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1.
Proc Natl Acad Sci U S A ; 120(45): e2309156120, 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37903261

RESUMO

Cobalt-containing alloys are useful for orthopedic applications due to their low volumetric wear rates, corrosion resistance, high mechanical strength, hardness, and fatigue resistance. Unfortunately, these prosthetics release significant levels of cobalt ions, which was only discovered after their widespread implantation into patients requiring hip replacements. These cobalt ions can result in local toxic effects-including peri-implant toxicity, aseptic loosening, and pseudotumor-as well as systemic toxic effects-including neurological, cardiovascular, and endocrine disorders. Failing metal-on-metal (MoM) implants usually necessitate painful, risky, and costly revision surgeries. To treat metallosis arising from failing MoM implants, a synovial fluid-mimicking chelator was designed to remove these metal ions. Hyaluronic acid (HA), the major chemical component of synovial fluid, was functionalized with British anti-Lewisite (BAL) to create a chelator (BAL-HA). BAL-HA effectively binds cobalt and rescues in vitro cell vitality (up to 370% of cells exposed to IC50 levels of cobalt) and enhances the rate of clearance of cobalt in vivo (t1/2 from 48 h to 6 h). A metallosis model was also created to investigate our therapy. Results demonstrate that BAL-HA chelator system is biocompatible and capable of capturing significant amounts of cobalt ions from the hip joint within 30 min, with no risk of kidney failure. This chelation therapy has the potential to mitigate cobalt toxicity from failing MoM implants through noninvasive injections into the joint.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Humanos , Prótese de Quadril/efeitos adversos , Ácido Hialurônico , Dimercaprol , Terapia por Quelação , Falha de Prótese , Artroplastia de Quadril/efeitos adversos , Metais , Cobalto , Quelantes/uso terapêutico , Íons
2.
Proc Natl Acad Sci U S A ; 119(33): e2208106119, 2022 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-35939692

RESUMO

Massive rotator cuff tears (MRCTs) of the shoulder cause disability and pain among the adult population. In chronic injuries, the tendon retraction and subsequently the loss of mechanical load lead to muscle atrophy, fat accumulation, and fibrosis formation over time. The intrinsic repair mechanism of muscle and the successful repair of the torn tendon cannot reverse the muscle degeneration following MRCTs. To address these limitations, we developed an electroconductive matrix by incorporating graphene nanoplatelets (GnPs) into aligned poly(l-lactic acid) (PLLA) nanofibers. This study aimed to understand 1) the effects of GnP matrices on muscle regeneration and inhibition of fat formation in vitro and 2) the ability of GnP matrices to reverse muscle degenerative changes in vivo following an MRCT. The GnP matrix significantly increased myotube formation, which can be attributed to enhanced intracellular calcium ions in myoblasts. Moreover, the GnP matrix suppressed adipogenesis in adipose-derived stem cells. These results supported the clinical effects of the GnP matrix on reducing fat accumulation and muscle atrophy. The histological evaluation showed the potential of the GnP matrix to reverse muscle atrophy, fat accumulation, and fibrosis in both supraspinatus and infraspinatus muscles at 24 and 32 wk after the chronic MRCTs of the rat shoulder. The pathological evaluation of internal organs confirmed the long-term biocompatibility of the GnP matrix. We found that reversing muscle degenerative changes improved the morphology and tensile properties of the tendon compared with current surgical techniques. The long-term biocompatibility and the ability of the GnP matrix to treat muscle degeneration are promising for the realization of MRCT healing and regeneration.


Assuntos
Grafite , Músculo Esquelético , Atrofia Muscular , Nanopartículas , Lesões do Manguito Rotador , Animais , Fibrose , Grafite/uso terapêutico , Músculo Esquelético/fisiologia , Atrofia Muscular/etiologia , Atrofia Muscular/patologia , Atrofia Muscular/prevenção & controle , Ratos , Ratos Sprague-Dawley , Regeneração , Lesões do Manguito Rotador/complicações , Lesões do Manguito Rotador/patologia , Lesões do Manguito Rotador/cirurgia , Ombro
3.
Proc Natl Acad Sci U S A ; 119(4)2022 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-35046053

RESUMO

Current treatment strategies for osteoarthritis (OA) predominantly address symptoms with limited disease-modifying potential. There is a growing interest in the use of adipose-derived stem cells (ADSCs) for OA treatment and developing biomimetic injectable hydrogels as cell delivery systems. Biomimetic injectable hydrogels can simulate the native tissue microenvironment by providing appropriate biological and chemical cues for tissue regeneration. A biomimetic injectable hydrogel using amnion membrane (AM) was developed which can self-assemble in situ and retain the stem cells at the target site. In the present study, we evaluated the efficacy of intraarticular injections of AM hydrogels with and without ADSCs in reducing inflammation and cartilage degeneration in a collagenase-induced OA rat model. A week after the induction of OA, rats were treated with control (phosphate-buffered saline), ADSCs, AM gel, and AM-ADSCs. Inflammation and cartilage regeneration was evaluated by joint swelling, analysis of serum by cytokine profiling and Raman spectroscopy, gross appearance, and histology. Both AM and ADSC possess antiinflammatory and chondroprotective properties to target the sites of inflammation in an osteoarthritic joint, thereby reducing the inflammation-mediated damage to the articular cartilage. The present study demonstrated the potential of AM hydrogel to foster cartilage tissue regeneration, a comparable regenerative effect of AM hydrogel and ADSCs, and the synergistic antiinflammatory and chondroprotective effects of AM and ADSC to regenerate cartilage tissue in a rat OA model.


Assuntos
Tecido Adiposo/citologia , Âmnio , Hidrogéis , Osteoartrite/terapia , Transplante de Células-Tronco , Células-Tronco/metabolismo , Âmnio/química , Animais , Diferenciação Celular , Células Cultivadas , Cromatografia Líquida , Citocinas/metabolismo , Hidrogéis/química , Imuno-Histoquímica , Injeções Intra-Articulares , Espectrometria de Massas , Osteoartrite/etiologia , Osteoartrite/patologia , Ratos , Análise Espectral Raman , Transplante de Células-Tronco/métodos , Células-Tronco/citologia , Resultado do Tratamento
4.
Chembiochem ; 25(10): e202400009, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38545627

RESUMO

Calcium (Ca2+) ions play a crucial role in the functioning of neurons, governing various aspects of neuronal activity such as rapid modulation and alterations in gene expression. Ca2+ signaling has a significant impact on the development of diseases and the impairment of neuronal functions. Herein, the study reports a Ca2+ ion sensor in neuronal cells using a gold nanorod. The gold nanorod (GA-GNR) conjugated glutamic acid developed in the study was used as a nano-bio probe for the experimental and in vitro detection of calcium. The nanosensor is colloidally stable, preserves plasmonic properties, and shows good viability in neuronal cells, as well as promoting neuron cell line growth. The cytotoxicity and cell penetration of the nanosensor are studied using Raman spectroscopy, brightfield and darkfield microscopy imaging, and MTT assays. The quantification of Ca2+ ions in neuronal cells is determined by monitoring the surface plasmon resonance (SPR) of the GA-GNR. The change in the intensity profile in the presence of Ca2+ incubated neurons was effectively used to develop a portable prototype of an optical Ca2+ sensor, proposing it as a tool for neurodegenerative disease diagnosis and neuromodulation evaluation.


Assuntos
Cálcio , Ácido Glutâmico , Ouro , Nanotubos , Neurônios , Ouro/química , Cálcio/metabolismo , Cálcio/análise , Neurônios/metabolismo , Neurônios/citologia , Neurônios/efeitos dos fármacos , Nanotubos/química , Ácido Glutâmico/análise , Ressonância de Plasmônio de Superfície , Animais , Técnicas Biossensoriais , Humanos , Íons/análise , Íons/química , Sobrevivência Celular/efeitos dos fármacos
5.
Clin Otolaryngol ; 49(5): 640-651, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38829037

RESUMO

INTRODUCTION: Study aimed to ole of surgery along with antimicrobials to improve clinical outcomes in treating refractory cases of skull base osteomyelitis (SBO). METHODS: A prospective observational study in a tertiary care centre with 70 SBO patients meeting eligibility criteria. The study population comprised 35 patients refractory to systemic antimicrobials of at least 4 weeks duration who later underwent surgery in addition to medication (surgical group). They were compared with a medical group that responded to medications alone. The outcome variables studied were the resolution of clinical features (pain, discharge, radiology, and inflammatory markers), culture yield, and total duration of treatment. RESULTS: According to our study, relief of pain was faster in the surgical group (1.66 against 4.57 months) with statistical significance (p < 0.001). Relief of symptoms (p < 0.001), radiological improvement (p = 0.001), and normalising of inflammatory markers (p < 0.001) were better in the surgical group than in the medical group. The duration of treatment was an average of 9.2 months in the surgical group compared to 11.3 months in the medical group (p = 0.019). Microbial culture from deep tissue sampling was positive in 24 surgical patients (68.57%). CONCLUSIONS: The treatment response in selected patients of refractory SBO who underwent surgery along with antimicrobials was better than the group who responded to antimicrobials alone. Surgery provided higher microbial yield resulting in culture-specific antimicrobials. The surgical group observed faster relief of symptoms, reduced hospital stay, and total treatment duration.


Assuntos
Osteomielite , Base do Crânio , Humanos , Estudos Prospectivos , Masculino , Feminino , Osteomielite/tratamento farmacológico , Osteomielite/cirurgia , Osteomielite/microbiologia , Base do Crânio/cirurgia , Pessoa de Meia-Idade , Adulto , Antibacterianos/uso terapêutico , Resultado do Tratamento , Idoso , Terapia Combinada
6.
Proc Natl Acad Sci U S A ; 117(46): 28655-28666, 2020 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-33144508

RESUMO

The gold standard treatment for anterior cruciate ligament (ACL) reconstruction is the use of tendon autografts and allografts. Limiting factors for this treatment include donor site morbidity, potential disease transmission, and variable graft quality. To address these limitations, we previously developed an off-the-shelf alternative, a poly(l-lactic) acid (PLLA) bioengineered ACL matrix, and demonstrated its feasibility to regenerate ACL tissue. This study aims to 1) accelerate the rate of regeneration using the bioengineered ACL matrix by supplementation with bone marrow aspirate concentrate (BMAC) and growth factors (BMP-2, FGF-2, and FGF-8) and 2) increase matrix strength retention. Histological evaluation showed robust tissue regeneration in all groups. The presence of cuboidal cells reminiscent of ACL fibroblasts and chondrocytes surrounded by an extracellular matrix rich in anionic macromolecules was up-regulated in the BMAC group. This was not observed in previous studies and is indicative of enhanced regeneration. Additionally, intraarticular treatment with FGF-2 and FGF-8 was found to suppress joint inflammation. To increase matrix strength retention, we incorporated nondegradable fibers, polyethylene terephthalate (PET), into the PLLA bioengineered ACL matrix to fabricate a "tiger graft." The tiger graft demonstrated the greatest peak loads among the experimental groups and the highest to date in a rabbit model. Moreover, the tiger graft showed superior osteointegration, making it an ideal bioengineered ACL matrix. The results of this study illustrate the beneficial effect bioactive factors and PET incorporation have on ACL regeneration and signal a promising step toward the clinical translation of a functional bioengineered ACL matrix.


Assuntos
Reconstrução do Ligamento Cruzado Anterior , Regeneração Tecidual Guiada , Peptídeos e Proteínas de Sinalização Intercelular/uso terapêutico , Regeneração/efeitos dos fármacos , Transplante de Células-Tronco/métodos , Alicerces Teciduais , Animais , Bioengenharia , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Osseointegração , Poliésteres , Polietilenotereftalatos , Coelhos
7.
Chemistry ; 26(13): 2826-2836, 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-31713928

RESUMO

Strong plasmon absorption in the near-infrared (NIR) region renders gold nanorods (GNRs) amenable for biomedical applications, particularly for photothermal therapy. However, these nanostructures have not been explored for their imaging potential because of their weak emission profile. In this study, the weak fluorescence emission of GNRs is tuned to match that of the absorption of a photosensitizer (PS) molecule, and energy transfer from the GNR to PS enhances the emission profile of the GNR-PS combination. GNR complexes generally quench the fluorescence emission of nearby chromophores. However, herein, the complex retains or rather enhances the fluorescence through competition in energy transfer. Excitation-dependent energy transfer has been explained experimentally and theoretically by using DFT calculations, the CIE chromaticity diagram, and power spectrum. The final GNR-PS complex modified for tumor specificity serves as an excellent organ-specific theranostic probe for bioimaging and dual therapy both in vitro and in vivo. Principal component analysis designates photodynamic therapy a better candidate than that of photothermal therapy for long-term efficacy in vivo.


Assuntos
Ouro/química , Nanotubos/química , Fármacos Fotossensibilizantes/química , Nanomedicina Teranóstica/métodos , Animais , Transferência de Energia , Humanos , Luminescência , Nanoestruturas
8.
Acc Chem Res ; 51(12): 3114-3124, 2018 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-30460847

RESUMO

Metal alloys exhibit functionalities unlike those of single metals. Such alloying has drawn considerable research interest, particularly for nanoscale particles (metal clusters/nanoparticles), from the viewpoint of creating new functional nanomaterials. In gas phase cluster research, generated alloy clusters can be spatially separated with atomic precision in vacuum. Thus, the influences of increases or decreases in each element on the overall electronic structure of the cluster can be elucidated. However, to further understand the related mixing and synergistic effects, alloy clusters need to be produced on a large scale and characterized by various techniques. Because alloy clusters protected by thiolate (SR) can be synthesized by chemical methods and are stable in both solution and the solid state, these clusters are ideal study materials to better understand the mixing and synergistic effects. Moreover, the alloy clusters thus created have potential applications as functional materials. Therefore, since 2008, we have been working on establishing a precise synthesis method for SR-protected alloy clusters and elucidating their mixing and synergistic effects. Early research focused on the precise synthesis of alloy clusters wherein some of the Au in the stable SR-protected gold clusters ([Au25(SR)18]- and [Au38(SR)24]0) is replaced by Pd, Ag, or Cu. These studies have shown that Pd, Ag, or Cu substitute at different metal sites. We also have examined the as-synthesized alloy clusters to clarify the effect of substitution by each element on the physical and chemical properties of the clusters. However, in early studies, the number of substitutions could not be controlled with atomic accuracy for [Au25- xM x(SR)18]- (M = Ag or Cu). Then, in following research, methods have been established to obtain alloy clusters with control over the composition. We have succeeded in developing a method for controlling the number of Ag substitutions with atomic precision and thereby elucidating the effect of Ag substitution on the electronic structure of clusters with atomic precision. Concurrently, we also studied alloy clusters containing multiple heteroelements with different preferential substitution sites. These results revealed that the effects of substitution of each element can be superimposed on the cluster by combining multiple elemental substitutions at different sites. In addition, we successfully developed methods to synthesize alloy clusters with heterometal core. These findings are expected to lead to clear design guidelines for developing new functional nanomaterials.

9.
J Reconstr Microsurg ; 35(7): 516-521, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31067582

RESUMO

BACKGROUND: Reconstruction of head and neck defects resulting from resection of head and neck masses is performed by both plastic surgeons and otolaryngologists. The American College of Surgeons National Surgical Quality Improvement (NSQIP) database allows one to directly compare the outcomes for a given procedure based upon specialty. The purpose of this study is to compare outcomes and resource utilization of microvascular head and neck reconstruction between plastic surgery and otolaryngology. METHODS: Institutional review board approval was obtained and NSQIP was queried from 2005 to 2015 with inclusion of Current Procedural Terminology codes for free tissue transfer performed for head and neck reconstruction. Outcomes were compared between cases having otolaryngology and plastic surgery as performing the free flap reconstruction. RESULTS: During 2005 to 2015, a total of 2,322 flaps were performed, 893 by plastic surgery and 1,429 by otolaryngology. Average length of stay (LOS) was 13.7 and 11.4 days for plastic surgery and otolaryngology, respectively. It was found that plastic surgery performed more osteocutaneous flaps than otolaryngology. Higher rates of superficial surgical site infection, deep surgical site infections, wound dehiscence, myocardial infarction, bleeding complications, sepsis, unplanned return to the operating room, and unplanned readmission were observed for patients treated by otolaryngology (p < 0.05). CONCLUSION: This study shows plastic surgery patients have superior outcomes with regards to free tissue transfers of the head and neck when compared with otolaryngology patients. Although plastic surgery patients experienced a longer LOS, the significantly lower complication rate supports an overall more optimal resource utilization. Future studies may elucidate potential cost savings in patients treated by plastic surgery.


Assuntos
Competência Clínica , Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Especialidades Cirúrgicas , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Microcirurgia , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia
11.
Clin Nephrol ; 88(9): 156-161, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28699887

RESUMO

Dapsone, a sulfone antibiotic, is used for prophylaxis of Pneumocystis jirovecii pneumonia in patients with documented sulfa allergy. Acquired methemoglobinemia caused by dapsone is not uncommon in patients with normal glucose-6-phosphate dehydrogenase (G6PD) levels. Discrepancy between oxygen saturation measured by pulse oximetry and arterial oxygen saturation (SpO2) readings, a phenomenon known as "saturation gap," is noted with cases of methemoglobinemia. Although its prevalence in renal transplant patients is poorly described, there is evidence that its incidence is increasing. Here we describe a case series of 4 patients who were switched from trimethoprim-sulfamethoxazole (TMP-SMX) to dapsone and subsequently developed methemoglobinemia. Symptoms occur at varying methemoglobin levels and are more severe in patients with pre-existing coronary disease or chronic lung disease. Early recognition and cessation of dapsone is imperative, especially in renal transplant.
.


Assuntos
Anti-Infecciosos/efeitos adversos , Dapsona/efeitos adversos , Transplante de Rim , Metemoglobinemia/induzido quimicamente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
Small ; 10(14): 2771-5, 2740, 2014 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-24692349

RESUMO

Hybrid nanomaterial based on quantum dots and SWCNTs is used for cellular imaging and photothermal therapy. Furthermore, the ligand conjugated hybrid system (FaQd@CNT) enables selective targeting in cancer cells. The imaging capability of quantum dots and the therapeutic potential of SWCNT are available in a single system with cancer targeting property. Heat generated by the system is found to be high enough to destroy cancer cells.


Assuntos
Nanotubos de Carbono , Fototerapia/métodos , Pontos Quânticos/uso terapêutico , Animais , Morte Celular , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular , Diagnóstico por Imagem , Feminino , Humanos , Terapia a Laser/métodos , Células MCF-7 , Camundongos , Microscopia Eletrônica de Transmissão , Nanotecnologia , Nanotubos de Carbono/ultraestrutura , Pontos Quânticos/química
14.
Nat Commun ; 15(1): 5098, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877006

RESUMO

Analog computing has reemerged as a promising avenue for accelerating deep neural networks (DNNs) to overcome the scalability challenges posed by traditional digital architectures. However, achieving high precision using analog technologies is challenging, as high-precision data converters are costly and impractical. In this work, we address this challenge by using the residue number system (RNS) and composing high-precision operations from multiple low-precision operations, thereby eliminating the need for high-precision data converters and information loss. Our study demonstrates that the RNS-based approach can achieve ≥99% FP32 accuracy with 6-bit integer arithmetic for DNN inference and 7-bit for DNN training. The reduced precision requirements imply that using RNS can achieve several orders of magnitude higher energy efficiency while maintaining the same throughput compared to conventional analog hardware with the same precision. We also present a fault-tolerant dataflow using redundant RNS to protect the computation against noise and errors inherent within analog hardware.

15.
J Mater Chem B ; 12(3): 720-729, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38165308

RESUMO

Nanoarchitectonics, an emerging strategy, presents a promising alternative for developing highly efficient next-generation functional materials. Multifunctional materials developed using nanoarchitectonics help to mimic biological molecules. Porphyrin-based molecules can be effectively utilized to design such assemblies. Metal nanocluster is one of the functional materials that can shed more insight into developing nanoarchitectonic materials. Herein, an inherently near-infrared (NIR) fluorescing copper nanocluster (CuC)-mediated structural assembly via protoporphyrin IX (PPIX) and doxorubicin (Dox) is demonstrated as the functional material. Dox-loaded porphyrin-mediated CuC assembly shows singlet oxygen generation and 66% drug release at 15 min. Furthermore, the efficacy of this material is tested for cancer diagnosis and bimodal therapeutic strategy due to the fluorescing ability of the cluster and loading of PPIX as well as the drug, respectively. The nanoarchitecture exhibits targeted imaging and 83% cell death in HeLa cells upon laser irradiation with 10 nmoles and 20 nmoles of PPIX and Dox, respectively.


Assuntos
Neoplasias , Porfirinas , Humanos , Cobre/química , Porfirinas/farmacologia , Células HeLa , Medicina de Precisão , Doxorrubicina/química , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico
16.
Biomed Mater ; 19(3)2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38574581

RESUMO

In terms of biomedical tools, nanodiamonds (ND) are a more recent innovation. Their size typically ranges between 4 to 100 nm. ND are produced via a variety of methods and are known for their physical toughness, durability, and chemical stability. Studies have revealed that surface modifications and functionalization have a significant influence on the optical and electrical properties of the nanomaterial. Consequently, surface functional groups of NDs have applications in a variety of domains, including drug administration, gene delivery, immunotherapy for cancer treatment, and bio-imaging to diagnose cancer. Additionally, their biocompatibility is a critical requisite for theirin vivoandin vitrointerventions. This review delves into these aspects and focuses on the recent advances in surface modification strategies of NDs for various biomedical applications surrounding cancer diagnosis and treatment. Furthermore, the prognosis of its clinical translation has also been discussed.


Assuntos
Nanodiamantes , Neoplasias , Humanos , Nanodiamantes/química , Nanodiamantes/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Diagnóstico por Imagem/métodos , Imunoterapia
17.
Clin Orthop Relat Res ; 471(8): 2422-33, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23436161

RESUMO

BACKGROUND: Composites of biodegradable polymers and bioactive ceramics are candidates for tissue-engineered scaffolds that closely match the properties of bone. We previously developed a porous, three-dimensional poly (D,L-lactide-co-glycolide) (PLAGA)/nanohydroxyapatite (n-HA) scaffold as a potential bone tissue engineering matrix suitable for high-aspect ratio vessel (HARV) bioreactor applications. However, the physical and cellular properties of this scaffold are unknown. The present study aims to evaluate the effect of n-HA in modulating PLAGA scaffold properties and human mesenchymal stem cell (HMSC) responses in a HARV bioreactor. QUESTIONS/PURPOSES: By comparing PLAGA/n-HA and PLAGA scaffolds, we asked whether incorporation of n-HA (1) accelerates scaffold degradation and compromises mechanical integrity; (2) promotes HMSC proliferation and differentiation; and (3) enhances HMSC mineralization when cultured in HARV bioreactors. METHODS: PLAGA/n-HA scaffolds (total number = 48) were loaded into HARV bioreactors for 6 weeks and monitored for mass, molecular weight, mechanical, and morphological changes. HMSCs were seeded on PLAGA/n-HA scaffolds (total number = 38) and cultured in HARV bioreactors for 28 days. Cell migration, proliferation, osteogenic differentiation, and mineralization were characterized at four selected time points. The same amount of PLAGA scaffolds were used as controls. RESULTS: The incorporation of n-HA did not alter the scaffold degradation pattern. PLAGA/n-HA scaffolds maintained their mechanical integrity throughout the 6 weeks in the dynamic culture environment. HMSCs seeded on PLAGA/n-HA scaffolds showed elevated proliferation, expression of osteogenic phenotypic markers, and mineral deposition as compared with cells seeded on PLAGA scaffolds. HMSCs migrated into the scaffold center with nearly uniform cell and extracellular matrix distribution in the scaffold interior. CONCLUSIONS: The combination of PLAGA/n-HA scaffolds with HMSCs in HARV bioreactors may allow for the generation of engineered bone tissue. CLINICAL RELEVANCE: In cases of large bone voids (such as bone cancer), tissue-engineered constructs may provide alternatives to traditional bone grafts by culturing patients' own MSCs with PLAGA/n-HA scaffolds in a HARV culture system.


Assuntos
Reatores Biológicos , Osso e Ossos/fisiologia , Cerâmica/química , Durapatita/química , Ácido Láctico/química , Células-Tronco Mesenquimais/fisiologia , Nanocompostos , Nanotecnologia , Ácido Poliglicólico/química , Engenharia Tecidual , Alicerces Teciduais , Animais , Biomarcadores/metabolismo , Osso e Ossos/citologia , Osso e Ossos/metabolismo , Calcificação Fisiológica , Diferenciação Celular , Movimento Celular , Proliferação de Células , Células Cultivadas , Matriz Extracelular/metabolismo , Humanos , Células-Tronco Mesenquimais/metabolismo , Osteogênese , Fenótipo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Propriedades de Superfície , Fatores de Tempo , Engenharia Tecidual/instrumentação , Engenharia Tecidual/métodos
18.
Dalton Trans ; 52(24): 8488, 2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37282662

RESUMO

Correction for 'An insight into the optical properties of a sub nanosize glutathione stabilized gold cluster' by Lakshmi V. Nair et al., Dalton Trans., 2016, 45, 11286-11291, https://doi.org/10.1039/C6DT01753C.

19.
Indian J Surg Oncol ; 14(1): 122-127, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36891414

RESUMO

Ki67 index is considered to be a reliable indicator of the proliferative activity of breast cancer. Additionally, the Ki67 proliferative marker may play a role in assessing response to systemic therapeutic strategies and can act as a prognostic biomarker. But its limited reproducibility which stems from a lack of standardization of procedures, inter-observer variability, and preanalytical and analytical variabilities all have hampered the use of the Ki67 index in clinical practice. Currently, clinical trials have been evaluating Ki67 as a predictive marker for needing adjuvant chemotherapy in luminal early breast cancer patients receiving neoadjuvant endocrine therapy. But the inconsistencies existing in the estimation of the Ki67 index limit the utility of Ki67 in standard clinical practice. The purpose of this review is to evaluate the benefits and drawbacks of utilizing Ki-67 in early-stage breast cancer to prognosticate the disease and predict the risk of recurrence.

20.
Ther Adv Vaccines Immunother ; 11: 25151355231190497, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37645011

RESUMO

Background: Patients with plasma cell dyscrasia are at a higher risk of developing a severe Coronavirus-2019 (COVID-19) infection. Here we present a systematic review of clinical studies focusing on the immune response to the COVID-19 vaccination in patients with plasma cell dyscrasia. Objectives: This study aims to evaluate the immune response to COVID-19 vaccines in patients with plasma cell dyscrasia and to utilize the results to improve day-to-day practice. Design: Systematic Review. Methods: Online databases (PubMed, CINAHL, Ovid, and Cochrane) were searched following the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. Only articles published in the English language were included. Out of 59 studies, nine articles (seven prospective and two retrospective studies) were included in this systematic review. Abstracts, case reports, and case series were excluded. Results: In all nine studies (N = 1429), seroconversion post-vaccination was the primary endpoint. Patients with plasma cell disorders had a lower seroconversion rate compared to healthy vaccinated individuals and the overall percentage of seroconversion ranged between 23% and 95.5%. Among patients on active therapy, lower seroconversion rates were seen on an anti-CD38 agent, ranging from 6.5 up to 100%. In addition, a significantly lower percentage was recorded in older patients, especially in those aged equal to or greater than 65 years and those who have been treated with multiple therapies previously. Only one study reported a statistically significant better humoral response rate with the mRNA vaccine compared to ADZ1222/Ad26.Cov.S. Conclusion: Variable seropositive rates are seen in patients with plasma cell dyscrasia. Lower rates are reported in patients on active therapy, anti-CD38 therapy, and elderly patients. Hence, we propose patients with plasma cell dyscrasias should receive periodic boosters to maintain clinically significant levels of antibodies against COVID-19. Registration: PROSPERO ID: CRD42023404989.


COVID-19 vaccine immune response in patients with plasma cell dyscrasia- a systematic review Background: Patients with plasma cell disorders are at a higher risk of developing a severe coronavirus-19 infection. Here we present a systematic review of clinical studies focusing on the immune response to the coronavirus-19 vaccination in patients with plasma cell dyscrasia. Objectives: This study aims to evaluate the immune response to COVID-19 vaccines in patients with plasma cell dyscrasia and to transcribe the results to day-to-day practice. Design: Systematic Review Data sources: PubMed, CINAHL, Ovid, and Cochrane. Methods: Online databases were searched following the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines. Only articles published in the English language were included. Abstracts, case reports, and case series were excluded. Out of 59 studies, nine articles were selected for a systematic review. Results: In all 9 studies (N = 1,429), seroconversion post-vaccination was the primary endpoint that our review assessed. Patients with plasma cell disorders had a lower seroconversion rate compared to healthy vaccinated individuals and the overall percentage of seroconversion ranged between 23 and 95.5%. Amongst patients on active therapy, lower seroconversion rates were seen in patients on an anti-CD38 agent, ranging from 6.5 up to 100%. In addition, a significantly lower percentage was recorded in older patients, especially those aged equal to or greater than 65 years and those who have been treated with multiple therapies previously. Only one study reported a statistically significant better humoral response rate with the mRNA vaccine compared to ADZ1222/Ad26.Cov.S. Conclusion: Variable seropositive rates are seen in patients with plasma cell dyscrasia. Lower rates are reported in patients on active therapy, anti-CD38 therapy, and elderly patients. Hence, we propose patients with plasma cell disorders should receive periodic boosters to maintain clinically significant levels of antibodies against COVID-19.

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