The pattern of bowel dysfunction in patients with rectal cancer following the multimodal treatment: anorectal manometric measurements at before and after chemoradiation therapy, and postoperative 1 year

Purpose Bowel dysfunction commonly occurs in patients with locally advanced rectal cancer treated with a multimodal approach of chemoradiation therapy (CRT) combined with sphincter-preserving rectal resection. This study investigated the decline in anorectal function using sequential anorectal manometric measurements obtained before and after the multimodal treatment as well as at a 1-year follow-up. Methods This was a retrospective cohort study conducted in a single center. The study population consisted of patients with locally advanced mid- to low rectal cancer who received the preoperative CRT followed by sphincter-preserving surgery from 2012 to 2016. The anorectal manometric value measured after each treatment modality was compared to demonstrate the degree of decline in anorectal function. A generalized linear model of repeated measures was performed using the manometric values measured pre- and post-CRT, and at 12 months postoperatively. Results Overall, 100 patients with 3 consecutive manometric data were included in the final analysis. In the overall cohort study, the mean resting and maximal squeezing pressures showed insignificant decrement post-neoadjuvant CRT. At a 1-year postoperative follow-up, the maximal squeezing pressure significantly decreased. The maximal rectal sensory threshold demonstrated significant reduction consecutively after each following treatment (P<0.001). Conclusion The short-term effect of neoadjuvant CRT on the anal sphincters was relatively trivial. The following sphincter-saving surgery resulted in a profound disruption of the anorectal function. Patients with rectal cancer should be consulted on the consequence of multimodal treatment

Impact of a multidomain lifestyle intervention on white matter integrity: the SUPERBRAIN exploratory sub-study

In the South Korean study to prevent cognitive impairment and protect BRAIN health through lifestyle intervention in at-risk elderly people (SUPERBRAIN), we evaluated the impact of a 24-week facility-based multidomain intervention (FMI) and home-based MI (HMI) on white matter integrity. Among 152 participants, aged 60–79 years without dementia but with ≥1 modifiable dementia risk factor, 19 FMI, 20 HMI, and 16 controls underwent brain MRI at baseline and 24 weeks. Between the intervention and control groups, we compared changes in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) at regions-of-interest (ROI) including the cingulum cingulate gyrus (CgC), cingulum hippocampus (CgH), superior longitudinal fasciculus (SLF), as well as the uncinate fasciculus (UF). In addition, correlations between total and standard scores cognitive domains of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) or serum brain-derived neurotrophic factor (BDNF) and changes in brain image measures were evaluated at a statistical significance level of p &lt; 0.05 (uncorrected for multiple corrections). The FA, MD, AD, and RD at each ROI at the baseline were not different among groups after Bonferroni correction. In the statistical analysis using two-way repeated measures ANOVA, any significant difference in longitudinal changes in the FA, MD, AD, and RD was not revealed. The statistical analysis, among the significant regions in paired t-test of the intervention group, compared with the control group, the FMI, HMI, and intervention group yielded significantly more beneficial effects on the AD of the CgC. In addition, longitudinal AD changes of the left CgC correlated with the BDNF changes (r = 0.280, p = 0.048). In this study, enhanced cognitive reserve after the multidomain lifestyle intervention could be revealed by changes in brain imaging for white matter integrity

Impact of a multidomain lifestyle intervention on regional spontaneous brain activity

In the SoUth Korean study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention in at-risk elderly people (SUPERBRAIN), we evaluated the impact of multidomain lifestyle intervention on regional homogeneity (ReHo) in resting-state functional brain magnetic resonance imaging (MRI) data. Of 152 participants aged 60–79 years without dementia assigned to either facility-based multidomain intervention (FMI), home-based MI, or controls, we analyzed 56 scanned MRIs at baseline and 24 weeks. ReHo values from regions with significant longitudinal changes were compared between the intervention and control groups and their correlations with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) or serum brain-derived neurotrophic factor (BDNF) were evaluated. ReHo values in the left medial orbitofrontal gyrus and right superior parietal lobule were increased [p = 0.021, correlated positively with serum BDNF changes (r = 0.504, p = 0.047)] and decreased [p = 0.021, correlated negatively with changes in the total (r = −0.509, p = 0.044) and attention (r = −0.562, p = 0.023). RBANS], respectively, in the participants assigned to the FMI group than those of the controls. Our results suggest that facility-based group preventive strategies may have cognitive benefits through neuroplastic changes in functional processing circuits in the brain areas which play a crucial role in the adaptive learning and internally directed cognition

Metadherin Contributes to the Pathogenesis of Diffuse Large B-cell Lymphoma

BACKGROUND: Metadherin (MTDH) has been demonstrated as a potentially crucial mediator of various types of human malignancies. However, the expression and role of MTDH in diffuse large-B-cell lymphoma (DLBCL) have not been reported yet. This study aimed to illuminate the role of MTDH in the pathogenesis of DLBCL. METHODOLOGY/PRINCIPAL FINDINGS: A remarkable elevation of MTDH on mRNA level was detected in DLBCL tissues by quantitative polymerase chain reaction (PCR). Using Western-blot analysis we found that the expression of MTDH protein was significantly upregulated in DLBCL cell lines and DLBCL tissues compared with peripheral blood mononuclear cells (PBMCs) from healthy samples and tissues from patients of reactive hyperplasia of lymph node. The results showed high expression of MTDH in 23 of 30 (76.67%) DLBCL tissues by using immunohistochemical analysis and the over expression of MTDH was strongly correlated to the clinical staging of patients with DLBCL (P<0.05). Furthermore, the finding suggested that the increase of MTDH in DLBCL cells could distinctly enhance cell proliferation and inhibit cell apoptosis; meanwhile, inhibition of MTDH expression by specific siRNA clearly enhanced LY8 cell apoptosis. Upregulation of MTDH elevated the protein level of total β-catenin and translocation of β-catenin to the nucleus directly or indirectly. Knockdown of MTDH decreased the level of total, cytoplasmic β-catenin and reduced nuclear accumulation of β-catenin protein. This indicated that the function of MTDH on the development of DLBCL was mediated through regulation of Wnt/β-catenin signaling pathway. CONCLUSIONS/SIGNIFICANCE: Our results suggest that MTDH contributes to the pathogenesis of DLBCL mediated by activation of Wnt/β-catenin pathway. This novel study may contribute to further investigation on the useful biomarkers and potential therapeutic target in the DLBCL patients

Analysis of Gene Expression in Mouse Alveolar Macrophages Stimulated with Quorum-Sensing Mutants of Vibrio vulnificus

Bacterial pathogens manipulate host cells to promote pathogen survival and dissemination. In this study, microarray technology was used to identify the genes that are affected by the Vibrio vulnificus quorum-sensing genes, luxS and smcR. By comparing the expression profiles of mouse macrophage cell lines stimulated with either the parent strains or a luxS smcR mutant, differentially expressed genes were identified. The genes included those that affect host cell death, stress, signaling transduction, inflammation, and immune response. Macrophages stimulated with the luxS smcR mutant differentially expressed genes associated with removal of toxins, the complement pathway, regulation of cytokine expression, and antigen presentation, indicating that macrophages stimulated with the luxS smcR mutant induced an appropriate inflammation reaction and immune response for removal of bacteria. In summary, quorum-sensing in V. vulnificus could contribute to bacterial survival and increased pathogenesis by inducing a changed expression profile in macrophages.This study was supported by KOSF, Brain Korea 21, KRF(KRF-2006-005-J02901) and the Research Institute for Veterinary Science, Seoul National University, Korea

Identification of quorum sensing-related regulons in Vibrio vulnificus by two-dimensional gel electrophoresis and differentially displayed reverse transcriptase PCR

Vibrio vulnificus is thought to employ a quorum-sensing system to control the expression of a global gene. In this study, proteomes and transcriptomes of a lacZ null mutant, VvSRDZ, and a luxS–smcR double mutant, VvSRDZSR, were compared with the parent strain, VvAR, by means of two-dimensional gel electrophoresis (2D-PAGE) and differentially displayed reverse transcriptase PCR (DDRT-PCR). 2D-PAGE analysis showed that 36 protein spots were differentially expressed, 14 of which have been identified by peptide-mass fingerprinting. The expression of eight cellular proteins was repressed by luxS and smcR mutation: Zn-dependent protease, 6-phosophofructokinase, periplasmic ABC-type Fe31 transport system, deoxyribose-phosphate aldolase, phosphomannomutase, orotidine-50-phosphate decarboxylase, uridylate kinase, and an unidentified protein. These proteins are involved in virulence, adaptation to environmental stress, biosynthesis of LPS, and cell multiplication. Phage shock protein A, a chemotaxis signal transduction protein, and an uncharacterized low-complexity protein were activated in the cellular components of the luxS-smcR mutant. However, only three proteins, of unknown function, were identified in the extracellular components of the mutants. Analysis of transcriptomes with DDRTPCR showed that two genes, phosphoribosylformylglycinamidine synthase and ATP-dependent protease HslVU protease were regulated at the transcriptional level by luxS and smcR gene mutation. The results from this study show conclusively that luxS/smcR quorum sensing endows a global change in gene expression to V. vulnificus.This study was supported by KOSF, Brain Korea 21, KRF (KRF-2006-005-J02901) and the Research Institute for Veterinary Science, Seoul National University, Korea

Sulfur Metabolism of the Gut Microbiome and Colorectal Cancer: The Threat to the Younger Generation

Colorectal cancer diagnosed in individuals under 50 years old is called early-onset colorectal cancer (EOCRC), and its incidence has been rising worldwide. Simultaneously occurring with increasing obesity, this worrisome trend is partly explained by the strong influence of dietary elements, particularly fatty, meaty, and sugary food. An animal-based diet, the so-called Western diet, causes a shift in dominant microbiota and their metabolic activity, which may disrupt the homeostasis of hydrogen sulfide concentration. Bacterial sulfur metabolism is recognized as a critical mechanism of EOCRC pathogenesis. This review evaluates the pathophysiology of how a diet-associated shift in gut microbiota, so-called the microbial sulfur diet, provokes injuries and inflammation to the colonic mucosa and contributes to the development of CRC

Reappraisal of the Lymphatic Drainage System of the Distal Rectum: Functional Lymphatic Flow into the Presacral Space and Its Clinical Implication in Rectal Cancer Treatment

Understanding the source and route of pelvic metastasis is essential to developing an optimal strategy for controlling local and systemic diseases of rectal cancer. This study aims to delineate the distribution of lymphatic channels and flow from the distal rectum. In fresh-frozen cadaveric hemipelvis specimens, the ligamentous attachment of the distal rectum to the pelvic floor muscles and the presacral fascia were evaluated. Using indocyanine green (ICG) fluorescence imaging, we simultaneously evaluated the gross anatomy of the lymphatic communication of the distal rectum. We also investigated the lymphatic flow in the pelvic cavity intraoperatively in rectal cancer patients who underwent radical rectal resection with total mesorectal excision (TME). In fresh cadavers, multiple small perforating lymphovascular branches exist in the retrorectal space, posteriorly connecting the mesorectum to the presacral fascia. The lymphatic flow from the distal rectum drains directly into the presacral space through the branches. In patients who underwent TME for rectal cancer, intraoperative ICG fluorescence signals were seen in the pelvic sidewalls and the presacral space. This anatomical study demonstrated that the lymphatic flow from the distal rectum runs directly to the pelvic lateral sidewalls and the presacral space, suggesting a possible route of metastasis in distal rectal cancer