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1.
Artigo em Inglês | MEDLINE | ID: mdl-39226613

RESUMO

Controlled Nutritional Status (CONUT) scores have been developed as quantitative tools that can be employed to gauge the nutritional status of individual patients. However, there has been very little research investigating the association between these CONUT scores and the function of the thyroid. As such, the present study was designed to address this research gap through the evaluation of a representative cohort of American adults. National Health and Nutrition Examination Survey (NHANES) data were herein used to separate subjects into those with normal nutritional status (CONUT score: 0-1) from those who were malnourished (CONUT scores > 1). Associations between these CONUT scores and the function of the thyroid were investigated through linear regression modeling, employing weighted analytical strategies and subgroup analyses. Overall, 8,082 individuals from the NHANES 2007-2012 cohort were enrolled in this analysis. These individuals exhibited a weighted mean CONUT score of 0.72 (0.02). 6661 (weighted proportion: 83.12%) in the normal nutritional status group and 1421 (16.88%) in the malnourished group. In adjusted analyses, subjects who were malnourished were found to present with an increase in FT4 levels (ß = 0.033; p < 0.001 together with reduced TT3 levels (ß = -3.526; p = 0.01). The present data offer evidence in support of higher CONUT scores, which correspond to malnutrition, being related to increases in FT4 levels together with reductions in TT3 levels. More studies will be crucial to further probe the mechanistic drivers of these results.

2.
Mol Genet Genomic Med ; 12(9): e70012, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39262298

RESUMO

BACKGROUND: Haemoglobinopathy refers to a group of common monogenic inherited conditions associated with variations in the haemoglobin molecule; however, there is relatively limited reporting on abnormal haemoglobinopathy in the Chinese population, especially rare abnormal haemoglobin (Hb). The aim of this study was to explore the clinical characteristics of haemoglobinopathy to supplement data for the epidemiological investigation of Hb variants in Guangdong province of China. METHODS: Peripheral blood was collected from five patients (including a family) for Complete blood count, Hb electrophoresis, High-performance liquid chromatography analysis and degenerative globin body testing. Hb variants were further analysed by PCR and DNA sequencing. RESULTS: The research subjects were diagnosed with different types of abnormal Hb. The blood routine of the Hb Fukuyama (HBB:c.232C>T) diagnosed individual showed microcytic hypochromic anaemia, with a lower Hb level (64 g/L), mean corpuscular volume (MCV) of 71.5 fL and mean corpuscular haemoglobin (MCH) of 21.5 pg. Individuals diagnosed with Hb Port Phillip (HBA2:c.275T>C) exhibit a MCH level that is slightly below average, at 26.4 pg. The Hb Saint Etienne (HBB:c.279C>G) diagnosed individual showed macrocytic hypochromic anaemia, and the proband had a low Hb level (116 g/L), MCV of 102.2 fL and MCH of 29.4 pg. CONCLUSION: We confirmed the presence of Hb Fukuyama (HBB:c.232C>T) in China for the first time. Three rare patients with the Hb Saint Etienne (HBB:c.279C>G) phenotype and one patient with Hb Port Phillip (HBA2:c.275T>C) phenotype were included. Our research enriches the gene mutation map of haemoglobinopathy in Guangdong province and improves the detection system of haemoglobinopathy for population prevention and eugenics.


Assuntos
Hemoglobinopatias , Hemoglobinas Anormais , Fenótipo , Humanos , Hemoglobinas Anormais/genética , Masculino , Feminino , Hemoglobinopatias/genética , Hemoglobinopatias/sangue , Hemoglobinopatias/epidemiologia , Hemoglobinopatias/diagnóstico , Adulto , Mutação , Criança , Índices de Eritrócitos , China , Adolescente , Pessoa de Meia-Idade
3.
Sci Rep ; 14(1): 19792, 2024 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-39187642

RESUMO

Dysmobility Syndrome (DMS), is a combination, that is analogous to the approach taken with metabolic syndrome, The diagnosis of DMS is complex. So this study aimed to explore the relationship between 25-(OH) Vit D with Dysmobility Syndrome (DMS)in type 2 diabetes mellitus(T2DM) patients. This is a cross-sectional study, including 330 patients (67.0 ± 8.8 years old) with T2DM who were admitted to the Qinhuangdao First Hospital from October 2020 to February 2022. Selected independent variables include grip strength, six-meter gait speed, level of 25-(OH) vitamin D, and bone mineral density (BMD) measured by Dual-energy X-ray (DXA). DMS includes six conditions: osteoporosis, low muscle mass, low muscle strength, slow gait speed, occurrences of falls in the past year ≥ 1, and obesity, having three or more of these conditions were diagnosed with DMS. Patients were classified based on DMS. The detection rate of DMS in patients with T2DM was 25.5%. The proportion of vitamin deficiency is 67.9% in patients with T2DM. The 25-(OH) Vit D deficiency was defined based on the 25th percentile into two groups; < 36.2 nmol/L. The vitamin D levels in Group DMS were significantly lower than that in Group Non-DMS (41.74 ± 14.60 vs. 47.19 ± 13.01, P < 0.05). After adjusting confounder factors including sex, age, vitamin D levels, HbA1c, ALB, HDLC, eGFR, diabetes microvascular complications and macrovascular, there was an independent association between risk of DMS and age (OR value = 1.160, 95% CI 1.091-1.234, P = 0.000), HbA1c(OR value = 1.262, 95% CI 1.046-1.532, P = 0.015), and vitamin D deficiency (< 36.2 nmol/L) (OR value = 2.990, 95% CI 1.284-6.964, P = 0.011). Our findings suggest that low levels of vitamin D are a predictor of DMS in middle-aged and elderly patients with poor control of type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Deficiência de Vitamina D , Vitamina D , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/sangue , Masculino , Feminino , Idoso , Vitamina D/sangue , Vitamina D/análogos & derivados , Estudos Transversais , Pessoa de Meia-Idade , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/sangue , Densidade Óssea , Força da Mão , Osteoporose/sangue , Osteoporose/etiologia , Osteoporose/diagnóstico , Síndrome
4.
BMC Pediatr ; 24(1): 437, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982398

RESUMO

BACKGROUND: Pilomatricoma (PM) is a cutaneous benign neoplasm derived from the hair matrix. It clinically presents as a solitary and firm nodule overlying normal epidermis and is usually not easy to be noticed at early stage. Nevertheless, when special bullous lesion occurs in a short time or even ulcerates, preoperative diagnosis by a dermatologist is often challenging especially when the pediatric patients refuse biopsy. CASE PRESENTATION: We present six bullous PM cases and particularly conduct correlation analysis on the dermotoscopy and histopathology detection data. The basic information, medical history, symptoms and lesion morphology results of the patients were also provided. We found that the incidence of bullous PM was higher in females than in males, and most patients were adolescents and the predilection location seem to be consistent in the vaccine injection site. The dermatoscopic features of bullous PM reported were luminous yellow structure below, with gray-blue homogeneous areas and branched capillary. The histological features were consistent with PM, and evident epidermis bullae were above the tumor with extraordinary dilation of lymphangion in the upper dermis. The patients described in this study were Chinese patients in Han population included 4 females and 2 males, coincidentally, they are almost teen-age, respectively are 5,11,17,19,21,22 year-old. CONCLUSIONS: This study reported and analyzed the dermotoscopy and clinical characteristics of bullous PM, dermotoscopy may guide as a rapid and reliable technique in bullous PM diagnosis.


Assuntos
Dermoscopia , Doenças do Cabelo , Pilomatrixoma , Neoplasias Cutâneas , Humanos , Masculino , Feminino , Adolescente , Pilomatrixoma/patologia , Pilomatrixoma/diagnóstico , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Doenças do Cabelo/diagnóstico , Doenças do Cabelo/patologia , Criança , Adulto Jovem
5.
Biochem Biophys Res Commun ; 727: 150270, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38917617

RESUMO

Neuroinflammation has been implicated in cognitive deficits of neurological and neurodegenerative diseases. There is abundant evidence that the application of ghrelin, an orexigenic hormone regulating appetite and energy balance, abrogates neuroinflammation and rescues associated memory impairment. However, the underlying mechanism is uncertain. In this study, we find that both intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of lipopolysaccharide (LPS) impairs spatial memory in mice. LPS treatment causes neuroinflammation and microglial activation in the hippocampus. Ghsr1a deletion suppresses LPS-induced microglial activation and neuroinflammation, and rescued LPS-induced memory impairment. Our findings thus suggest that GHS-R1a signaling may promote microglial immunoactivation and contribute to LPS-induced neuroinflammation. GHS-R1a may be a new therapeutic target for cognitive dysfunction associated with inflammatory conditions.


Assuntos
Lipopolissacarídeos , Transtornos da Memória , Camundongos Endogâmicos C57BL , Microglia , Receptores de Grelina , Memória Espacial , Animais , Memória Espacial/efeitos dos fármacos , Receptores de Grelina/deficiência , Receptores de Grelina/genética , Receptores de Grelina/metabolismo , Transtornos da Memória/genética , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/metabolismo , Camundongos , Masculino , Microglia/metabolismo , Microglia/efeitos dos fármacos , Microglia/patologia , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Camundongos Knockout , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/patologia
7.
Int. j. morphol ; 42(2): 409--415, abr. 2024. ilus, tab
Artigo em Inglês | LILACS | ID: biblio-1558119

RESUMO

SUMMARY: The objective of this study was to observe the clinical efficacy of apatinib (AP) combined with 131I in the treatment of radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) and the prognostic significance of MIP-1α after treatment, and to provide reference and guidance for future treatment and disease assessment of RAIR-DTC. One hundred and six patients with RAIR- DTC admitted to our hospital from January 2019 to October 2020 were selected for the study. All the patients were treated with TC surgery with 131I at our hospital, and 58 of them were subsequently transferred to AP treatment, which was considered as the research group; the other 48 patients were transferred to thyroid stimulating hormone (TSH) suppression treatment, which was considered as the control group. The clinical efficacy of the research group was better than that of the control group (P 0.05). After treatment, Tg, TL, maximum diameter of C/B lymph nodes, number of lymph nodes and number of calcified spots were lower in the research group than in the control group (P < 0.05). ROC analysis revealed that the predictive sensitivity of MIP-1α for prognosis of 3-year RAIR-DTC death in the research group of patients was 84.63 % and the specificity was 72.16 %. AP combined with 131I is effective in the treatment of RAIR-DTC and is worth using in the clinical practice. In addition, elevated levels of MIP-1α predicted a poor prognosis for patients with RAIR-DTC.


El objetivo de este estudio fue observar la eficacia clínica de apatinib (AP) combinado con 131I en el tratamiento del cáncer de tiroides diferenciado refractario al yodo radiactivo (RAIR-DTC) y la importancia pronóstica de MIP-1α después del tratamiento, y proporcionar referencia y orientación para futuros tratamientos y enfermedades. Evaluación de RAIR- DTC. Se seleccionaron para el estudio 106 pacientes con RAIR- DTC ingresados en nuestro hospital desde enero de 2019 hasta octubre de 2020. Todos los pacientes fueron tratados con cirugía CT con 131I, y 58 de ellos fueron trasladados posteriormente a tratamiento AP, los que fueron considerados como grupo de investigación; los otros 48 pacientes fueron transferidos a tratamiento de supresión de la hormona estimulante de la tiroides (TSH), que se consideró como grupo de control. La eficacia clínica del grupo de investigación fue mejor que la del grupo de control (P 0,05). Después del tratamiento, Tg, TL, diámetro máximo de los linfonodos C/B, número linfonodos y número de manchas calcificadas fueron menores en el grupo de investigación que en el grupo de control (P <0,05). El análisis ROC reveló que la sensibilidad predictiva de MIP-1α para el pronóstico de muerte por RAIR-DTC a 3 años en el grupo de pacientes de investigación fue del 84,63 % y la especificidad fue del 72,16 %. AP combinado con 131I es eficaz en el tratamiento del RAIR-DTC y vale la pena utilizarlo en la práctica clínica. Además, los niveles elevados de MIP-1α predijeron un mal pronóstico para los pacientes con RAIR- DTC.


Assuntos
Humanos , Piridinas/uso terapêutico , Neoplasias da Glândula Tireoide/terapia , Radioisótopos do Iodo/uso terapêutico , Antineoplásicos/uso terapêutico , Prognóstico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/radioterapia , Resultado do Tratamento , Terapia Combinada , Proteínas Inflamatórias de Macrófagos
8.
Biochem Genet ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38565759

RESUMO

Gestational diabetes mellitus (GDM) is one of the most common metabolic diseases in pregnant women, posing significant risks to the life and health of both mothers and fetuses. With improving living standards, the incidence of GDM is increasing rapidly. Therefore, understanding the underlying mechanism of GDM is of paramount importance. We downloaded two datasets from the Gene Expression Omnibus (GEO) database, containing sequencing data specifically related to "gestational diabetes" and "placenta". By merging these two datasets, a mRNA expression dataset was obtained and subjected to bioinformatics analyses. To screen out corresponding genes, differential analysis and weighted correlation network analysis (WGCNA) were carried out. Lasso, support vector machine and random forest analyses were subsequently performed for identifying key genes from the differentially expressed genes (DEGs) jointly screened out through differential analysis and WGCNA. Afterwards, immunoinfiltration and correlation analysis were performed to screen immune cells that play a role in disease progression and explore the correlation between the screened key genes and immune cells, after which Western Blot, quantitative real-time polymerase chain reaction, Immunohistochemistry, methyl thiazolyl tetrazolium, flow cytometry, scratch and Transwell assays were, respectively, performed for verification. For further verification, we found that the expression levels of MAP6D1 and SCUBE1 in embryonic tissues of GDM patients was higher compared to those of healthy pregnant women, which was consistent with the results of bioinformatics analysis. Consequently, SCUBE1 was selected for follow-up experiment. In order to explore the role of SCUBE1 in the development of GDM, we treated the trophoblastic cells HTR-8/SVneo with high glucose, and on this basis downregulated the expression of SCUBE1. Through further analysis, we observed that SCUBE1 had a role in reducing cell activity, migration and invasion, and promoting cell apoptosis. In summary, SCUBE1 promotes the development of GDM by increasing cell apoptosis and reducing cell activity, migration, and invasion.

9.
Heliyon ; 10(7): e29082, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38617964

RESUMO

Objective: Composite Dietary Antioxidant Index (CDAI) values serve as a summary of an individual's combined dietary antioxidant intake. Although specific antioxidants are known to reduce thyroid damage from oxidative stress, the relationship between the CDAI and thyroid function remains uncertain. The purpose of this study was thus to investigate this relationship in greater detail while focusing on a representative American adult population. Methods: A total of 6,860 subjects from the 2007-2012 NHANES cohort were included in this study. Associations between CDAI values and thyroid function were evaluated with weighted linear regression models and smoothed curve fitting. Subgroup analyses were also performed. Results: The weighted mean (SD) values for variables analyzed in this study included a CDAI of 0.13 (0.06), serum free T4 (FT4) levels of 0.80 (0.01) ng/dL, and serum total T4 (TT4) levels of 7.80 (0.03) ug/dL. Lower CDAI values were found to be associated with higher levels of FT4 and TT4 using both unadjusted and adjusted models that accounted for relevant confounders (adjusted model, FT4 ß = -0.003, p = 0.005; TT4 ß = -0.035, p < 0.001). This negative correlation persisted when CDAI was categorized into quartiles (FT4, p for trend = 0.014; TT4, p for trend = 0.003). Conclusion: These findings suggest that a diet rich in antioxidants, as reflected by higher CDAI scores, is associated with significant decreases in levels of free and total T4. Further analyses will be necessary to better clarify the underlying mechanisms behind these observations.

10.
Int J Mol Med ; 53(4)2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38426604

RESUMO

The effects of adipocyte­rich microenvironment (ARM) on chemoresistance have garnered increasing interest. Ovarian cancer (OVCA) is a representative adipocyte­rich associated cancer. In the present study, epithelial OVCA (EOC) was used to investigate the influence of ARM on chemoresistance with the aim of identifying novel targets and developing novel strategies to reduce chemoresistance. Bioinformatics analysis was used to explore the effects of ARM­associated mechanisms contributing to chemoresistance and treated EOC cells, primarily OVCAR3 cells, with human adipose tissue extracts (HATES) from the peritumoral adipose tissue of patients were used to mimic ARM in vitro. Specifically, the peroxisome proliferator­activated receptor Î³ (PPARγ) antagonist GW9662 and the ABC transporter G family member 2 (ABCG2) inhibitor KO143, were used to determine the underlying mechanisms. Next, the effect of HATES on the expression of PPARγ and ABCG2 in OVCAR3 cells treated with cisplatin (DDP) and paclitaxel (PTX) was determined. Additionally, the association between PPARγ, ABCG2 and chemoresistance in EOC specimens was assessed. To evaluate the effect of inhibiting PPARγ, using DDP, a nude mouse model injected with OVCAR3­shPPARγ cells and a C57BL/6 model injected with ID8 cells treated with GW9662 were established. Finally, the factors within ARM that contributed to the mechanism were determined. It was found that HATES promoted chemoresistance by increasing ABCG2 expression via PPARγ. Expression of PPARγ/ABCG2 was related to chemoresistance in EOC clinical specimens. GW9662 or knockdown of PPARγ improved the efficacy of chemotherapy in mice. Finally, angiogenin and oleic acid played key roles in HATES in the upregulation of PPARγ. The present study showed that the introduction of ARM­educated PPARγ attenuated chemoresistance in EOC, highlighting a potentially novel therapeutic adjuvant to chemotherapy and shedding light on a means of improving the efficacy of chemotherapy from the perspective of ARM.


Assuntos
Anilidas , Neoplasias Ovarianas , Animais , Feminino , Humanos , Camundongos , Adipócitos/metabolismo , Apoptose , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Carcinoma Epitelial do Ovário/tratamento farmacológico , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Camundongos Endogâmicos C57BL , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Microambiente Tumoral , Regulação para Cima
11.
Medicine (Baltimore) ; 103(10): e37350, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457537

RESUMO

Mean corpuscular volume (MCV) is an important indicator used to determine the etiology of anemia and is associated with a variety of diseases. However, the link between thyroid function and MCV has yet to be clarified. This study was thus developed to assess relationships between thyroid function and MCV in a population of adults in the US. Results from the National Health and Nutrition Examination Survey study performed from 2007 to 2012 were used to conduct a cross-sectional analysis. Key thyroid-related variables included in this analysis were thyroid-stimulating hormone, total thyroxine (TT4), free triiodothyronine (FT3), total triiodothyronine (TT3), free thyroxine (FT4), antithyroglobulin, thyroglobulin, and antithyroid peroxidase levels. Generalized linear regression models were employed when estimating associations between MCV quartiles and thyroid parameters in 8104 adults 18 + years of age. In these participants, the weighted mean (SD) MCV was 89.36 (0.16) fL, with thyroid-stimulating hormone levels of 1.86 (0.03) mIU/mL, FT3 levels of 3.20 (0.01) pg/mL, FT4 levels of 0.80 (0.01) ng/dL, TT3 levels of 115.09 (0.64) ng/dL, and TT4 levels of 7.81 (0.04) µg/dL. When analyses were not adjusted, higher MCV values were related to reduced serum levels of FT3, TT3, or TT4. Following adjustment for possible confounding variables, this significant negative correlation between MCV and levels of FT3, TT3, and TT4 remained, and subgroup analysis revealed that this negative correlation was present in the male group and in the age group >50 years, but not in the female group and in the age group less than or equal to 50 years. These results suggest a significant negative correlation between MCV and FT3, TT3, and TT4, and this negative correlation originated more from the male population and those older than 50 years of age. The underlying mechanisms warrant additional investigation.


Assuntos
Glândula Tireoide , Tri-Iodotironina , Adulto , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Tiroxina , Inquéritos Nutricionais , Estudos Transversais , Índices de Eritrócitos , Hormônios Tireóideos , Tireotropina
12.
GEN Biotechnol ; 3(1): 35-44, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38415050

RESUMO

Recent advances in insect genetic engineering offer alternative genetic biocontrol solutions to control populations of pests and disease vectors. While success has been achieved, sex-sorting remains problematic for scaling many genetic biocontrol interventions. Here, we describe the development of a genetically stable sex-sorting technique for female and male selection with a proof of concept in Drosophila melanogaster termed SEPARATOR (Sexing Element Produced by Alternative RNA-splicing of A Transgenic Observable Reporter). This elegant approach utilizes dominantly expressed fluorescent proteins and differentially spliced introns to ensure sex-specific expression. The system has the potential for adaptability to various insect species and application for high-throughput insect sex-sorting.

13.
Br J Haematol ; 204(3): 976-987, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38246862

RESUMO

The presence of transient abnormal protein banding (M-protein immune reconstitution) in serum immunofixation electrophoresis after autologous haematopoietic stem cell transplantation in patients with multiple myeloma has been reported. The purpose of this study was to investigate the impact of post-transplant M-protein immune reconstitution on the prognosis of patients with multiple myeloma. M-protein immune reconstitution was observed in 25.9% (75/290) of patients. The CR rate and MRD negativity were higher in the M-protein immune reconstitution group (85.3% vs. 69.3%, p = 0.013, 81.9% vs. 66.5%, p = 0.014). Although there were no significant differences between the groups, the overall median survival time was longer in the M-protein immune reconstruction group (80 vs. 72 m, p = 0.076; not reached vs. 105 m, p = 0.312). Among patients in the cytogenetic high-risk group, the occurrence of M-protein immune reconstitution predicted better PFS and OS (80 vs. 31 m, p = 0.010; not reached vs. 91 m, p = 0.026). Additionally, in revised-International Staging System stage III patients, PFS and OS were better in those who achieved M-protein immune reconstitution (80 vs. 20 m, p = 0.025; 57 vs. 32 m, p = 0.103). The better prognosis of M-protein immune reconstitution patients may be associated with the acquisition of a deeper response. In high-risk patients, early acquisition of M-protein immune reconstitution may suggest a better prognosis.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Reconstituição Imune , Mieloma Múltiplo , Humanos , Prognóstico , Transplante de Células-Tronco Hematopoéticas/métodos , Análise Citogenética , Transplante Autólogo , Estudos Retrospectivos , Transplante de Células-Tronco , Resultado do Tratamento
14.
Ann Hematol ; 103(5): 1601-1611, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38267561

RESUMO

High-dose cyclophosphamide (HD-Cy) (3 g/m2) plus granulocyte colony-stimulating factor (G-CSF) is a very effective regimen for peripheral blood stem cell (PBSC) mobilization. Unfortunately, it is associated with an increased risk of neutropenic fever (NF). We analyzed the effect of NF on PBSC apheresis results and the efficacy of prophylactic antibiotics for the prevention of NF associated with HD-Cy plus G-CSF for PBSC mobilization in patients with newly diagnosed multiple myeloma (MM). First, patients were divided into NF ( +) and NF ( -) groups according to whether they suffered from NF during mobilization. Second, we divided patients into an antibiotic prophylaxis group and a nonantibiotic prophylaxis group according to whether antibiotic prophylaxis was used during the mobilization period. Our study showed that NF( +) patients (n = 44) had lower CD34 + cell dose collection (median 2.60 versus 5.34 × 106/kg, P < 0.001) and slower neutrophil engraftment and platelet engraftment (median 11 versus 10 days, P = 0.002, and median 13 versus 11 days, P = 0.043, respectively) than NF( -) patients (n = 234). Of note, the nonantibiotic prophylaxis group patients (n = 30) had a 26.7% incidence of NF. In the patients receiving antibiotic prophylaxis (n = 227), the incidence was reduced to 9.3% (P = 0.01). The antibiotic prophylaxis patients had higher CD34 + cell collection (median 5.41 versus 2.27 × 106/kg, P < 0.001) and lower hospitalization cost of mobilization ($ median 3108.02 versus 3702.39, p = 0.012). Thus, our results demonstrate that NF is associated with lower CD34 + cell collection and that antibiotic prophylaxis can reduce the incidence of NF and improve stem cell mobilization and collection outcomes, which reduces the hospitalization cost of mobilization.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/complicações , Mieloma Múltiplo/tratamento farmacológico , Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Ciclofosfamida/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Antibacterianos/uso terapêutico , Antígenos CD34/metabolismo
15.
Artigo em Inglês | MEDLINE | ID: mdl-38204223

RESUMO

BACKGROUND: Dapagliflozin is commonly used to treat type 2 diabetes mellitus (T2DM). However, research into the specific anti-T2DM mechanisms of dapagliflozin remains scarce. OBJECTIVE: This study aimed to explore the underlying mechanisms of dapagliflozin against T2DM. METHODS: Dapagliflozin-associated targets were acquired from CTD, SwissTargetPrediction, and SuperPred. T2DM-associated targets were obtained from GeneCards and DigSee. VennDiagram was used to obtain the overlapping targets of dapagliflozin and T2DM. GO and KEGG analyses were performed using clusterProfiler. A PPI network was built by STRING database and Cytoscape, and the top 30 targets were screened using the degree, maximal clique centrality (MCC), and edge percolated component (EPC) algorithms of CytoHubba. The top 30 targets screened by the three algorithms were intersected with the core pathway-related targets to obtain the key targets. DeepPurpose was used to evaluate the binding affinity of dapagliflozin with the key targets. RESULTS: In total, 155 overlapping targets of dapagliflozin and T2DM were obtained. GO and KEGG analyses revealed that the targets were primarily enriched in response to peptide, membrane microdomain, protein serine/threonine/tyrosine kinase activity, PI3K-Akt signaling pathway, MAPK signaling pathway, and AGE-RAGE signaling pathway in diabetic complications. AKT1, PIK3CA, NOS3, EGFR, MAPK1, MAPK3, HSP90AA1, MTOR, RELA, NFKB1, IKBKB, ITGB1, and TP53 were the key targets, mainly related to oxidative stress, endothelial function, and autophagy. Through the DeepPurpose algorithm, AKT1, HSP90AA1, RELA, ITGB1, and TP53 were identified as the top 5 anti-targets of dapagliflozin. CONCLUSION: Dapagliflozin might treat T2DM mainly by targeting AKT1, HSP90AA1, RELA, ITGB1, and TP53 through PI3K-Akt signaling.

16.
Mol Neurobiol ; 61(1): 308-325, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37607993

RESUMO

Microglia are immunocompetent cells in the central nervous system. Following cerebral ischemia, microglia will be rapidly activated and undergo proliferation, morphological transformation, and changes in gene expression and function. At present, the regulatory mechanisms of microglial activation following ischemia remain largely unclear. In this study, we took advantage of CX3CR1GFP/+ fluorescent mice and a global cerebral ischemia-reperfusion model to investigate the mechanisms of microglial activation following different degrees of global ischemia. Our results showed that the proliferation of microglia was gated by the degree of ischemia. Marked microglial de-ramification and proliferation were observed after 60 min of ischemia but not in transient ischemia (20 min). Immunohistology, qRT-PCR, and Western blotting analysis showed that microglial activation was accompanied with a reduction in Wnt/ß-catenin signaling after cerebral ischemia. Downregulation of Wnt/ß-catenin signaling using Wnt antagonist XAV939 during 20 min ischemia promoted microglial de-ramification and proliferation. In contrast, enhancing Wnt/ß-catenin signaling using Wnt agonist LiCl during 60 min ischemia-reduced microglial de-ramification and proliferation. Importantly, we found that Wnt agonist inhibited inflammation in the ischemic brain and was conducive to animal behavioral recovery. Collectively, these data demonstrated that Wnt/ß-catenin signaling played a key role in microglial activation following cerebral ischemia, and regulating microglial activation may be a potential therapeutic strategy for the treatment of ischemic stroke.


Assuntos
Isquemia Encefálica , Microglia , Camundongos , Animais , Microglia/metabolismo , beta Catenina/metabolismo , Isquemia Encefálica/patologia , Via de Sinalização Wnt/fisiologia , Infarto Cerebral/patologia
17.
Ann Med ; 55(2): 2289603, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38104533

RESUMO

OBJECTIVES: This study aimed to clarify the effectiveness and safety of two different infusion durations of cyclophosphamide (CTX) plus granulocyte colony-stimulating factor (G-CSF) for peripheral blood stem cell mobilization in patients with newly diagnosed multiple myeloma (NDMM). METHODS: One hundred and fifty-six consecutive NDMM patients receiving CTX plus G-CSF mobilization and autologous stem cell transplantation during the period of September 2008 to May 2020 were selected for retrospective analysis. According to differences in prolonged infusion time of CTX, they were divided into a 24-h group (24-h continuous infusion) and a control group (4-6 h of infusion). Mobilization and safety of infusion were analyzed. Flow cytometry was used to detect the peripheral blood CD34+ cell count. Multivariate analysis was performed to determine the factors influencing the number of CD34+ cells. RESULTS: The mean CD34+ cell counts collected in 24-h and control groups were 6.78 (interquartile range [IQR] 3.59-11.69) and 4.48 (IQR 2.39-6.30) ×106/kg, respectively (p < 0.001). Meanwhile, the target number of CD34+ cells/kg (defined as ≥4 × 106/kg) was collected from 51 (75%) of cases in 24-h group vs. 45 (51%) in the control group (p = 0.002). Multivariate analysis identified the independence of CTX infusion time as a factor influencing the target number of CD34+ cells/kg [odds ratio OR, 4.045; 95% CI: 1.630-10.038, p = 0.003]. The post-transplantation time to neutrophil engraftment was 10 (IQR 9-11) in 24-h group and 11 (IQR 10-12) in control group (p < 0.001). Finally, no statistical differences were identified between groups in terms of hematologic and non-hematologic toxicities. CONCLUSIONS: For patients with NDMM, 24-h continuous infusion of CTX plus G-CSF contributes to improved mobilization efficiency and equivalent toxicity as a stem cell mobilization regimen.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos , Estudos Retrospectivos , Transplante Autólogo , Ciclofosfamida/efeitos adversos
18.
Sci Rep ; 13(1): 19866, 2023 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-37964160

RESUMO

Tephritid fruit fly pests pose an increasing threat to the agricultural industry due to their global dispersion and a highly invasive nature. Here we showcase the feasibility of an early-detection SEPARATOR sex sorting approach through using the non-model Tephritid pest, Ceratitis capitata. This system relies on female-only fluorescent marker expression, accomplished through the use of a sex-specific intron of the highly-conserved transformer gene from C. capitata and Anastrepha ludens. The herein characterized strains have 100% desired phenotype outcomes, allowing accurate male-female separation during early development. Overall, we describe an antibiotic and temperature-independent sex-sorting system in C. capitata, which, moving forward, may be implemented in other non-model Tephritid pest species. This strategy can facilitate the establishment of genetic sexing systems with endogenous elements exclusively, which, on a wider scale, can improve pest population control strategies like sterile insect technique.


Assuntos
Ceratitis capitata , Tephritidae , Animais , Masculino , Feminino , Ceratitis capitata/genética , Ceratitis capitata/metabolismo , Fenótipo , Controle Biológico de Vetores/métodos
19.
Immun Inflamm Dis ; 11(9): e1016, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37773715

RESUMO

OBJECTIVE: Researchers have developed the Dietary Inflammatory Index (DII) as a tool to quantify the inflammatory potential of a given diet. Higher DII scores indicated a more proinflammatory diet. While inflammation is known to have a strong impact on thyroid function, the precise nature of the association between DII scores and thyroid function has yet to be clarified. This study was conducted with the goal of exploring this relationship in a representative population of adults from the United States. METHODS: For this study, we used data from the National Health and Nutrition Examination Survey (NHANES). Standardized questionnaires were used to collect demographic and dietary data from the participants, and laboratory tests were used to collect data on the participants' thyroid parameters and other relevant data. Linear regression models and smoothed curve fitting were used to assess the relationship between DII scores and thyroid function, with weighted data analyses and subgroup analyses being conducted as appropriate. RESULTS: In total, 7712 subjects were recruited from the NHANES 2007-2012 cohort. Their weighted mean age was 44.87 (0.47) years, mean DII score was 1.41 (0.05). Mean FT3 was 3.20 (0.01) pg/mL and mean TT4 was 7.81 (0.03) µg/dL. In adjusted analyses, higher DII values were related to increases in FT3 (ß = .007; p = .027) and TT4 (ß = .050; p = .005) levels. Subgroup analyses showed a negative correlation between FT3 levels and DII scores in a population with high urinary iodine concentrations. CONCLUSION: These data indicate that the consumption of a more proinflammatory diet, as evidenced by elevated DII scores, is correlated with significant increases in FT3 and TT4 levels. However, for people with high urinary iodine concentrations, a more proinflammatory diet was associated with lower FT3 levels. Additional research will be vital to clarify the mechanistic basis for these findings.

20.
PLoS One ; 18(9): e0291799, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37733750

RESUMO

OBJECTIVE: Sleep disturbance is a common problem in the general population. Sleep deprivation or dysfunction can have profound health consequences. However, how sleep duration is associated with thyroid function remains unclear. This study was thus developed to examine the association between sleep duration and thyroid function in the US adult population. METHODS: A total of 8102 participants from the NHANES 2007-2012 dataset were included in this study. Weighted data analyses were conducted, and the link between sleep duration and thyroid function was probed using linear regression models with smoothed curve fitting. Stratified analyses were also performed. RESULTS: Weighted mean (standard deviation) values for study variables were as follows: sleep duration 6.85 (0.02) hours, thyroid-stimulating hormone (TSH) 1.86 (0.03) mIU/ml, serum free T3 3.20 (0. 01) pg/mL, serum free T4 0.80 (0.01) ng/dL, serum total T3 115.12 (0.64) ng/dL, serum total T4 7.81 (0.04) ug/dL, TPOAb 16.20 (1.53) IU/mL, TgAb 5.75 (0.73) IU/mL, and Tg 15.11 (0.46) ng/mL. In unadjusted analyses, increased sleep duration was associated with higher serum TSH levels and decreased FT3 levels. After adjustment for potential confounders, a significant negative relationship was detected between sleep duration and FT3 levels in participants with ≤7 hours of sleep. When sleep duration exceeded 7 hours, no significant changes in FT3 levels were observed after further increases in sleep duration. CONCLUSION: Increased sleep duration was related to decreased FT3 levels, primarily at short sleep durations, and this correlation was no longer evident when participants reached the recommended healthy sleep duration.


Assuntos
Duração do Sono , Transtornos do Sono-Vigília , Humanos , Adulto , Inquéritos Nutricionais , Glândula Tireoide , Sono , Tireotropina
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