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1.
Anal Chim Acta ; 1308: 342664, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38740454

RESUMO

Nanozymes is a kind of nanomaterials with enzyme catalytic properties. Compared with natural enzymes, nanozymes merge the advantages of both nanomaterials and natural enzymes, which is highly important in applications such as biosensing, clinical diagnosis, and food inspection. In this study, we prepared ß-MnOOH hexagonal nanoflakes with a high oxygen vacancy ratio by utilizing SeO2 as a sacrificial agent. The defect-rich MnOOH hexagonal nanoflakes demonstrated excellent oxidase-like activity, catalyzing the oxidation substrate in the presence of O2, thereby rapidly triggering a color reaction. Consequently, a colorimetric sensing platform was constructed to assess the total antioxidant capacity in commercial beverages. The strategy of introducing defects in situ holds great significance for the synthesis of a series of high-performance metal oxide nanozymes, driving the development of faster and more efficient biosensing and analysis methods.


Assuntos
Antioxidantes , Compostos de Manganês , Óxidos , Óxidos/química , Antioxidantes/química , Antioxidantes/metabolismo , Antioxidantes/análise , Compostos de Manganês/química , Colorimetria , Oxirredutases/química , Oxirredutases/metabolismo , Oxirredução , Nanoestruturas/química , Catálise
2.
Research (Wash D C) ; 7: 0378, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38766643

RESUMO

The accumulation of senescent cells in kidneys is considered to contribute to age-related diseases and organismal aging. Mitochondria are considered a regulator of cell senescence process. Atrazine as a triazine herbicide poses a threat to renal health by disrupting mitochondrial homeostasis. Melatonin plays a critical role in maintaining mitochondrial homeostasis. The present study aims to explore the mechanism by which melatonin alleviates atrazine-induced renal injury and whether parkin-mediated mitophagy contributes to mitigating cell senescence. The study found that the level of parkin was decreased after atrazine exposure and negatively correlated with senescent markers. Melatonin treatment increased serum melatonin levels and mitigates atrazine-induced renal tubular epithelial cell senescence. Mechanistically, melatonin maintains the integrity of mitochondrial crista structure by increasing the levels of mitochondrial contact site and cristae organizing system, mitochondrial transcription factor A (TFAM), adenosine triphosphatase family AAA domain-containing protein 3A (ATAD3A), and sorting and assembly machinery 50 (Sam50) to prevent mitochondrial DNA release and subsequent activation of cyclic guanosine 5'-monophosphate-adenosine 5'-monophosphate synthase pathway. Furthermore, melatonin activates Sirtuin 3-superoxide dismutase 2 axis to eliminate the accumulation of reactive oxygen species in the kidney. More importantly, the antisenescence role of melatonin is largely determined by the activation of parkin-dependent mitophagy. These results offer novel insights into measures against cell senescence. Parkin-mediated mitophagy is a promising drug target for alleviating renal tubular epithelial cell senescence.

3.
Cardiol Res ; 15(2): 108-116, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38645829

RESUMO

Background: This study aimed to identify the association of cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase-stimulator interferon genes (cGAS-STING) pathway with heart failure (HF) in atrial fibrillation (AF) patients. Methods: We prospectively enrolled 106 AF patients without evidence of HF. The serum levels of 2'3'-cyclic GMP-AMP (2'3'-cGAMP) and interleukin (IL)-1ß were measured by enzyme-linked immunoassay (ELISA). To determine the underlying mechanism, we supplemented the complex I inhibitor rotenone and the specific cGAS inhibitor RU.521 in neonatal rat ventricular cardiomyocytes. Results: During 18-month follow-up, serum concentrations of 2'3'-cGAMP (baseline 51.82 ± 11.34 pg/mL vs. follow-up 124.50 ± 75.83 pg/mL, Ppaired t < 0.01) and IL-1ß (baseline 436.07 ± 165.82 vs. follow-up 632.48 ± 119.25 ng/mL, Ppaired t < 0.01) were substantially upregulated in AF patients with HF as compared with those without HF. Furthermore, serum 2'3'-cGAMP and IL-1ß levels at 18-month follow-up were independently associated with the occurrence of HF in AF patients. Inhibition of cGAS by RU.521 effectively reversed the upregulation of 2'3'-cGAMP and STING phosphorylation induced by mitochondrial dysfunction, accompanied with inhibition of nod-like receptor protein 3 (NLRP3) inflammasome, IL-1ß and IL-18 secretion. Conclusions: Induction of mitochondrial dysfunction causes an upregulation of 2'3'-cGAMP and activation of NLRP3 inflammasome through cGAS-STING pathway in cardiomyocytes.

4.
Adv Healthc Mater ; : e2400109, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38676445

RESUMO

Proteolysis targeting chimeras (PROTACs) technology is rapidly developed as a novel and selective medicinal strategy for the degradation of cellular proteins in cancer therapy. However, the applications of PROTACs as heterobifunctional molecules are largely limited by high molecular weight, low bioavailability, poor permeability, insufficient targeting, and low efficacy in vivo. Herein, self-assembling micelles of FA-PEG-PROTAC are designed for cancer cell selective targeting and reductive-response proteolysis in tumor-bearing mice. FA-PEG-PROTAC is prepared by conjugating folic acid (FA)-PEG with EGFR-targeting PROTAC via a disulfide bond. The FA-PEG-PROTAC micelles, formed by self-assembling, are demonstrated to significantly improve tumor targeting efficacy and exhibit excellent anti-tumor efficacy in the mouse xenograft model compared to the traditional PROTACs. The strategy of applying self-assembled FA-PEG-PROTAC micelles in tumor therapy can not only improve targeted proteolysis efficiency but also broaden applications in the development of PROTAC-based drugs.

5.
Stem Cell Res Ther ; 15(1): 115, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38650029

RESUMO

BACKGROUND: Studies have shown that chemotherapy and radiotherapy can cause premature ovarian failure and loss of fertility in female cancer patients. Ovarian cortex cryopreservation is a good choice to preserve female fertility before cancer treatment. Following the remission of the disease, the thawed ovarian tissue can be transplanted back and restore fertility of the patient. However, there is a risk to reintroduce cancer cells in the body and leads to the recurrence of cancer. Given the low success rate of current in vitro culture techniques for obtaining mature oocytes from primordial follicles, an artificial ovary with primordial follicles may be a good way to solve this problem. METHODS: In the study, we established an artificial ovary model based on the participation of mesenchymal stem cells (MSCs) to evaluate the effect of MSCs on follicular development and oocyte maturation. P2.5 mouse ovaries were digested into single cell suspensions and mixed with bone marrow derived mesenchymal stem cells (BM-MSCs) at a 1:1 ratio. The reconstituted ovarian model was then generated by using phytohemagglutinin. The phenotype and mechanism studies were explored by follicle counting, immunohistochemistry, immunofluorescence, in vitro maturation (IVM), in vitro fertilization (IVF), real-time quantitative polymerase chain reaction (RT-PCR), and Terminal-deoxynucleotidyl transferase mediated nick end labeling(TUNEL) assay. RESULTS: Our study found that the addition of BM-MSCs to the reconstituted ovary can enhance the survival of oocytes and promote the growth and development of follicles. After transplanting the reconstituted ovaries under kidney capsules of the recipient mice, we observed normal folliculogenesis and oocyte maturation. Interestingly, we found that BM-MSCs did not contribute to the formation of follicles in ovarian aggregation, nor did they undergo proliferation during follicle growth. Instead, the cells were found to be located around growing follicles in the reconstituted ovary. When theca cells were labeled with CYP17a1, we found some overlapped staining with green fluorescent protein(GFP)-labeled BM-MSCs. The results suggest that BM-MSCs may participate in directing the differentiation of theca layer in the reconstituted ovary. CONCLUSIONS: The presence of BM-MSCs in the artificial ovary was found to promote the survival of ovarian cells, as well as facilitate follicle formation and development. Since the cells didn't proliferate in the reconstituted ovary, this discovery suggests a potential new and safe method for the application of MSCs in clinical fertility preservation by enhancing the success rate of cryo-thawed ovarian tissues after transplantation.


Assuntos
Células-Tronco Mesenquimais , Oócitos , Ovário , Feminino , Animais , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Camundongos , Ovário/citologia , Oócitos/citologia , Oócitos/metabolismo , Transplante de Células-Tronco Mesenquimais/métodos , Folículo Ovariano/metabolismo , Folículo Ovariano/citologia
6.
Artigo em Inglês | MEDLINE | ID: mdl-38521483

RESUMO

BACKGROUND: Locking plates are widely used in open reduction internal fixation (ORIF) for proximal humeral fracture (PHF). However, the optimal surgical treatment of unstable, displaced PHF in elderly patients remains controversial. This study aimed to compare the radiological and clinical outcomes of surgical treatment of PHF in the elderly with locking plate (LP) alone and locking plate combined with 3D printed polymethylmethacrylate (PMMA) prosthesis augmentation (LP-PA). METHODS: From May 2015 to April 2021, a total of 97 patients aged ≥ 60 years with acute unstable PHF who underwent osteosynthesis with either LP (46 patients) or LP-PA (51 patients) were retrospectively analyzed. For the LP-PA group, a customized proximal humeral prosthesis made of PMMA cement was intra-operatively fabricated by a three-dimensional (3D) printed prototype mold for the humeral medial support. Radiological outcomes were analyzed by measuring the value of neck-shaft angle (NSA) and humeral head height (HHH). The clinical outcomes were evaluated using Constant-Murley Score (CMS), Disabilities of the Arm Shoulder and Hand (DASH) score, American Shoulder and Elbow Surgeons (ASES) score, and the shoulder range of motion (ROM). Pain was measured using a visual analogue scale (VAS). RESULTS: At the one-year follow-up, all fractures healed radiologically and clinically. The mean changes of NSA and HHH over the follow-up period were markedly smaller in the LP-PA group (3.8 ± 0.9° and 1.7 ± 0.3 mm) than those in the LP group (9.7 ± 2.1° and 3.2 ± 0.6 mm, both P < 0.0001). The LP-PA group also presented lower DASH score (17.1 ± 3.6), higher ASES score (89.5 ± 11.2) and better ROM in forward elevation (142 ± 26°) and external rotation (59 ± 11°) compared to the LP group (28.9 ± 4.8 for DASH score, P < 0.0001; 82.3 ± 9.0 for ASES score, P < 0.001; 129 ± 21° for forward elevation, P = 0.008; and 52 ± 9° for external rotation, P = 0.001). There was no significant difference in overall complication rate between the two groups, although the complication rate of screw perforation was higher in the LP-PA group (P = 0.172). CONCLUSIONS: For PHF in elderly patients, the combination of LP fixation and PMMA prosthesis augmentation effectively improved humeral head support and reduction maintenance, providing satisfactory outcomes both radiologically and clinically. This technique also reduced the incidence of screw perforation associated with plate fixation alone, making it a reasonable option to ensure satisfactory clinical outcomes.

7.
BMC Genomics ; 25(1): 161, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38331763

RESUMO

BACKGROUND: DNA N6-methyladenosine (6mA), as an important epigenetic modification, widely exists in bacterial genomes and participates in the regulation of toxicity, antibiotic resistance, and antioxidant. With the continuous development of sequencing technology, more 6mA sites have been identified in bacterial genomes, but few studies have focused on the distribution characteristics of 6mA at the whole-genome level and its association with gene expression and function. RESULTS: This study conducted an in-depth analysis of the 6mA in the genomes of two pathogenic bacteria, Aeromonas veronii and Helicobacter pylori. The results showed that the 6mA was widely distributed in both strains. In A. veronii, 6mA sites were enriched at 3' end of protein-coding genes, exhibiting a certain inhibitory effect on gene expression. Genes with low 6mA density were associated with cell motility. While in H. pylori, 6mA sites were enriched at 5' end of protein-coding genes, potentially enhancing gene expression. Genes with low 6mA density were closely related to defense mechanism. CONCLUSIONS: This study elucidated the distribution characteristics of 6mA in A. veronii and H. pylori, highlighting the effects of 6mA on gene expression and function. These findings provide valuable insights into the epigenetic regulation and functional characteristics of A. veronii and H. pylori.


Assuntos
Helicobacter pylori , Helicobacter pylori/genética , Epigênese Genética , Aeromonas veronii/genética , DNA/metabolismo , Adenosina/genética , Adenosina/metabolismo , Metilação de DNA
8.
J Clin Rheumatol ; 30(2): 73-78, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38268091

RESUMO

OBJECTIVE: The purpose of this research was to ascertain the effectiveness of the newly established criteria for classifying IgG4-related disease (IgG4-RD), as applied to a large Chinese cohort in real-world clinical settings. METHODS: Patient data were procured from the digital health records of 4 prominent academic hospitals. The criterion standard for identifying IgG4-RD patients was from a seasoned rheumatologist. The control group consisted of individuals with other ailments such as cancer, other forms of pancreatitis, infectious diseases, and illnesses that mimic IgG4-RD. RESULTS: A total of 605 IgG4-RD patients and 760 mimickers were available for analysis. The 2019 EULAR/ACR criteria have a sensitivity of 69.1% and a specificity of 90.9% in this large Chinese cohort. IgG4-RD had a greater proportion of males (55.89% vs 36.25%, p < 0.001), an older average age at diagnosis (54.91 ± 13.44 vs 48.91 ± 15.71, p < 0.001), more pancreatic (29.59% vs 6.12%, p < 0.001) and salivary gland (63.30% vs 27.50%, p < 0.001) involvement, and a larger number of organ involvement (3.431 ± 2.054 vs 2.062 ± 1.748, p < 0.001) compared with mimickers. CONCLUSIONS: The 2019 EULAR/ACR criteria are effective in classifying IgG4-RD in Chinese patients, demonstrating high specificity and moderate sensitivity.


Assuntos
Doença Relacionada a Imunoglobulina G4 , Pancreatite , Humanos , Masculino , Povo Asiático , China , Doença Relacionada a Imunoglobulina G4/diagnóstico , Pancreatite/diagnóstico , Glândulas Salivares , Feminino
9.
ACS Nano ; 18(4): 3497-3508, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38215492

RESUMO

Two-dimensional (2D) materials have attracted intense interest due to their potential for applications in fields ranging from chemical sensing to catalysis, energy storage, and biomedicine. Recently, peptoids, a class of biomimetic sequence-defined polymers, have been found to self-assemble into 2D crystalline sheets that exhibit unusual properties, such as high chemical stability and the ability to self-repair. The structure of a peptoid is close to that of a peptide except that the side chains are appended to the amide nitrogen rather than the α carbon. In this study, we investigated the effect of peptoid sequence on the mechanism and kinetics of 2D assembly on mica surfaces using in situ AFM and time-resolved X-ray scattering. We explored three distinct peptoid sequences that are amphiphilic in nature with hydrophobic and hydrophilic blocks and are known to self-assemble into 2D sheets. The results show that their assembly on mica starts with deposition of aggregates that spread to establish 2D islands, which then grow by attachment of peptoids, either monomers or unresolvable small oligomers, following well-known laws of crystal step advancement. Extraction of the solubility and kinetic coefficient from the dependence of the growth rate on peptoid concentration reveals striking differences between the sequences. The sequence with the slowest growth rate in bulk and with the highest solubility shows almost no detachment; i.e., once a growth unit attaches to the island edge, there is almost no probability of detaching. Furthermore, a peptoid sequence with a hydrophobic tail conjugated to the final carboxyl residue in the hydrophilic block has enhanced hydrophobic interactions and exhibits rapid assembly both in the bulk and on mica. These assembly outcomes suggest that, while the π-π interactions between adjacent hydrophobic blocks play a major role in peptoid assembly, sequence details, particularly the location of charged groups, as well as interaction with the underlying substrate can significantly alter the thermodynamic stability and assembly kinetics.


Assuntos
Peptoides , Peptoides/química , Peptídeos/química , Silicatos de Alumínio , Amidas/química
10.
Genesis ; 62(1): e23557, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37830136

RESUMO

Engrailed-1 (EN1) is a developmental gene that encodes En1, a highly conserved transcription factor involved in regionalization during early embryogenesis and in the later maintenance of normal neurons. After birth, EN1 still plays a role in the development and physiology of the body; for example, it exerts a protective effect on midbrain dopaminergic (mDA) neurons, and loss of EN1 causes mDA neurons in the ventral midbrain to gradually die approximately 6 weeks after birth, resulting in motor and nonmotor symptoms similar to those observed in Parkinson's disease. Notably, EN1 has been identified as a possible susceptibility gene for idiopathic Parkinson's disease in humans. EN1 is involved in the processes of wound-healing scar production and tissue and organ fibrosis. Additionally, EN1 can lead to tumorigenesis and thus provides a target for the treatment of some tumors. In this review, we summarize the effects of EN1 on embryonic organ development, describe the consequences of the deletion or overexpression of the EN1 gene, and discuss the pathways in which EN1 is involved. We hope to clarify the role of EN1 as a developmental gene and present potential therapeutic targets for diseases involving the EN1 gene.


Assuntos
Proteínas de Homeodomínio , Doença de Parkinson , Humanos , Proteínas de Homeodomínio/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Neurônios/metabolismo , Regulação da Expressão Gênica , Genes Homeobox , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia
11.
J Mol Med (Berl) ; 102(2): 231-245, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38051341

RESUMO

Ischemic stroke is a devastative nervous system disease associated with high mortality and morbidity rates. Unfortunately, no clinically effective neuroprotective drugs are available now. In ischemic stroke, S100 calcium-binding protein b (S100b) binds to receptor for advanced glycation end products (Rage), leading to the neurological injury. Therefore, disruption of the interaction between S100B and Rage can rescue neuronal cells. Here, we designed a peptide, termed TAT-W61, derived from the V domain of Rage which can recognize S100b. Intriguingly, TAT-W61 can reduce the inflammatory caused by ischemic stroke through the direct binding to S100b. The further investigation demonstrated that TAT-W61 can improve pathological infarct volume and reduce the apoptotic rate. Particularly, TAT-W61 significantly improved the learning ability, memory, and motor dysfunction of the mouse in the ischemic stroke model. Our study provides a mechanistic insight into the abnormal expression of S100b and Rage in ischemic stroke and yields an invaluable candidate for the development of drugs in tackling ischemic stroke. KEY MESSAGES: S100b expression is higher in ischemic stroke, in association with a high expression of many genes, especially of Rage. S100b is directly bound to the V-domain of Rage. Blocking the binding of S100b to Rage improves the injury after ischemic stroke.


Assuntos
AVC Isquêmico , Camundongos , Animais , Receptor para Produtos Finais de Glicação Avançada , AVC Isquêmico/patologia , Neurônios , Peptídeos/farmacologia , Subunidade beta da Proteína Ligante de Cálcio S100/farmacologia
12.
Front Bioeng Biotechnol ; 11: 1263751, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38026854

RESUMO

Background: Lateral lumbar fusion is an advanced, minimally invasive treatment for degenerative lumbar diseases. It involves different cage designs, primarily varying in size. This study aims to investigate the biomechanics of the long cage spanning the ring apophysis in both normal and osteoporotic models, considering endplate damage, using finite element analysis. Methods: Model 1 was an intact endplate with a long cage spanning the ring apophysis. Model 2 was an endplate decortication with a long cage spanning the ring apophysis. Model 3 was an intact endplate with a short cage. Model 4 was an endplate decortication with a short cage. On the basis of the four original models, further osteoporosis models were created, yielding a total of eight finite element models. The provided passage delineates a study that elucidates the utilization of finite element analysis as a methodology to simulate and analyze the biomechanical repercussions ensuing from the adoption of two distinct types of intervertebral fusion devices (cages) within the physiological framework of a human body. Results: The investigation found no appreciable changes between Models 1 and 2 in the range of motion at the fixed and neighboring segments, the L3-4 IDP, screw-rod stress, endplate stress, or stress on the trabecular bone of the L5. Increases in these stresses were seen in models 3 and 4 in the ranges of 0.4%-676.1%, 252.9%-526.9%, 27.3%-516.6%, and 11.4%-109.3%, respectively. The osteoporotic models for scenarios 3 and 4 exhibit a similar trend to their respective normal bone density models, but these osteoporotic models consistently have higher numerical values. In particular, except for L3-4 IDP, the maximum values of these parameters in osteoporotic Models 3 and 4 were much higher than those in normal bone quality Models 1 and 2, rising by 385.3%, 116%, 435.1%, 758.3%, and 786.1%, respectively. Conclusion: Regardless of endplate injury or osteoporosis, it is advised to utilize a long cage that is 5 mm longer on each side than the bilateral pedicles because it has good biomechanical features and may lower the likelihood of problems after surgery. Additionally, using Long cages in individuals with osteoporosis may help avoid adjacent segment disease.

13.
J Orthop Surg Res ; 18(1): 776, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37845750

RESUMO

PURPOSE: To compare the clinical efficacy of oblique lateral interbody fusion (OLIF) combined with unilateral (UPSF) and bilateral pedicle screw internal fixation (BPSF) in patients with osteoporosis. METHODS: Clinical data of 57 patients who underwent single-segment OLIF surgery with a clear diagnosis of osteoporosis from December 2018 to May 2021 were retrospectively analyzed, of which 27 patients underwent OLIF + UPSF and 30 patients underwent OLIF + BPSF. Surgical technique-related indexes were recorded, including operative time, operative blood loss and postoperative hospital stay; clinical outcome-related indexes included postoperative complications, Visual analogue scale (VAS) and Oswestry disability index (ODI) at preoperative, 1 week, 1 month, 3 months, and 12 months postoperative follow-up; and imaging outcome-related indexes included the measurement of preoperative and postoperative segmental lordosis (SL), and observation of the degree of cage subsidence and bone graft fusion. RESULTS: The surgery was successfully performed in 57 patients, and there was no statistical difference in operative blood loss and postoperative hospital stay between UPSF group and BPSF group (P > 0.05). In terms of operative time, there was a significant difference (UPSF group: 92.30 ± 11.03 min, BPSF group: 119.67 ± 16.41, P < 0.05). Postoperative VAS and ODI scores exhibited significant improvement (P < 0.05). At the 12 months postoperative follow-up, the VAS and ODI scores in the BPSF group were significantly better than those in the UPS group (P < 0.05). Compared with the preoperative images, the SL was significantly improved in both groups after surgery (P < 0.05). At 6 months postoperatively, the fusion rate in the UPSF group was significantly lower than that in the BPSF group (P < 0.05). At 1 year postoperatively, the fusion rate in the UPSF group was not significantly different from that in the BPSF group (P > 0.05). At 1 year postoperatively, the rate and degree of cage subsidence was higher in the UPSF group than in the BPSF group (P < 0.05). CONCLUSION: In the long term, OLIF combined with bilateral posterior fixation applied to the osteoporosis patients is superior to OLIF surgery combined with unilateral posterior fixation in terms of clinical and imaging outcomes. It is effective in improving pain relief and functional improvement, accelerating bone graft fusion, and reducing cage subsidence compared with UPSF.


Assuntos
Lordose , Osteoporose , Parafusos Pediculares , Fusão Vertebral , Humanos , Estudos Retrospectivos , Perda Sanguínea Cirúrgica , Fusão Vertebral/métodos , Resultado do Tratamento , Osteoporose/complicações , Osteoporose/diagnóstico por imagem , Osteoporose/cirurgia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia
14.
Adv Clin Exp Med ; 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37747442

RESUMO

BACKGROUND: Osteosarcoma is a pleomorphic cancer that frequently affects children and teenagers. Although several chemotherapy regimens have been utilized for many years, the best therapeutic option for the treatment of osteosarcoma has not yet been determined. OBJECTIVES: This meta-analysis was designed to assess the clinical efficacy of a high-dose methotrexate, doxorubicin and cisplatin (MAP) regimen and compare its survival outcomes with those of other chemotherapy strategies in patients diagnosed with osteosarcoma. MATERIAL AND METHODS: We systematically searched databases, namely Embase, the Cochrane Library and PubMed, up to August 2022, for relevant studies investigating the impact of the MAP chemotherapy protocol on survival among patients with osteosarcoma. The odds ratio (OR) pooled estimates and their 95% confidence intervals (95% CIs) were calculated. RESULTS: Twelve studies including 4102 patients were eligible for analysis in this study. The estimated pooled ORs of the 3-year overall survival (OS) and event-free survival (EFS) were OR = 1.08 (95% CI: 0.72-1.62, p = 0.70) and OR = 1.04 (95% CI: 0.81-1.32, p = 0.78, respectively). The 5-year OS and EFS were OR = 0.87 (95% CI: 0.62-1.23, p = 0.42) and OR = 1.13 (95% CI: 0.76-1.68, p = 0.54), respectively, with no statistical differences. The subgroup analysis of MAP compared to a 2-drug regimen (doxorubicin and cisplatin) revealed a significant difference between the 2 chemotherapy strategy groups in 3-year OS rates (OR = 0.72 (95% CI: 0.56-0.92, p = 0.009)) and 5-year EFS rates (OR = 0.57 (95% CI: 0.43-0.76, p < 0.001)). CONCLUSION: The MAP chemotherapy strategy for osteosarcoma showed superiority over other regimens, especially over the 2-drug regimen (doxorubicin/cisplatin), in terms of better prognosis and safety.

15.
Turk J Biol ; 47(3): 170-185, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37529419

RESUMO

Recent clinical developments in tissue bioengineering have applications in acute cardiac ischemia and infarction and include the use of stem cells that combine injectable scaffold material. This study aimed to evaluate the effects of adipose-derived stem cells (ADSCs) that combine the Matrigel scaffold on cardiac morphology/functions. The autologous ADSCs myocardial infarction (MI) model was induced by the permanent ligation method of the left anterior descending coronary artery (LAD). MI-operated rats were randomly divided into PBS group, Matrigel group, PBS plus ADSCs group (PBS+ADSCs), and Matrigel plus ADSCs group (Matrigel+ADSCs). Matrigel was used as an injectable scaffold. Rats with a 1-week-old myocardial infarction were injected with 2 × 106 labeled ADSCs in the border area of the ischemic heart. Heart function was determined by echocardiography. The hemodynamics, cardiac structure, and graft characteristics were evaluated. The ADSCs were successfully isolated and identified, demonstrating a good proliferative status and cell retention in the Matrigel. ADSCs+Matrigel exhibited the most improved heart functions (LVESD, LVEDD, LVFS, LVEF) compared to those of other groups (p < 0.05). ADSCs+Matrigel significantly reduced infarct size compared to other groups (p < 0.05). Cotransplantation of ADSCs and Matrigel showed the best effect on maintaining the thickness of the ventricular wall compared to the other groups (p < 0.05). Engrafted ADSCs played a role in the formation of the neovasculature in myocardial infarction. ADSCs+Matrigel triggered the greatest enhancement in arteriole density than other groups (p < 0.05). Cotransplanting with ADSCs and Matrigel showed significantly higher levels of cardiac troponin T (cTnT), NK2-transcription factor related locus-5 (Nkx2.5), von Willebrand factor (vWF) than the other groups (p < 0.05). In conclusion, this study demonstrated that cotransplanting ADSCs with Matrigel resulted in improved cardiac morphology and cardiac function in the rat model of myocardial infarction.

16.
Front Neurol ; 14: 1184864, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37602239

RESUMO

Background: Acute necrotizing encephalopathy (ANE) is a devastating neurologic condition that can arise following a variety of systemic infections, including influenza and SARS-Cov-2. The clinical features of COVID-19-associated ANE in pediatric patients based on multi-case data have not yet been described and remain obscure. We reviewed 12 pediatric patients to better describe the clinical features of ANE with COVID-19. Methods: We retrospectively collected and summarized the clinical features of ANE in children with COVID-19. Clinical data were collected from 12 children, including their general status, clinical symptoms, laboratory tests, and neuroimaging features. Results: Among the subjects, 10 were over 5 years old and they accounted for 83.33%. A large percentage of those affected (66.67%) were females. The major manifestations included fever (100%), impaired consciousness (100%), and convulsions (75%). We determined that increased interleukin (IL)-6 and IL-10, and tumor necrosis factor-α and interferon gamma were not predictive of severe ANE and mortality in children with COVID-19 in this study. All children presented with abnormal neuroimaging with multiple and symmetrically distributed lesions, involving the thalamus, basal ganglia, cerebellum, and brain hemispheres. Eight of the 12 children died, resulting in a mortality rate of 66.67%, and 75% of these children were females. Importantly, we found the timely administration of mannitol after an acute onset of convulsions or disturbance of consciousness may be decreased the high mortality induced by ANE children with COVID-19. Conclusion: COVID-19 associated with ANE in children is characterized by sudden symptom onset, rapid disease progression, and high mortality.

17.
Inorg Chem ; 62(33): 13195-13204, 2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37555777

RESUMO

Three gallium(III)- and thallium(III)-containing polyoxopalladates (POPs) have been synthesized and structurally characterized in the solid state and in solution, namely, the phosphate-capped 12-palladate nanocubes [XPd12O8(PO4)8]13- (X = GaIII, GaPd12P8; X = TlIII, TlPd12P8) and the 23-palladate double-cube [Tl2IIIPd23P14O70(OH)2]20- (Tl2Pd23P14). The cuboid POPs, GaPd12P8 and TlPd12P8, are solution stable as verified by the respective 31P, 71Ga, and 205Tl nuclear magnetic resonance (NMR) spectra. Of prime interest, the spin-spin coupling schemes allowed for an intimate study of the solution behavior of the TlIII-containing POPs via a combination of 31P and 205Tl NMR, including the stoichiometry of the major fragments of Tl2Pd23P14. Moreover, biological studies demonstrated the antitumor and antiviral activity of GaPd12P8 and TlPd12P8, which were validated to be as efficient as cis-platinum against human melanoma and acute promyelocytic leukemia cells. Furthermore, GaPd12P8 and TlPd12P8 exerted inhibitory activity against two herpetic viruses, HSV-2 and HCMV, in a dose-response manner.


Assuntos
Gálio , Tálio , Humanos , Tálio/química , Gálio/farmacologia , Gálio/química , Ressonância Magnética Nuclear Biomolecular , Espectroscopia de Ressonância Magnética , Imageamento por Ressonância Magnética
18.
Photodiagnosis Photodyn Ther ; 43: 103737, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37549816

RESUMO

The intercellular tight junction inhibits tumor imaging efficiency of nanomaterials, and enhanced cellular drug delivery with efficient detection is an important tool for tumor diagnosis. Herein, we fabricate fluorescence gold nanoclusters (Au NCs) decorated gas vesicles (GV-Au) for ultrasound (US)-mediated enhanced cellular delivery and imaging, in which GVs are living cell derived protein bubbles. GV-Au is rod-shaped sack-like structure around 230 nm, and displays improved stability and fluorescence ability compared with free Au NCs. Flow cytometry assay confirms the intracellular localization of Au NCs and GV-Au with a respective 2.20-fold enhanced cellular uptake post US treatment. Confocal images reveal the efficient cellular uptake of GV-Au under US impact, indicating that GV-Au is suitable for cellular and in vivo fluorescence imaging. Our strategy provides a new idea for efficient fluorescence imaging by penetrating cell membranes at the presence of US treatment.


Assuntos
Nanopartículas Metálicas , Fotoquimioterapia , Ouro/química , Fármacos Fotossensibilizantes , Fotoquimioterapia/métodos , Fluorescência , Imagem Óptica , Nanopartículas Metálicas/química
19.
World J Clin Cases ; 11(22): 5365-5372, 2023 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-37621591

RESUMO

BACKGROUND: Chest wall tuberculosis (TB) and triple-negative essential thrombocythemia (TN-ET) are rare medical conditions, and their combination is extremely rare globally. Only one case of TB peritonitis with thrombocytosis has been reported, which was identified in 1974. CASE SUMMARY: Herein, we report the case of a 23-year-old man with concurrent chest wall mass and TN-ET. The patient presented to a local hospital due to having a headache and low-grade fever for 2 d, with their bodily temperature fluctuating at around 36.8 °C. Hematological analysis showed a high platelet count of 1503 × 109/L. Subsequently, the patient visited our hospital for further investigation. Computed tomography of the chest suggested a submural soft tissue density shadow in the left lower chest wall. After surgical resection, the pathological findings of the swelling were reported as TB with massive caseous necrosis. According to the World Health Organization diagnostic criteria, the patient was diagnosed with TN-ET, as they met the requirement of four main criteria or the first three main criteria and one secondary criterion. The patient was eventually diagnosed with chest wall TB with TN-ET, which is extremely rare. CONCLUSION: Chest wall TB is rare. TN-ET diagnosis requires secondary factor exclusion and satisfaction of primary diagnostic criteria. miRNA, combined with the methylation process, could explain suppressor of cytokine signaling (SOCS) 1 and SOCS3 downregulation in ET-JAK2V617F-negative patients. The miRNA could participate in JAK2 pathway activation. SOCS3 may be a novel MPN biomarker.

20.
World J Gastrointest Surg ; 15(6): 1169-1177, 2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37405107

RESUMO

BACKGROUND: Radical gastrectomy (RG) is commonly used in the treatment of patients with gastric cancer (GC), but this procedure may lead to stress responses, postoperative cognitive dysfunction, and blood coagulation abnormalities in patients. AIM: To investigate the influences of dexmedetomidine (DEX) on stress responses and postoperative cognitive and coagulation functions in patients undergoing RG under general anesthesia (GA). METHODS: One hundred and two patients undergoing RG for GC under GA from February 2020 to February 2022 were retrospectively reviewed. Of these, 50 patients had received conventional anesthesia intervention [control group (CG)] and 52 patients had received DEX in addition to routine anesthesia intervention [observation group (OG)]. Inflammatory factor (IFs; tumor necrosis factor-α, TNF-α; interleukin-6, IL-6), stress responses (cortisol, Cor; adrenocorticotropic hormone, ACTH), cognitive function (CF; Mini-Mental State Examination, MMSE), neurological function (neuron-specific enolase, NSE; S100 calcium-binding protein B, S100B), and coagulation function (prothrombin time, PT; thromboxane B2, TXB2; fibrinogen, FIB) were compared between the two groups before surgery (T0), as well as at 6 h (T1) and 24 h (T2) after surgery. RESULTS: Compared with T0, TNF-α, IL-6, Cor, ACTH, NSE, S100B, PT, TXB2, and FIB showed a significant increase in both groups at T1 and T2, but with even lower levels in OG vs CG. Both groups showed a significant reduction in the MMSE score at T1 and T2 compared with T0, but the MMSE score was notably higher in OG compared with CG. CONCLUSION: In addition to a potent inhibitory effect on postoperative IFs and stress responses in GC patients undergoing RG under GA, DEX may also alleviate the coagulation dysfunction and improve the postoperative CF of these patients.

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