No abstract

Let's twist again! Remarkable broad and twisted ribbons were generated from the self-assembly of oligo(p- phenylene ethylene) (OPE) bearing dimeric deoxycholic acid pendant groups (see graphic). Varying the bile acid led to nanostructures with drastically different morphologies. The distinctive aggregate shapes of these steroid-OPE conjugates are attributed to the subtle differences in their molecular structures.A series of novel oligo(p-phenylene ethynylene) (OPE) derivatives bearing dimeric cholic acid (OPE1), deoxycholic acid (OPE2) and lithocholic acid (OPE3) was synthesized. The self-assembly behavior of these derivatives were systematically studied and compared in a THF/water solvent mixture. The addition of water to THF can induce the helical stacking of oligo(p-phenylene ethylene) bearing dimeric deoxycholic acid end groups, which leads to highly interesting twisted assemblies. Variation of the bile acid group led to nanostructures with drastically different morphologies. The application of spectroscopy in combination with X-ray diffraction techniques provided a reasonable view of the final self-assembled structures. The observed distinctive aggregate shapes and the preference in the type of molecular packing of these steroid-OPE conjugates are attributed to the subtle differences in their molecular features.

RationaleLeptomeningeal metastasis (LM) is an important cause of mortality in patients with non-small cell lung cancer (NSCLC). As the symptoms of LM and its early clinical manifestations are nonspecific, early diagnosis of LM is difficult. However, there are few treatment options for LM, which leads to a poor prognosis; thus, increased clinical attention is necessary. The effects of most systemic chemotherapies on metastatic brain tumors (brain metastases and LMs) are limited as they cannot pass the blood–brain barrier; therefore, whole-brain radiation therapy is a therapeutic option. Osimertinib is a potent and irreversible third-generation oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). It binds to EGFR with high affinity when the EGFR T790M mutation is present together with sensitizing mutations. The clinical efficacy of osimertinib in NSCLC patients carrying the T790M mutation has been demonstrated in clinical trial NCT02468661. Intrathecal injection of chemotherapeutic drugs can be directed to a specific lesion. Temozolomide is one such drug, and its effect has been confirmed.Patient and interventionsWe treated a 38-year-old patient with NSCLC who carried the EGFR L858R mutation. We administered a combination of oral osimertinib and oral temozolomide plus an intrathecal injection of cytarabine and whole-brain radiation therapy for symptomatic multiple brain metastases.OutcomesThe patient showed a marked response to this combination therapy. To date (after ~18 months), no recurrence or new lesions have been observed and he is asymptomatic. His disease-free survival surpasses that achieved with any monotherapy for LM.LessonsThis is the first report to demonstrate the response to combination therapy in an NSCLC patient with LM. These findings indicate the potential utility of chemotherapy combined with radiotherapy combined with targeted therapy combined with local treatment, as each treatment acts via a different mechanism, enhancing their therapeutic effects.

Objective This study identified underlying genetic molecules associated with histologically unstable carotid atherosclerotic plaques through bioinformatics analysis that may be potential biomarkers and therapeutic targets. Methods Three transcriptome datasets (GSE41571, GSE120521 and E-MTAB-2055) and one non-coding RNA dataset (GSE111794) that met histological grouping criteria of unstable plaque were downloaded. The common differentially expressed genes (co-DEGs) of unstable plaques identified from three mRNA datasets were annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomics (KEGG). A protein–protein interaction (PPI) network was constructed to present the interaction between co-DEGs and screen out hub genes. MiRNet database and GSE111794 dataset were used to identify the miRNAs targeting hub genes. Associated transcription factors (TFs) and drugs were also predicted. These predicted results were used to construct miRNA/TFs-hub gene and drug-hub gene regulatory networks. Results A total of 105 co-DEGs were identified, including 42 up-regulated genes and 63 down-regulated genes, which were mainly enriched in collagen-containing extracellular matrix, focal adhesion, actin filament bundle, chemokine signaling pathway and regulates of actin cytoskeleton. Ten hub genes (up-regulated: HCK, C1QC, CD14, FCER1G, LCP1 and RAC2; down-regulated: TPM1, MYH10, PLS3 and FMOD) were screened. HCK and RAC2 were involved in chemokine signaling pathway, MYH10 and RAC2 were involved in regulation of actin cytoskeleton. We also predicted 12 miRNAs, top5 TFs and 25 drugs targeting hub genes. In the miRNA/TF-hub gene regulatory network, PLS3 was the most connected hub genes and was targeted by six miRNAs and all five screened TFs. In the drug-hub gene regulatory network, HCK was targeted by 20 drugs including 10 inhibitors. Conclusions We screened 10 hub genes and predicted miRNAs and TFs targeting them. These molecules may play a crucial role in the progression of histologically unstable carotid plaques and serve as potential biomarkers and therapeutic targets.

Objective The study aimed to assess the gene expression profile of biopsies obtained from the neck of human abdominal aortic aneurysm (AAA) and the main site of AAA dilatation and to investigate the molecular mechanism underlying the development of AAA. Methods The microarray profile of GSE47472 and GSE57691 were obtained from the Gene Expression Omnibus (GEO) database. The GSE47472 was a microarray dataset of tissues from the aortic neck of AAA patients versus normal controls. The GSE57691 was a microarray dataset including the tissues from main site of AAA dilatation versus normal controls. Differentially expressed genes (DEGs) were chosen using the R package and annotated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomics (KEGG). The hub genes were identified in the protein–protein interaction (PPI) network. Results 342 upregulated DEGs and 949 downregulated DEGs were obtained from GSE47472. The upregulated DEGs were mainly enriched in biological regulation (ontology: BP), the membrane (ontology: CC), and protein binding (ontology: MF), and the downregulated genes were mainly enriched in biological regulation (ontology: BP), the membrane (ontology: CC), and protein blinding (ontology: MF). In the KEGG enrichment analysis, the DEGs mainly involved glycosaminoglycan degradation, vasopressin-regulated water reabsorption, and pyruvate metabolism. The hub genes in GSE47472 mainly include VAMP8, PTPRC, DYNLL1, RPL38, RPS4X, HNRNPA1, PRMT1, TGOLN2, PA2G4, and CUL2. From GSE57691, 248 upregulated DEGs and 1120 downregulated DEGs were selected. The upregulated DEGs of GSE57691 were mainly enriched in biological regulation (ontology: BP), the membrane (ontology: CC), and protein binding (ontology: MF), and the downregulated genes were mainly enriched in metabolic process (ontology: BP), the membrane (ontology: CC), and protein blinding (ontology: MF). In the KEGG enrichment analysis, the DEGs mainly involved the mitochondrial respiratory, respiratory chain complex, and respiratory chain. RPS15A, RPS5, RPL23, RPL27A, RPS24, RPL35A, RPS4X, RPL7, RPS25, and RPL21 were identified as the hub genes . Conclusion At the early stage of AAA, the current study indicated the importance of glycosaminoglycan degradation and anaerobic metabolism. We also identified several hub genes closely related to AAA ( VAMP8, PTPRC, DYNLL1, etc. ). At the progression of the AAA, the dysfunctional mitochondria played a critical role in AAA formation and the RPS15A, RPS5, RPL23, etc., were identified as the hub genes.

Glioma is the foremost recurrent type of brain tumor in humans; in particular, glioblastoma (GBM) is the main form of brain tumor (GBM) that is highly proliferative and impervious to apoptosis. Triphlorethol‐A (TA), a phlorotannin isolated from Ecklonia cava, exhibited cytoprotective, antioxidant, and anticancer properties. However, the exact molecular action of TA in the U251 human GBM cells remains unknown. This may be the first report on the antiproliferative and apoptotic mechanisms of TA on GBM. The cytotoxicity, intracellular reactive oxygen species (ROS), matrix metalloproteinase (MMP), and cell apoptosis activity of TA have been evaluated by the MTT assay and by DCFH‐DA, Rh‐123, AO/EB, and western blot analysis. The results obtained showed that TA abridged the viability of U251 cells, while MMP increased apoptosis by increasing the ROS levels in a time‐dependent manner. The results showed that a reduction in U251 cell proliferation was associated with the regulation of JAK2/STAT3 and p38 MAPK/ERK signaling pathways. TA was found to suppress pJAK, pSTAT3, p38 MAPK, and pERK phosphorylation, thereby causing Bax/Bcl‐2 imbalance, activating the caspase cascade and cytochrome c, and inducing apoptosis. Our findings showed that the suppression of JAK2/STAT3 and p38 MAPK/ERK signaling by TA results in cell growth arrest and stimulation of apoptosis in GBM cells. These studies justify the protective remedy of TA against GBM.

Objective There is no medical treatment proven to limit abdominal aortic aneurysm (AAA) progression. This systematic review aimed to summarise available trial evidence on the efficacy of pharmacotherapy in limiting AAA growth and AAA-related events. Methods A systematic literature search was performed to examine the efficacy of pharmacotherapy in reducing AAA growth and AAA-related events. Pubmed, Embase (Excerpta Medica Database), and the Cochrane library were searched from March, 1999 to March 29, 2022. AAA growth (mm/year) in the intervention and control groups was expressed as mean and standard deviation (SD). The results of AAA growth were expressed as mean difference (MD) and its 95% confidence interval (95% CI). Odds ratios (ORs) were calculated for the AAA-related events.Heterogeneity was quantified using the I2 statistic. Forest plots were created to show the pooled results of each outcome. Outcomes A total of 1373 articles were found in different databases according to the search strategy, and 10 articles were identified by hand searching. A total of 26 articles were included in our systematic review after the screening. For the studies of metformin, the meta-analysis demonstrated that metformin use was associated with a lower AAA growth rate (MD: −0.81 mm/y, 95% CI: −1.19 to −0.42, P < 0.0001, I2 = 87%), Metformin use also was related to the lower rates of AAA-related events (OR: 0.53, 95% CI: 0.36 to 0.76, P = 0.0007, I2 = 60%). The hypotensive drugs of the studies mainly included angiotensin-converting enzyme inhibitors (ACEI), angiotensin II type 1 receptor blockers (ARB), and propranolol. The overall meta-analysis of blood pressure-lowering drugs reported no significant effect in limiting the AAA growth (MD: 0.31mm/year, 95%CI: −0.03 to 0.65, P = 0.07, I2 = 66%) and AAA-related events (OR: 1.33, 95%CI: 0.76 to 2.32, P = 0.32, I2 = 98%), In the subgroup analysis of the hypotensive drugs, the ACEI/ARB and propranolol also showed no significant in reducing the AAA growth and AAA-related events. The meta-analysis of the antibiotics demonstrated that the antibiotics were not associated with a lower AAA growth rate (MD: −0.27 mm/y, 95% CI: −0.88 to 0.34, P = 0.39, I2 = 77%) and AAA-related events (OR: 0.94, 95%CI: 0.65 to 1.35, P = 0.72, I2 = 0%). The results of statins also showed no significant effect in limiting AAA growth (MD: −1.11mm/year, 95%CI: −2.38 to 0.16, P = 0.09, I2 = 96%) and AAA-related events (OR: 0.53, 95%CI: 0.26 to 1.06, P = 0.07, I2 = 92%). Conclusion In conclusion, effective pharmacotherapy for AAA was still lacking. Although the meta-analysis showed that metformin use was associated with lower AAA growth and AAA-related events, all of the included studies about metformin were cohort studies or case-control studies. More randomized controlled trials (RCTs) are needed for further verification.

Background The association between triglyceride glucose (TYG) index and depression is unclear. We conducted this analysis to explore whether higher TYG index is associated with a higher odd of depression. Aims The objective was to investigate the relationship between TYG and abdominal aortic calcification (AAC) in people over 60 years old. Methods The National Health and Nutrition Examination Survey data were analyzed using logistic regression models to examine the independent association between TYG index and the Kauppila AAC-24 score. Results A total of 1,408 people took part in our study. Participants with higher TYG quartiles had higher AAC scores. SAAC was defined as a Kauppila score > 6, and the prevalence of SAAC was 17.0%. After adjusting for relevant covariates, the multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CI) for participants in the third and fourth quartiles were 1.970 (1.232–3.150, P = 0.005) and 2.261 (1.404–3.644, P < 0.001). Subgroup analyses indicated that the positive association between TYG and SAAC persisted across population subgroups. Conclusion Triglyceride glucose index was negatively correlated with SAAC in the elderly.