Stereotactic body radiation therapy suppresses myeloid-derived suppressor cells by regulating miR-21/Sorbin and SH3 Domain-containing Protein 1 axis.

BACKGROUND: Stereotactic body radiation therapy (SBRT) is a targeted form of radiotherapy used to treat early-stage cancers. Despite its effectiveness, the impact of SBRT on myeloid-derived suppressor cells (MDSCs) is not well understood. In this study, we examined how SBRT affects the differentiation and survival of MDSCs, as well as delved into the molecular mechanisms involved. METHODS AND RESULTS: SBRT was utilized on bone marrow (BM)-derived MDSCs to investigate its impact on the differentiation and survival of MDSCs using flow cytometry. An animal model of lung cancer was created to assess the anti-cancer properties of SBRT and the role of miR-21 expression in MDSCs. The interplay of miR-21 and Sorbin and SH3 domain-containing protein 1 (SORBS1) in MDSC differentiation was explored through dual luciferase activity assay, RT-qPCR, and Western blot analysis. The findings suggest that SBRT led to an increase in miR-21 levels, inhibited MDSC differentiation, and triggered cell apoptosis in BM cells. Inhibition of miR-21 reversed the effects of SBRT on MDSC differentiation and apoptosis. Additionally, it was revealed that SORBS1 was a downstream target of miR-21 in BM cells, and the miR-21/SORBS1 axis played a role in regulating MDSC differentiation and apoptosis induced by SBRT. Modulating miR-21 levels in vivo impinged on the response to SBRT treatment and the quantity of MDSCs in a mouse model of lung cancer. CONCLUSION: Our data indicate that the upregulation of miR-21 induced by SBRT may contribute to the inhibition of MDSC expansion in a lung cancer model.

Influencing factors for placenta accreta in recent 5 years: a systematic review and meta-analysis.

OBJECTIVE: Assess influencing factors for placenta accreta in pregnant women documented in recent literature. METHODS: A systematic review and meta-analysis were conducted based on English- and Chinese-language articles published from January 2014 to June 2019. Articles were retrieved from the following Chinese databases, CNKI, Wanfang Data, China Science and Technology Journal Database, CBM and English databases, PubMed, Web of Science, the Cochrane Library and Embase. RESULTS: Eleven studies with 2,152,014 cases were included in the meta-analysis. The odds ratios of influencing factors were as follows: hypertension 2.51 (95% CI, 1.50-4.20), multifetal gestations 1.90 (95% CI, 1.26-2.88), male fetus 0.79 (95% CI, 0.74-0.84), and low socioeconomic status 0.51 (95% CI, 0.37-0.71). CONCLUSION: Evidence from English- and Chinese-language literature indicates that hypertension and multifetal gestations are risk factors for placenta accreta, while male fetus and low socioeconomic status are protective factors.

Influence factors and pregnancy outcomes for pernicious placenta previa with placenta accreta. / å‡¶é™©åž‹å‰ç½®èƒŽç›˜æ¤å ¥çš„å½±å“å› ç´ åŠå¦Šå¨ ç»“å±€.

OBJECTIVES: To explore the influence factors for pernicious placenta previa (PPP) with placenta accreta and pregnancy outcomes of different types of PPP. METHODS: A case-control study was conducted to collect 410 PPP patients admitted to a general hospital in Changsha from December 2013 to February 2018. Two hundred and fifty cases of PPP with placenta accreta were treated as a case group, and 160 cases of PPP without placenta accreta were treated as a control group. The relationship between clinical data and placenta accreta was analyzed, and the pregnancy outcomes of PPP was observed according to different types of placenta previa. RESULTS: Logistic regression showed that delivery times were more than 2 (OR=3.221), cesarean section times were more than 2 (OR=3.048), central placenta previa (OR=3.607), placental attachment site (anterior wall) (OR=4.592) were independent risk factors for PPP with placenta accrete (P<0.05). Living in cities (OR=0.614), systematic prenatal examination (OR=0.590) were protective factors (P<0.05). Average intraoperative blood loss, postpartum bleeding rate, hysterectomy rate in the central group were all higher than those in the marginal and low-set group. The incidence rates of ICU transfer, complications, and hospital stay were higher or longer than those in the marginal group (P'<0.008). There was no significant difference in stillbirth rate among the 4 groups (P>0.05). Preterm delivery rate was higher than that of the marginal and low-set group, and the birth weight was lower than that of the low-set group. Apgar score at 1 min and asphyxia rate were lower and higher than those of the other 3 groups, respectively (P'<0.008). CONCLUSIONS: Delivery times (>2), cesarean section times (≥2), central placenta previa, placenta attachment site (anterior wall) are independent risk factors for PPP with placenta accreta. Living in cities, systematic prenatal examination were protective factors. The central PPP is more likely to lead to postpartum hemorrhage, hysterectomy, and increases in the risk of preterm birth, low birth weight as well as asphyxia of fetus, which seriously threatens maternal and fetal life.

Construction of a Conditionally Asporogenous Bacillus thuringiensis Recombinant Strain Overproducing Cry Protein by Deletion of the leuB Gene.

One of the common shortcomings with Bacillus thuringiensis (Bt) biopesticides in field application is their instability under UV irradiation. In Bt, the leuB gene encodes the 3-isopropylmalate dehydrogenase. In addition to its role in leucine biosynthesis, LeuB would be likely recruited to catalyze the dehydrogenation of malate in the final step of tricarboxylic acid cycle during sporulation. In this study, we constructed a Bt recombinant strain in which the gene leuB was deleted by using the markerless gene deletion system. The ΔleuB mutant strain showed a conditionally asporogenous phenotype while overproducing insecticidal crystal proteins and retaining its insecticidal activity well in both fermentation and LB media. Furthermore, the metabolic regulation mechanisms of LeuB was elucidated by iTRAQ-based quantitative proteomics approach. Evidences from proteomics data suggested that the inhibited supply of pyruvate (carbon source) was an important factor related to the conditionally asporogenous feature of the mutant. Consistently, the mutant regained its ability to sporulate in LB medium by adding 1% glucose or 1% sodium pyruvate. Taken together, our study demonstrated that deletion of the leuB gene resulted in delayed or completely blocked mother cell lysis, allowing the crystals encapsulated within cells, which makes this recombinant strain a good candidate for developing Bt preparations with better UV-stability.

Alteration of the gut microbiome and immune factors of grass carp infected with Aeromonas veronii and screening of an antagonistic bacterial strain (Streptomyces flavotricini).

Aeromonas veronii is a widely distributed novel pathogen that can affect humans and animals, it can cause sepsis in fish with high mortality and serious economic losses to aquaculture. In the study, the gut microbiome of the infected and uninfected grass carp with Aeromonas veronii were analyzed probiotics and pathogenic bacteria by the Miseq high-throughput sequencing, the results showed that the infected fish were significantly higher in Proteobacteria, Firmicutes, Fusobacteria, and the immune factors in liver and kidney were up-regulated by qRT-PCR. In order to effectively inhibit the pathogen, we screened an actinomycete strain and had good antibacterial effect on Aeromonas veronii. The new antagonistic bacteria was named as Streptomyces flavotricini X101, the whole genome sequencing revealed that the metabolic process was most active. After grass carp was inoculated with the minimum inhibitory concentration of 900 µg/mL of the strain's fermentation supernatant, then Aeromonas veronii was injected, we found that the pathological symptoms such as body surface, anus and abdominal congestion were alleviated by H&E staining. Cellular experiments showed that it wasn't toxic to liver cells of grass carp. Overall, this is the first study of changes in intestinal flora, phenotype, and immune factors in grass crap infected with Aeromonas veronii, it had important theoretical significance and application value for immunization and prevention.

Role of hsp20 in the Production of Spores and Insecticidal Crystal Proteins in Bacillus thuringiensis.

The small heat shock protein plays an important role in response to stresses. We wanted to investigate how Hsp20 affects sporulation and production of insecticidal crystal proteins (ICPs) in Bacillus thuringiensis (Bt) at the stationary growth phase when cells are starved. The hsp20 gene was knocked out in Bt4.0718 (wide type), which is a B. thuringiensis strain screened in our laboratory, using endonuclease I-SceI mediated unmarked gene replacement method. Deletion of Hsp20 resulted in a decrease in both sporulation and ICPs production. Bt4-Δhsp20 cells and its ICP did not have a significant difference in shape and size but entered the decline phase 2 h earlier than the Bt4.0718. In order to find the mechanism that underlies these phenotypes, we completed a proteomic study of differentially expressed proteins (DEPs). In Bt4-Δhsp20 cells, 11 DEPs were upregulated and 184 DEPs downregulated. These affected DEPs are involved in multiple metabolic pathways: (1) six DEPs (two upregulated and four downregulated) are directly related to the sporulation and ICPs synthesis; (2) supply of amino acids including amino acid synthesis and protein recycling; (3) the energy supplementation (the tricarboxylic acid cycle and glycolysis); (4) purine metabolism and mRNA stability. These results suggest that hsp20 may be critical in maintaining the homeostasis of B. thuringiensis during the production of spores and ICPs, and could provide new sight into the sporulation and ICPs formation in B. thuringiensis.