Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 161
Filtrar
1.
Clin Shoulder Elb ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38738324

RESUMO

Background: In rotator cuff repair, the long head of the biceps tendon (LHB) is a common graft material. However, the factors associated with LHB tear severity are poorly understood, and predicting grade II LHB tears is difficult. This study aimed to identify those factors before surgery. Methods: The demographics, medical parameters, and pain severity of 750 patients who underwent arthroscopic surgery from January 2010 to February 2021 were evaluated to determine the factors associated with LHB tear severity and grade II LHB tears. Both the overall study population and the large-to-massive rotator cuff tear (RCT) cohorts were analyzed using ordinal and binary logistic regression analyses. Predictive accuracy for grade II LHB tears was determined using the area under the receiver operating characteristic curve (AUC) curve. Results: In the overall cohort, high-sensitivity C-reactive protein (hs-CRP) >1 mg/L, a subscapularis tear, hypothyroidism, and the tangent sign (P≤0.031) were significantly associated with LHB tear severity, and hs-CRP>1 mg/L, a subscapularis tear, and the Patte retraction degree were significantly associated with grade II LHB tears (P<0.001). In the large-to-massive RCT cohort, hs-CRP>1 mg/L, hypertension, and age ≥50 years (P≤0.034) were significantly associated with LHB tear severity, and hs-CRP>1 mg/L and hypertension were significantly associated with grade II LHB tears (P≤0.026). In both cohorts, hs-CRP >1 mg/L demonstrated good predictive accuracy for grade II LHB tears (AUCs: 0.72 and 0.70). Conclusions: Serum hs-CRP >1 mg/L is associated with LHB tear severity and serves as a reliable predictor of grade II LHB tears, facilitating preoperative assessment of the LHB as potential graft material in arthroscopic rotator cuff repair.

2.
Mater Today Bio ; 26: 101016, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38516171

RESUMO

Bone damage is a complex orthopedic problem primarily caused by trauma, cancer, or bacterial infection of bone tissue. Clinical care management for bone damage remains a significant clinical challenge and there is a growing need for more advanced bone therapy options. Nanotechnology has been widely explored in the field of orthopedic therapy for the treatment of a severe bone disease. Among nanomaterials, gold nanoparticles (GNPs) along with other biomaterials are emerging as a new paradigm for treatment with excellent potential for bone tissue engineering and regenerative medicine applications. In recent years, a great deal of research has focused on demonstrating the potential for GNPs to provide for enhancement of osteogenesis, reduction of osteoclastogenesis/osteomyelitis, and treatment of bone cancer. This review details the latest understandings in regards to GNPs based therapeutic systems, mechanisms, and the applications of GNPs against various bone disorders. The present review aims to summarize i) the mechanisms of GNPs in bone tissue remodeling, ii) preparation methods of GNPs, and iii) functionalization of GNPs and its decoration on biomaterials as a delivery vehicle in a specific bone tissue engineering for future clinical application.

3.
Arch Craniofac Surg ; 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38447589

RESUMO

A 76-year-old woman, initially thought to have a simple abscess on her right upper eyelid, presented to our department of plastic and reconstructive surgery. Enhanced three-dimensional facial computed tomography (CT) revealed an abscess on the right upper lid, with a pyomucocele present in the right frontal sinus, accompanied by bone erosion in the superior wall of the right orbit. Based on the results of the CT scan, we diagnosed an atypical Pott's puffy tumor (PPT) with an abscess on the upper lid originating from the frontal sinusitis. First, surgical incision and drainage were performed in our department, and a percutaneous vacuum drain was placed. To provide a more definitive treatment, endoscopic sinus surgery (ESS) was subsequently performed by otorhinolaryngologists. The patient was discharged without any complications 5 days after ESS. At a 1-year follow-up, no recurrence or notable neurological symptoms were observed. In the case we observed, the patient presented with an upper eyelid abscess and cellulitis, indicating possible orbital involvement. For such patients, a CT scan is necessary. Given the possibility of PPT, it is critical to perform a comprehensive differential diagnosis rather than defaulting to a straightforward approach involving abscess treatment.

4.
Arch Craniofac Surg ; 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38447588

RESUMO

A 59-year-old woman presented to our clinic with a 3.5× 3-cm protruding mass on her forehead. A skull X-ray revealed a radiolucent osteolytic lesion on the left side of the frontal bone. Additionally, computed tomography showed a 3.1× 1.7× 3.6-cm mass exhibiting a "sunburst" pattern situated between the outer and inner tables of the skull, just superior and lateral to the left frontal sinus. This pattern suggested the presence of an intraosseous vascular malformation (IVM). The lesion was approached via a bicoronal incision. En-bloc resection was performed, removing the mass along with approximately 0.5 cm of the surrounding normal bone without injury to the exposed frontal sinus mucosa. The exposed mucosa was reinforced with a galeal flap, and cranioplasty with bone cement was performed to repair the resulting bony defect. Pathological examination confirmed a diagnosis of intraosseous cavernous-type malformation with mixed cavernous and capillary histological features. We report this case of IVM and review the existing literature, highlighting the satisfactory functional and aesthetic outcomes after surgery.

5.
Adv Sci (Weinh) ; 11(16): e2304861, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38355304

RESUMO

An ideal hydrogel for stem cell therapy would be injectable and efficiently promote stem cell proliferation and differentiation in body. Herein, an injectable, single-component hydrogel with hyaluronic acid (HA) modified with phenylboronic acid (PBA) and spermidine (SM) is introduced. The resulting HAps (HA-PBA-SM) hydrogel is based on the reversible crosslinking between the diol and the ionized PBA, which is stabilized by the SM. It has a shear-thinning property, enabling its injection through a syringe to form a stable hydrogel inside the body. In addition, HAps hydrogel undergoes a post-injection "self-curing," which stiffens the hydrogel over time. This property allows the HAps hydrogel to meet the physical requirements for stem cell therapy in rigid tissues, such as bone, while maintaining injectability. The hydrogel enabled favorable proliferation of human mesenchymal stem cells (hMSCs) and promoted their differentiation and mineralization. After the injection of hMSCs-containing HAps into a rat femoral defect model, efficient osteogenic differentiation of hMSCs and bone regeneration is observed. The study demonstrates that simple cationic modification of PBA-based hydrogel enabled efficient gelation with shear-thinning and self-curing properties, and it would be highly useful for stem cell therapy and in vivo bone regeneration.


Assuntos
Regeneração Óssea , Ácidos Borônicos , Diferenciação Celular , Hidrogéis , Células-Tronco Mesenquimais , Animais , Regeneração Óssea/fisiologia , Ratos , Hidrogéis/química , Células-Tronco Mesenquimais/citologia , Humanos , Ácido Hialurônico/química , Ratos Sprague-Dawley , Encapsulamento de Células/métodos , Proliferação de Células , Osteogênese/fisiologia , Modelos Animais de Doenças , Espermidina/farmacologia , Espermidina/química
6.
Adv Ther ; 41(3): 932-944, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38185778

RESUMO

INTRODUCTION: Cryoballoon ablation (CBA) is a standard catheter ablation technology with demonstrated clinical effectiveness for the treatment of paroxysmal atrial fibrillation (PAF); however, it can be associated with major adverse events, including phrenic nerve paralysis. Pulsed field ablation (PFA) is a novel, minimally thermal technology with comparable effectiveness and low safety risk. This study aimed to compare the safety profiles of PFA and CBA through critical analyses of the literature and indirect treatment comparisons. METHODS: Studies were identified by searching the MEDLINE database and the Clinicaltrials.gov registry. Registered clinical trials and/or Food and Drug Administration Investigation Device Exemption (FDA IDE) studies evaluating PFA or CBA in adult patients with drug-refractory PAF between January 2008 and March 2023 were selected. Comparative safety between PFA and CBA was assessed for major and prespecified adverse events. Indirect comparisons were conducted using the proportion of patients experiencing adverse events and confirmed with single-arm meta-analyses and sensitivity analyses. RESULTS: Data were extracted from three PFA publications including a total of 497 patients and six CBA studies including a total of 1113 patients. The analysis revealed that PFA was associated with significantly lower risk of major adverse events {risk difference - 4.3% [95% confidence interval (CI) - 5.8, - 2.8]; risk ratio 0.16 [95% CI 0.07, 0.45]} and prespecified adverse events [risk difference - 2.5% (95% CI - 4.4, - 0.5); risk ratio 0.53 (95% CI 0.31, 0.96)]. Meta-analyses confirmed the lower rate of major adverse events for PFA [0.4% (95% CI 0.0, 1.3)] vs. CBA [5.6% (95% CI 2.6, 8.6)] and prespecified adverse events for PFA [2.7% (95% CI 1.2, 4.1)] vs. CBA [5.8% (95% CI 2.7, 9.0)]. Sensitivity analyses exploring heterogeneity across studies confirmed robustness of the main analyses. CONCLUSION: The findings of this study show that PFA has a more favorable safety profile than CBA, with significantly lower risks of major and prespecified adverse events. These indirect comparisons help contextualize the safety of PFA compared to CBA for the treatment of drug-refractory PAF in the absence of head-to-head studies.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Criocirurgia , Veias Pulmonares , Adulto , Humanos , Fibrilação Atrial/cirurgia , Criocirurgia/efeitos adversos , Veias Pulmonares/cirurgia , Resultado do Tratamento , Ablação por Cateter/efeitos adversos , Recidiva
7.
Investig Clin Urol ; 65(1): 69-76, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38197753

RESUMO

PURPOSE: To investigate the prevalence of lower urinary tract symptoms/benign prostatic hyperplasia in a Korean population. MATERIALS AND METHODS: The Korean Prostate & Voiding Health Association provided free prostate-related community health care and conducted surveys in all regions of Korea from 2001 to 2022 with the cooperation of local government public health centers. A total of 72,068 males older than 50 were surveyed and analyzed. History taking, International Prostate Symptom Score (IPSS), transrectal ultrasonography, prostate-specific antigen (PSA) testing, uroflowmetry, and urine volume testing were performed. RESULTS: The mean prostate volumes in males in their 50s, 60s, 70s, and 80s or above were 24.7 g, 27.7 g, 31 g, and 33.7 g, respectively. The proportion of males with high PSA greater than 3 ng/mL was 3.8% among males in their 50s, 7.7% among males in their 60s, 13.1% among males in their 70s, and 17.9% among males 80 years of age or older. The mean IPSS total scores in males in their 50s, 60s, 70s, and 80s or above were 10.7, 12.7, 14.5, and 16, respectively. Severe symptoms were reported by 27.3% of males, whereas 51.7% reported moderate symptoms. The mean Qmax in males in their 50s, 60s, 70s, and 80s or above were 20 mL/s, 17.4 mL/s, 15.4 mL/s, and 13.8 mL/s, respectively. CONCLUSIONS: In this population-based study, mean prostate volume, IPSS, PSA, and Qmax were 30.6±15.1 g, 14.8±8.2, 1.9±4.7 ng/mL, and 15.6±6.5 mL/s, respectively. Aging was significantly associated with increased prostate volume, PSA levels, and IPSS scores, and with decreased Qmax and urine volume.


Assuntos
Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Masculino , Humanos , Hiperplasia Prostática/complicações , Hiperplasia Prostática/epidemiologia , Antígeno Prostático Específico , Próstata , Sintomas do Trato Urinário Inferior/epidemiologia , Sintomas do Trato Urinário Inferior/etiologia , República da Coreia/epidemiologia
8.
Adv Mater ; 36(13): e2306602, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38091378

RESUMO

Single-atom nanozymes (SAzymes) constitute a promising category of enzyme-mimicking materials with outstanding catalytic performance. The performance of SAzymes improves through modification of the coordination environments around the metal center. However, the catalytic turnover rates of SAzymes, which are key measures of the effectiveness of active site modifications, remain lower than those of natural enzymes, especially in peroxidase-reactions. Here, the first and second shell coordination tuning strategy that yields SAzymes with structures and activities analogous to those of natural enzymes is reported. The optimized SAzyme exhibits a turnover rate of 52.7 s-1 and a catalytic efficiency of 6.97 × 105 M-1 s-1. A computational study reveals that axial S-ligands induce an alternative reaction mechanism, and SO2- functional groups provide hydrogen bonds to reduce the activation energy. In addition, SAzyme shows superior anti-tumor ability in vitro and in vivo. These results demonstrate the validity of coordination engineering strategies and the carcinostatic potential of SAzymes.


Assuntos
Carbono , Ferro , Ferro/química , Carbono/química , Catálise
9.
J Control Release ; 366: 104-113, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38128883

RESUMO

Although peptides notoriously have poor intrinsic pharmacokinetic properties, it is well-known that nanostructures with excellent pharmacokinetic properties can be designed. Noticing that peptide inhibitors are generally nonpolar, here, we consolidate the peptide inhibitor targeting intracellular protein-protein interactions (PPIs) as an integral part of biodegradable self-assembled depsipeptide nanostructures (SdPNs). Because the peptide inhibitor has the dual role of PPI inhibition and self-assembly in this design, problems associated with the poor pharmacokinetics of peptides and encapsulation/entrapment processes can be overcome. Optimized SdPNs displayed better tumor targeting and PPI inhibition properties than the comparable small molecule inhibitor in vivo. Kinetics of PPI inhibition for SdPNs were gradual and controllable in contrast to the rapid inhibition kinetics of the small molecule. Because SdPN is modular, any appropriate peptide inhibitor can be incorporated into the platform without concern for the poor pharmacokinetic properties of the peptide.


Assuntos
Depsipeptídeos , Nanoestruturas , Cinética
10.
Clin Lab ; 69(11)2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37948498

RESUMO

BACKGROUND: The emergence of next-generation sequencing (NGS) is currently leading the diagnosis of acute myeloid leukemia (AML) and its treatment using a more genetic-level approach. The study aimed to find clinical and prognostic correlations with genomic mutation profiles in Korean patients with AML using NGS. METHODS: This retrospective study enrolled a total of 30 patients who were newly diagnosed with AML from February 2021 to October 2022 in Korea. NGS was used to identify the genetic profiles of 40 genes relevant to AML. The clinical and laboratory data of the patients were analyzed with their genomic mutation profiles. RESULTS: NGS revealed at least one mutation in all patients, with a range of one to seven mutations (median of three mutations). Mutations were commonly associated with TET2, CEBPA, RUNX1, FLT3, IDH2, NPM1, and SRSF2 genes. The TET2 mutation correlated with older (77 vs. 72) patients, and the FLT3 mutation was associated with a higher WBC count (33.4 x 109/L vs. 6.4 x 109/L). The RUNX1 mutation correlated with a lower (44.0 x 109/L vs. 65.5 x 109/L) platelet count, and the NPM1 mutation showed a higher number of blasts in peripheral blood (56.5% vs. 13.0%). Among 16 patients who received induction chemotherapy, mutations in SRSF2, ASXL1, PHF6, SF3B1, and PTPN11 were detected only in patients who failed to achieve complete remission (CR). Meanwhile, mutations in NRAS, TP53, IKZF1, DNMT3A, SH2B3, U2AF1, and WT1 were detected in patients who achieved CR. CONCLUSIONS: Clinical and prognostic correlations were observed according to genomic mutation profiles detected by NGS in Korean patients with AML. An NGS study with a larger cohort of patients would be beneficial to establish the significant prognostic impact on patients with AML.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core , Leucemia Mieloide Aguda , Humanos , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Nucleofosmina , Estudos Retrospectivos , Perfil Genético , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Prognóstico , Mutação , Genômica , República da Coreia
11.
Front Cardiovasc Med ; 10: 1272433, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37915745

RESUMO

Background: Cardiovascular disease continues to be the leading cause of death globally. Clinical practice guidelines aimed at improving disease management and positively impacting major cardiac adverse events recommend genetic testing for inherited cardiovascular conditions such as dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), long QT syndrome (LQTS), hereditary amyloidosis, and familial hypercholesterolemia (FH); however, little is known about how consistently practitioners order genetic testing for these conditions in routine clinical practice. This study aimed to assess the adoption of guideline-directed genetic testing for patients diagnosed with DCM, HCM, LQTS, hereditary amyloidosis, or FH. Methods: This retrospective cohort study captured real-world evidence of genetic testing from ICD-9-CM and ICD-10-CM codes, procedure codes, and structured text fields of de-identified patient records in the Veradigm Health Insights Ambulatory EHR Research Database linked with insurance claims data. Data analysis was conducted using an automated electronic health record analysis engine. Patient records in the Veradigm database were sourced from more than 250,000 clinicians serving over 170 million patients in outpatient primary care and specialty practice settings in the United States and linked insurance claims data from public and private insurance providers. The primary outcome measure was evidence of genetic testing within six months of condition diagnosis. Results: Between January 1, 2017, and December 31, 2021, 224,641 patients were newly diagnosed with DCM, HCM, LQTS, hereditary amyloidosis, or FH and included in this study. Substantial genetic testing care gaps were identified. Only a small percentage of patients newly diagnosed with DCM (827/101,919; 0.8%), HCM (253/15,507; 1.6%), LQTS (650/56,539; 1.2%), hereditary amyloidosis (62/1,026; 6.0%), or FH (718/49,650; 1.5%) received genetic testing. Conclusions: Genetic testing is underutilized across multiple inherited cardiovascular conditions. This real-world data analysis provides insights into the delivery of genomic healthcare in the United States and suggests genetic testing guidelines are rarely followed in practice.

12.
Biomaterials ; 302: 122342, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37804721

RESUMO

Directional differentiation of stem cells is a key step in stem cell therapy. In this study, we developed saponin-based nanoparticles (Ad-SNPs) containing dexamethasone (Dex) and alpha-lipoic acid (ALA) to promote osteogenic differentiation of human mesenchymal stem cells (hMSCs) and bone regeneration. The Ad-SNPs can achieve rapid cellular uptake through a pore-forming effect without cytotoxic cationic charges. They also provide extended retention in cell cytosol due to their uptake route. These properties are advantageous in efficiently supplying drugs to the hMSCs. The combination of Dex and ALA facilitated mitochondrial fusion and prevented reactive oxygen species-induced DNA damage. It also helped to preserve mitochondrial dynamics, and the efficient supply of it provided by the Ad-SNPs induced differentiation of hMSCs into osteoblasts. The Ad-SNPs showed outstanding performance in osteoblast differentiation, maturation, and mineralization in 3D culture compared with NPs without saponin and with free drugs. When Ad-SNP-treated hMSCs were tested in a rat femoral bone defect model, they showed the fastest regeneration of bones and complete repair in the shortest period among all groups. To the best of our knowledge, this study is the first application of pore-forming saponin-based NPs with rapid cellular uptake and extended retention to stem cell therapy, and we demonstrated their promising potential in bone regeneration and efficient delivery of Dex and ALA.


Assuntos
Células-Tronco Mesenquimais , Nanopartículas , Ratos , Animais , Humanos , Osteogênese , Preparações Farmacêuticas , Citosol , Diferenciação Celular , Regeneração Óssea , Células-Tronco , Células Cultivadas
13.
Mater Today Bio ; 22: 100774, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37664795

RESUMO

Ferrocene-based nanoparticles have garnered interest as reactive oxygen species (ROS)-responsive nanocarriers of anticancer drugs and imaging agents. However, their biomedical applications remain limited due to their poor physiological stability. PEGylation of nanocarriers improves their stability and biocompatibility. In this study, we aimed to develop novel PEG-ferrocene nanoparticles (PFNPs) with enhanced stability and ROS responsiveness for the delivery of paclitaxel (PTX) and imaging agents. PEGylation improved the stability of ferrocene nanoparticles, inhibiting their ROS-responsive destruction. Several PEG-ferrocene polymers containing different molar ratios of methacrylic acid and poly (ethylene glycol) methyl ether methacrylate was designed for optimization. ROS-responsive polymers with optimal monomer ratios were self-assembled into PFNPs with enhanced stability. The PFNPs distended, effectively releasing encapsulated PTX and imaging agents within 8 h in the presence of ROS. Furthermore, they remained stable, with no changes in their hydrodynamic diameters or polydispersity indexes after storage in an aqueous solution and biological buffer. The accumulation of PFNPs in a tumor model in vivo was 15-fold higher than a free dye. PTX-loaded PFNPs showed a substantial tumor-suppression effect, reducing tumor size to approximately 18% of that in the corresponding control group. These findings suggest a promising application of ROS-responsive PFNPs in tumor treatment as biocompatible nanocarriers of anticancer drugs and imaging agents.

14.
World J Clin Cases ; 11(26): 6200-6205, 2023 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-37731550

RESUMO

BACKGROUND: Mixed-phenotype acute leukemia (MPAL) is characterized by acute undifferentiated leukemia with blasts co-expressing myeloid and lymphoid antigens. However, consensus regarding the ideal management strategy for MPAL is yet to be established, owing to its rarity. CASE SUMMARY: A 55-year-old male was diagnosed with T/myeloid MPAL. Vincristine, prednisolone, daunorubicin, and L-asparaginase were administered as induction chemotherapy. Septic shock occurred 10 days after induction, and bone marrow examination following recovery from sepsis revealed refractory disease. Venetoclax and decitabine were administered as chemotherapy-free induction therapy to reduce the infection risk. There were no serious infections, including febrile neutropenia, at the end of the treatment. After receiving two additional cycles of venetoclax/decitabine, the patient underwent haploidentical peripheral blood stem-cell transplantation and achieved complete response (CR) to treatment. CONCLUSION: CR was maintained in a patient with MPAL who underwent haploidentical peripheral blood stem-cell transplantation after additional venetoclax/decitabine cycles.

15.
Clin Lab ; 69(9)2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37702669

RESUMO

BACKGROUND: Administration of granulocyte colony-stimulating factors G-SCFs can cause diagnostic challenges because of morphologic alteration of hematopoietic cells. METHODS: We experienced a patient who showed distinctive clinical and morphologic findings after short time use of G-CSF. The clinical information and examination results of the morphology of bone marrow (BM) specimen and karyotype were analyzed by reviewing relevant literature. RESULTS: White blood cell (WBC) counts of the patient were unresponsive to G-CSF and marrow fibrosis and megakaryocytic hyperplasia were accompanied with increase of blasts in BM. Presence of malignant clones was confirmed by cytogenetic aberrations of monosomy 7. CONCLUSIONS: We concluded, BM study including cytogenetic analysis should be performed when such clinical findings are encountered and the possibility of hematologic malignancy should be considered.


Assuntos
Medula Óssea , Mielofibrose Primária , Humanos , Hiperplasia , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Leucócitos
16.
BMB Rep ; 56(11): 618-623, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37605615

RESUMO

Most cancer cells utilize glucose at a high rate to produce energyand precursors for the biosynthesis of macromolecules such as lipids, proteins, and nucleic acids. This phenomenon is called the Warburg effect or aerobic glycolysis- this distinct characteristic is an attractive target for developing anticancer drugs. Here, we found that Phosphofructokinase-1 (PFK-1) is a substrate of the Protein Phosphatase 4 catalytic subunit (PP4C)/PP4 regulatory subunit 1 (PP4R1) complex by using immunoprecipitation and in vitro assay. While manipulation of PP4C/PP4R1 does not have a critical impact on PFK-1 expression, the absence of the PP4C/PP4R1 complex increases PFK-1 activity. Although PP4C depletion or overexpression does not cause a dramatic change in the overall glycolytic rate, PP4R1 depletion induces a considerable increase in both basal and compensatory glycolytic rates, as well as the oxygen consumption rate, indicating oxidative phosphorylation. Collectively, the PP4C/PP4R1 complex regulates PFK-1 activity by reversing its phosphorylation and is a promising candidate for treating glycolytic disorders and cancers. Targeting PP4R1 could be a more efficient and safer strategy to avoid pleiotropic effects than targeting PP4C directly. [BMB Reports 2023; 56(11): 618-623].


Assuntos
Fosfofrutoquinase-1 , Fosfoproteínas Fosfatases , Fosforilação , Fosfoproteínas Fosfatases/metabolismo , Fosfofrutoquinase-1/genética , Fosfofrutoquinase-1/metabolismo , Metabolismo dos Carboidratos , Glicólise
17.
Adv Drug Deliv Rev ; 199: 114959, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37301512

RESUMO

The endocrine system, consisting of the hypothalamus, pituitary, endocrine glands, and hormones, plays a critical role in hormone metabolic interactions. The complexity of the endocrine system is a significant obstacle to understanding and treating endocrine disorders. Notably, advances in endocrine organoid generation allow a deeper understanding of the endocrine system by providing better comprehension of molecular mechanisms of pathogenesis. Here, we highlight recent advances in endocrine organoids for a wide range of therapeutic applications, from cell transplantation therapy to drug toxicity screening, combined with development in stem cell differentiation and gene editing technologies. In particular, we provide insights into the transplantation of endocrine organoids to reverse endocrine dysfunctions and progress in developing strategies for better engraftments. We also discuss the gap between preclinical and clinical research. Finally, we provide future perspectives for research on endocrine organoids for the development of more effective treatments for endocrine disorders.


Assuntos
Transplante de Células , Organoides , Humanos , Sistema Endócrino
18.
Tissue Eng Regen Med ; 20(4): 621-635, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37269439

RESUMO

Cell-based therapies have been used as promising treatments for several untreatable diseases. However, cell-based therapies have side effects such as tumorigenesis and immune responses. To overcome these side effects, therapeutic effects of exosomes have been researched as replacements for cell-based therapies. In addition, exosomes reduced the risk that can be induced by cell-based therapies. Exosomes contain biomolecules such as proteins, lipids, and nucleic acids that play an essential role in cell-cell and cell-matrix interactions during biological processes. Since the introduction of exosomes, those have been proven perpetually as one of the most effective and therapeutic methods for incurable diseases. Much research has been conducted to enhance the properties of exosomes, including immune regulation, tissue repair, and regeneration. However, yield rate of exosomes is the critical obstacle that should be overcome for practical cell-free therapy. Three-dimensional (3D) culture methods are introduced as a breakthrough to get higher production yields of exosomes. For example, hanging drop and microwell were well known 3D culture methods and easy to use without invasiveness. However, these methods have limitation in mass production of exosomes. Therefore, a scaffold, spinner flask, and fiber bioreactor were introduced for mass production of exosomes isolated from various cell types. Furthermore, exosomes treatments derived from 3D cultured cells showed enhanced cell proliferation, angiogenesis, and immunosuppressive properties. This review provides therapeutic applications of exosomes using 3D culture methods.


Assuntos
Exossomos , Exossomos/metabolismo , Células Cultivadas , Cicatrização
19.
Photoacoustics ; 31: 100512, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37252650

RESUMO

Photoacoustic (PA) imaging has gained much attention, providing structural and functional information in combination with clinical ultrasound (US) imaging systems. 2D PA and US imaging is easily implemented, but its heavy dependence on operator skills makes 3D imaging preferable. In this study, we propose a panoramic volumetric clinical PA and US imaging system equipping a handheld imaging scanner weighing 600 g and measuring 70 × 62 × 110 mm3. Multiple PA/US scans were performed to cover a large field-of-view (FOV), and the acquired PA/US volumes were mosaic-stitched after manually correcting the positions and rotations in a total of 6 degrees of freedom. PA and US maximum amplitude projection images were visualized online, while spectral unmixed data was quantified offline. The performance of the system was tested via tissue-mimicking phantom experiments. The system's potential was confirmed in vivo by panoramically imaging vascular networks in human arms and necks, with FOVs of 331 × 38 and 129 × 120 mm2, respectively. Further, we quantified hemoglobin oxygen saturation levels in the radial artery, brachial artery, carotid artery, and jugular vein. We hope that this system can be applied for various clinical fields such as cardiovascular imaging, dermatology, vascular surgery, internal medicine, and oncology.

20.
Ann Transl Med ; 11(8): 303, 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37181336

RESUMO

Background: As a complication of total knee arthroplasty (TKA), patella tendon disruption has been scarcely reported. Moreover, combined periprosthetic joint infection with patellar tendon disruption is even rare. This is a case report on successful treatment of a recurred periprosthetic joint infection accompanying the patellar tendon disruption after revision of TKA. Case Description: A 63-year-old woman presented with pain and exudate in the right knee. she had a history of two-stage revision TKA at another hospital for periprosthetic joint infection of right knee. With repeated incision and debridement, Achromobacter xylosoxidan was identified in samples collected from deep tissue. Therefore, two-stage revision TKA was performed. Intra-operatively, a complete defect of the patellar tendon was observed. Re-revision TKA was performed as a routine of two-stage revision of TKA for periprosthetic joint infection. Reconstruction of the patellar tendon defect was performed using an Achilles tendon-bone block allograft. Stability of allograft was confirmed at 30 degrees of flexion, and excellent implant placement was confirmed by postoperative radiographs. At the final follow-up 3 years after surgery, evidence of infectious sign was absent, and the range of flexion up to 120 degrees was recovered without extension lag. Normal locomotive gait was restored, and recreational activities previously performed were possible without discomfort. Conclusions: Proper reconstruction of extensor mechanism was achieved by patellar wrapping technique using an Achilles tendon-bone block allograft.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA