Journal of Biomedical Research最新文献

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.

Glioblastoma multiforme (GBM) is a highly aggressive and lethal brain tumor with limited treatment options. To improve therapeutic efficacy, we developed a novel multifunctional nanoplatform, GM@P(T/S), comprised of polymeric nanoparticles coated with GBM cell membranes as well as co-loaded with temozolomide (TMZ) and superparamagnetic iron oxide (SPIO) nanoparticles. The successful preparation was confirmed in terms of particle size, morphology, stability, the in vitro drug release, and cellular uptake assays. We demonstrated that GM@P(T/S) exhibited the enhanced homotypic targeting, the prolonged blood circulation, and efficient blood-brain barrier penetration in both in vitro and in vivo studies. The combination of TMZ and SPIO nanoparticles within GM@P(T/S) synergistically improved chemo-radiation therapy, leading to a reduced tumor growth, an increased survival, and minimal systemic toxicity in the orthotopic GBM mouse models. Our findings suggest that GM@P(T/S) holds a great promise as a targeted and efficient therapeutic strategy for GBM.

Most papillary thyroid carcinoma (PTC) patients have a good prognosis. However, lymph node metastasis (LNM), the most common manifestation of disease progression, is frequently associated with a poor prognosis. Nevertheless, few studies have focused on the underlying mechanisms of LNM. In the current study, we aimed to investigate the potential role of exosomal circRNAs that contribute to LNM in PTC. We identified 9000 differentially expressed exosomal circRNAs in PTC patients with LNM, including 684 upregulated and 2193 downregulated circRNAs. Functional enrichment analysis revealed that these differentially expressed circRNAs were primarily involved in a variety of molecular and signaling pathways correlated with PTC progression and LNM. Through bioinformatics analysis, we identified 14 circRNA-miRNA-mRNA networks related to LNM-associated signaling pathways in PTC. Moreover, both circTACC2-miR-7- EGFR and circBIRC6-miR-24-3p- BCL2L11 axes were verified for their potential involvement in PTC with LNM. Additionally, we identified four upregulated circRNA-related hub genes and eight hub genes correlated with downregulated circRNAs, some of which were validated as being potentially involved in LNM in PTC. Collectively, our findings provide a novel framework for an in-depth investigation of the function of dysregulated exosomal circRNAs and their potential as biomarkers in PTC patients with LNM.

Given the extremely high inter-patient heterogeneity of acute myeloid leukemia (AML), the identification of biomarkers for prognostic assessment and therapeutic guidance is critical. Cell surface markers (CSMs) have been shown to play an important role in AML leukemogenesis and progression. In the current study, we evaluated the prognostic potential of all human CSMs in 130 AML patients from The Cancer Genome Atlas (TCGA) based on differential gene expression analysis and univariable Cox proportional hazards regression analysis. By using multi-model analysis, including Adaptive LASSO regression, LASSO regression, and Elastic Net, we constructed a 9-CSMs prognostic model for risk stratification of the AML patients. The predictive value of the 9-CSMs risk score was further validated at the transcriptome and proteome levels. Multivariable Cox regression analysis showed that the risk score was an independent prognostic factor for the AML patients. The AML patients with high 9-CSMs risk scores had a shorter overall and event-free survival time than those with low scores. Notably, single-cell RNA-sequencing analysis indicated that patients with high 9-CSMs risk scores exhibited chemotherapy resistance. Furthermore, PI3K inhibitors were identified as potential treatments for these high-risk patients. In conclusion, we constructed a 9-CSMs prognostic model that served as an independent prognostic factor for the survival of AML patients and held the potential for guiding drug therapy.

Premature ovarian insufficiency (POI) caused by chemotherapy is a common complication in female cancer survivors of childbearing age. Traditional methods, including mesenchymal stem cell (MSC) transplant and hormone replacement therapy, have limited clinical application because of their drawbacks, and more methods need to be developed. In the current study, the potential effects and underlying mechanisms of human umbilical cord MSC-derived extracellular vesicles (hUCMSC-EVs) were investigated in a cisplatin (CDDP)-induced POI mouse model and a human granulosa cell (GC) line. The results showed that hUCMSC-EVs significantly attenuated body weight loss, ovarian weight loss, ovary atrophy, and follicle loss in moderate-dose (1.5 mg/kg) CDDP-induced POI mice, similar to the effects observed with hUCMSCs. We further found that the hUCMSC-EVs inhibited CDDP-induced ovarian GC apoptosis by upregulating anti-apoptotic miRNA levels in GCs, thereby downregulating the mRNA levels of multiple pro-apoptotic genes. In general, our findings indicate that the moderate-dose chemotherapy may be a better choice for clinical oncotherapy, considering effective rescue of the oncotherapy-induced ovarian damage with hUCMSC-EVs. Additionally, multiple miRNAs in hUCMSC-EVs may potentially be used to inhibit the chemotherapy-induced ovarian GC apoptosis, thereby restoring ovarian function and improving the life quality of female cancer patients.