RESUMO
AIMS AND OBJECTIVES: The purpose of this study was to comprehensively evaluate the association of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) with neurological adverse events using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database, with the aim of guiding the rational use of statins. METHODS: The number and clinical characteristics of adverse events (AEs) to statins in the FAERS database between 2012 and March, 2023, were extracted. Neurological AEs were defined by the system organ classes (SOCs) of "Nervous System Disorders (10029205)" and the corresponding PT. Disproportionality was calculated using the reporting dominance ratio (ROR), proportional reporting ratio (PRR), and information component (IC025). RESULTS: Between January, 2012 and March, 2023, a total of 90,357 AEs were reported for the three statins (atorvastatin, resuvastatin, and simvastatin). The majority of reports on AEs came from the United States (n = 7284). A total of 8409 reports described neurological AEs following the use of the three statins, with atorvastatin accounting for more than half of the reports (n = 4430). The mean age of patients who developed neurological AEs was 55 years and older. The prevalence was similar in female patients (2230/4480) and male patients (1999/4480). Disproportionate analyses showed that at the SOC level, only the correlation between atorvastatin and neurological AEs suggested a positive signal (ROR: 9.77 (9.56-9.99); IC025: 3.28; PRR (χ2): 9.76 (16.07)) and in total, there were 32 PTs with a positive signal. The median time for neurological AEs was 71 days (IQR: 14-559 days), and the most common AEs were other serious effects (important medical event) (OT) (n = 2283) and hospitalization (HO) (n = 715). CONCLUSION: This study suggests that atorvastatin may be associated with an increased risk of neurological AEs. This study provides realistic evidence of the potential risk of statin-related adverse events.
RESUMO
Triple-negative breast cancer (TNBC) is a prevalent malignancy in women, casting a formidable shadow on their well-being. Positioned within the nucleolus, SUMO-specific protease 3 (SENP3) assumes a pivotal role in the realms of development and tumorigenesis. However, the participation of SENP3 in TNBC remains a mystery. Here, we elucidate that SENP3 exerts inhibitory effects on migration and invasion capacities, as well as on the stem cell-like phenotype, within TNBC cells. Further experiments showed that YAP1 is the downstream target of SENP3, and SENP3 regulates tumorigenesis in a YAP1-dependent manner. YAP1 is found to be SUMOylated and SENP3 deconjugates SUMOylated YAP1 and promotes degradation mediated by the ubiquitin-proteasome system. More importantly, YAP1 with a mutation at the SUMOylation site impedes the capacity of WT YAP1 in TNBC tumorigenesis. Taken together, our findings firmly establish the pivotal role of SENP3 in the modulation of YAP1 deSUMOylation, unveiling novel mechanistic insight into the important role of SENP3 in the regulation of TNBC tumorigenesis in a YAP1-dependent manner.
RESUMO
High maternal and neonatal mortality rates persist in Mozambique, with stillbirths remaining understudied. Most maternal and neonatal deaths in the country are due to preventable and treatable childbirth-related complications that often occur in low-resource settings. The World Health Organization introduced the Safe Childbirth Checklist (SCC) in 2015 to reduce adverse birth outcomes. The SCC, a structured list of evidence-based practices, targets the main causes of maternal and neonatal deaths and stillbirths in healthcare facilities. The SCC has been tested in over 35 countries, demonstrating its ability to improve the quality of care. However, it has not been adopted in Mozambique. This study aimed to identify potential facilitators and barriers to SCC implementation from the perspective of birth attendants, clinical administrators, and decision-makers to inform future SCC implementation in Mozambique. We conducted a qualitative study involving focus group discussions with birth attendants (n = 24) and individual interviews with clinical administrators (n = 6) and decision-makers (n = 8). The Consolidated Framework for Implementation Research guided the questions used in the interviews and focus group discussions, as well as the subsequent data analysis. A deductive thematic analysis of Portuguese-to-English translated transcripts was performed. In Mozambique, most barriers to potential SCC implementation stem from the challenges within a weak health system, including underfunded maternal care, lack of infrastructure and human resources, and low provider motivation. The simplicity of the SCC and the commitment of healthcare providers to better childbirth practices, combined with their willingness to adopt the SCC, were identified as major facilitators. To improve the feasibility of SCC implementation and increase compatibility with current childbirth routines for birth attendants, the SCC should be tailored to context-specific needs. Future research should prioritize conducting pre-implementation assessments to align the SCC more effectively with local contexts and facilitate sustainable enhancements in childbirth practices.
RESUMO
BACKGROUND: Temporal concavities result from reduced subcutaneous fat and bone structure variations, impacting facial aesthetics. Filling treatments, including autologous fat grafts, synthetic fillers, and biological materials, are used for enhancement. Autologous fat grafting is promising but limited by unpredictable fat absorption and nonstandardized procedures. This study aims to assess the clinical effectiveness of mechanical micronized fat in combination with autologous granular fat grafting for lipofilling in the correction of temporal deformities. METHODS: Patients (n = 37, mean age = 37.48) with temporal concavity caused by aging and Inherently inadequate capacity were enrolled and divided into control group (n = 10) and study group (n = 9) according to different fat grafts. Control group received pure autologous granular fat, with an average volume of approximately 19.30 mL. In contrast, the study group used mechanical micronized fat along with autologous granular fat co-injection through an 18G needle with an average injection volume of about 18.89 mL. All autologous fat collected from patients' abdominal and thighs. Information, including postoperative clinical efficacy scored by various plastic surgeons for the comparison of preoperative and postoperative photos of patients, patient satisfaction, and complications between the two groups, was documented. Additionally, changes in patients' quality of life were evaluated using the FACE-Q scale. RESULTS: Six months after surgery, the efficacy of temporal filling in the study group (6.69 ± 0.64) was higher than the control group (6.37 ± 0.67) (P = 0.0048). The patient satisfaction was more prominent in the study group (6.28 ± 0.87) than in the control group (5.80 ± 0.71) (P = 0.0449). Differences between above two observation indicators were statistically significant (P < 0.05). The FACE-Q scale items, which assess psychological health, social functioning, and early life impact, showed higher scores in the study group both before the surgery (psychological health: 59.22 ± 3.53, social functioning: 64.75 ± 3.15) and 6 months after the surgery (psychological health: 69.44 ± 4.50, social functioning: 75.33 ± 3.81, early life impact: 74.21 ± 0.70) (P > 0.05). Notably, only one micronodule formation was detected among all patients. CONCLUSION: Mechanical micronized fat combined with autologous granular fat improve the clinical effect of treating concavity in temporal region, which is worthy of further promotion and application.
Assuntos
Tecido Adiposo , Humanos , Feminino , Adulto , Masculino , Tecido Adiposo/transplante , Pessoa de Meia-Idade , Resultado do Tratamento , Transplante Autólogo , Satisfação do Paciente , Estética , Qualidade de Vida , Gordura Subcutânea/transplanteRESUMO
Brain metastases and lung metastases are major causes of treatment failure and related mortality in melanoma. Fluoxetine hydrochloride (FXT), a widely-used antidepressant, has emerged as a potential anticancer agent in preclinical studies. Previous research has shown its potential to inhibit melanoma. However, its efficacy and the underlying mechanisms in melanoma metastasis, especially concerning brain metastases and lung metastases, remain underexplored. This study investigates FXT's inhibitory effects on melanoma growth and metastasis to the lung and brain. Employing a combination of in vitro assays, we demonstrate FXT's potent suppression of melanoma growth through induction of intrinsic apoptosis, disruption of autophagic flux, and cell cycle arrest at the G0/G1 phase. In in vivo mouse models, we found that FXT exhibits strong inhibitory activity against melanoma brain metastases and lung metastases. Our findings provide a foundation for future clinical exploration of FXT as a novel treatment strategy for melanoma, underscoring its ability to target both primary and metastatic lesions.
RESUMO
Congenital heart disease (CHD) is a type of major defect that occurs during embryonic development. Although significant advances have been made in the treatment of CHD, its etiology and molecular mechanism remain unclear. To identify the critical role of SUMOylation in cardiac development, we generated SENP3 knockout mice and showed that SENP3 knockout mice die on embryonic day 8.5 with an open neural tube and reversed left-right cardiac asymmetry. Moreover, SENP3 knockout promoted apoptosis and senescence of H9C2 cells. Further studies showed that Nodal, a critical gene that forms left-right asymmetry, is regulated by SENP3 and that SENP3 regulates cell apoptosis and senescence in a Nodal-dependent manner. Furthermore, Nodal was hyper-SUMOylated after SENP3 knockout, and SUMOylation of Nodal inhibited its ubiquitination and ubiquitin-proteasome degradation pathway. Nodal overexpression enhanced cell apoptosis and senescence; however, the mutation at the SUMOylation site of Nodal reversed its effect on the apoptosis and senescence of H9C2 cells. More importantly, the SENP3-Nodal axis regulates cell senescence by inducing cell autophagy. These results suggest that the SENP3-Nodal signaling axis regulates cardiac senescence-autophagy homeostasis, which in turn affects cardiac development and results in the occurrence of CHD.
Assuntos
Apoptose , Cisteína Endopeptidases , Proteína Nodal , Transdução de Sinais , Sumoilação , Animais , Cisteína Endopeptidases/metabolismo , Cisteína Endopeptidases/genética , Camundongos , Apoptose/genética , Proteína Nodal/metabolismo , Proteína Nodal/genética , Coração/embriologia , Camundongos Knockout , Autofagia/genética , Senescência Celular/genética , Linhagem CelularRESUMO
Ulcerative colitis (UC) is a chronic immune-mediated disease that affects the entire colon and rectum with a relapsing and remitting course, causing lifelong morbidity. When medical treatment is ineffective, especially in cases of massive gastrointestinal bleeding, perforation, toxic megacolon, or carcinogenesis, surgery becomes the last line of defense to cure UC. Total colorectal resection and ileal pouch-anal anastomosis (IPAA) offer the best chance for long-term treatment. Pouchitis is the most common and troublesome postoperative complication. In this investigation, microsurgery is employed to create an ileal pouch model in experimental rats via IPAA surgery. Subsequently, a sustained rat model of pouchitis is established by inducing inflammation of the ileal pouch with dextran sulfate sodium (DSS). The successful establishment of rat pouchitis is validated through analysis of postoperative general status, weight, food and water intake, fecal data, as well as pouch tissue pathology, immunohistochemistry, and inflammatory factor analysis. This experimental animal model of pouchitis provides a foundation for studying the pathogenesis and treatment of the condition.
Assuntos
Bolsas Cólicas , Sulfato de Dextrana , Modelos Animais de Doenças , Pouchite , Proctocolectomia Restauradora , Animais , Pouchite/etiologia , Ratos , Proctocolectomia Restauradora/métodos , Proctocolectomia Restauradora/efeitos adversos , Bolsas Cólicas/efeitos adversos , Complicações Pós-Operatórias/etiologia , Masculino , Anastomose Cirúrgica/métodos , Anastomose Cirúrgica/efeitos adversosRESUMO
There are several modifiable factors that can be targeted to prevent and manage the occurrence and progression of cancer, and maintaining adequate exercise is a crucial one. Regular physical exercise has been shown to be a beneficial strategy in preventing cancer, potentially amplifying the effectiveness of established cancer therapies, alleviating certain cancer-related symptoms, and possibly mitigating side effects resulting from treatment. Nevertheless, the exact mechanisms by which exercise affects tumors, especially its impact on the tumor microenvironment (TME), remain uncertain. This review aims to present an overview of the beneficial effects of exercise in the context of cancer management, followed by a summary of the exercise parameters, especially exercise intensity, that need to be considered when prescribing exercise for cancer patients. Finally, we discuss the influence of exercise on the TME, including its effects on crucial immune cells (e.g., T cells, macrophages, neutrophils, natural killer cells, myeloid-derived suppressor cells, B cells), intratumor angiogenesis, and cancer metabolism. This comprehensive review provides up-to-date scientific evidence on the effects of exercise training on cancer and offers guidance to clinicians for the development of safe and feasible exercise training programs for cancer patients in clinical practice.
Assuntos
Exercício Físico , Neoplasias , Microambiente Tumoral , Humanos , Neoplasias/terapia , Terapia por Exercício , Neovascularização PatológicaRESUMO
BACKGROUND: Our study aims to delineate the miRSNP-microRNA-gene-pathway interactions in the context of hypertrophic scars (HS) and keloids. MATERIALS AND METHODS: We performed a computational biology study involving differential expression analysis to identify genes and their mRNAs in HS and keloid tissues compared to normal skin, identifying key hub genes and enriching their functional roles, comprehensively analyzing microRNA-target genes and related signaling pathways through bioinformatics, identifying MiRSNPs, and constructing a pathway-based network to illustrate miRSNP-miRNA-gene-signaling pathway interactions. RESULTS: Our results revealed a total of 429 hub genes, with a strong enrichment in signaling pathways related to proteoglycans in cancer, focal adhesion, TGF-ß, PI3K/Akt, and EGFR tyrosine kinase inhibitor resistance. Particularly noteworthy was the substantial crosstalk between the focal adhesion and PI3K/Akt signaling pathways, making them more susceptible to regulation by microRNAs. We also identified specific miRNAs, including miRNA-1279, miRNA-429, and miRNA-302e, which harbored multiple SNP loci, with miRSNPs rs188493331 and rs78979933 exerting control over a significant number of miRNA target genes. Furthermore, we observed that miRSNP rs188493331 shared a location with microRNA302e, microRNA202a-3p, and microRNA20b-5p, and these three microRNAs collectively targeted the gene LAMA3, which is integral to the focal adhesion signaling pathway. CONCLUSIONS: The study successfully unveils the complex interactions between miRSNPs, miRNAs, genes, and signaling pathways, shedding light on the genetic factors contributing to HS and keloid formation.
Assuntos
Cicatriz Hipertrófica , Queloide , MicroRNAs , Humanos , Cicatriz Hipertrófica/genética , Cicatriz Hipertrófica/metabolismo , Biologia Computacional , Queloide/genética , Queloide/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Polimorfismo de Nucleotídeo Único , Transdução de Sinais/genéticaRESUMO
BACKGROUND: The incidence of melanoma brain metastasis (MBM) is high and significantly compromises patient survival and quality of life. Effective treatment of MBM is made difficult by the blood-brain barrier (BBB), since it restricts the entry of drugs into the brain. Certain anti-psychotic drugs able to cross the BBB have demonstrated efficacy in suppressing brain metastasis in preclinical studies. However, the activity of zuclopenthixol against MBM is not yet clear. METHODS: Cell viability assays were employed to investigate the potential of zuclopenthixol in the treatment of MBM. Subsequently, the mechanism of action was investigated by RNA-sequencing (RNAseq), flow cytometry-based cell cycle and apoptosis assays, protein expression analysis, and autophagy flux detection. Additionally, the efficacy of zuclopenthixol against tumor growth was investigated in vivo, including MBM models. RESULTS: Zuclopenthixol inhibited the proliferation of various melanoma cell lines at minimal doses by causing cell cycle arrest in the G0/G1 phase and mitochondrial-mediated intrinsic apoptosis. Zuclopenthixol also induced cytoprotective autophagy, and inhibition of autophagy enhanced the anti-melanoma effects of zuclopenthixol. Furthermore, zuclopenthixol inhibited the growth of human melanoma tumors in nude mice, as well as the growth of intracranial metastases in a mouse model of MBM. CONCLUSIONS: These results demonstrate that zuclopenthixol has significant potential as an effective therapeutic agent for MBM.
Assuntos
Apoptose , Neoplasias Encefálicas , Pontos de Checagem do Ciclo Celular , Proliferação de Células , Melanoma , Apoptose/efeitos dos fármacos , Animais , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Melanoma/tratamento farmacológico , Melanoma/patologia , Melanoma/metabolismo , Proliferação de Células/efeitos dos fármacos , Camundongos , Antipsicóticos/farmacologia , Autofagia/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Nus , Sobrevivência Celular/efeitos dos fármacosRESUMO
Two-dimensional correlation spectroscopy is used to investigate the intermolecular interaction between two substances dissolved in the same solutions, where the intermolecular interaction is described by two reversible reactions producing two supramolecular aggregates. The severe overlappings expected among the characteristic peaks of the original solute and aggregates make conventional one-dimensional spectra difficult to accurately reflect the physiochemical nature of the intermolecular interaction. The double asynchronous orthogonal sample design (DAOSD) approach is utilized to analyze the simulated data for proof-of-principle demonstration. The patterns of cross-peaks are much more complex compared with the intermolecular interaction described by only a single reaction. Four major groups of cross-peaks with characteristic patterns observed in the pair of DAOSD asynchronous spectra are systematically analyzed and classified. Further analysis of the spectral feature of the cross-peaks of the DAOSD asynchronous spectra is helpful to exact additional information concerning the variation of the peak position and peak width of the aggregates compared with those of the original solute. The result is important to reveal the physicochemical nature of intermolecular interaction between the solutes (e.g., changes in conformation, dynamical behavior, etc.). The pattern of cross-peaks in the corresponding 2D asynchronous spectra may become rather complex when the peak position, peak width, and peak intensity of two supramolecular aggregates change simultaneously. Further work using artificial intelligence techniques to interpret the complex cross-peaks is still being carried out.
RESUMO
Introduction: Melanoma is a highly aggressive and recurrent form of skin cancer, posing challenges in prognosis and therapy prediction. Methods: In this study, we developed a novel TIPRGPI consisting of 20 genes using Univariate Cox regression and the LASSO algorithm. The high and low-risk groups based on TIPRGPI exhibited distinct mutation profiles, hallmark pathways, and immune cell infiltration in the tumor microenvironment. Results: Notably, significant differences in tumor immunogenicity and TIDE were observed between the risk groups, suggesting a better response to immune checkpoint blockade therapy in the low-TIPRGPI group. Additionally, molecular docking predicted 10 potential drugs that bind to the core target, PTPRC, of the TIPRGPI signature. Discussion: Our findings highlight the reliability of TIPRGPI as a prognostic signature and its potential application in risk classification, immunotherapy response prediction, and drug candidate identification for melanoma treatment. The "TIP genes" guided strategy presented in this study may have implications beyond melanoma and could be applied to other cancer types.
Assuntos
Melanoma , Humanos , Melanoma/genética , Melanoma/terapia , Simulação de Acoplamento Molecular , Reprodutibilidade dos Testes , Imunoterapia , Fenótipo , Microambiente Tumoral/genéticaRESUMO
Anus eczema is a chronic and recurrent inflammatory skin disease affecting the area around the anus. While the lesions primarily occur in the anal and perianal skin, they can also extend to the perineum or genitalia. ShiDuGao (SDG) has been found to possess significant reparative properties against anal pruritus, exudation control, moisture reduction, and skin repair. However, the genetic targets and pharmacological mechanisms of SDG on anal eczema have yet to be comprehensively elucidated and discussed. Consequently, this study employed a network pharmacological approach and utilized gene expression omnibus (GEO) datasets to investigate gene targets. Additionally, a protein-protein interaction network (PPI) was established, resulting in the identification of 149 targets, of which 59 were deemed hub genes, within the "drug-target-disease" interaction network. The gene function of SDG in the treatment of perianal eczema was assessed through the utilization of the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis. Subsequently, the anti-perianal eczema function and potential pathway of SDG, as identified in network pharmacological analysis, were validated using molecular docking methodology. The biological processes associated with SDG-targeted genes and proteins in the treatment of anus eczema primarily encompass cytokine-mediated responses, inflammatory responses, and responses to lipopolysaccharide, among others. The results of the pathway enrichment and functional annotation analyses suggest that SDG plays a crucial role in preventing and managing anal eczema by regulating the Shigellosis and herpes simplex virus 1 infection pathways. Network pharmacology and GEO database analysis confirms the multi-target nature of SDG in treating anal eczema, specifically by modulating TNF, MAPK14, and CASP3, which are crucial hub targets in the TNF and MAPK signaling pathways. These findings provide a clear direction for further investigation into SDG's therapeutic mechanism for anal eczema while highlighting its potential as an effective treatment approach for this debilitating condition.
Assuntos
Canal Anal , Eczema , Humanos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Eczema/tratamento farmacológico , Eczema/genética , CitocinasRESUMO
Endothelial-mesenchymal transition (EndoMT) is a complex biological process in which endothelial cells are transformed into mesenchymal cells, and dysregulated EndoMT causes a variety of pathological processes. Transforming growth factor beta (TGF-ß) signaling effectively induces the EndoMT process in endothelial cells, and Smad2 is the critical protein of the TGF-ß signaling pathway. However, whether small ubiquitin-like modifier modification (SUMOylation) is involved in EndoMT remains unclear. Here, we show that Smad2 is predominantly modified by SUMO1 at two major SUMOylation sites with PIAS2α as the primary E3 ligase, whereas SENP1 (sentrin/SUMO-specific protease 1) mediates the deSUMOylation of Smad2. In addition, we identified that SUMOylation significantly enhances the transcriptional activity and protein stability of Smad2, regulating the expression of downstream target genes. SUMOylation increases the phosphorylation of Smad2 and the formation of the Smad2-Smad4 complex, thus promoting the nuclear translocation of Smad2. Ultimately, the wildtype, but not SUMOylation site mutant Smad2 facilitated the EndoMT process. More importantly, TGF-ß enhances the nuclear translocation of Smad2 by enhancing its SUMOylation and promoting the EndoMT process. These results demonstrate that SUMOylation of Smad2 plays a critical role in the TGF-ß-mediated EndoMT process, providing a new theoretical basis for the treatment and potential drug targets of EndoMT-related clinical diseases.
RESUMO
BACKGROUND: Implantable Collamer Lens (ICL) surgery has been proven to be a safe, effective, and predictable method for correcting myopia and myopic astigmatism. However, predicting the vault and ideal ICL size remains technically challenging. Despite the growing use of artificial intelligence (AI) in ophthalmology, no AI studies have provided available choices of different instruments and combinations for further vault and size predictions. This study aimed to fill this gap and predict post-operative vault and appropriate ICL size utilizing the comparison of numerous AI algorithms, stacking ensemble learning, and data from various ophthalmic devices and combinations. RESULTS: This retrospective and cross-sectional study included 1941 eyes of 1941 patients from Zhongshan Ophthalmic Center. For both vault prediction and ICL size selection, the combination containing Pentacam, Sirius, and UBM demonstrated the best results in test sets [R2 = 0.499 (95% CI 0.470-0.528), mean absolute error = 130.655 (95% CI 128.949-132.111), accuracy = 0.895 (95% CI 0.883-0.907), AUC = 0.928 (95% CI 0.916-0.941)]. Sulcus-to-sulcus (STS), a parameter from UBM, ranked among the top five significant contributors to both post-operative vault and optimal ICL size prediction, consistently outperforming white-to-white (WTW). Moreover, dual-device combinations or single-device parameters could also effectively predict vault and ideal ICL size, and excellent ICL selection prediction was achievable using only UBM parameters. CONCLUSIONS: Strategies based on multiple machine learning algorithms for different ophthalmic devices and combinations are applicable for vault predicting and ICL sizing, potentially improving the safety of the ICL implantation. Moreover, our findings emphasize the crucial role of UBM in the perioperative period of ICL surgery, as it provides key STS measurements that outperformed WTW measurements in predicting post-operative vault and optimal ICL size, highlighting its potential to enhance ICL implantation safety and accuracy.
Assuntos
Implante de Lente Intraocular , Lentes Intraoculares Fácicas , Humanos , Acuidade Visual , Implante de Lente Intraocular/métodos , Inteligência Artificial , Estudos Retrospectivos , Estudos Transversais , Aprendizado de MáquinaRESUMO
BACKGROUND: The discovery of the glymphatic system and meningeal lymphatic vessels challenged the traditional view regarding the lack of a lymphatic system in the central nervous system. It is now known that the intracranial lymphatic system plays an important role in fluid transport, macromolecule uptake, and immune cell trafficking. Studies have also shown that the function of the intracranial lymphatic system is significantly associated with neurological diseases; for example, an impaired intracranial lymphatic system can lead to Tau deposition and an increased lymphocyte count in the brain tissue of mice with subarachnoid hemorrhage. METHODS: In this study, we assessed the changes in the intracranial lymphatic system after intracerebral hemorrhage and the regulatory effects of repeated transcranial magnetic stimulation on the glymphatic system and meningeal lymphatic vessels in an intracerebral hemorrhage (ICH) model of male mice. Experimental mice were divided into three groups: Sham, ICH, and ICH + repeated transcranial magnetic stimulation (rTMS). Three days after ICH, mice in the ICH+rTMS group were subjected to rTMS daily for 7 days. Thereafter, the function of the intracranial lymphatic system, clearance of RITC-dextran and FITC-dextran, and neurological functions were evaluated. RESULTS: Compared with the Sham group, the ICH group had an impaired glymphatic system. Importantly, rTMS treatment could improve intracranial lymphatic system function as well as behavioral functions and enhance the clearance of parenchymal RITC-dextran and FITC-dextran after ICH. CONCLUSION: Our results indicate that rTMS can abrogate ICH-induced brain parenchymal metabolite clearance dysfunction by regulating intracranial lymphatic drainage.
Assuntos
Dextranos , Estimulação Magnética Transcraniana , Masculino , Camundongos , Animais , Dextranos/metabolismo , Hemorragia Cerebral , EncéfaloRESUMO
An apparatus and relevant approach to obtaining IR spectra of solutes from the corresponding aqueous solution were developed. In the experiment, aqueous solutions were converted into aerosols using an ultrasonic or a pneumatic device. Subsequently, water in the nebulized solution is completely gasified under a high-speed flow and low vacuum environment. Via this process, the aqueous solution changes into a mixture of a solute or solutes and gaseous water, whose single-beam IR spectra are collected. Then, the newly developed RMF (retrieving moisture-free IR spectrum) method and the relevant approach described in our recent papers have been adopted to treat the resultant single-beam sample spectrum. As a result, the spectral contribution of the vibrational-rotational peaks of gaseous water can be removed or significantly attenuated, and IR spectra of solutes can be obtained. The approach shows an obvious advantage in retrieving the IR spectrum of volatile solutes from its aqueous solution. This capability is showcased by obtaining IR spectra of isopropanol and ethyl acetate successfully. IR spectra of these compounds can be retrieved even if the concentration of the solute is below 10 wt%. Moreover, atomization via ultrasonic/pneumatic methods offers a mild way to gasify solutes whose boiling points are remarkably higher than that of water. This advantage is manifested by acquiring IR spectra of 1-butanol and 1,2-propanediol in the gaseous phase under ambient conditions.
RESUMO
BACKGROUND: Adipose-derived stromal vascular fraction (SVF) and mesenchymal stem cells have been proven to reduce the effects of skin photoaging. However, there is no standardized protocol for their preparation. This study aimed to investigate the skin rejuvenation potential of micronized fat, obtained using a novel device attached with a trifoliate blade, in the ultraviolet B (UV-B)-induced human dermal fibroblast model. METHODS: Micronized fat was prepared to obtain adipose-derived SVF, and the adipose-derived mesenchymal stem cell-to-SVF ratio was determined by flow cytometry. The UV-B-induced human dermal fibroblasts model was constructed to identify the characteristics of the human dermal fibroblasts using vimentin and S-100 immunostaining, observe their morphology, and measure the levels of photoaging-related factors. After the previous steps were completed, different cell groups were co-cultured with UV-B-induced human dermal fibroblasts, and the extent of improvement of photoaging was evaluated. RESULTS: Micronized fat had a higher adipose-derived mesenchymal stem cell-to-SVF ratio than the control fat preparations. The UV-B-induced human dermal fibroblasts model showed lowered levels of type I collagen and transforming growth factor-ß and increased expression of matrix metalloproteinases (MMPs), which are the characteristics of photoaging in normal human dermal fibroblasts. Compared with different cell groups co-cultured with UV-B-induced human dermal fibroblasts, micronized fat could lower the expression of MMPs and increase the level of type I collagen but lower the level of transforming growth factor-ß. CONCLUSIONS: Obtaining micronized fat is more effortless and clinically safer. Micronized fat has an antiphotoaging effect by inhibiting the expression of MMPs by means of the mitogen-activated protein kinases signaling pathway. CLINICAL RELEVANCE STATEMENT: The authors' work has potential clinical applications in fat grafting for facial rejuvenation.
RESUMO
We proposed a modified and improved approach to removing the interference of moisture from an IR spectrum and the corresponding second derivative spectrum. The temperature fluctuation in the air of the optical path and baseline-drift lead to the small but persistent presence of the interference of moisture. The problem has been successfully addressed by adopting a double-matching strategy. Additionally, two-dimensional correlationspectra (2D-COS) are generated using the second derivative or third derivative spectrum of the negative base 10 logarithms of the single-beam spectra, thereby removing the linear slope or quadratic portion of baseline-drift. Using the newly adopted approach, the residual interferences of moisture are attenuated. We applied the new approach to the IR spectra and the second derivative spectra of neat hexadecanol and biaxially oriented polypropylene (BOPP) film, and some promising preliminary results are obtained. In hexadecanol, two highly overlapping peaks at 1464 and 1463 cm-1 are revealed. In BOPP, the envelope at 1458 cm-1 is found to be composed of a number of sub-peaks.