Journal of Biomedical Research最新文献

The prevalence of stunting in Indonesian children under five years of age is approximately 20%. Chronic maternal malnutrition contributes to the risk of stunting by affecting global DNA methylation. In the present study, we aimed to evaluate the levels of 5-methyl-cytosine (5mC) as a surrogate marker of global DNA methylation in buccal swabs and its potential association with the risk of stunting and cognitive performance. The levels of 5mC were measured using an enzyme-linked immunosorbent assay. The Wechsler Preschool and Primary Scale of Intelligence (WPPSI) was used to measure cognitive function. Buccal swab DNA samples and anthropometric data were collected from a total of 231 children aged zero to five years. In this cross-sectional cohort, the prevalence of stunting was 37% in 138 children aged zero to two years and 30% in 93 children aged over two years. The univariable analysis revealed that the levels of 5mC in buccal swab DNA were significantly lower in severely stunted children (median, 2.84; interquartile range [IQR], 2.39-4.62) and children aged less than two years (median, 2.81; IQR, 2.53-4.62) than those in normal children (median, 3.75; IQR, 2.80-4.74; P-value, 0.028) and children aged over four years (median, 4.01; IQR, 3.39-4.87; P-value < 0.001), respectively. We also found that the average cognitive scores tended to be low in boys and stunted children, although the differences were not statistically significant. Furthermore, the levels of 5mC found in buccal swab and mouthwash DNA were not associated with cognitive scores.

Achondroplasia is a genetic condition characterized by skeletal dysplasia that results in characteristic craniofacial and spinal abnormalities. It is the most common form of short-limbed skeletal dysplasia. A morbidly obese pregnant patient warrants specific anatomical and physiological considerations, such as a difficult airway with potential hypoxia, full stomach precautions, and a reduced functional residual capacity. Achondroplasia increases the risks of maternal and fetal complications. Although neuraxial techniques are generally preferred for cesarean sections, there is no consensus among patients with achondroplasia. We aimed to discuss the anesthetic challenges in an achondroplastic patient and report our regional anesthesia approach for an elective cesarean section.

Although p21-activated kinase 2 (PAK2) is an essential serine/threonine protein kinase, its role in the progression of lung squamous cell carcinoma (LUSC) has yet to be fully understood. We analyzed PAK2 mRNA levels, DNA copy numbers, and protein levels by quantitative reverse transcription-PCR and immunohistochemical staining in both human LUSC tissues and adjacent normal tissues. Then, we performed colony formation assays, cell counting kit-8 assays, Matrigel invasion assays, wound healing assays, and xenograft models in nude mice to investigate the functions of PAK2 in LUSC progression. We demonstrated that PAK2 mRNA levels, DNA copy numbers, and protein levels were upregulated in human LUSC tissues, compared with adjacent normal tissues. Additionally, higher PAK2 expression was associated with poorer prognosis in LUSC patients. In the in vitro study, we found that PAK2 promoted cell growth, migration, invasion, epithelial-mesenchymal transition, and cell morphology regulation in LUSC cells. Mechanistically, PAK2 promoted tumor cell proliferation, migration, and invasion by regulating actin dynamics through the LIMK1/cofilin signaling pathway. Our findings indicate that the PAK2/LIMK1/cofilin signaling pathway may serve as a potential clinical marker and therapeutic target for LUSC.

The current study aimed to assess the effect of timosaponin AⅢ (T-AⅢ) on drug-metabolizing enzymes during anticancer therapy. The in vivo experiments were conducted on nude and ICR mice. Following a 24-day administration of T-AⅢ, the nude mice exhibited an induction of CYP2B10, MDR1, and CYP3A11 expression in the liver tissues. In the ICR mice, the expression levels of CYP2B10 and MDR1 increased after a three-day T-AⅢ administration. The in vitro assessments with HepG2 cells revealed that T-AⅢ induced the expression of CYP2B6, MDR1, and CYP3A4, along with constitutive androstane receptor (CAR) activation. Treatment with CAR siRNA reversed the T-AⅢ-induced increases in CYP2B6 and CYP3A4 expression. Furthermore, other CAR target genes also showed a significant increase in the expression. The up-regulation of murine CAR was observed in the liver tissues of both nude and ICR mice. Subsequent findings demonstrated that T-AⅢ activated CAR by inhibiting ERK1/2 phosphorylation, with this effect being partially reversed by the ERK activator t-BHQ. Inhibition of the ERK1/2 signaling pathway was also observed in vivo. Additionally, T-AⅢinhibited the phosphorylation of EGFR at Tyr1173 and Tyr845, and suppressed EGF-induced phosphorylation of EGFR, ERK, and CAR. In the nude mice, T-AⅢ also inhibited EGFR phosphorylation. These results collectively indicate that T-AⅢ is a novel CAR activator through inhibition of the EGFR pathway.

Systemic lupus erythematosus (SLE) is characterized by a systemic dysfunction of both the innate and adaptive immune systems, leading to an attack on healthy tissues of the body. During the development of SLE, pathogenic features, such as the formation of autoantibodies against self-nuclear antigens, cause tissue damage including necrosis and fibrosis, with increased expression levels of the type Ⅰ interferon-regulated genes. Standard treatments for lupus with immunosuppressants and glucocorticoids are not effective enough but cause side effects. As an alternative, more effective immunotherapies have been developed, including monoclonal and bispecific antibodies that target B cells, T cells, co-stimulatory molecules, cytokines or their receptors, and signaling molecules. Encouraging results have been observed in clinical trials with some of these therapies. Furthermore, a chimeric antigen receptor T cell therapy has emerged as the most effective, safe, and promising treatment option for SLE, as demonstrated by successful pilot studies. Additionally, some emerging evidence suggests that gut microbiota dysbiosis may significantly contribute to the severity of SLE, and the normalization of the gut microbiota through methods such as fecal microbiota transplantation presents new opportunities for effective treatment of SLE.