Bacterial outer membrane vesicles in cancer: Biogenesis, pathogenesis, and clinical application.

Outer membrane vesicles (OMVs) are spherical, nano-sized particles of bilayer lipid structure secreted by Gram-negative bacteria. They contain a series of cargos from bacteria and are important messengers for communication between bacteria and their environment. OMVs play multiple roles in bacterial survival and adaptation and can affect host physiological functions and disease development by acting on host cell membranes and altering host cell signaling pathways. This paper summarizes the mechanisms of OMV genesis and the multiple roles of OMVs in the tumor microenvironment. Also, this paper discusses the prospects of OMVs for a wide range of applications in drug delivery, tumor diagnosis, and therapy.

Phenotypic and genetic characteristics of 130 patients with mucopolysaccharidosis type II: A single-center retrospective study in China.

Background: Mucopolysaccharidosis Type II (MPS II) is a rare, progressive and ultimately fatal X-linked lysosomal storage disorder caused by mutations in the iduronate-2-sulfatase (IDS) gene. This report conducted a retrospective analysis to investigate the clinical characteristics, genotypes and management strategies in a large cohort of Chinese patients with MPS II. Methods: In this study, we explored 130 Chinese patients with MPS II between September 2008 and April 2022. Clinical manifestations, auxiliary examination, IDS pathogenic gene variants and IDS enzyme activity, surgical history were analysed in the study. Results: A total of 130 patients were enrolled and the mean age at diagnosis was 5 years old. This study found the most common symptoms in our patients were claw-like hands, followed by coarse facial features, birthmarks (Mongolian spot), delayed development, inguinal or umbilical hernia. The most commonly cardiac manifestations were valve abnormalities, which were mitral/tricuspid valve regurgitation (71.9%) and aortic/pulmonary valve regurgitation (36.8%). We had found 43 different IDS pathogenic gene variants in 55 patients, included 16 novel variants. The variants were concentrated in exon 9 (20% = 11/55), exon 3 (20% = 11/55) and exon 8 (15% = 8/55). A total of 50 patients (38.5%) underwent surgical treatment, receiving a total of 63 surgeries. The average age of first surgery was 2.6 years, and the majority of surgery (85.7%, 54/63) was operated before 4 years old. The most common and earliest surgery was hernia repair. Three patients were died of respiratory failure. Conclusion: This study provided additional information on the clinical, cardiac ultrasound and surgical procedure in MPS II patients. Our study expanded the genotype spectrum of MPS II. Based on these data, characterization of MPS II patients group could be used to early diagnosis and treatment of the disease.

Application of patient decision aids in treatment selection of cardiac surgery patients: a scoping review.

BACKGROUND: The choice of treatment is an unavoidable challenge faced in the day to day medical decision making pertaining to patients with organic heart disease. As a professional discipline, cardiac surgery focuses on creating and using the most advanced evidence-based patient decision aids (PtDAs) to achieve high-quality decision-making. OBJECTIVES: To describe the basic situation, influencing factors, and the outcome of indicators of PtDAs among cardiac surgery patients. METHODS: Seven electronic databases were systematically searched for relevant reviews on the application of PtDAs among cardiac surgery patients. The methodological framework proposed by Arskey and O'Malley was used to guide the scoping review. The extracted data was analyzed qualitatively and quantitatively. RESULTS: After dual, blinded screening of titles and abstracts, 12 articles were included in the review. 10 were quantitative studies, 1 was a mixed study, 1 was a qualitative study. CONCLUSIONS: Compared with the burden of heart disease and the huge evidence base, the application of PtDAs in cardiac surgery is obviously insufficient. The published literature mainly provide information about the factors to be solved from the perspective of researchers, and also summarize obstacle factors. This is the basis for the application and construction of PtDAs in cardiac surgery patients.

Comparative metagenomic analysis of the vaginal microbiome in healthy women.

The composition of these vaginal microbiome has a significant impact on women's health. However, few studies have characterized the vaginal microbiome of healthy Chinese women using metagenomic sequencing. Here, we carried out a comparative metagenomic analysis to survey taxonomic, functional levels, and microbial communities' genome content in healthy women's vaginal microbiome. Overall, we observed a total of 111 species, including all dominant vaginal Lactobacillus species, such as L. iners, L. crispatus, L. gasseri, and L. jensenii. Unlike microbial taxa, several pathways were ubiquitous and prevalent across individuals, including adenosine ribonucleotides de novo biosynthesis and pyruvate fermentation to acetate and lactate II. Notably, our diversity analysis confirmed a significant difference in healthy women from different ethnic groups. Moreover, we binned vaginal assemblies into 62 high-quality genomes, including 9 L. iners, 7 A. vaginae, 5 L. jensenii, and 5 L. crispatus. We identified the pan and core genomes of L. iners and A. vaginae and revealed the genetic diversity. Primary differences between strains were the hypothetical genes and mobile element-like genes. Our results provide a framework for understanding the implications of the female reproductive tract's composition and functional potential and highlight the importance of genome-resolved metagenomic analysis to further understand the human vaginal microbiome.

Cobalt-Catalyzed Cross-Dehydrogenative C(sp2 )-C(sp3 ) Coupling of Oxazole/Thiazole with Ether or Cycloalkane.

Direct C5-alkylation of oxazole/thiazole with ether or cycloalkane has been achieved through a cobalt-catalyzed cross-dehydrogenative coupling (CDC) process in moderate to good yields. This transformation represents the first C(sp2 )-C(sp3 ) cross-coupling at the C5-position of the oxazole/thiazole via double C-H bond cleavages. Various functional groups on oxazole/thiazole substrates, as well as water and air, are well-tolerated with this concise and practical protocol, constituting straightforward access to heterocycles with great medicinal significance. A preliminary mechanism involving a radical process has also been proposed.

Capsaicin mediates cell cycle arrest and apoptosis in human colon cancer cells via stabilizing and activating p53.

Capsaicin is the major pungent ingredient in red peppers which is world widely consumed. Except its potent pain relieving efficacy as reported, capsaicin also exerted its antitumor activity in several tumor models. Here, we reported that capsaicin had a profound anti-proliferative effect on human colon cancer cells via inducing cell cycle G0/G1 phase arrest and apoptosis, which was associated with an increase of p21, Bax and cleaved PARP. The underlying mechanism of capsaicin's antitumor potency was mainly attributed to the stabilization and activation of p53. Capsaicin substantially prolonged the half-life of p53 and significantly elevated the transcriptional activity of p53. Through suppressing the interaction between p53 and MDM2, MDM2-mediated p53 ubiquitination was remarkably decreased after capsaicin treatment, which resulted in the stabilization and accumulation of p53. The results of p53-shRNA experiment further demonstrated that p53 knockdown severely impaired the sensitivity of tested cells to capsaicin, G0/G1 phase arrest and the apoptosis induced by capsaicin in p53-knockdown cells was also dramatically decreased, implicating the important role of p53 played in capsaicin's antitumor activity. In summary, our data suggested that capsaicin, or a related analogue, may have a role in the management of human colon cancer.

Fast fixing and comprehensive identification to help improve real-time ligands discovery based on formaldehyde crosslinking, immunoprecipitation and SDS-PAGE separation.

BACKGROUND: Fast Fixation is necessary to study real-time protein-protein interactions under physiological conditions. Fast formaldehyde cross-linking can fix transient and weak protein interactions, thereby reducing the number of false negatives but producing great complexity. To reduce this complexity, immunoaffinity purification can Fish out complexes that include particular target proteins, but affinity-based co-purification has a limited capacity to eliminate nonspecific binding to beads and/or antibodies. To Filter out these complexes, SDS-PAGE is used to disrupt non-covalent bonds, thereby eliminating uncross-linked complexes and simultaneously providing molecular weight information for identification. RESULTS: We described a 4 F strategy to help improve real-time ligands discovery based on formaldehyde crosslinking, immunoprecipitation and SDS-PAGE separation: Fast Fix, Fish, and Filter, using albumin interactome as an example. The use of gel excision without staining makes this strategy comprehensive and sensitive. The target protein must be identified in the same slice as its ligands. The ligands must be identified in slices for the experimental group but not in the corresponding control slices. Only proteins that appear in the range of molecular weights equal to or greater than the sum of the proteins' theoretical molecular weights, together with the target, are considered ligands. In this study, 5 s of cross-linking with 10% formaldehyde was achieved in human blood. The use of this strategy identified 35 ligands for albumin. Comparison with four major previous studies of the albuminome revealed that 68.57% of the 35 ligands identified in our study were identified in these other studies. CONCLUSIONS: Fast cross-linking was achieved. The 4 F strategy can be used to identify real-time in situ interactions without prior intervention and to comprehensively identify ligands of particular target proteins with fewer false positives.

Differential protein expression in perfusates from metastasized rat livers.

BACKGROUND: Liver perfusates exhibit theoretical advantages regarding the discovery of disease biomarkers because they contain proteins that readily enter the blood-stream, and perfusion preserves the disease state in its natural context. The purpose of the study is to explore the value of liver perfusate proteome in the biomarker discovery of liver diseases. RESULTS: In this study, 86 differentially expressed proteins were identified in perfusates from isolated rat livers metastasized by Walker-256 tumor cells. Among these proteins, 27 were predicted to be secreted, and 59 were intracellular or membrane proteins. Most of the secretory proteins (70.4%) were decreased in metastasized liver perfusates. The main canonical ingenuity pathway to which these secretory proteins belonged was acute phase response, which indicated that the liver-associated immune reaction was damaged by the metastasis. In contrast, most of the intracellular or membrane proteins (86.4%) exhibited higher relative abundances in the metastasized liver perfusates. Some of these proteins, including Rpl21, Atic, Eif3s2, Echs1, Eps15 and Ywhab, have previously been reported to be involved in cancer genesis and progression. As a member of the 14-3-3 protein family, Ywhab plays a key role in cellular proliferation and oncogenic transformation and has been reported to be involved in the development of breast cancer. Its abundance was elevated by 3.5-fold in the metastasized perfusates. Validation by Western blotting revealed a 3.7-fold increase in the abundance of this protein in metastasized plasma. CONCLUSIONS: These results show that perfusate proteome can be used as an alternative initial resource for biomarker identification, which ultimately requires validation in serum.