Cervical microbiota composition is associated with cervical HPV infection and CIN severity. Previous studies only assessed the total association between cervical microbiota and HPV infections or CINs, and yet no study reported the direct and indirect associations between cervical microbiota and CINs mediated by HPV infection, respectively. The aim of this study was to investigate the direct and indirect associations between microbiotas and CIN severity. Cervical microbiota of 126 women with CIN 1− (normal cytology and CIN 1) and 40 with CIN 2+ (CIN 2 and CIN 3) were analyzed using Illumina sequencing based on the 16S rRNA gene. HPV was detected using a highly sensitive PCR primer set (SPF1/GP6+). Indirect effects of Pseudomonas stutzeri, Bacteroides fragilis, Lactobacillus delbrueckii, Atopobium vaginae, and Streptococcus agalactiae mediated by HPV infection on CIN status were observed. The directions of the direct and the indirect associations between CIN status and Ps. stutzeri were opposite. The directions of the direct and the indirect associations between CIN status and A. vaginae were the same. B. fragilis, L. delbrueckii, and S. agalactiae only had indirect association with CIN status. In summary, our study provided suggestive evidence that some microbial populations could have direct or indirect effects mediated by affecting HPV infection on CIN progression. Besides HPV infection, microbial community composition possibly plays a role in cervical carcinogenesis.

Background: Preoperative neoadjuvant chemoradiation (nCRT) has been the standard treatment for locally advanced rectal cancer. Serum biomarkers to stratify patients with respect to prognosis and response to nCRT are needed due to the diverse response to the therapy. Methods: Thirteen paired pre- and post-nCRT sera from rectal cancer patients were analyzed by isobaric tags for relative and absolute quantitation (iTRAQ) method. Twenty-five proteins were selected for validation by parallel reaction monitoring (PRM) in ninety-one patients. Results: Totally, 310 proteins were identified and quantified in sera samples. Reactome pathway analysis showed that the immune activation-related pathways were enriched in response to nCRT. Twenty-five proteins were selected for further validation. PRM result showed that the level of PZP was higher in pathological complete response (pCR) patients than non-pCR patients. The Random Forest algorithm identified a prediction model composed of 10 protein markers, which allowed discrimination between pCR patients and non-pCR patients (area under the curve (AUC) = 0.886 on testing set). Higher HEP2 and GELS or lower S10A8 in baseline sera were associated with better prognosis. Higher APOA1 in post nCRT sera was associated with better disease-free survival (DFS). Conclusions: We identified and confirmed a 10-protein panel for nCRT response prediction and four potential biomarkers HEP2, GELS, S10A8 and APOA1 for prognosis of rectal cancer based on iTRAQ-based comparative proteomics screening and PRM-based targeted proteomic validation.

Hypertension in adolescents is associated with adverse cardiac and vascular events. In addition to lowering blood pressure, it is not clear whether pharmacological therapy in early life can improve vascular remodeling. This study aimed to evaluate the effects of long-term administration of losartan, aspirin, and atorvastatin on vascular remodeling in juvenile spontaneously hypertensive rats (SHRs). Losartan, aspirin, and atorvastatin were administered via gavage at doses of 20, 10, and 10 mg/kg/day, respectively, on SHRs aged 6–22 weeks. Paraffin sections of the blood vessels were stained with hematoxylin-eosin (H&E) and Sirius Red to evaluate the changes in the vascular structure and the accumulation of different types of collagen. The plasma levels of renin, angiotensin II (Ang II), aldosterone (ALD), endothelin-1 (ET-1), interleukin-6 (IL-6), and neutrophil elastase (NE) were determined using ELISA kits. After the 16-week treatment with losartan, aspirin, and atorvastatin, the wall thickness of the thoracic aorta and carotid artery decreased. The integrity of the elastic fibers in the tunica media was maintained in an orderly manner, and collagen deposition in the adventitia was retarded. The plasma levels of renin, ALD, ET-1, IL-6, and NE in the SHRs also decreased. These findings suggest that losartan, aspirin, and atorvastatin could improve vascular remodeling beyond their antihypertensive, anti-inflammatory, and lipid-lowering effects. Many aspects of the protection provided by pharmacological therapy are important for the prevention of cardiovascular diseases in adults and older adults.