engraftment of primary breast cancer. METHODS: We integrated clinicopathological data with morphological attributes quantified using a trained artificial intelligence (AI) model to identify the principal factors affecting PDX engraftment. RESULTS: Multivariate logistic regression analyses demonstrated that several factors, including a high Ki-67 labeling index (Ki-67LI) (p < 0.001), younger age at diagnosis (p = 0.032), post neoadjuvant chemotherapy (NAC) (p = 0.006), higher histologic grade (p = 0.039), larger tumor size (p = 0.029), and AI-assessed higher intratumoral necrosis (p = 0.027) and intratumoral invasive carcinoma (p = 0.040) proportions, were significant factors for successful PDX engraftment (area under the curve [AUC] 0.905). In the NAC group, a higher Ki-67LI (p < 0.001), lower Miller-Payne grade (p < 0.001), and reduced proportion of intratumoral normal breast glands as assessed by AI (p = 0.06) collectively provided excellent prediction accuracy for successful PDX engraftment (AUC 0.89). CONCLUSIONS: We found that high Ki-67LI, younger age, post-NAC status, higher histologic grade, larger tumor size, and specific morphological attributes were significant factors for predicting successful PDX engraftment of primary breast cancer.


Assuntos
Neoplasias da Mama , Animais , Humanos , Feminino , Neoplasias da Mama/terapia , Neoplasias da Mama/diagnóstico , Xenoenxertos , Inteligência Artificial , Modelos Animais de Doenças , Ensaios Antitumorais Modelo de Xenoenxerto
12.
J Pathol Transl Med ; 58(2): 91-97, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38499005

RESUMO

Pancreatic neuroendocrine microtumor (PNEMT) is a neuroendocrine tumor (NET) < 0.5 cm in diameter, and it is considered benign. We report a PNEMT with high-grade transformation (HGT). A man in his 60s with von Hippel-Lindau syndrome underwent surgical resection of a NET. A second sub-centimeter nodule with a nodule-in-nodule pattern was discovered. The 0.4 cm outer nodule contained clear columnar cells with round nuclei and indistinct nucleoli, while the 0.1 cm inner nodule had eosinophilic cells with an increased nuclear to cytoplasmic ratio, vesicular nuclei, and prominent nucleoli. Tumor cells in the outer and inner nodules were synaptophysin and chromogranin positive. Only the inner nodule was p53 positive, while the outer nodule was exclusively positive for carbonic anhydrase 9 and vimentin. The Ki-67 labeling indices for the outer and inner nodules were 2.1% (grade 1) and 44.3% (grade 3), respectively. This nodule was determined to be a PNEMT with HGT. Our findings suggest that a PNEMT may not always be benign and can undergo HGT.

13.
Hip Pelvis ; 36(1): 1-11, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38420734

RESUMO

Gout is triggered by the accumulation of uric acid in the body, leading to hyperuricemia. Genetic, metabolic, and environmental factors can influence this condition. Excessive uric acid buildup results in the formation of monosodium urate (MSU) crystals, which precipitate in specific areas of the body, including the joints, where they can cause symptoms of gout. While the acute and chronic symptoms of gout have been well-documented, diagnosis of gout affecting the hip joint poses significant challenges. The global incidence of gout, the most prevalent form of inflammatory arthritis, is on the rise. Evaluation of the clinical signs, laboratory results, and imaging results is generally required for diagnosis of gout in cases where MSU crystals have not been detected. Hyperuricemia is considered a primary cause of arthritis symptoms, and comprehensive guidelines for treatment are available. Therefore, the choice of medication is straightforward, and moderate effectiveness of treatment has been demonstrated. Gout is a chronic disease, requiring lifelong uric acid-lowering medications, thus application of a treatment strategy based on the target blood uric acid concentration is necessary. Consequently, cases of gout will likely be observed more frequently by hip surgeons in clinical scenarios in the future. The objective of this review is to provide an overview of the pathophysiology of gout and subsequently examine recent advances in diagnostic methods and therapeutic agents based on an understanding of its underlying mechanisms. In addition, literature on gout-related issues affecting the hip joint, providing a useful reference for hip surgeons is examined.

14.
Curr Issues Mol Biol ; 46(2): 1485-1502, 2024 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-38392214

RESUMO

Vascular dementia (VaD) is the second most common type of dementia after Alzheimer's disease. In our previous studies, we showed that wheat bran extract (WBE) reduced white matter damage in a rat VaD model and improved memory in a human clinical trial. However, starch gelatinization made the large-scale preparation of WBE difficult. To simplify the manufacturing process and increase efficacy, we attempted to find a decoction containing an optimum ratio of wheat bran, sliced citrus peel, and sliced jujube (WCJ). To find an optimal ratio, the cell survival of C6 (rat glioma) cultured under hypoxic conditions (1% O2) was measured, and apoptosis was assessed. To confirm the efficacies of the optimized WCJ for VaD, pupillary light reflex, white matter damage, and the activation of astrocytes and microglia were assessed in a rat model of bilateral common carotid artery occlusion (BCCAO) causing chronic hypoperfusion. Using a combination of both searching the literature and cell survival experiments, we chose 6:2:1 as the optimal ratio of wheat bran to sliced citrus peel to sliced jujube to prepare WCJ. We showed that phytic acid contained only in wheat bran can be used as an indicator component for the quality control of WCJ. We observed in vitro that the WCJ treatment improved cell survival by reducing apoptosis through an increase in the Bcl-2/Bax ratio. In the BCCAO experiments, the WCJ-supplemented diet prevented astrocytic and microglial activation, mitigated myelin damage in the corpus callosum and optic tract, and, consequently, improved pupillary light reflex at dosages over 100 mg/kg/day. The results suggest that the consumption of WCJ can prevent VaD by reducing white matter damage, and WCJ can be developed as a safe, herbal medicine to prevent VaD.

15.
Talanta ; 271: 125715, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38280264

RESUMO

Determining the activity of lysosomal ß-hexosaminidase in cells is of great importance for understanding the roles that these enzymes play in pathophysiological events. Herein, we designed the new fluorescent probe, ßGalNAc-Rhod-CM(NEt2), which consisted of a ßGalNAc-linked rhodol unit serving as a ß-hexosaminidase reactive fluorogenic moiety and a N,N'-diethylaminocoumarin (CM(NEt2)) group acting as a fluorescence marker for determining the degree of cell permeabilization. Treatment of ßGalNAc-Rhod-CM(NEt2) with ß-hexosaminidase promoted generation of Rhod-CM(NEt2), thereby leading to an increase in the intensity of fluorescence of Rhod. However, this probe did not respond to the functionally related glycosidase, O-GlcNAcase. The detection limit of ßGalNAc-Rhod-CM(NEt2) for ß-hexosaminidase was determined to be 0.52 nM, indicating that it has high sensitivity for this enzyme. Furthermore, the probe functioned as an excellent fluorogenic substrate for ß-hexosaminidase with kcat and Km values of 17 sec-1 and 22 µM, respectively. The results of cell studies using ßGalNAc-Rhod-CM(NEt2) showed that levels of ß-hexosaminidase activity in cells can be determined by measuring the intensity of fluorescence arising from Rhod and that the intensity of fluorescence of CM(NEt2) can be employed to determine the degree of cell permeabilization of the probe. Utilizing the new probe, we assessed ß-hexosaminidase activities in several types of cells and evaluated the effect of glucose concentrations in culture media on the activity of this enzyme.


Assuntos
Corantes Fluorescentes , beta-N-Acetil-Hexosaminidases , Corantes Fluorescentes/metabolismo , beta-N-Acetil-Hexosaminidases/metabolismo , Lisossomos/metabolismo , Acetilglucosaminidase/metabolismo
16.
Cell Mol Life Sci ; 81(1): 29, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38212474

RESUMO

Involution of the mammary gland after lactation is a dramatic example of coordinated cell death. Weaning causes distension of the alveolar structures due to the accumulation of milk, which, in turn, activates STAT3 and initiates a caspase-independent but lysosome-dependent cell death (LDCD) pathway. Although the importance of STAT3 and LDCD in early mammary involution is well established, it has not been entirely clear how milk stasis activates STAT3. In this report, we demonstrate that protein levels of the PMCA2 calcium pump are significantly downregulated within 2-4 h of experimental milk stasis. Reductions in PMCA2 expression correlate with an increase in cytoplasmic calcium in vivo as measured by multiphoton intravital imaging of GCaMP6f fluorescence. These events occur concomitant with the appearance of nuclear pSTAT3 expression but prior to significant activation of LDCD or its previously implicated mediators such as LIF, IL6, and TGFß3, all of which appear to be upregulated by increased intracellular calcium. We further demonstrate that increased intracellular calcium activates STAT3 by inducing degradation of its negative regulator, SOCS3. We also observed that milk stasis, loss of PMCA2 expression and increased intracellular calcium levels activate TFEB, an important regulator of lysosome biogenesis through a process involving inhibition of CDK4/6 and cell cycle progression. In summary, these data suggest that intracellular calcium serves as an important proximal biochemical signal linking milk stasis to STAT3 activation, increased lysosomal biogenesis, and lysosome-mediated cell death.


Assuntos
Cálcio , Leite , Feminino , Animais , Leite/metabolismo , Cálcio/metabolismo , Morte Celular , Lactação , Lisossomos/metabolismo , Glândulas Mamárias Animais/metabolismo , Fator de Transcrição STAT3/metabolismo
17.
Small Methods ; 8(3): e2301294, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37988680

RESUMO

Graphitic carbon-coated ZnPS3 is prepared via direct phosphosulfurization and high energy mechanical milling (HEMM) with multiwall carbon nanotubes (MWCNTs) and first introduced as an anode for lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs). The HEMM process with MWCNTs reduces the particle size of as-synthesized ZnPS3 bulk to 100-500 nm and yields the ≈5 nm thick graphitic carbon coated ZnPS3 nanoparticles, which are the nanocomposites of 5 nm sized nanocrystallites embedded in the amorphous matrix. The ZnPS3 electrode undergoes the combined conversion and alloying reactions with Li and Na ions and exhibits high initial discharge and charge capacities in both LIBs and SIBs. The graphitic carbon-coated ZnPS3 electrode exhibits excellent high-rate capability and long-term cyclability. The superior electrochemical properties can be attributed to high electrical conductivity, high Li ion mobility, and high reversibility and structural stability derived from the graphitic carbon-coated nanoparticles. This study demonstrates that the novel graphitic carbon-coated ZnPS3 is a promising anode material for both LIBs and SIBs and the graphitic carbon coating methodology by HEMM is expected to apply to the various metal oxides, sulfides, and phosphides.

18.
Nano Lett ; 23(19): 9003-9010, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37756214

RESUMO

Nonlinear optical metasurfaces offer a possibility to perform frequency mixing without the phase-matching constraints of bulk nonlinear crystals and with control of the local nonlinear response at a sub-wavelength scale. Nonlinear inter-subband polaritonic metasurfaces created by combining the semiconductor heterostructures with quantum-engineered inter-subband nonlinear response and electromagnetically engineered metal-clad nanoresonators offer by far the largest second-order nonlinear response of all condensed matter systems reported to date. However, the nonlinear optical response of these metasurfaces is limited by optical intensity saturation in the nanoresonator hot spots that prevented the achievement of power conversion efficiencies over 0.2% in three-wave mixing experiments. In this study, we propose and experimentally demonstrate dielectric inter-subband polaritonic metasurfaces for second-harmonic generation that achieve 0.37% power conversion efficiency. Our structure is created by a new design approach that combines dielectric resonators inducing Mie resonant modes with a lattice resonance to achieve a uniform and high field enhancement throughout the meta-atom volume.

19.
J Neurosci ; 43(46): 7766-7779, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37734946

RESUMO

The medial nucleus of the trapezoid body (MNTB) in the auditory brainstem is the principal source of synaptic inhibition to several functionally distinct auditory nuclei. Prominent projections of individual MNTB neurons comprise the major binaural nuclei that are involved in the early processing stages of sound localization as well as the superior paraolivary nucleus (SPON), which contains monaural neurons that extract rapid changes in sound intensity to detect sound gaps and rhythmic oscillations that commonly occur in animal calls and human speech. While the processes that guide the development and refinement of MNTB axon collaterals to the binaural nuclei have become increasingly understood, little is known about the development of MNTB collaterals to the monaural SPON. In this study, we investigated the development of MNTB-SPON connections in mice of both sexes from shortly after birth to three weeks of age, which encompasses the time before and after hearing onset. Individual axon reconstructions and electrophysiological analysis of MNTB-SPON connectivity demonstrate a dramatic increase in the number of MNTB axonal boutons in the SPON before hearing onset. However, this proliferation was not accompanied by changes in the strength of MNTB-SPON connections or by changes in the structural or functional topographic precision. However, following hearing onset, the spread of single-axon boutons along the tonotopic axis increased, indicating an unexpected decrease in the tonotopic precision of the MNTB-SPON pathway. These results provide new insight into the development and organization of inhibition to SPON neurons and the regulation of developmental plasticity in diverging inhibitory pathways.SIGNIFICANCE STATEMENT The superior paraolivary nucleus (SPON) is a prominent auditory brainstem nucleus involved in the early detection of sound gaps and rhythmic oscillations. The ability of SPON neurons to fire at the offset of sound depends on strong and precise synaptic inhibition provided by glycinergic neurons in the medial nucleus of the trapezoid body (MNTB). Here, we investigated the anatomic and physiological maturation of MNTB-LSO connectivity in mice before and after the onset of hearing. We observed a period of bouton proliferation without accompanying changes in topographic precision before hearing onset. This was followed by bouton elimination and an unexpected decrease in the tonotopic precision after hearing onset. These results provide new insight into the development of inhibition to the SPON.


Assuntos
Complexo Olivar Superior , Corpo Trapezoide , Masculino , Feminino , Camundongos , Animais , Humanos , Vias Auditivas/fisiologia , Núcleo Olivar/fisiologia , Neurônios/fisiologia
20.
Knee Surg Sports Traumatol Arthrosc ; 31(11): 5238-5247, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37594502

RESUMO

PURPOSE: Joint stiffness after arthroscopic rotator cuff repair is a major concern for orthopaedic surgeons. Various antiadhesive agents are commonly administered after rotator cuff repair for its prevention. This study aimed to compare the outcomes among patients injected with different types and amounts of anti-adhesive agents after rotator cuff repair. It was hypothesized that the outcomes might differ depending on the use of the anti-adhesive agent and its type and dose. METHODS: A total of 267 patients who underwent arthroscopic rotator cuff repair with or without subacromial injection of anti-adhesive agents were enrolled. The first group (group A; 51 patients) were injected with 3 mL of poloxamer/sodium alginate-based anti-adhesive agent. The second group (group B; 93 patients) were injected with 3 mL of sodium hyaluronate-based anti-adhesive agent. The third group (group C; 82 patients) were injected with 1.5 mL of sodium hyaluronate-based anti-adhesive agent. Finally, the last group (group D; 41 patients) who did not use anti-adhesive agents served as the control. The range of motion (ROM) and pain VAS scores were measured preoperatively and at 5 weeks, 3 months, 6 months, and 1 year postoperatively. Functional outcomes were evaluated using American Shoulder and Elbow Surgeons and Constant scores, whereas cuff integrity was assessed via MRI or ultrasonography at least 6 months postoperatively. RESULTS: All ROM measurements, pain VAS scores, and functional scores were significantly improved regardless of the use, type, and dose of the anti-adhesive agents. In addition shoulder ROM and rotator cuff healing did not significantly differ among the groups (all n.s.). CONCLUSIONS: No significant differences were found in the clinical and anatomical outcomes according to the type and dose of the anti-adhesive agents subacromially injected after rotator cuff repair. LEVEL OF EVIDENCE: III.

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