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1.
Chemistry ; : e202402871, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39219235

RESUMO

The differential sensing approach uses fingerprint patterning to distinguish uncharacterized biological samples. Inspired by natural sensory systems, an array of cross-reactive sensors generates unique response fingerprint depending on the samples. Until today, this array system has been developed using various materials, including the library of surface-charged nanoparticles and chemosensors. Many differential array systems have demonstrated accurate identification of bacterial species, viral subtypes, and cancer cells, as well as distinguishing disease states in blood or urine. This capability is particularly important for distinguishing between normal and abnormal states when specific marker molecules have not yet been identified, providing a powerful diagnostic tool. In this concept, we summarized representative outcomes of differential sensing applications for biological sample discrimination.

2.
Nat Commun ; 15(1): 7689, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39227575

RESUMO

Controlling the succession of chemical processes with high specificity in complex systems is advantageous for widespread applications, from biomedical research to drug manufacturing. Despite synthetic advances in bioorthogonal and photochemical methodologies, there is a need for generic chemical approaches that can universally modulate photodynamic reactivity in organic photosensitizers. Herein we present a strategy to fine-tune the production of singlet oxygen in multiple photosensitive scaffolds under the activation of bioresponsive and bioorthogonal stimuli. We demonstrate that the photocatalytic activity of nitrobenzoselenadiazoles can be fully blocked by site-selective incorporation of electron-withdrawing carbamate moieties and restored on demand upon uncaging with a wide range of molecular triggers, including abiotic transition-metal catalysts. We also prove that this strategy can be expanded to most photosensitizers, including diverse structures and spectral properties. Finally, we show that such advanced control of singlet oxygen generation can be broadly applied to the photodynamic ablation of human cells as well as to regulate the release of singlet oxygen in the semi-synthesis of natural product drugs.


Assuntos
Fármacos Fotossensibilizantes , Oxigênio Singlete , Oxigênio Singlete/química , Oxigênio Singlete/metabolismo , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Humanos , Catálise/efeitos da radiação , Fotoquimioterapia/métodos , Carbamatos/química , Células HeLa
3.
Anim Cells Syst (Seoul) ; 28(1): 353-366, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39040684

RESUMO

Taste buds, the neuroepithelial organs responsible for the detection of gustatory stimuli in the oral cavity, arise from stem/progenitor cells among nearby basal keratinocytes. Using genetic lineage tracing, Lgr5 and Lgr6 were suggested as the specific markers for the stem/progenitor cells of taste buds, but recent evidence implied that taste buds may arise even in the absence of these markers. Thus, we wanted to verify the genetic lineage tracing of lingual Lgr5- and Lgr6-expressing cells. Unexpectedly, we found that antibody staining revealed more diverse Lgr5-expressing cells inside and outside the taste buds of circumvallate papillae than was previously suggested. We also found that, while tamoxifen-induced genetic recombination occurred only in cells expressing the Lgr5 reporter GFP, we did not see any increase in the number of recombined daughter cells induced by consecutive injections of tamoxifen. Similarly, we found that cells expressing Lgr6, another stem/progenitor cell marker candidate and an analog of Lgr5, also do not generate recombined clones. In contrast, Lgr5-expressing cells in fungiform papillae can transform into Lgr5-negative progeny. Together, our data indicate that lingual Lgr5- and Lgr6-expressing cells exhibit diversity in their capacity to transform into Lgr5- and Lgr6-negative cells, depending on their location. Our results complement previous findings that did not distinguish this diversity.

4.
Microorganisms ; 12(6)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38930524

RESUMO

The bacterial communities related to seaweed can vary considerably across different locations, and these variations influence the seaweed's nutrition, growth, and development. To study this further, we evaluated the bacteria found on the green marine seaweed Ulva prolifera from Garorim Bay and Muan Bay, two key locations on Republic of Korea's west coast. Our analysis found notable differences in the bacterial communities between the two locations. Garorim Bay hosted a more diverse bacterial population, with the highest number of ASVs (871) compared to Muan Bay's 156 ASVs. In Muan Bay, more than 50% of the bacterial community was dominated by Pseudomonadota. On the other hand, Garorim Bay had a more balanced distribution between Bacteroidota and Pseudomonadota (37% and 35.5%, respectively). Additionally, Cyanobacteria, particularly Cyanothece aeruginosa, were found in significant numbers in Garorim Bay, making up 8% of the community. Mineral analysis indicated that Garorim Bay had higher levels of S, Na, Mg, Ca, and Fe. Function-wise, both locations exhibited bacterial enrichment in amino acid production, nucleosides, and nucleotide pathways. In conclusion, this study broadens our understanding of the bacterial communities associated with Ulva prolifera in Korean waters and provides a foundation for future research on the relationships between U. prolifera and its bacteria.

5.
Int J Mol Sci ; 25(12)2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38928436

RESUMO

Chronic graft-versus-host disease (cGVHD) is a long-term complication of allogeneic hematopoietic stem cell transplantation associated with poor quality of life and increased morbidity and mortality. Currently, there are several approved treatments for patients who do not respond to steroids, such as ruxolitinib. Nevertheless, a significant proportion of patients fail second-line treatment, indicating the need for novel approaches. Mesenchymal stem cells (MSCs) have been considered a potential treatment approach for steroid-refractory cGVHD. To evaluate the safety and efficacy of repeated infusions of MSCs, we administered intravenous MSCs every two weeks to ten patients with severe steroid-refractory cGVHD in a prospective phase I clinical trial. Each patient received a total of four doses, with each dose containing 1 × 106 cells/kg body weight from the same donor and same passage. Patients were assessed for their response to treatment using the 2014 National Institutes of Health (NIH) response criteria during each visit. Ten patients with diverse organ involvement were enrolled, collectively undergoing 40 infusions as planned. Remarkably, the MSC infusions were well tolerated without severe adverse events. Eight weeks after the initial MSC infusion, all ten patients showed partial responses characterized by the amelioration of clinical symptoms and enhancement of their quality of life. The overall response rate was 60%, with a complete response rate of 20% and a partial response (PR) rate of 40% at the last follow-up. Overall survival was 80%, with a median follow-up of 381 days. Two patients died due to relapse of their primary disease. Immunological analyses revealed a reduction in inflammatory markers, including Suppression of Tumorigenicity 2 (ST2), C-X-C motif chemokine ligand (CXCL)10, and Secreted phosphoprotein 1(SPP1), following the MSC treatment. Repeated MSC infusions proved to be both feasible and safe, and they may be an effective salvage therapy in patients with steroid-refractory cGVHD. Further large-scale clinical studies with long-term follow-up are needed in the future to determine the role of MSCs in cGVHD.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Humanos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/terapia , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Estudos Prospectivos , Doença Crônica , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Resultado do Tratamento , Esteroides/uso terapêutico , Adulto Jovem , Qualidade de Vida , Síndrome de Bronquiolite Obliterante
6.
Neurospine ; 21(1): 116-127, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38569638

RESUMO

OBJECTIVE: This study aimed to assess the degree of interest in robot-assisted spine surgery (RASS) among residents and to investigate the learning curve for beginners performing robotic surgery. METHODS: We conducted a survey to assess awareness and interest in RASS among young neurosurgery residents. Subsequently, we offered a hands-on training program using a dummy to educate one resident. After completing the program, the trained resident performed spinal fusion surgery with robotic assistance under the supervision of a mentor. The clinical outcomes and learning curve associated with robotic surgery were then analyzed. RESULTS: Neurosurgical residents had limited opportunities to participate in spinal surgery during their training. Despite this, there was a significant interest in the emerging field of robotic surgery. A trained resident performed RASS under the supervision of a senior surgeon. A total of 166 screw insertions were attempted in 28 patients, with 2 screws failing due to skiving. According to the Gertzbein-Robbins classification, 85.54% of the screws were rated as grade A, 11.58% as grade B, 0.6% as grade C, and 1.2% as grade D. The clinical acceptance rate was approximately 96.99%, which is comparable to the results reported by senior experts and time per screw statistically significantly decreased as experience was gained. CONCLUSION: RASS can be performed with high accuracy within a relatively short timeframe, if residents receive adequate training.

7.
Angew Chem Int Ed Engl ; 63(24): e202405525, 2024 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-38607969

RESUMO

Cancer stem cells are pivotal players in tumors initiation, growth, and metastasis. While several markers have been identified, there remain challenges particularly in heterogeneous malignancies like adult soft tissue sarcomas, where conventional markers are inherently overexpressed. Here, we designed BODIPY scaffold fluorescence probes (BD-IMC-1, BD-IMC-2) that activate via disaggregation targeting for cyclooxygenase (COX), a potential marker for CSCs in sarcoma in clinical pathology. Based on their structures, BD-IMC-1 showcased higher susceptibility to disaggregation compared to BD-IMC-2, consistent with their selective interaction with COX. Notably, the BD-IMC-1 revealed positive cooperativity binding to COX-2 at sub-micromolar ranges. Both probes showed significant fluorescence turn-on upon LPS or PMA triggered COX-2 upregulation in live RAW264.7, HeLa, and human sarcoma cell line (Saos-LM2) up to 2-fold increase with negligible toxicity. More importantly, the BD-IMC-1 demonstrated their practical imaging for COX-2 positive cells in paraffin-fixed human sarcoma tissue. Considering the fixed tissues are most practiced pathological sample, our finding suggests a potential of disaggregation activated chemosensor for clinical applications.


Assuntos
Ciclo-Oxigenase 2 , Corantes Fluorescentes , Sarcoma , Humanos , Sarcoma/diagnóstico por imagem , Sarcoma/patologia , Sarcoma/metabolismo , Ciclo-Oxigenase 2/metabolismo , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Imagem Óptica , Compostos de Boro/química , Animais , Camundongos , Linhagem Celular Tumoral , Estrutura Molecular
8.
J Korean Neurosurg Soc ; 67(5): 550-559, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38356349

RESUMO

OBJECTIVE: This study focuses on identifying potential complications following oblique lumbar interbody fusion (OLIF) through routine magnetic resonance (MR) scans. METHODS: From 650 patients who underwent OLIF from April 2018 to April 2022, this study included those with MR scans taken 1-week post-operatively, and only for indirect decompression patients. The analysis evaluated postoperative MR images for hematoma, cage insertion angles, and indirect decompression efficiency. Patient demographics, post-operatively symptoms, and complications were also evaluated. RESULTS: Out of 401 patients enrolled, most underwent 1- or 2-level OLIF. Common findings included approach site hematoma (65.3%) and contralateral psoas hematoma (19%). The caudal level OLIF was related with less orthogonality and deep insertion of cage. Incomplete indirect decompression occurred in 4.66% of cases but did not require additional surgery. Rare but symptomatic complications included remnant disc rupture (four cases, 1%) and synovial cyst rupture (four cases, 1%). CONCLUSION: This study has identified potential complications associated with OLIF, including approach site hematoma, contralateral psoas hematoma, cage malposition risk at caudal levels, and radiologically insufficient indirect decompression. Additionally, it highlights rare, yet symptomatic complications such as remnant disc rupture and synovial cyst rupture. These findings contribute insights into the relatively under-explored area of OLIF complications.

9.
J Mov Disord ; 17(2): 189-197, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38419488

RESUMO

OBJECTIVE: Exercise can improve both motor and nonmotor symptoms in people with Parkinson's disease (PwP), but there is an unmet need for accessible and sustainable exercise options. This study aimed to evaluate the effect, feasibility, and safety of a regularly performed live-streaming tele-exercise intervention for PwP. METHODS: A live-streaming exercise intervention for PwP was implemented twice a week for 12 weeks. We measured the motor and nonmotor symptom scores of the included patients before and after the intervention. Changes in clinical scores from baseline to postintervention were analyzed using paired t-tests. Factors associated with improvements in clinical scores and compliance were analyzed using Pearson's correlation analysis. RESULTS: Fifty-six participants were enrolled in the study. There were significant improvements in Hospital Anxiety and Depression Scale (HADS)-anxiety (p = 0.007), HADS-depression (p < 0.001), Unified Parkinson's Disease Rating Scale (UPDRS) part III (p < 0.001), UPDRS total (p = 0.015), Hoehn and Yahr stage (p = 0.027), and Parkinson's Disease Fatigue Scale-16 (p = 0.026) scores after the intervention. Improvements in motor symptoms were associated with improvements in mood symptoms and fatigue. Higher motor impairment at baseline was associated with a greater compliance rate and better postintervention composite motor and nonmotor outcomes (ΔUPDRS total score). Overall, the 12-week tele-exercise program was feasible and safe for PwP. No adverse events were reported. The overall adherence rate was 60.0% in our cohort, and 83.4% of the participants were able to participate in more than half of the exercise routines. CONCLUSION: The live-streaming tele-exercise intervention is a safe, feasible, and effective nonpharmacological treatment option that can alleviate fatigue and improve mood and motor symptoms in PwP.

10.
J Korean Neurosurg Soc ; 67(1): 60-72, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38224963

RESUMO

OBJECTIVE: Recently, robotic-assisted spine surgery (RASS) has been considered a minimally invasive and relatively accurate method. In total, 495 robotic-assisted pedicle screw fixation (RAPSF) procedures were attempted on 100 patients during a 14-month period. The current study aimed to analyze the accuracy, potential risk factors, and learning curve of RAPSF. METHODS: This retrospective study evaluated the position of RAPSF using the Gertzbein and Robbins scale (GRS). The accuracy was analyzed using the ratio of the clinically acceptable group (GRS grades A and B), the dissatisfying group (GRS grades C, D, and E), and the Surgical Evaluation Assistant program. The RAPSF was divided into the no-breached group (GRS grade A) and breached group (GRS grades B, C, D, and E), and the potential risk factors of RAPSF were evaluated. The learning curve was analyzed by changes in robot-used time per screw and the occurrence tendency of breached and failed screws according to case accumulation. RESULTS: The clinically acceptable group in RAPSF was 98.12%. In the analysis using the Surgical Evaluation Assistant program, the tip offset was 2.37±1.89 mm, the tail offset was 3.09±1.90 mm, and the angular offset was 3.72°±2.72°. In the analysis of potential risk factors, the difference in screw fixation level (p=0.009) and segmental distance between the tracker and the instrumented level (p=0.001) between the no-breached and breached group were statistically significant, but not for the other factors. The mean difference between the no-breach and breach groups was statistically significant in terms of pedicle width (p<0.001) and tail offset (p=0.042). In the learning curve analysis, the occurrence of breached and failed screws and the robot-used time per screw screws showed a significant decreasing trend. CONCLUSION: In the current study, RAPSF was highly accurate and the specific potential risk factors were not identified. However, pedicle width was presumed to be related to breached screw. Meanwhile, the robot-used time per screw and the incidence of breached and failed screws decreased with the learning curve.

11.
Chemistry ; 30(5): e202302916, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-37902438

RESUMO

Blood continually contributes to the maintenance of homeostasis of the body and contains information regarding the health state of an individual. However, current hematological analyses predominantly rely on a limited number of CD markers and morphological analysis. In this work, differentially sensitive fluorescent compounds based on TCF scaffolds are introduced that are designed for fluorescent phenotyping of blood. Depending on their structures, TCF compounds displayed varied responses to reactive oxygen species, biothiols, redox-related biomolecules, and hemoglobin, which are the primary influential factors within blood. Contrary to conventional CD marker-based analysis, this unbiased fluorescent phenotyping method produces diverse fingerprints of the health state. Precise discrimination of blood samples from 37 mice was demonstrated based on their developmental stages, ranging from 10 to 19 weeks of age. Additionally, this fluorescent phenotyping method enabled the differentiation between drugs with distinct targets, serving as a simple yet potent tool for pharmacological analysis to understand the mode of action of various drugs.


Assuntos
Envelhecimento , Corantes Fluorescentes , Camundongos , Animais , Corantes Fluorescentes/química , Espécies Reativas de Oxigênio/análise , Oxirredução , Células Sanguíneas/química
13.
Angew Chem Int Ed Engl ; 63(3): e202312942, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38062619

RESUMO

The development of a small-molecule probe designed to selectively target neurons would enhance the exploration of intricate neuronal structures and functions. Among such probes, NeuO stands out as the pioneer and has gained significant traction in the field of research. Nevertheless, neither the mechanism behind neuron-selectivity nor the cellular localization has been determined. Here, we introduce NeuM, a derivative of NeuO, designed to target neuronal cell membranes. Furthermore, we elucidate the mechanism behind the selective neuronal membrane trafficking that distinguishes neurons. In an aqueous buffer, NeuM autonomously assembles into micellar structures, leading to the quenching of its fluorescence (Φ=0.001). Upon exposure to neurons, NeuM micelles were selectively internalized into neuronal endosomes via clathrin-mediated endocytosis. Through the endocytic recycling pathway, NeuM micelles integrate into neuronal membrane, dispersing fluorescent NeuM molecules in the membrane (Φ=0.61). Molecular dynamics simulations demonstrated that NeuM, in comparison to NeuO, possesses optimal lipophilicity and molecular length, facilitating its stable incorporation into phospholipid layers. The stable integration of NeuM within neuronal membrane allows the prolonged monitoring of neurons, as well as the visualization of intricate neuronal structures.


Assuntos
Clatrina , Micelas , Clatrina/metabolismo , Endocitose/fisiologia , Endossomos/metabolismo , Neurônios/metabolismo
14.
World J Clin Cases ; 11(35): 8392-8398, 2023 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-38130625

RESUMO

BACKGROUND: Ligamentum flavum cysts, which are most common in mobile junctional levels of the spine, can be a rare cause of spinal stenosis. There have been several case reports of ligamentum flavum cysts. However, there is yet to be a documented case report of a calcified ligamentum flavum cyst. Herein, we report the first case of a calcified ligamentum flavum cyst causing ankle and toe weakness. CASE SUMMARY: A 66-year-old male visited our hospital complaining of claudication as well as thigh and calf pain in his left leg, all beginning two weeks prior. Physical examination revealed motor weakness of the left ankle dorsiflexion and great toe dorsiflexion. Lumbar spinal computed tomography scans showed spinal stenosis combined with a calcified mass at the left side of the L4-5 level. Magnetic resonance imaging showed dural sac compression caused by the calcified mass at the left ligamentum flavum of the L4-5 level. We performed decompressive laminectomy and excision of the calcified mass combined with posterior lumbar interbody fusion at the L4-5 level. Intra-operatively, we found a firm and nodule like mass originating from the ventral surface of ligamentum flavum. Pathological examination suggested a calcified pseudocyst without a capsular lining. After the operation, the patient's motor weakness in the ankle and great toe improved gradually. CONCLUSION: The patient's ankle and great toe weakness were improved successfully after surgical removal of the calcified cyst.

15.
Front Neurol ; 14: 1326571, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38156084

RESUMO

Introduction: Subjective cognitive complaints (SCC) refer to self-reported cognitive decline that may or may not be reflected in objective neuropsychological evaluations. Such SCC are prevalent in neurodegenerative diseases, including Parkinson's disease (PD), but the prevalence and clinical features in patients with progressive supranuclear palsy (PSP) have not been investigated. Methods: We recruited 83 PSP patients without dementia and investigated their SCC using a semi-structured interview. Comprehensive neuropsychological test results and patient clinical features were compared according to presence of SCC and underlying cognitive state. Results: Among the 83 patients, 16 had normal cognition (NC), 67 had mild cognitive impairment (MCI), and 36 (43.4%) reported SCC. Among NC patients, 37.5% (6/16) had SCC, while 44.8% (30/67) of MCI patients reported SCC. There were no differences between the neuropsychological test results or demographic and clinical characteristics of PSP patients with or without SCC in the NC group. The demographic and clinical characteristics of the MCI+SCC (MCI with SCC)and MCI-SCC (MCI without SCC) groups were comparable, but the MCI+SCC group had significantly worse neuropsychological scores than the MCI-SCC group, particularly in tests assessing attention, language, visual memory, and fronto-executive function domains. Discussion: While SCC are commonly reported by PSP patients, patients with PSP and MCI+SCC had worse cognitive function than those who did not report SCC. These findings suggest that SCC in PSP patients with MCI could be a worsening sign of cognitive function. Therefore, it is crucial for physicians to assess SCC in PSP patients and to provide timely diagnosis and management of cognitive decline.

16.
Bioengineering (Basel) ; 10(10)2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37892844

RESUMO

(1) Background: Recently, Escherichia coli-derived recombinant human bone morphogenetic protein-2 (E. coli-derived rhBMP-2) has been increasingly applied to different types of spinal surgeries and reported to achieve successful fusion. This pilot study aimed to evaluate the clinical efficacy and safety of rhBMP-2 in patients undergoing posterior instrumented fusions for unstable spinal fractures. (2) Methods: This study included ten consecutive patients undergoing spinal surgery using E. coli-derived rhBMP-2 with more than one year of follow-up. Radiologic outcomes were compared, including the average fracture healing period, local kyphosis correction, and clinical outcomes between preoperative and the last follow-up. (3) Results: The average time of radiographic union was 99.9 ± 45.4 (62-192) days, with an average use of 5.2 ± 3.9 months of anabolic agents. Radiologic parameters such as anterior vertebral height and vertebral wedge angle were significantly corrected postoperatively and at the last follow-up. Clinical outcomes other than leg pain were significantly improved after the surgery. In addition, four patients with preoperative neurologic deficits showed improved neurologic status. (4) Conclusions: Combined with the anabolic agents, applying E. coli-derived rhBMP-2 to the fractured vertebral body could be an effective surgical treatment for unstable spinal fractures. Further trials are needed to validate this result.

18.
Eur J Med Chem ; 261: 115779, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-37776574

RESUMO

A series of 36 pyrazol-4-yl pyridine derivatives (8a-i, 9a-i, 10a-i, and 11a-i) was designed, synthesized, and evaluated for its antiproliferative activity over NCI-60 cancer cell line panel and inhibitory effect against JNK isoforms (JNK1, JNK2, and JNK3). All the synthesized compounds were tested against the NCI-60 cancer cell line panel. Compounds 11b, 11c, 11g, and 11i were selected to determine their GI50s and exerted a superior potency over the reference standard SP600125 against the tested cell lines. 11c showed a GI50 of 1.28 µM against K562 leukemic cells. Vero cells were used to assess 11c cytotoxicity compared to the tested cancer cells. The target compounds were tested against hJNK isoforms in which compound 11e exhibited the highest potency against JNK isoforms with IC50 values of 1.81, 12.7, and 10.5 nM against JNK1, JNK2, and JNK3, respectively. Kinase profiling of 11e showed higher JNK selectivity in 50 kinase panels. Compounds 11c and 11e showed cell population arrest at the G2/M phase, induced early apoptosis, and slightly inhibited beclin-1 production at higher concentrations in K562 leukemia cells relative to SP600125. NanoBRET assay of 11e showed intracellular JNK1 inhibition with an IC50 of 2.81 µM. Also, it inhibited CYP2D6 and 3A4 with different extent and its hERG activity showed little cardiac toxicity with an IC50 of 4.82 µM. hJNK3 was used as a template to generate the hJNK1 crystal structure to explore the binding mode of 11e (PDB ID: 8ENJ) with a resolution of 2.8 °A and showed a typical type I kinase inhibition against hJNK1. Binding energy scores showed that selectivity of 11e towards JNK1 could be attributed to additional hydrophobic interactions relative to JNK3.


Assuntos
Azóis , Proteínas Quinases JNK Ativadas por Mitógeno , Animais , Chlorocebus aethiops , Células Vero , Azóis/farmacologia , Isoformas de Proteínas , Piridinas/farmacologia , Proliferação de Células
19.
Life Sci ; 332: 122101, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37730110

RESUMO

AIMS: We investigated whether modulation of white adipose tissue (WAT) vasculature regulates rebound weight gain (RWG) after caloric restriction (CR) in mice fed a high-fat diet (HFD). MAIN METHODS: We compared changes in energy balance, hypothalamic neuropeptide gene expression, and characteristics of WAT by RT-qPCR, ELISA, immunohistochemistry, and adipose-derived stromal vascular fraction spheroid sprouting assay in obese mice fed a HFD ad libitum (HFD-AL), mice under 40 % CR for 3 or 4 weeks, mice fed HFD-AL for 3 days after CR (CRAL), and CRAL mice treated with TNP-470, an angiogenic inhibitor. KEY FINDINGS: WAT angiogenic genes were expressed at low levels, but WAT vascular density was maintained in the CR group compared to that in the HFD-AL group. The CRAL group showed RWG, fat regain, and hyperphagia with higher expression of angiogenic genes and reduced pericyte coverage of the endothelium in WAT on day 3 after CR compared to the CR group, indicating rapidly increased angiogenic activity after CR. Administration of TNP-470 suppressed RWG, fat regain, and hyperphagia only after CR compared to the CRAL group. Changes in circulating leptin levels and hypothalamic neuropeptide gene expression were correlated with changes in weight and fat mass, suggesting that TNP-470 suppressed hyperphagia independently of the hypothalamic melanocortin system. Additionally, TNP-470 increased gene expression related to thermogenesis, fuel utilization, and browning in brown adipose tissue (BAT) and WAT, indicating TNP-470-induced increase in thermogenesis. SIGNIFICANCE: Modulation of the WAT vasculature attenuates RWG after CR by suppressing hyperphagia and increasing BAT thermogenesis and WAT browning.

20.
Turk Neurosurg ; 33(6): 1132, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37528718

RESUMO

Oblique lateral interbody fusion (OLIF) has recently gained widespread use as a minimally invasive surgical procedure for degenerative lumbar disease. OLIF has several advantages but can also lead to several possible complications. For example, although less common, access through the retroperitoneal cavity can cause ureteral injury. Here, we report two cases of ureteral complications that occurred during consecutive OLIF procedures. One involved a 77-year-old female patient who had a double-J catheter inserted due to ureteral injury during surgery, and the other involved a 69-year-old male patient suspected of having a ureteral stricture due to retractor compression. To prevent ureteral complications in OLIF, it is necessary to accurately identify the anatomy of the ureter through preoperative imaging and to pay special attention during surgery.


Assuntos
Fusão Vertebral , Ureter , Masculino , Feminino , Humanos , Idoso , Ureter/diagnóstico por imagem , Ureter/cirurgia , Fusão Vertebral/efeitos adversos , Fusão Vertebral/métodos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Região Lombossacral , Estudos Retrospectivos , Resultado do Tratamento
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