Mammals sustain amino acid homochirality against chiral conversion by symbiotic microbes.

Mammals exhibit systemic homochirality of amino acids in L-configurations. While ribosomal protein synthesis requires rigorous chiral selection for L-amino acids, both endogenous and microbial enzymes convert diverse L-amino acids to D-configurations in mammals. However, it is not clear how mammals manage such diverse D-enantiomers. Here, we show that mammals sustain systemic stereo dominance of L-amino acids through both enzymatic degradation and excretion of D-amino acids. Multidimensional high performance liquidchromatography analyses revealed that in blood, humans and mice maintain D-amino acids at less than several percent of the corresponding L-enantiomers, while D-amino acids comprise ten to fifty percent of the L-enantiomers in urine and feces. Germ-free experiments showed that vast majority of D-amino acids, except for D-serine, detected in mice are of microbial origin. Experiments involving mice that lack enzymatic activity to catabolize D-amino acids showed that catabolism is central to the elimination of diverse microbial D-amino acids, whereas excretion into urine is of minor importance under physiological conditions. Such active regulation of amino acid homochirality depends on maternal catabolism during the prenatal period, which switches developmentally to juvenile catabolism along with the growth of symbiotic microbes after birth. Thus, microbial symbiosis largely disturbs homochirality of amino acids in mice, whereas active host catabolism of microbial D-amino acids maintains systemic predominance of L-amino acids. Our findings provide fundamental insight into how the chiral balance of amino acids is governed in mammals and further expand the understanding of interdomain molecular homeostasis in host-microbial symbiosis.

[Evaluation of modified OPTIMOX1 plus bevacizumab as the neoadjuvant therapy for highly advanced rectal cancers].

UNLABELLED: We evaluated the efficacy and safety of neoadjuvant chemotherapy using modified OPTIMOX1 plus bevacizumab for advanced rectal cancer. PATIENTS AND METHODS: Nine cases with highly advanced rectal cancer for which curative surgery was potentially difficult were enrolled(clinical T4 in 7 cases, lateral node metastasis in 3 cases, M1 in 2 cases). RESULTS: The number of courses of modified OPTIMOX1(mFOLFOX6 and sLV5FU2, alternating administration)plus bevacizumab ranged from 1 to 21(median: 10). Surgical procedures consisted of internal sphincter resection(ISR)in 4 patients, ultra-low anterior resection(ULAR)in 2 patients, pelvic exenteration(TPE)in 2 patients, and Hartmann's procedure in 1 patient. Liver resection was conducted in 2 patients. RM1 was confirmed in 2 patients, but curative surgery was performed in the other patients. Histological efficacy of grade x/1a/1b/2were seen in the above 1/4/2/2 cases, respectively. Neurotoxicity associated with oxaliplatin was mild; no grade 3 neurotoxicity was noted. Recurrence has been confirmed in 5 patients at the median follow-up period of 650 days. CONCLUSION: It was suggested that modified OPTIMOX1 plus bevacizumab is effective and safe to administer as a neoadjuvant chemotherapy for curative resection or anus-preserving surgery in patients with highly advanced rectal cancer.

[An analysis of palliative surgery for the patients with malignant bowel obstruction].

PURPOSE: The objective of this study was to clarify the surgical outcome of patients with palliative surgery for malignant bowel obstruction. OBJECTIVE AND METHODS: This study investigated the clinical features, operative procedures and postoperative course of 35 patients who underwent a palliative surgery for malignant bowel obstruction. And then the patients were divided into two groups; Patients in A group were consisted of 4 patients with hospital death and 7 patients with postoperative complications. Patients in B group were consisted of 24 patients without hospital death or postoperative complications. RESULT: Eighteen patients who had been inserted nasogastric tube or ileus tube in the preoperative state could be removed. Thirty-three of 35 patients(94.3%)could become an oral ingestion. Four of 35 patients(11.4%)could not be discharged; 3 patients died of cancer and 1 patient died of acute myocardial infarction. Postoperative complications were seen in 7 patients except 4 patients with hospital death. The median postoperative stay was 18 days(3-58). Twenty six of 35 patients(74.3%) underwent chemotherapy. The median survival time was 137 days(3-1,614). The patients in A group showed a lower level of albumin(p=0.0071)and hemoglobin,(p=0.0006)and poorer performance status(p=0.0178)than the patients in B group. The median hospital stay of the patients in A group and B group were 28 days and 16 days, respectively(p=0.0823). The median survival time of the patients in A group and B group were 42 days and 119 days, respectively(p=0.0035). CONCLUSION: We concluded that the palliative surgery made an oral ingestion possible and improved a quality of life of the patients with malignant bowel obstruction. However, the surgical indication should be carefully decided for the patients with low albumin, hemoglobin and poor performance status.