Abnormal proliferation of vascular smooth muscle cells (VSMCs) is important in the pathogenesis of vascular disorders such as atherosclerosis and restenosis. Hinokitiol, a tropolone derivative found in Chamacyparis taiwanensis, has been found to exhibit anticancer activity in a variety of cancers through inhibition of cell proliferation. In the present study, the possible anti-proliferative effect of hinokitiol was investigated on VSMCs. Our results showed that hinokitiol significantly attenuated the PDGF-BB-stimulated proliferation of VSMCs without cytotoxicity. Hinokitiol suppressed the expression of proliferating cell nuclear antigen (PCNA), a maker for cell cycle arrest, and caused G0/G1 phase arrest in cell cycle progression. To investigate the mechanism underlying the anti-proliferative effect of hinokitiol, we examined the effects of hinokitiol on phosphorylations of Akt, ERK1/2, p38 and JNK1/2. Phospholipase C (PLC)-γ1 phosphorylation, its phosphorylated substrates and p27^kip1 expression was also analyzed. Pre-treatment of VSMCs with hinikitiol was found to significantly inhibit the PDGF-BB-induced phosphorylations of JNK1/2 and PLC-γ1, however no effects on Akt, ERK1/2, and p38. The up-regulation of p27^kip1 was also observed in hinokitiol-treated VSMCs. Taken together, our results suggest that hinokitiol inhibits PDGF-BB-induced proliferation of VSMCs by inducing cell cycle arrest, suppressing JNK1/2 phosphorylation and PLC-γ1, and stimulating p27^kip1 expression. These findings suggest that hinokitiol may be beneficial for the treatment of vascular-related disorders and diseases.

There is little research about the stress, quality of life (QOL) and gut microbiota in newly diagnosed breast cancer patients. In this study addressing the dearth of research on stress, quality of life (QOL), and gut microbiota in newly diagnosed breast cancer patients, 82 individuals were prospectively observed. Utilizing the Functional Assessment of Chronic Illness Therapy (FACT)-Breast questionnaire to assess health-related quality of life (HRQOL) and the Distress Thermometer (DT) to gauge distress levels, the findings revealed a mean FACT-B score of 104.5, underscoring HRQOL's varied impact. Significantly, 53.7% reported moderate to severe distress, with a mean DT score of 4.43. Further exploration uncovered compelling links between distress levels, FACT-B domains, and microbial composition. Notably, Alcaligenaceae and Sutterella were more abundant in individuals with higher DT scores at the family and genus levels (p = 0.017), while Streptococcaceae at the family level and Streptococcus at the genus level were prevalent in those with lower DT scores (p = 0.028 and p = 0.023, respectively). This study illuminates the intricate interplay of stress, QOL, and gut microbiota in newly diagnosed breast cancer patients, offering valuable insights for potential interventions of biomarker or probiotics aimed at alleviating stress and enhancing QOL in this patient cohort.

Background: Bloodstream infections (BSI) are an important source of postoperative mortality in hepatobiliary–pancreatic surgery (HBPS) patients, and no prediction model has been analyzed before.Methods: Using big data from the electronic medical records of the administrative and culture databases of MacKay Memorial Hospital, we identified the potential risk factors for community‐acquired and healthcare‐associated BSI and mortality of patients who received HBPS. Subsequently, we analyzed the microorganisms’ profiles and antimicrobial susceptibility patterns for these BSI.Results: BSI were found in 6.3% patients (349 of 5513 HBPS patients), and hospital mortality was 1.48% (82 of 5513). Dividing patients into low‐, intermediate‐, and high‐risk groups on the basis of sex, age, status of comorbidity (renal failure, peptic ulcer disease, fluid and electrolyte disorders, and acute cholecystitis), a predictive BSI risk score model was developed. According to this model, BSI risk ranged from 1.43% to 11.95%; AUROC to predict BSI risk was 0.72 (95% CI 0.69–0.75). From this retrospective study, Enterobacteriaceae were the most common microorganisms that were isolated from BSI. For both community‐acquired and healthcare‐associated BSI, imipenem and colistin are the most successful.Conclusion: This novel model can be useful to predict who is at risk of BSI after HBPS, and new prophylactic protocols for these patients are needed.

This prospective study of 90 breast cancer patients examined gut microbiota composition relative to hormone receptor status and endocrine therapy changes. Initial analysis suggested hormone receptor-negative patients had higher Fusobacteriaceae and Fusobacterium abundance, while hormone receptor-positive patients showed Ruminiclostridium enrichment, though differences lacked statistical significance after correction. Hormone receptor-positive patients without lymph node metastasis demonstrated potentially greater microbial diversity, but associations were non-significant after multiple comparison correction. Longitudinal analysis of 52 hormone receptor-positive patients revealed the most robust finding: statistically significant Blautia increases after hormone therapy and aromatase inhibitor treatment. Tamoxifen showed trends toward increased Lachnospiraceae but lost significance after correction due to small sample size. LHRH agonist treatment demonstrated significant Dialister and Megasphaera increases. This study identified limited but robust associations between gut microbiota and endocrine treatments, with Blautia as the most consistently affected genus across multiple therapies, though most findings require validation in larger cohorts.

Predicting a patient’s risk of recurrence after the resection of liver metastases from colorectal cancer is critical for evaluating and selecting therapeutic approaches. Clinical and pathologic parameters have shown limited accuracy thus far. Therefore, we combined the clinical status with a genomic approach to stratify relapse-free survival in colorectal cancer liver metastases patients. To identify new molecular and genetic signatures specific to colorectal cancer with liver metastasis (CRCLM) patients, we conducted DNA copy number profiling on a cohort of 21 Taiwanese CRCLM patients using a comparative genomic hybridization (CGH) array. We identified a three-gene signature based on differential copy number alteration between patients with different statuses of (1) recurrence and (2) synchronous metastasis. In relapse hotspot regions, only three genes (S100PBP, CSMD2, and TGFBI) were significantly associated with the synchronous liver metastasis factor. A final set of three genes—S100PBP, CSMD2, TGFBI—significantly predicted relapse-free survival in our cohort (p = 0.04) and another CRCLM cohort (p = 0.02). This three-gene signature is the first genomic signature validated for relapse-free survival in post-hepatectomy CRCLM patients. Our three-gene signature was developed using a whole-genome CGH array and has a good prognostic position for the relapse-free survival of CRCLM patients after hepatectomy.