Effect of different preoperative nutritional treatments on postoperative recovery and clinical outcomes in patients with gastric cancer and early gastric outlet obstruction.

Patients with gastric cancer and early gastric outlet obstruction often experience malnutrition and require various nutritional support strategies. This study aimed to evaluate the impact of different preoperative nutritional treatments on their postoperative recovery and prognosis. The present retrospective study collected data from 467 patients with gastric cancer and early gastric outlet obstruction who underwent surgery at Harbin Medical University Cancer Hospital (Harbin, China) between January 2016 and December 2018. All patients received preoperative nutritional treatment, with a mean treatment duration of 8.23±2.33 days. The present study analyzed associations and survival in different groups using χ2, independent-samples t-test, ANOVA and log-rank tests. Furthermore, single- and multi-factor survival analyses were conducted and nomograms and calibration curves constructed to investigate factors influencing patient survival. In this study, 230 patients (49.3%) received only parenteral nutrition (PN; Group 1), 162 patients (34.7%) received PN combined with enteral nutrition (EN; Group 2) and 75 patients (16.0%) received PN combined with a full- or semi-liquid diet (Group 3). No significant differences in clinical and pathological parameters were observed among the groups. However, Group 2 showed significant advantages in postoperative recovery, including faster time to first postoperative bowel sounds, flatus and bowel movement. Survival analysis indicated that Group 3 had shorter progression-free survival (χ2=30.485) and overall survival (χ2=31.249). Preoperative nutritional treatment was identified as an independent prognostic factor. Preoperative PN combined with EN proved advantageous for postoperative recovery of patients with gastric cancer and early gastric outlet obstruction. Furthermore, PN combined with full- or semi-liquid diets may not have fully met the nutritional needs of these patients, resulting in less favorable clinical outcomes.

FERMT1 promotes cell migration and invasion in non-small cell lung cancer via regulating PKP3-mediated activation of p38 MAPK signaling.

BACKGROUND: Fermitin family member 1 (FERMT1) is highly expressed in many tumors and acts as an oncogene. Nonetheless, the precise function of FERMT1 in non-small cell lung cancer (NSCLC) has not been clearly elucidated. METHODS: Bioinformatics software predicted the FERMT1 expression in NSCLC. Transwell assays facilitated the detection of NSCLC cell migration and invasion. Western blotting techniques were employed to detect the protein levels regulated by FERMT1. RESULTS: FERMT1 exhibited high expression levels in NSCLC and was linked to the patients' poor prognosis, as determined by a variety of bioinformatics predictions combined with experimental verification. FERMT1 promoted the migration and invasion of NSCLC and regulated epithelial to mesenchymal transition (EMT) -related markers. Further studies showed that FERMT1 could up-regulate the expression level of plakophilin 3(PKP3). Further research has indicated that FERMT1 can promote cell migration and invasion via up-regulating PKP3 expression. By exploring downstream signaling pathways, we found that FERMT1 has the capability to activate the p38 mitogen-activated protein kinases (p38 MAPK) signaling pathway, and knocking down PKP3 can counteract the activation induced by FERMT1 overexpression. CONCLUSIONS: FERMT1 was highly expressed in NSCLC and can activate the p38 MAPK signaling pathway through up-regulation of PKP3, thus promoting the invasion and migration of NSCLC.

Biocatalytic reductive aminations with NAD(P)H-dependent enzymes: enzyme discovery, engineering and synthetic applications.

Chiral amines are pivotal building blocks for the pharmaceutical industry. Asymmetric reductive amination is one of the most efficient and atom economic methodologies for the synthesis of optically active amines. Among the various strategies available, NAD(P)H-dependent amine dehydrogenases (AmDHs) and imine reductases (IREDs) are robust enzymes that are available from various sources and capable of utilizing a broad range of substrates with high activities and stereoselectivities. AmDHs and IREDs operate via similar mechanisms, both involving a carbinolamine intermediate followed by hydride transfer from the co-factor. In addition, both groups catalyze the formation of primary and secondary amines utilizing both organic and inorganic amine donors. In this review, we discuss advances in developing AmDHs and IREDs as biocatalysts and focus on evolutionary history, substrate scope and applications of the enzymes to provide an outlook on emerging industrial biotechnologies of chiral amine production.

Whole-Cell Biotransformation of Penicillin G by a Three-Enzyme Co-expression System with Engineered Deacetoxycephalosporin†C Synthase.

Deacetoxycephalosporin C synthase (DAOCS) catalyzes the transformation of penicillin G to phenylacetyl-7-aminodeacetoxycephalosporanic acid (G-7-ADCA) for which it depends on 2-oxoglutarate (2OG) as co-substrate. However, the low activity of DAOCS and the expense of 2OG restricts its practical applications in the production of G-7-ADCA. Herein, a rational design campaign was performed on a DAOCS from Streptomyces clavuligerus (scDAOCS) in the quest to construct novel expandases. The resulting mutants showed 25∼58 % increase in activity compared to the template. The dominant DAOCS variants were then embedded into a three-enzyme co-expression system, consisting of a catalase and an L-glutamic oxidase for the generation of 2OG, to convert penicillin G to G-7-ADCA in E. coli. The engineered whole-cell enzyme cascade was applied to an up-scaled reaction, exhibiting a yield of G-7-ADCA up to 39.21 mM (14.6 g ⋅ L-1 ) with a conversion of 78.42 mol %. This work highlights the potential of the integrated whole-cell system that may inspire further research on green and efficient production of 7-ADCA.

Biosynthesis of ß-lactam nuclei in yeast.

We have engineered brewer's yeast as a general platform for de novo synthesis of diverse ß-lactam nuclei starting from simple sugars, thereby enabling ready access to a number of structurally different antibiotics of significant pharmaceutical importance. The biosynthesis of ß-lactam nuclei has received much attention in recent years, while rational engineering of non-native antibiotics-producing microbes to produce ß-lactam nuclei remains challenging. Benefited by the integration of heterologous biosynthetic pathways and rationally designed enzymes that catalyze hydrolysis and ring expansion reactions, we succeeded in constructing synthetic yeast cell factories which produce antibiotic cephalosporin C (CPC, 170.1 ± 4.9 µg/g DCW) and the downstream ß-lactam nuclei, including 6-amino penicillanic acid (6-APA, 5.3 ± 0.2 mg/g DCW), 7-amino cephalosporanic acid (7-ACA, 6.2 ± 1.1 µg/g DCW) as well as 7-amino desacetoxy cephalosporanic acid (7-ADCA, 1.7 ± 0.1 mg/g DCW). This work established a Saccharomyces cerevisiae platform capable of synthesizing multiple ß-lactam nuclei by combining natural and artificial enzymes, which serves as a metabolic tool to produce valuable ß-lactam intermediates and new antibiotics.