Resistance phenotype and genetic features of a heterogeneous vancomycin intermediate-resistant Staphylococcus aureus strain from an immunocompromised patient.

Strain C1 was successfully isolated from an immunosuppressed patient with persistent bacteremia, who had not previously been exposed to glycopeptide antibiotics. This strain was found to be a heterogeneous vancomycin intermediate-resistant Staphylococcus aureus (hVISA). It is noteworthy that, following a brief period of vancomycin treatment, strains C6, C8, and C9, which were obtained from blood and other body parts, exhibited a significant reduction in heterogeneity as determined by population analysis profile-area under the curve (PAP-AUC) detection. Genotyping analysis revealed that these bacterial strains belonged to the same SCCmecIVa-ST59-t437-agrI genotype and shared the same virulome and resistome. In this study, a comparative genomics analysis was conducted between strain C1 and strain N315 to identify potential hVISA-associated mutations. Ultimately, a total of 205 mutation sites in 19 candidate genes, likely associated with the hVISA phenotype, were identified.

Effects of contusion and exhaustive exercise on murf1 and mafbx in the skeletal muscle of rats / Efectos de la contusión y del ejercicio exhaustivo sobre murf1 y mafbx en el músculo esquelético de ratas / Efeitos do trauma contuso e do exercício exaustivo no em murf1 e mafbx no músculo esquelético de ratos

ABSTRACT Objective To study the effects of contusion and exhaustive exercise on the expression of degradation-related factors MuRF1 and MAFbx in the skeletal muscle of rats and describe the repair mechanism of skeletal muscle injury. Methods Forty-two male SD rats were randomly divided into 7 groups. The rats in each group were killed at different time points (0h, 24h, 48h) after exhaustive exercise (E0, E24, E48) and contusion (D0, D24, D48), respectively, and in the resting state in control group (C). The right gastrocnemius muscles were resected and divided into two parts, one for the mRNAs of MuRF1 and MAFbx by real-time PCR, and the other for protein measurement by Western blotting. Results Compared with the control group, the MuRF1 mRNA and protein expression of the skeletal muscle in the E0 group was markedly increased (P <0.05) and followed by a downward trend in E24 the E48 groups. On the other hand, MuRF1 mRNA expression of the skeletal muscle in the D24 group was significantly upregulated (P <0.01), then decreased in the D48 group (P <0.01). Meanwhile, compared with the C group, MAFbx mRNA gene expression continued to be upregulated in D24 and D48 (P <0.05), but decreased in E24 and E48 (p<0.01). On the other hand, the NF-κB protein contents of the skeletal muscle in the D0, D24, and D48 groups, as well as in the E48 group, were markedly downregulated (P <0.05), and the one in E48 was also remarkably downregulated (P <0.05). Conclusion NF-κB may negatively regulate the process of protein degradation by the NF-κB / MuRF1 signal pathway. Level of evidence III; Therapeutic studies investigating the results of treatment.

RESUMEN Objetivo Estudiar los efectos de la contusión y del ejercicio exhaustivo sobre la expresión de los factores relacionados con la degradación MuRF1 y MAFbx en el músculo esquelético de ratas y describir el mecanismo de reparación de la lesión muscular esquelética. Métodos Cuarenta y dos ratas macho SD fueron divididas aleatoriamente en 7 grupos. Las ratas de cada grupo fueron sacrificadas en diferentes momentos (0h, 24h, 48h) después del ejercicio exhaustivo (E0, E24, E48) y de la contusión (D0, D24, D48), respectivamente, y en estado de reposo en el grupo de control (C). Se resecaron los músculos gastrocnemios derechos y se dividieron en dos partes, una para los ARNm de MuRF1 y MAFbx mediante PCR en tiempo real y la otra para la medición de proteínas mediante Western blot. Resultados En comparación con el grupo control, el ARNm de MuRF1 y la expresión proteica del músculo esquelético en el grupo E0 se incrementó notablemente (P <0,05) y fueron seguidos por una tendencia a la baja en los grupos E24 y E48. Por otra parte, la expresión del ARNm de MuRF1 del músculo esquelético en el grupo D24 fue significativamente regulada al alza (P <0,01), y luego disminuyó en el grupo D48 (P <0,01). Mientras tanto, en comparación con el grupo C, la expresión génica del ARNm de MAFbx permaneció regulada al alza en D24 y D48 (P <0,05), pero disminuyó en E24 y E48 (p<0,01). Por otro lado, el contenido de proteína NF-κB del músculo esquelético en los grupos D0, D24 y D48, así como en el grupo E48, se vio notablemente regulado a la baja (P <0,05), y el del grupo E48 también se vio notablemente regulado a la baja (P <0,05). Conclusión NF-κB puede regular negativamente el proceso de degradación de la proteína a través de la vía NF-κB / MuRF1. Nivel de evidencia III; Estudios terapéuticos que investigan los resultados del tratamiento.

RESUMO Objetivo Estudar os efeitos do trauma contuso e do exercício exaustivo na expressão dos fatores relacionados à degradação MuRF1 e MAFbx no músculo esquelético de ratos e descrever o mecanismo de reparo da lesão muscular esquelética. Métodos Quarenta e dois ratos SD machos foram divididos aleatoriamente em 7 grupos. Os ratos de cada grupo foram mortos em diferentes momentos (0h, 24h, 48h) após exercício exaustivo (E0, E24, E48) e trauma contuso (D0, D24, D48), respectivamente, e no estado de repouso no grupo controle (C). Os músculos gastrocnêmios direitos foram ressecados e divididos em duas partes, uma para os mRNAs de MuRF1 e MAFbx por PCR em tempo real e outra para a medição de proteínas a partir do Western blot. Resultados Em comparação com o grupo controle, o mRNA de MuRF1 e a expressão proteica do músculo esquelético no grupo E0 foram acentuadamente aumentados (P <0,05) e seguidos por uma tendência descendente nos grupos E24 e E48. Por outro lado, a expressão do mRNA de MuRF1 do músculo esquelético no grupo D24 foi significativamente regulada para cima (P <0,01), depois diminuiu no grupo D48 (P <0,01). Enquanto isso, em comparação com o grupo C, a expressão gênica do mRNA de MAFbx continuou regulada para cima em D24 e D48 (P <0,05), mas diminuiu em E24 e E48 (p<0,01). Por outro lado, os teores de proteína NF-κB do músculo esquelético nos grupos D0, D24 e D48, bem como no grupo E48, foram marcadamente regulados para baixo (P <0,05), e o do grupo E48 também foi notavelmente regulado para baixo (P <0,05). Conclusão NF-κB pode regular negativamente o processo de degradação da proteína pela via NF-κB / MuRF1. Nível de evidência III; Estudos terapêuticos que investigam os resultados do tratamento.

MicroRNA-218-5p accelerates malignant behaviors of breast cancer through LRIG1

Abstract Objective: MicroRNAs play crucial roles in the pathogenesis of cancers. MiRNA-218-5p may act as either an oncogene or a tumor suppressor, but its role in the pathogenesis of Breast Cancer (BC) remains unclear. Methods: Infiltrative breast ductal carcinoma as well as corresponding adjacent normal samples were collected from 30 patients. Mimics and inhibitors of miRNA-218-5p or corresponding negative controls were transfected into BC cells. miRNA-218-5p expression was detected by quantitative PCR. The effects of miRNA-218-5p on the malignant behaviors of BC were assessed. Dual-luciferase reporter assay was employed to evaluate the binding of miRNA-218-5p to LRIG1. Results: BC tissues showed higher miRNA-218-5p expression as compared to the adjacent normal tissues. Ectopic miRNA-218-5p expression accelerated the cell cycle, cell growth and migration of BC, while repressed cell apoptosis. Interestingly, ectopic miRNA-218-5p expression down-regulated LRIG1 expression, and miRNA-218-5p could bind to LRIG1. Also, our study indicated that miRNA-218-5p up-regulated ErbB2 and EGFR expression by targeting LRIG1, suggesting that the LRIG1-mediated signaling pathway contributed to the pro-tumor effects of miRNA-218-5p on BC. Conclusion: MiRNA-218-5p up-regulates ErbB2 and EGFR expression by suppressing LRIG1 expression, thus promoting the malignant behaviors of BC. miRNA-218-5p may exert a pro-tumor effect on BC and serve as a therapeutic target for BC treatment.

Risk Factors for Orthostatic Hypertension in Children.

OBJECTIVE: To investigate the risk factors for orthostatic hypertension in children. STUDY DESIGN: Eighty children with orthostatic hypertension were enrolled in the group with orthostatic hypertension, and 51 healthy children served as the control group. Demographic characteristics, clinical history, daily water intake, nightly sleep duration, the results of the standing test, and complete blood count were recorded and compared between the 2 groups. The risk factors for pediatric orthostatic hypertension were determined by logistic regression analysis. RESULTS: Body mass index and red blood cell distribution width were higher in the group with orthostatic hypertension than in healthy children, whereas daily water intake and sleep duration were lower. Logistic regression analyses showed that, if a child suffered from overweight, suffered from obesity, had a daily water intake of less than 800 mL, or had a red blood cell distribution width that was increased by 1%, the risk of orthostatic hypertension would be increased by 6.069 times (95% CI, 1.375-26.783; P < .05), 7.482 times (95% CI, 1.835-30.515; P < .01), 4.027 times (95% CI, 1.443-11.241; P < .01), or 4.008 times (95% CI, 1.698-9.461; P < .01), respectively. However, if the sleep duration was increased by 1 hour, the risk of developing orthostatic hypertension would be decreased by 74.3% (95% CI, 54.6%-85.4%, P < .01). CONCLUSIONS: Increased body mass index, inadequate water intake and sleep duration, and elevated red blood cell distribution width were identified as risk factors for pediatric orthostatic hypertension.