Preoperative albumin-to-globulin ratio and prognostic nutritional index predict the prognosis of colorectal cancer: a retrospective study.

The immunonutritional status has important effects on outcomes for cancer patients. Albumin-to-globulin ratio (AGR) and the prognostic nutrition index (PNI) are often used to assess the immunonutritional status of cancer patients. However, the clinical significance of these factors in colorectal cancer (CRC) remains unclear. We aimed to evaluate the clinical significance of the AGR and PNI in CRC. We reviewed the clinical data of 511 patients with CRC in two hospitals. Data from one institution was used as the training cohort. The optimal cutoff values for AGR and PNI in the training cohort were 1.4 and 48.65, respectively. Patients in both the low AGR and low PNI groups had poor overall survival (OS) and progression-free survival (PFS), while those in the low AGR-low PNI group had the lowest OS and PFS. Multivariate analysis revealed that preoperative AGR, preoperative PNI, gross type, and TNM stage were independent prognostic factors influencing OS in patients with CRC. Preoperative AGR, preoperative PNI, and TNM stage were independently associated with PFS in patients with CRC. According to the results of multivariate analysis in the training cohort, we developed the nomograms for OS and PFS and performed internal and external validation, which showed good prediction ability of the nomograms. In conclusion, preoperative AGR and PNI can be used as effective indicators to predict survival for patients with CRC. AGR and PNI may help develop effective adjuvant-therapy schedules.

Investigating dysbiosis and microbial treatment strategies in inflammatory bowel disease based on two modified Koch's postulates.

Inflammatory bowel disease (IBD) is a chronic non-specific inflammatory disease that occurs in the intestinal tract. It is mainly divided into two subtypes, i.e., the Crohn's disease (CD) and ulcerative colitis (UC). At present, its pathogenesis has not been fully elucidated, but it has been generally believed that the environment, immune disorders, genetic susceptibility, and intestinal microbes are the main factors for the disease pathogenesis. With the development of the sequencing technology, microbial factors have received more and more attention. The gut microbiota is in a state of precise balance with the host, in which the host immune system is tolerant to immunogenic antigens produced by gut commensal microbes. In IBD patients, changes in the balance between pathogenic microorganisms and commensal microbes lead to changes in the composition and diversity of gut microbes, and the balance between microorganisms and the host would be disrupted. This new state is defined as dysbiosis. It has been confirmed, in both clinical and experimental settings, that dysbiosis plays an important role in the occurrence and development of IBD, but the causal relationship between dysbiosis and inflammation has not been elucidated. On the other hand, as a classic research method for pathogen identification, the Koch's postulates sets the standard for verifying the role of pathogens in disease. With the further acknowledgment of the disease pathogenesis, it is realized that the traditional Koch's postulates is not applicable to the etiology research (determination) of infectious diseases. Thus, many researchers have carried out more comprehensive and complex elaboration of Koch's postulates to help people better understand and explain disease pathogenesis through the improved Koch's postulates. Therefore, focusing on the new perspective of the improved Koch's postulates is of great significance for deeply understanding the relationship between dysbiosis and IBD. This article has reviewed the studies on dysbiosis in IBD, the use of microbial agents in the treatment of IBD, and their relationship to the modified Koch's postulates.

Pan-immune-inflammation value is associated with the clinical stage of colorectal cancer.

Objective: We investigated the clinical significance of preoperative pan-immune-inflammation value (PIV) in patients with colorectal cancer (CRC). Methods: In this retrospective study, 366 cases who underwent surgery for CRC were enrolled. Their clinical data were collected. PIV was calculated with the formula PIV = [neutrophil count (109/L)× platelet count (109/L) × monocyte count (109/L) /lymphocyte count (109/L). Patients were divided into high PIV (> median PIV) and low PIV (< median PIV) groups. The relationship between PIV and clinicopathological features of CRC was investigated. Receiver operating characteristic (ROC) curve was plotted to indicate the value of immune-inflammatory biomarkers (IIBs) in predicting the TNM stage of CRC, and the area under the curve (AUC) was calculated to evaluate the actual clinical value of IIBs. AUC > 0.5 and closer to 1 indicated the better predictive efficacy. The influencing factors of PIV in CRC were analyzed. Results: We found that PIV was positively correlated with tumor size (r = 0.300, p < 0.05), carcinoembryonic antigen (CEA) (r = 0.214, p < 0.05) and carbohydrate antigen 125 (CA-125) (r = 0.249, p < 0.05), but negatively correlated with albumin (Alb) (r = -0.242, p < 0.05). PIV was significantly different in patients with different tumor locations (left or right), surgical methods (laparotomy versus laparoscopic surgery) (p < 0.05), and patients with different pathological T stages, N-stage and TNM stages (p < 0.05). ROC curve analysis of IIBs showed the AUC of PIV was greater than other markers when combined with CEA or carbohydrate antigen 19-9 (CA19-9). Multivariate regression analysis identified T stage, CEA, Alb, and tumor size as the independent influential factors of PIV in CRC. Conclusion: PIV is associated with the tumor stage in patients with CRC, which may be useful in preoperative assessment of CRC.

Single-Cell RNA Sequencing for Analyzing the Intestinal Tract in Healthy and Diseased Individuals.

The intestinal tract is composed of different cell lineages with distinct functions and gene expression profiles, providing uptake of nutrients and protection against insults to the gut lumen. Changes in or damage to the cellulosity or local environment of the intestinal tract can cause various diseases. Single-cell RNA sequencing (scRNA-seq) is a powerful tool for profiling and analyzing individual cell data, making it possible to resolve rare and intermediate cell states that are hardly observed at the bulk level. In this review, we discuss the application of intestinal tract scRNA-seq in identifying novel cell subtypes and states, targets, and explaining the molecular mechanisms involved in intestinal diseases. Finally, we provide future perspectives on using single-cell techniques to discover molecular and cellular targets and biomarkers as a new approach for developing novel therapeutics for intestinal diseases.

PlexinA1 activation induced by ß2-AR promotes epithelial-mesenchymal transition through JAK-STAT3 signaling in human gastric cancer cells.

With the medical model shifting from a single biomedical model to a biopsychological-social model, the impact of psychosocial factors on cancer patients has attracted attention. Studies have shown that chronic stress caused by long-term psychological stress, such as anxiety and depression, can promote the malignant progression of tumors by acting on ß2-adrenergic receptor (ß2-AR). ß2-AR can promote tumor migration by activating epithelial-mesenchymal transition (EMT). However, the underlying mechanisms in the regulation of EMT by ß2-AR are still unclear. In this study, we established a chronic stress model by treating MGC-803 and SGC-7901 human gastric cancer cells with isoproterenol (ISO), a ß2-AR agonist. EMT in the two gastric cancer cell lines was enhanced after ISO treatment. Thereafter, we found that the interaction between ß2-AR and PlexinA1 was involved in the process by which chronic stress affects EMT in both MGC-803 and SGC-7901 cells. Moreover, the activation of ß2-AR by ISO increased the expression of PlexinA1, activated JAK-STAT3 signaling and further promoted EMT in human gastric cancer cells. Importantly, the knockdown of PlexinA1 by small hairpin RNAs inhibited JAK-STAT3 signaling and abolished the EMT induced by ß2-AR. In conclusion, PlexinA1 was an important downstream target of ß2-AR, through which ß2-AR promoted EMT in human gastric cancer cells by activating JAK-STAT3 signaling.

Chronic stress model simulated by salbutamol promotes tumorigenesis of gastric cancer cells through ß2-AR/ERK/EMT pathway.

Chronic stress induced by long-term anxiety and depression can promote the malignant progression of gastric cancer. ß2-adrenergic receptor (ß2-AR) is a critical mediator for chronic stress-induced multiple processes of tumor cells. However, the function of chronic stress in gastric cancer and its potential mechanisms in vivo and in vitro, especially at the cellular level, remain unknown. Here, we provide further evidence that chronic stress affected behavior and hypothalamus pituitary adrenal axis related hormone levels in mice. Furthermore, immunofluorescence showed that emotion affected the expression of epithelial-mesenchymal transition (EMT) markers in patients' tissues. To address this, salbutamol, a specific agonist of ß2-AR, was utilized for simulating chronic stress and demonstrating the mechanism of stress in tumor progression at the molecular level both in vivo and in vitro. Salbutamol significantly induced EMT, migration and invasion via ERK (Extracellular-signal-regulated kinase) phosphorylation, and the effects were reversed by the ß2-AR antagonist ICI-118,551. The promoting effects of salbutamol on EMT, migration and invasion were inhibited by phosphorylation inhibitor of ERK PD98059 in vitro. Analysis of xenograft models revealed that salbutamol significantly promoted tumor growth and adrenal volume, while ICI-118,551 inhibited these effects. In addition, salbutamol increased the expression of mesenchymal marker N-cadherin and decreased epithelial marker E-cadherin in transplanted tumor tissue. In conclusion, salbutamol simulates a chronic stress model, which promotes tumorigenesis of gastric cancer cells through ß2-AR/ERK/EMT pathway.

Chronic Stress Activates PlexinA1/VEGFR2-JAK2-STAT3 in Vascular Endothelial Cells to Promote Angiogenesis.

It is known that chronic stress modulates multiple processes in a complex microenvironment, such as angiogenesis and immune function. However, the role of chronic stress inducing tumor angiogenesis and how it contributes to tumor progression are not quite clear. The following study assess psychological state from numerous ambulatory cancer cases (n=332), and chronic stress-related hormone levels were further measured. Here, we show that chronic stress not only causes behavioral changes in human, most importantly attributed to an elevated level of stress-related hormones. To address this, isoprenaline, the agonist of ß2-adrenergic receptor (ß2-AR), was utilized for simulating chronic stress and demonstrating the mechanism of stress in tumor angiogenesis at molecular level both in vivo and in vitro. As suggested by this study, isoprenaline promote VEGF autocrine of HUVECs, which can induce plexinA1 and VEGFR2 expression. Moreover, we show that isoprenaline promoted the expression of p-JAK2 and p-STAT3 in vitro. The results reveal that, isoprenaline enhances the autocrine of VEGF in HUVECs and up-regulating plexinA1 and VEGFR2 levels, thus activating the phosphorylation of JAK2-STAT3 pathway, the two essential parts during angiogenesis. The present work indicates that, the mechanism of chronic stress in enhancing angiogenesis is probably achieved through activating the plexinA1/VEGFR2-JAK2-STAT3 signal transduction pathway within HUVECs, and this is probably a candidate target for developing a strategy against angiogenesis in cancer.

miR-27 inhibits adipocyte differentiation via suppressing CREB expression.

miR-27 plays a negative role in the regulation of adipogenesis. However, the molecular mechanism still remains to be clarified. In the present study, we found that miR-27 inhibits adipogenesis partially by repressing the early adipogenic transcription factor cAMP response element-binding protein by directly targeting its 3' untranslated region. In addition, we demonstrated that tumor necrosis factor-α (TNF-α) treatment up-regulates miR-27 through the NF-κB pathway. Furthermore, anti-miR-27 reduces the TNF-α-induced inhibition of adipogenesis. Simultaneously, the levels of miR-27 expression were decreased in mature adipocytes of obese mice when compared with lean mice. Our data revealed a novel mechanism of miR-27 in the regulation of adipogenesis.