Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 224
Filtrar
1.
Biomed Mater ; 19(4)2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38857605

RESUMO

Chronic skin wounds pose a global clinical challenge, necessitating effective treatment strategies. This study explores the potential of 3D printed Poly Lactic Acid (PLA) scaffolds, enhanced with Whey Protein Concentrate (WPC) at varying concentrations (25, 35, and 50% wt), for wound healing applications. PLA's biocompatibility, biodegradability, and thermal stability make it an ideal material for medical applications. The addition of WPC aims to mimic the skin's extracellular matrix and enhance the bioactivity of the PLA scaffolds. Fourier Transform Infrared Spectroscopy results confirmed the successful loading of WPC into the 3D printed PLA-based scaffolds. Scanning Electron Microscopy (SEM) images revealed no significant differences in pore size between PLA/WPC scaffolds and pure PLA scaffolds. Mechanical strength tests showed similar tensile strength between pure PLA and PLA with 50% WPC scaffolds. However, scaffolds with lower WPC concentrations displayed reduced tensile strength. Notably, all PLA/WPC scaffolds exhibited increased strain at break compared to pure PLA. Swelling capacity was highest in PLA with 25% WPC, approximately 130% higher than pure PLA. Scaffolds with higher WPC concentrations also showed increased swelling and degradation rates. Drug release was found to be prolonged with increasing WPC concentration. After seven days of incubation, cell viability significantly increased in PLA with 50% WPC scaffolds compared to pure PLA scaffolds. This innovative approach could pave the way for personalized wound care strategies, offering tailored treatments and targeted drug delivery. However, further studies are needed to optimize the properties of these scaffolds and validate their effectiveness in clinical settings.


Assuntos
Bandagens , Materiais Biocompatíveis , Poliésteres , Impressão Tridimensional , Resistência à Tração , Alicerces Teciduais , Proteínas do Soro do Leite , Cicatrização , Proteínas do Soro do Leite/química , Poliésteres/química , Alicerces Teciduais/química , Cicatrização/efeitos dos fármacos , Humanos , Materiais Biocompatíveis/química , Teste de Materiais , Espectroscopia de Infravermelho com Transformada de Fourier , Microscopia Eletrônica de Varredura , Sobrevivência Celular/efeitos dos fármacos , Porosidade , Liberação Controlada de Fármacos , Pele/metabolismo
2.
Sci Rep ; 14(1): 12868, 2024 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834690

RESUMO

Acute myeloid leukemia (AML) is fatal in the majority of adults. Identification of new therapeutic targets and their pharmacologic modulators are needed to improve outcomes. Previous studies had shown that immunization of rabbits with normal peripheral WBCs that had been incubated with fluorodinitrobenzene elicited high titer antibodies that bound to a spectrum of human leukemias. We report that proteomic analyses of immunoaffinity-purified lysates of primary AML cells showed enrichment of scaffolding protein IQGAP1. Immunohistochemistry and gene-expression analyses confirmed IQGAP1 mRNA overexpression in various cytogenetic subtypes of primary human AML compared to normal hematopoietic cells. shRNA knockdown of IQGAP1 blocked proliferation and clonogenicity of human leukemia cell-lines. To develop small molecules targeting IQGAP1 we performed in-silico screening of 212,966 compounds, selected 4 hits targeting the IQGAP1-GRD domain, and conducted SAR of the 'fittest hit' to identify UR778Br, a prototypical agent targeting IQGAP1. UR778Br inhibited proliferation, induced apoptosis, resulted in G2/M arrest, and inhibited colony formation by leukemia cell-lines and primary-AML while sparing normal marrow cells. UR778Br exhibited favorable ADME/T profiles and drug-likeness to treat AML. In summary, AML shows response to IQGAP1 inhibition, and UR778Br, identified through in-silico studies, selectively targeted AML cells while sparing normal marrow.


Assuntos
Proliferação de Células , Leucemia Mieloide Aguda , Proteínas Ativadoras de ras GTPase , Humanos , Proteínas Ativadoras de ras GTPase/metabolismo , Proteínas Ativadoras de ras GTPase/genética , Proteínas Ativadoras de ras GTPase/antagonistas & inibidores , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/genética , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Simulação por Computador , Antineoplásicos/farmacologia , Domínios Proteicos , Animais , Proteômica/métodos
3.
Dermatology ; 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38934138

RESUMO

BACKGROUND: Value-based healthcare (VBHC) is an increasingly employed strategy to transform healthcare organizations into economically sustainable systems that deliver high-value care. In dermatology, the need for VBHC is evident as chronic skin diseases require long-term, often expensive treatments. This narrative review aims to introduce dermatologists to the principles and implementation of VBHC. SUMMARY: VBHC emphasizes maximizing outcomes that are directly relevant to patients. Key components of VBHC include a systematic assessment of standardized patient-relevant outcomes by using core outcome sets and measurement of healthcare cost for the individual patient. Systematic reporting and comparing of risk-adjusted outcomes across the full cycle of care for a specific condition provide benchmarked feedback and actionable insights to promote high-value care and reduce low-value care. VBHC aims to organize care around the patient in condition-specific and team-based integrated practice units with multidisciplinary collaboration, utilize information technology platforms to enable digital data monitoring, reduce cost and eventually reform payment systems to support bundled payments for the overall care cycle. VBHC implementation in practice necessitates the establishment of a systematic framework for outcome-based quality improvement, the incorporation of value and outcomes in shared decision-making practices, and the cultivation of a value-centric culture among healthcare professionals through continuous training. Key-messages: Dermatologists can benefit from implementing VBHC principles in their practice. An essential step towards value-driven dermatological care is to start measuring outcomes relevant for patients for each patient, which is lacking partly due to the absence of core outcome sets developed for clinical practice. By reducing low-value care and emphasizing optimal patient-centered outcomes, VBHC has the potential to improve the quality of care and ensuring cost-containment. Efforts are needed to enhance the development and uptake of VBHC in dermatological clinical practice to realize these benefits.

4.
Cureus ; 16(3): e56511, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38646296

RESUMO

An attractive smile enhances an individual's self-confidence. The overall harmony of a smile can be attributed to the interplay of the teeth's shape, color, and position along with the gingival tissue. Gingival pigmentation is observed across all human races, exhibiting variations from one race to another. Typically, gingival hyperpigmentation results from the abnormal buildup of melanin in the gingival tissue, imparting a dark appearance on the gums. Various procedures, collectively known as gingival depigmentation, are employed to address gingival hyperpigmentation. While the initial outcomes of depigmentation procedures are often promising, one common issue associated with them is the potential for re-pigmentation. This article aims to evaluate the clinical effectiveness and patient-reported outcomes of intraepidermal (oral mesotherapy) vitamin C injection for nonsurgical management of physiologic gingival melanin hyperpigmentation.

5.
Int J Biol Macromol ; 268(Pt 2): 131841, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38679260

RESUMO

BACKGROUND: Targeted nanoparticles (NPs) are aimed at improving clinical outcomes by enhancing the diagnostic and therapeutic efficacy of drugs in the treatment of Alzheimer's disease (AD). METHODS: Curcumin (CUR)-loaded poly-lactic-co-glycolic acid (PLGA) NPs (CNPs) were produced to demonstrate a prolonged release and successfully embedded into 3D printed sodium alginate (SA)/gelatin (GEL) scaffolds that can dissolve rapidly sublingually. Characterization and in vitro activity of the NPs and scaffolds were evaluated. RESULTS: Based on the in vitro drug release studies, 99.6 % of the encapsulated CUR was released in a controlled manner within 18 days for the CNPs. In vitro cell culture studies showed that all samples exhibited cell viability above 84.2 % and no significant cytotoxic effect on SH-SY5Y cells. The samples were analyzed through 2 different pathways by PCR analysis. Real-time PCR results indicated that CNP and CNP-embedded SA/GEL scaffolds (CNPSGS) may show neuroprotective effects by modulating the Wnt/ß-catenin pathway. The gene expression level of ß-catenin slightly increased compared to the gene expression levels of other proteins and enzymes with these treatments. However, the PI3K/Akt/GSK-3ß signaling pathway was regulated at the same time because of the crosstalk between these 2 pathways. CONCLUSION: CNPSGS might be an effective therapeutic alternative for AD treatment.


Assuntos
Alginatos , Doença de Alzheimer , Curcumina , Gelatina , Nanopartículas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Impressão Tridimensional , Alicerces Teciduais , Alginatos/química , Gelatina/química , Curcumina/farmacologia , Curcumina/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Humanos , Doença de Alzheimer/tratamento farmacológico , Nanopartículas/química , Alicerces Teciduais/química , Liberação Controlada de Fármacos , Sobrevivência Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Portadores de Fármacos/química
6.
Childs Nerv Syst ; 40(5): 1591-1596, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38305878

RESUMO

BACKGROUND: Atypical teratoid/rhabdoid tumours (AT/RT) are uncommon but aggressive, malignant tumours in the paediatric age group. Presentation of concomitant supratentorial and infratentorial lesions in an infant is extremely rare. We discuss an infant diagnosed with such lesions. Systematic PubMed search was conducted using keywords 'atypical teratoid /rhabdoid tumor', 'paediatric' and 'multifocal'. Reports were included for patients younger than 18 years with two or more lesions. The search yielded additional five cases and were tabulated. Age, sex, location, treatment given and survival/outcome were noted. CASE REPORT: A 10-month-old child presented with complaints of drowsiness and intractable vomiting. Imaging showed multifocal supra- and infratentorial lesions with obstructive hydrocephalus. The child underwent ventriculoperitoneal shunt followed by surgical removal of the posterior fossa lesion. Histopathological features were consistent with AT/RT. CONCLUSIONS: Multifocal AT/RT are very rare. The impact of multifocality in the outcome is not known as very few reports are available. Newer targeted therapies may offer insight in improving outcomes in the future.


Assuntos
Neoplasias Encefálicas , Neoplasias do Sistema Nervoso Central , Hidrocefalia , Tumor Rabdoide , Teratoma , Humanos , Lactente , Neoplasias Encefálicas/patologia , Tumor Rabdoide/diagnóstico , Teratoma/cirurgia
7.
Plants (Basel) ; 13(3)2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38337979

RESUMO

In today's time, agricultural productivity is severely affected by climate change and increasing pollution. Hence, several biotechnological approaches, including genetic and non-genetic strategies, have been developed and adapted to increase agricultural productivity. One of them is nano-priming, i.e., seed priming with nanomaterials. Thus far, nano-priming methods have been successfully used to mount desired physiological responses and productivity attributes in crops. In this review, the literature about the utility of nano-priming methods for increasing seed vigor, germination, photosynthetic output, biomass, early growth, and crop yield has been summarized. Moreover, the available knowledge about the use of nano-priming methods in modulating plant antioxidant defenses and hormonal networks, inducing salinity tolerance and disease resistance, as well as alleviating heavy metal toxicity in plants, is reviewed. The significance of nano-priming methods in the context of phytotoxicity and environmental safety has also been discussed. For future perspectives, knowledge gaps in the present literature are highlighted, and the need for optimization and validation of nano-priming methods and their plant physiological outcomes, from lab to field, is emphasized.

8.
Disabil Health J ; 17(3): 101585, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38280827

RESUMO

BACKGROUND: Motor Neurone Disease (MND), is a debilitating neurodegenerative condition, which significantly impacts the quality of life of those affected. Neck weakness is one challenge faced by those living with MND and as such may require a neck collar to assist. However, the user experience and requirements related to these neck collars have not been comprehensively explored. Understanding these priorities is crucial for enhancing the well-being of MND patients. OBJECTIVE: To understand the priorities of people living with Motor Neurone Disease (MND) including user experience, requirements and the importance of neck collars used to aid neck weakness. METHODS: An online survey was used to investigate the perspectives and experiences of off the shelf neck collars used by people living with MND. The MND Association was selected as a strategic partner by their affiliations and access to large data base of MND patients. RESULTS: Survey highlighted a disparity between the actual duration MND patients wear their current neck collars and their desired duration, emphasising the need to integrate collars into daily activities. Key areas for improvement with existing neck collars centred on comfort and reduced restriction, with respondents expressing a preference for collars that offer support without impeding movement. Additionally, addressing pressure on the anterior neck region during collar use emerged as a critical requirement. CONCLUSION: Current collars do not cause any clinical complications; however, they do fall short of meeting the expected needs of people living with MND, including discomfort, restricted movement, and pressure to the anterior region of the neck. This study highlights need to improve current collar designs to provide better quality of life for MND patients.


Assuntos
Doença dos Neurônios Motores , Qualidade de Vida , Humanos , Doença dos Neurônios Motores/psicologia , Masculino , Feminino , Pessoa de Meia-Idade , Inquéritos e Questionários , Idoso , Adulto , Pescoço , Pessoas com Deficiência/psicologia , Atividades Cotidianas , Preferência do Paciente/psicologia , Preferência do Paciente/estatística & dados numéricos , Debilidade Muscular , Tecnologia Assistiva/estatística & dados numéricos , Aparelhos Ortopédicos/estatística & dados numéricos
9.
JAMA Dermatol ; 160(5): 550-563, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38265774

RESUMO

Importance: Multiple patient-reported outcome measures (PROMs) for health-related quality of life (HRQL) exist for patients with psoriasis. Evidence for the content validity and other measurement properties of these PROMs is critical to determine which HRQL PROMs could be recommended for use. Objective: To systematically review the validity of HRQL-focused PROMs used in patients with psoriasis. Evidence Review: Using PubMed and Embase, full-text articles published in English or Spanish on development or validation studies for psoriasis-specific, dermatology-specific, or generic HRQL PROMs were included. Development studies included original development studies, even if not studied in psoriasis patients per Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) recommendations. If a study included multiple diagnoses, more than 50% of patients had to have psoriasis or psoriasis-specific subgroup analyses available. Data extraction and analysis followed the COSMIN guidelines. Two independent reviewers extracted and analyzed the data, including PROM characteristics, quality of measurement properties (structural validity, internal consistency, cross-cultural validity, reliability, measurement error, criterion validity, construct validity, and responsiveness), and level of evidence. PROMs were classified into 3 levels of recommendations: (1) PROM recommended for use; (2) PROM requires further validation; and (3) PROM not recommended for use. Findings: Overall, 97 articles were identified for extraction. This included 19 psoriasis-specific, 8 skin-specific, and 6 generic PROMs. According to COSMIN standards, most measures identified received a B recommendation for use, indicating their potential but requiring further validation. Only the Rasch reduced version of the Impact of Psoriasis Questionnaire (IPSO-11 Rasch) received an A recommendation for use given that it had sufficient content validity, structural validity, and internal consistency. Conclusions and Relevance: This study identified a significant lack of information concerning the quality of HRQL measures in psoriasis. This gap in knowledge can be attributed to the fact that traditional measures were developed using validation criteria that differ from the current standards in use. Consequently, additional validation studies in accordance with contemporary standards will be useful in aiding researchers and clinicians in determining the most suitable measure for assessing HRQL in patients with psoriasis.


Assuntos
Medidas de Resultados Relatados pelo Paciente , Psoríase , Qualidade de Vida , Psoríase/psicologia , Psoríase/terapia , Humanos , Reprodutibilidade dos Testes
10.
Int J Biol Macromol ; 258(Pt 2): 128635, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38065445

RESUMO

Alzheimer's disease (AD) is a neurodegeneration type that is biologically recognizable via ß-amyloid plaques and tau neurofibril tangles. Global estimation for the total count of individuals enduring AD will rise up to 131 million by 2050. Investigations suggested the existence of a direct proportion between the likelihood of AD occurrence and vitamin B12 (VB12) hypovitaminosis. Approved VB12 administrations, intramuscular and oral, each has serious defects broaching the demand for alternative routes. This work developed VB12-loaded chitosan/tripolyphosphate/polyvinyl alcohol (CS/TPP/PVA) nanoparticles (NPs) embedded in polyvinylpyrrolidone (PVP) and polyvinylpyrrolidone/polycaprolactone (PVP/PCL) nanofibrous (NFs) produced by pressurized gyration (PG) for sublingual and transdermal routes, respectively. Biomaterials were investigated morphologically, chemically, and thermally. Moreover, degradation, disintegration, release behavior, and release kinetics were analyzed. The effectiveness and safety of nanomaterials were assessed and proven with the alamarBlue test on the Aß1-42-induced SH-SY5Y model. The final evaluation suggested the feasibility, safety, and effectiveness of produced systems. Consequently, two alternative VB12 application routes were developed with high effectivity and low toxicity with the power of nanotechnology.


Assuntos
Quitosana , Nanofibras , Nanopartículas , Neuroblastoma , Humanos , Vitamina B 12 , Povidona , Vitaminas
11.
Biomimetics (Basel) ; 8(8)2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38132551

RESUMO

Silk has been consistently popular throughout human history due to its enigmatic properties. Today, it continues to be widely utilized as a polymer, having first been introduced to the textile industry. Furthermore, the health sector has also integrated silk. The Bombyx mori silk fibroin (SF) holds the record for being the most sustainable, functional, biocompatible, and easily produced type among all available SF sources. SF is a biopolymer approved by the FDA due to its high biocompatibility. It is versatile and can be used in various fields, as it is non-toxic and has no allergenic effects. Additionally, it enhances cell adhesion, adaptation, and proliferation. The use of SF has increased due to the rapid advancement in tissue engineering. This review comprises an introduction to SF and an assessment of the relevant literature using various methods and techniques to enhance the tissue engineering of SF-based hydrogels. Consequently, the function of SF in skin tissue engineering, wound repair, bone tissue engineering, cartilage tissue engineering, and drug delivery systems is therefore analysed. The potential future applications of this functional biopolymer for biomedical engineering are also explored.

12.
Front Bioeng Biotechnol ; 11: 1244323, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38107613

RESUMO

Epilepsy is a medical condition that causes seizures and impairs the mental and physical activities of patients. Unfortunately, over one-third of patients do not receive adequate relief from oral Antiepileptic Drugs (AEDs) and continue to experience seizures. In addition to that, long term usage of Antiepileptic Drugs can cause a range of side effects. To overcome this problem, the precision of 3D printing technology is combined with the controlled release capabilities of biodegradable polymers, allowing for tailored and localized AED delivery to specific seizure sites. As a result of this novel technique, therapeutic outcomes can be enhanced, side effects of AEDs are minimized, and patient-specific dosage forms can be created. This study focused on the use of ethosuximide, an antiepileptic drug, at different concentrations (10, 13, and 15 mg) loaded into 3D-printed sodium alginate and polyethylene oxide scaffolds. The scaffolds contained varying concentrations (0.25%, 0.50%, and 0.75% w/v) and had varying pores created by 3D patterning sizes from 159.86 ± 19.9 µm to 240.29 ± 10.7 µm to optimize the releasing system for an intracranial administration. The addition of PEO changed the Tg and Tm temperatures from 65°C to 69°C and from 262°C to 267°C, respectively. Cytotoxicity assays using the human neuroblastoma cell line (SH-SY5Y) showed that cell metabolic activity reached 130% after 168 h, allowing the cells to develop into mature neural cells. In vitro testing demonstrated sustained ethosuximide release lasting 2 hours despite crosslinking with 3% CaCl2. The workpaves the way for the use of ethosuximide -loaded scaffolds for treating epilepsy.

13.
Materials (Basel) ; 16(21)2023 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-37959540

RESUMO

Cardiovascular diseases continue to be a major contributor to illness and death on a global scale, and the implementation of stents has given rise to a revolutionary transformation in the field of interventional cardiology. The thrombotic and restenosis complications associated with stent implantation pose ongoing challenges. In recent years, bioactive coatings have emerged as a promising strategy to enhance stent hemocompatibility and reduce thrombogenicity. This review article provides an overview of the surface engineering techniques employed to improve the hemocompatibility of stents and reduce thrombus formation. It explores the mechanisms underlying thrombosis and discusses the factors influencing platelet activation and fibrin formation on stent surfaces. Various bioactive coatings, including anticoagulant agents, antiplatelet agents, and surface modifications, are discussed in detail, highlighting their potential in reducing thrombogenicity. This article also highlights a multitude of surface modification techniques which can be harnessed to enhance stent hemocompatibility including plasma treatment, physical vapor deposition (PVD), chemical vapor deposition (CVD), and electrodeposition. These techniques offer precise control over surface properties such as roughness, charge, and composition. The ultimate goal is to reduce platelet adhesion, tailor wettability, or facilitate the controlled release of bioactive agents. Evaluation methods for assessing hemocompatibility and thrombogenicity are also reviewed, ranging from in vitro assays to animal models. Recent advances in the field, such as nanotechnology-based coatings and bioactive coatings with controlled drug release systems, are highlighted. Surface engineering of bioactive coatings holds great promise for enhancing the long-term outcomes of stent implantation by enhancing hemocompatibility and reducing thrombogenicity. Future research directions and potential clinical applications are discussed, underscoring the need for continued advancements in this field.

14.
Ann 3D Print Med ; 11: None, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37592961

RESUMO

Adolescent idiopathic scoliosis (AIS) is a noticeable spinal deformity in both adult and adolescent population. In majority of the cases, the gold standard of treatment is surgical intervention. Technological advancements in medical imaging and 3D printing have revolutionised the surgical planning and intraoperative decision making for surgeons in spinal surgery. However, its applicability for planning complex spinal surgeries is poorly documented with human subjects. The objective of this study is to evaluate the accuracy of 3D printed models for complex spinal deformities based on Cobb angles between 40° to 95°.This is a retrospective cohort study where, five CT scans of the patients with AIS were segmented and 3D printed for evaluating the accuracy. Consideration was given to the Inter-patient and acquisition apparatus variability of the CT-scan dataset to understand the effect on trueness and accuracy of the developed CAD models. The developed anatomical models were re-scanned for analysing quantitative surface deviation to assess the accuracy of 3D printed spinal models. Results show that the average of the root mean square error (RMSE) between the 3DP models and virtual models developed using CT scan of mean surface deviations for the five 3d printed models was found to be 0.5±0.07 mm. Based on the RMSE, it can be concluded that 3D printing based workflow is accurate enough to be used for presurgical planning for complex adolescent spinal deformities. Image acquisition and post processing parameters, type of 3D printing technology plays key role in acquiring required accuracy for surgical applications.

15.
Cancers (Basel) ; 15(13)2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37444542

RESUMO

Small-molecule inhibitors of PD-L1 are postulated to control immune evasion in tumors similar to antibodies that target the PD-L1/PD-1 immune checkpoint axis. However, the identity of targetable PD-L1 inducers is required to develop small-molecule PD-L1 inhibitors. In this study, using chromatin immunoprecipitation (ChIP) assay and siRNA, we demonstrate that vitamin D/VDR regulates PD-L1 expression in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) cells. We have examined whether a VDR antagonist, MeTC7, can inhibit PD-L1. To ensure that MeTC7 inhibits VDR/PD-L1 without off-target effects, we examined competitive inhibition of VDR by MeTC7, utilizing ligand-dependent dimerization of VDR-RXR, RXR-RXR, and VDR-coactivators in a mammalian 2-hybrid (M2H) assay. MeTC7 inhibits VDR selectively, suppresses PD-L1 expression sparing PD-L2, and inhibits the cell viability, clonogenicity, and xenograft growth of AML cells. MeTC7 blocks AML/mesenchymal stem cells (MSCs) adhesion and increases the efferocytotic efficiency of THP-1 AML cells. Additionally, utilizing a syngeneic colorectal cancer model in which VDR/PD-L1 co-upregulation occurs in vivo under radiation therapy (RT), MeTC7 inhibits PD-L1 and enhances intra-tumoral CD8+T cells expressing lymphoid activation antigen-CD69. Taken together, MeTC7 is a promising small-molecule inhibitor of PD-L1 with clinical potential.

16.
J Plast Reconstr Aesthet Surg ; 84: 582-594, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37441855

RESUMO

BACKGROUND: Approximately one quarter of women are affected by asymmetry as a result of abnormal breast development, which can lead to significant emotional distress. Despite this, there is currently no widely accepted approach for managing this prevalent condition. This systematic review aimed to review the available literature on the management of developmental breast asymmetry. METHODS: A comprehensive search in MEDLINE, EMBASE, and CENTRAL databases was conducted for primary clinical studies reporting on the management of developmental breast asymmetry from 1962 to November 2022. The primary outcome measures were long-term aesthetic outcomes and patient-reported outcomes. RESULTS: Eleven case series and 2 cohort studies were included, comprising a total of 1237 patients with a mean age of 26.5 years (range 14-65 years). Twelve studies (92%) addressed asymmetry through surgical means, using various augmentation and reduction procedures, whereas one study (8%) utilized external prostheses. Meta-analysis of the data was not deemed to be possible because of heterogeneity of data; a narrative synthesis of the literature was provided. CONCLUSIONS: There is no consensus on how to manage developmental breast asymmetry. Furthermore, there is a lack of consistency in the classification of patients with developmental breast asymmetry and in the reporting of outcomes, highlighting the need for a consensus. Further research outlining long-term aesthetic and patient-reported outcomes is needed to understand which procedures provide optimal outcomes. In addition, external breast prosthesis is a promising nonsurgical alternative, and further studies into its efficacy are needed.


Assuntos
Mama , Próteses e Implantes , Adolescente , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Mama/cirurgia
17.
Biotechnol Adv ; 67: 108180, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37236328

RESUMO

The recent advancement in the human glycome and progress in the development of an inclusive network of glycosylation pathways allow the incorporation of suitable machinery for protein modification in non-natural hosts and explore novel opportunities for constructing next-generation tailored glycans and glycoconjugates. Fortunately, the emerging field of bacterial metabolic engineering has enabled the production of tailored biopolymers by harnessing living microbial factories (prokaryotes) as whole-cell biocatalysts. Microbial catalysts offer sophisticated means to develop a variety of valuable polysaccharides in bulk quantities for practical clinical applications. Glycans production through this technique is highly efficient and cost-effective, as it does not involve expensive initial materials. Metabolic glycoengineering primarily focuses on utilizing small metabolite molecules to alter biosynthetic pathways, optimization of cellular processes for glycan and glycoconjugate production, characteristic to a specific organism to produce interest tailored glycans in microbes, using preferably cheap and simple substrate. However, metabolic engineering faces one of the unique challenges, such as the need for an enzyme to catalyze desired substrate conversion when natural native substrates are already present. So, in metabolic engineering, such challenges are evaluated, and different strategies have been developed to overcome them. The generation of glycans and glycoconjugates via metabolic intermediate pathways can still be supported by glycol modeling achieved through metabolic engineering. It is evident that modern glycans engineering requires adoption of improved strain engineering strategies for creating competent glycoprotein expression platforms in bacterial hosts, in the future. These strategies include logically designing and introducing orthogonal glycosylation pathways, identifying metabolic engineering targets at the genome level, and strategically improving pathway performance (for example, through genetic modification of pathway enzymes). Here, we highlight current strategies, applications, and recent progress in metabolic engineering for producing high-value tailored glycans and their applications in biotherapeutics and diagnostics.


Assuntos
Produtos Biológicos , Humanos , Produtos Biológicos/metabolismo , Polissacarídeos/química , Glicosilação , Glicoconjugados/genética , Glicoconjugados/metabolismo , Engenharia Metabólica/métodos , Bactérias/genética
18.
Cureus ; 15(4): e37167, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37168160

RESUMO

An inflammatory myofibroblastic tumor (IMT) is a very rare tumor of mesenchymal origin with unclear etiopathogenesis, no unique diagnostic features, and no specific management protocol. It is often confused with inflammatory pseudotumor in literature, and the distinction needs further study. The average size, recurrence risk, and metastatic potential differ as per the site of origin. The abdomen is a very rare site for IMTs. Hepatic IMTs (H-IMTs) are reported to be solid tumors with sizes ranging from 1 cm to 20 cm in literature, and gastric IMTs (G-IMTs) range from 3 cm to 10 cm in size and can be solid-cystic. We report here a case of a 36-year-old gentleman with a 34x27x17 cm solid-cystic lesion in the lesser sac with loss of fat planes with stomach and left hemi-liver. The patient was managed by complete surgical resection of the lesion with wedge gastrectomy and wedge hepatectomy and recovered uneventfully. To our knowledge and based on our literature review, this case presents the largest reported and solid-cystic G-IMT with the involvement of left hemi-liver in a young gentleman and discusses its management as well as the relevant literature on this rare entity. This clinical presentation of G-IMT should be kept in the differential diagnosis in a relevant case presenting in the future. Immunohistochemistry is a must to establish the diagnosis, and surgical resection to negative margins is the management option of choice in resectable cases.

19.
Interact J Med Res ; 12: e43274, 2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36917160

RESUMO

A majority of people living with motor neuron disease (MND) experience weakness of the neck and as a result, experience head drop. This exacerbates problems with everyday activities (eating, talking, breathing, etc). Neck collars are often used to support head drop; however, these are typically designed for prehospitalization settings to manage and brace the cervical region of the spine. As a result, it has been recorded that people living with MND often reject these collars for a variety of reasons but most notably because they are too restricting. The current standardized outcome measures (most notably restricting cervical range of motion) used for neck collars are summarized herein along with whether they are suitable for a bespoke neck collar specifically designed for people living with MND.

20.
Food Res Int ; 166: 112596, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36914347

RESUMO

In the modern world, animal and plant protein may not meet the sustainability criteria due to their high need for arable land and potable water consumption, among other practices. Considering the growing population and food shortage, finding alternative protein sources for human consumption is an urgent issue that needs to be solved, especially in developing countries. In this context, microbial bioconversion of valuable materials in nutritious microbial cells represent a sustainable alternative to the food chain. Microbial protein, also known as single-cell protein (SCP), consist of algae biomass, fungi or bacteria that are currently used as food source for both humans and animals. Besides contributing as a sustainable source of protein to feed the world, producing SCP, is important to reduce waste disposal problems and production costs meeting the sustainable development goals. However, for microbial protein as feed or food to become an important and sustainable alternative, addressing the challenges of raising awareness and achieving wider public regulatory acceptance is real and must be addressed with care and convenience. In this work, we critically reviewed the potential technologies for microbial protein production, its benefits, safety, and limitations associated with its uses, and perspectives for broader large-scale implementation. We argue that the information documented in this manuscript will assist in developing microbial meat as a major protein source for the vegan world.


Assuntos
Desenvolvimento Sustentável , Veganos , Animais , Humanos , Bactérias , Carne , Proteínas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA