Metabolic engineering of Halomonas campaniensis strain XH26 to remove competing pathways to enhance ectoine production.

Ectoine has gained considerable attention as a high-value chemical with significant application potential and market demand. This study aimed to increase ectoine yields by blocking the metabolic shunt pathway of L-aspartate-4-semialdehyde, the precursor substrate in ectoine synthesis. The homoserine dehydrogenase encoded by hom in H. campaniensis strain XH26 is responsible for the metabolic shunt of L-aspartate-4-semialdehyde to glycine. CRISPR/Cas9 technology was used to seamlessly knockout hom, blocking the metabolic shunt pathway to increase ectoine yields. The ectoine yield of XH26/Δhom was 351.13 mg (g CDW)-1 after 48 h of incubation in 500 mL shake flasks using optimal medium with 1.5 mol L-1 NaCl, which was significantly higher than the 239.18 mg (g CDW)-1 of the wild-type strain. Additionally, the absence of the ectoine metabolic shunt pathway affects betaine synthesis, and thus the betaine yields of XH26/Δhom was 19.98 mg (g CDW)-1, considerably lower than the 69.58 mg (g CDW)-1 of the wild-type strain. Batch fermentation parameters were optimized, and the wild-type strain and XH26/Δhom were fermented in 3 L fermenters, resulting in a high ectoine yield of 587.09 mg (g CDW)-1 for the defective strain, which was significantly greater than the ectoine yield of 385.03 mg (g CDW)-1 of the wild-type strain. This study showed that blocking the metabolic shunt of synthetic substrates effectively increases ectoine production, and a reduction in the competitively compatible solute betaine appears to promote increased ectoine synthesis.

Research on Mindfulness-Based Stress Reduction in Breast Cancer Patients Undergoing Chemotherapy: An Observational Pilot Study.

Objective: Mindfulness-Based Stress Reduction (MBSR) therapy has been very effective intervention across worldwide. Herein we aimed to investigate the effect of MBSR intervention on anxiety, depression among breast cancer patients undergoing postoperative chemotherapy. Methods: 225 breast cancer patients in our hospital were divided into two groups, 106 patients in the MBSR group received Mindfulness-Based Stress Reduction intervention, while 111 patients in the control group were given routine nursing. The Self-rating Anxiety Scale (SAS), self-rating depression scale (SDS), and functional assessment of cancer therapy-breast cancer (FACT-B) were used to assess the effect of MBSR intervention on breast cancer patients undergoing postoperative chemotherapy. Results: There were significant differences in the scores of physiological statuses, social and family status, emotional status, functional status, additional attention and total score after intervention between two groups (P < .05). The difference between SDS and SAS were statistically significant between the two groups (P < .05). The score of SDS and SAS were significantly improved in the MBSR group compared with the control group (P < .05). Conclusion: MBSR therapy could effectively improve the quality of life of patients with breast cancer patients with chemotherapy, mainly focusing on psychological aspects, while the effect of the physiological intervention was not significant.

[Advances in the microbial production of the compatible solute ectoine: a review].

Ectoine is an amino acid derivative and an important natural product in halophilic microorganisms. It plays an important role in protecting cells and stabilizing biological macromolecules, and can be widely used in biomedical fields such as drug preparation adjuvants, organ transplantation and preservation, skin wound repair and cosmetics. Due to the medical value and commercial market demand of ectoine, this article summarized the recent advances in the microbial production of ectoine, including the mutation and breeding of hyper-producing strains, construction of genetically and metabolically engineered strains, optimization of fermentation processes, and extraction and purification processes. The application of multi-omics technologies and computational biology to develop an ectoine producing cell factory was prospected, with the aim to provide a reference for ectoine overproduction.

Hypoxia Tumor Microenvironment Activates GLI2 through HIF-1α and TGF-ß2 to Promote Chemotherapy Resistance of Colorectal Cancer.

BACKGROUND: A majority of relapse cases have been reported in colorectal cancer patients due to cancer stem cell progenitors. The factors responsible for chemoresistance have yet to be discovered and investigated as CSCs have reported escaping from chemotherapy's killing action. OBJECTIVE: In this study, we have investigated the effects of HIF-1α and TGF-ß2 in hypoxia conditions on the expression of GLI2, which is a potential factor for causing chemoresistance. Material and Methods. Colorectal samples of treated patients were collected from the Hospital Biological Sample Library. Culture of patient-derived TSs and fibroblasts was performed. The collected patient samples and cells were used for immunohistochemistry, quantitative PCR, and western blotting studies which were performed. RESULTS: It was reported that HIF-1α (hypoxia-inducible factor) and TGF-ß2 secreted from cancer-associated fibroblasts (CAFs) synergistically work to express GLI2 in cancer stem cells. Hence, it increased the stemness as well as resistance to chemotherapy. CONCLUSION: The HIF-1α/TGF-ß2-mediated GLI2 signaling was responsible for causing chemoresistance in the hypoxia environment. High expressions of HIF1α/TGF-ß2/GLI2 cause the relapsing of colorectal cancer, thus making this a potential biomarker for identifying the relapse and resistance in patients. The study uncovers the mechanism involved in sternness and chemotherapy resistance which will help in targeted treatment.