Effects of fructooligosaccharides and Saccharomyces boulardii on the compositional structure and metabolism of gut microbiota in students.

Fructooligosaccharides (FOS) are a common prebiotic widely used in functional foods. Meanwhile, Saccharomyces boulardii is a fungal probiotic frequenly used in the clinical treatment of diarrhea. Compared with single use, the combination of prebiotics and probiotics as symbiotics may be more effective in regulating gut microbiota as recently reported in the literature. The present study aimed to investigate the effects of FOS, S. boulardii and their combination on the structure and metabolism of the gut microbiota in healthy primary and secondary school students using an in vitro fermentation model. The results indicated that S. boulardii alone could not effectively regulate the community structure and metabolism of the microbiota. However, both FOS and the combination of FOS and S. boulardii could effectively regulate the microbiota, significantly inhibiting the growth of Escherichia-Shigella and Bacteroides, and controlling the production of the gases including H2S and NH3. In addition, both FOS and the combination could significantly promote the growth of Bifidobacteria and Lactobacillus, lower environmental pH, and enhance several physiological functions related to synthesis and metabolism. Nevertheless, the combination had more unique benefits as it promoted the growth of Lactobacillus, significantly increased CO2 production and enhanced the functional pathways of carbon metabolism and pyruvic acid metabolism. These findings provide guidance for clinical application and a theoretical basis for the development of synbiotic preparations.

Lactobacillus rhamnosus GG ameliorates hyperuricemia in a novel model.

Hyperuricemia (HUA) is a metabolic syndrome caused by abnormal purine metabolism. Although recent studies have noted a relationship between the gut microbiota and gout, whether the microbiota could ameliorate HUA-associated systemic purine metabolism remains unclear. In this study, we constructed a novel model of HUA in geese and investigated the mechanism by which Lactobacillus rhamnosus GG (LGG) could have beneficial effects on HUA. The administration of antibiotics and fecal microbiota transplantation (FMT) experiments were used in this HUA goose model. The effects of LGG and its metabolites on HUA were evaluated in vivo and in vitro. Heterogeneous expression and gene knockout of LGG revealed the mechanism of LGG. Multi-omics analysis revealed that the Lactobacillus genus is associated with changes in purine metabolism in HUA. This study showed that LGG and its metabolites could alleviate HUA through the gut-liver-kidney axis. Whole-genome analysis, heterogeneous expression, and gene knockout of LGG enzymes ABC-type multidrug transport system (ABCT), inosine-uridine nucleoside N-ribohydrolase (iunH), and xanthine permease (pbuX) demonstrated the function of nucleoside degradation in LGG. Multi-omics and a correlation analysis in HUA patients and this goose model revealed that a serum proline deficiency, as well as changes in Collinsella and Lactobacillus, may be associated with the occurrence of HUA. Our findings demonstrated the potential of a goose model of diet-induced HUA, and LGG and proline could be promising therapies for HUA.

TBC1D5 reverses the capability of HIF-2α in tumor progression and lipid metabolism in clear cell renal cell carcinoma by regulating the autophagy.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is known for abnormal lipid metabolism and widespread activation of HIF-2α. Recently, the importance of autophagy in ccRCC has been focused, and it has potential connections with HIF-2α and lipid metabolism. However, the specific regulatory mechanism between HIF-2α, autophagy, and lipid metabolism in ccRCC is still unclear. METHODS: In this study, Bioinformatics Analysis and Sequencing of the whole transcriptome were used to screen our target. The expression of TBC1D5 in renal clear cell carcinoma was confirmed by database analysis, immunohistochemistry, PCR and Western blot. The effects of TBC1D5 on tumor cell growth, migration, invasion and lipid metabolism were examined by CCK8, Transwell and oil red staining, and the mechanism of TBC1D5 on autophagy was investigated by Western blot, fluorescence microscopy and electron microscopy. Chloroquine and rapamycin were used to verified the key role of autophagy in effects of TBC1D5 on tumor cell. The regulatory mechanism of TBC1D5 in renal clear cell carcinoma (RCC) was investigated by shhif-2α, shTBC1D5, mimic, inhibitor, ChIP and Luciferase experiments. The animal model of ccRCC was used to evaluate the biological function of TBC1D5 in vivo. RESULTS: In this study, TBC1D5 was found to be an important bridge between autophagy and HIF-2α. Specifically, TBC1D5 is significantly underexpressed in ccRCC, serving as a tumor suppressor which inhibits tumor progression and lipid accumulation, and is negatively regulated by HIF-2α. Further research has found that TBC1D5 regulates the autophagy pathway to reverse the biological function of HIF-2α in ccRCC. Mechanism studies have shown that HIF-2α regulates TBC1D5 through hsa-miR-7-5p in ccRCC, thereby affecting tumor progression and lipid metabolism through autophagy. CONCLUSIONS: Our research reveals a completely new pathway, HIF-2α/hsa-miR-7-5p/TBC1D5 pathway affects ccRCC progression and lipid metabolism by regulating autophagy.

Reprogrammable Magnetic Soft Actuators with Microfluidic Functional Modules via Pixel-Assembly.

Magnetic soft actuators and robots have attracted considerable attention in biomedical applications due to their speedy response, programmability, and biocompatibility. Despite recent advancements, the fabrication process of magnetic actuators and the reprogramming approach of their magnetization profiles continue to pose challenges. Here, a facile fabrication strategy is reported based on arrangements and distributions of reusable magnetic pixels on silicone substrates, allowing for various magnetic actuators with customizable architectures, arbitrary magnetization profiles, and integration of microfluidic technology. This approach enables intricate configurations with decent deformability and programmability, as well as biomimetic movements involving grasping, swimming, and wriggling in response to magnetic actuation. Moreover, microfluidic functional modules are integrated for various purposes, such as on/off valve control, curvature adjustment, fluid mixing, dynamic microfluidic architecture, and liquid delivery robot. The proposed method fulfills the requirements of low-cost, rapid, and simplified preparation of magnetic actuators, since it eliminates the need to sustain pre-defined deformations during the magnetization process or to employ laser heating or other stimulation for reprogramming the magnetization profile. Consequently, it is envisioned that magnetic actuators fabricated via pixel-assembly will have broad prospects in microfluidics and biomedical applications.

The multifaceted roles of small extracellular vesicles in metabolic reprogramming in the tumor microenvironments.

The link between metabolism and tumor progression has been extensively researched for a long time. With the increasing number of studies uncovering the multiple functions of metabolic reprogramming in tumor microenvironments, the regulatory network seems to become even more intricate at the same time. Small extracellular vesicles (sEV), as crucial mediators facilitating intercellular communications, exhibit significant involvement in regulating metabolic reprogramming within the complicated network of tumor microenvironments. sEV derived from tumor cells and those released by other cell populations such as tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) can mutually influence each other, giving rise to diverse complex feedback loops. This review includes multiple studies conducted in recent years to summarize the functions of sEV in altering metabolism in various cell types within tumor microenvironments. Additionally, it aims to highlight potential therapeutic targets based on the commonly observed mechanisms identified in different studies.

Comparison of dexmedetomidine and opioids as local anesthetic adjuvants in patient controlled epidural analgesia: a meta-analysis.

BACKGROUND: Data on the efficacy and incidence of adverse effects associated with dexmedetomidine (DEX) as a local anesthetic adjuvant for patient-controlled epidural analgesia (PCEA) are inconclusive. This meta-analysis assessed the efficacy and risks of DEX for PCEA using opioids as a reference. METHODS: Two researchers independently searched PubMed, Embase, Cochrane Library, and China Biology Medicine for randomized controlled trials comparing DEX and opioids as local anesthetic adjuvants in PCEA. RESULTS: In total, 636 patients from seven studies were included in this meta-analysis. Postoperative patients who received DEX had lower visual analog scale (VAS) scores than those who received opioids at 4-8 h (mean difference [MD]: 0.61, 95% CI [0.45, 0.76], P < 0.001, I2 = 0%), 12 h (MD: 0.85, 95% CI [0.61, 1.09], P < 0.001, I2 = 0%), 24 h (MD: 0.59, 95% CI [0.06, 1.12], P = 0.030, I2 = 82%), and 48 h (MD: 0.54, 95% CI [0.05, 1.02], P = 0.030, I2 = 91%). Additionally, patients who received DEX had a lower incidence of itching (odds ratio [OR]: 2.86, 95% CI [1.18, 6.95], P = 0.020, I2 = 0%) and nausea and vomiting (OR: 6.83, 95% CI [3.63, 12.84], P < 0.001, I2 = 24%). In labor analgesia, no significant differences in neonatal (pH and PaO2 of cord blood, fetal heart rate) or maternal outcomes (duration of labor stage, mode of delivery) were found between the DEX and opioid groups. CONCLUSIONS: Compared with opioids, using DEX as a local anesthetic adjuvant in PCEA improved postoperative analgesia and reduced the incidence of itching and nausea and vomiting without increasing the incidence of adverse events.

Slow-digestive yeast protein concentrate: An investigation of its in vitro digestibility and digestion behavior.

Yeast protein concentrate, a by-product of the fermentation industry waste, is a potential alternative protein source with high nutritional quality, environmental sustainability, and functional properties. However, its digestibility and digestion behavior are poorly understood. In this study, we compared the in vitro digestion behavior of yeast protein concentrate and whey protein concentrate using simulated gastrointestinal conditions. We found that yeast protein concentrate had lower digestibility than whey protein concentrate (31.25% vs. 86.23% at 120 min of pepsin digestion and 75.12% vs. 95.2% at 120 min of pancreatin digestion). Yeast protein concentrate differed from whey protein concentrate in microstructure, secondary structure, and amino acid composition, which may affect its digestion behavior. Compared to whey protein concentrate, a higher level of ß-sheets and a lower zeta potential explain the slow-digesting property of yeast protein concentrate. Yeast protein concentrate also underwent depolymerization and Plastein reaction during digestion. These results provided valuable information for developing and applying yeast protein concentrate as an alternative to conventional animal protein.

Anti-oxidative and anti-aging effects of mannoprotein-rich yeast cell wall enzymatic hydrolysate by modulating gut microbiota and metabolites in Caenorhabditis elegans.

In this study, antioxidant and anti-aging studies were carried out by mannoprotein-rich yeast cell wall enzymatic hydrolysate (MYH) obtained by enzymatic hydrolysis of yeast cell wall through the Caenorhabditis elegans (C. elegans) model. It was found that MYH could improve the lifespan and anti-stress ability of C. elegans by increasing the activity of antioxidant enzymes such as T-SOD, GSH-PX and CAT, and reducing the levels of MDA, ROS and apoptosis. At the same time, through the verification expression of corresponding mRNA, it was found that MYH exerted antioxidant and anti-aging activities by up-regulating the translation of MTL-1, DAF-16, SKN-1 and SOD-3 mRNA, and down-regulating the translation of AGE-1 and DAF-2 mRNA. In addition, it was found that MYH could improve the composition and distribution of the gut microbiota of C. elegans, and significantly improve the level of metabolites through the sequencing of gut microbiota and untargeted metabolomic studies. It has contributed to studying the antioxidant and anti-aging activities of microorganisms such as yeast through the level of gut microbiota and metabolites and the development of related functional foods.

Protein-rich yeast extract (®fermgard) has potential antioxidant and anti-aging activities.

There existed a deficiency in the research on the nutritional activities of microbial (yeast) active substances in antioxidant and anti-aging activities, although the research objects were concentrated in animals and plants in recent years. In this study, the anti-oxidant and anti-aging activities of protein-rich yeast extract (®fermgard) (YE) were investigated through Caenorhabditis elegans (C. elegans). The results indicated that YE could improve the lifespan and anti-stress ability by up-regulating the activities of antioxidant enzymes in C. elegans. Meanwhile, the mRNA transcriptional level of daf-16, skn-1 and sod-3 was significantly up-regulated. In addition, the composition and level of the gut microbiota and metabolite were modulated. YE exerts antioxidant and anti-aging activities by regulating the expression of anti-oxidation-related mRNA, gut microbiota and metabolites in C. elegans, providing a basis for exploring the deep mechanism of YE improving health. At the same time, it provides new ideas for the development of functional foods.

Epigenetic differences in NCOA2: a novel biomarker that predicts prognosis in clear cell renal cell carcinoma.

OBJECTIVES: Kidney cancer is one of the top ten cancers worldwide, and clear cell renal cell carcinoma (ccRCC) is the most common pathohistological type of kidney cancer. This study aimed to decipher the diagnostic and prognostic value of NCOA2 for ccRCC survival based on its expression and methylation. METHODS: We explored the mRNA and protein expression, DNA methylation, prognosis, cell function, and relevant immune infiltration of NCOA2 in ccRCC using data from public databases. Furthermore, GSEA (Gene Set Enrichment Analysis) was used to dissect the cell functions and signal pathways associated with NCOA2 involved in ccRCC and evaluated the close correlation between NCOA2 expression and immune cells. Finally, RT-qPCR (quantitative reverse transcription PCR) and IHC (immunohistochemistry) were utilized to verify the expression of NCOA2 in ccRCC among the tumor and adjacent normal tissues collected from patients. RESULTS: NCOA2 was lowly expressed in ccRCC tissue, which resulted from its methylation. High NCOA2 expression and low beta value of one of the CpG sites predicted better prognosis in patients with ccRCC. GSEA results and analysis of immune infiltration revealed that NCOA2 was associated with PD-1/PD-L1 expression and infiltration of other immune cells in ccRCC. CONCLUSIONS: NCOA2 has great potential to serve as a novel biomarker that can predict prognosis in ccRCC and may become a new therapeutic target in patients with late-stage ccRCC.

Anti-Oxidative and Anti-Aging Effects of Probiotic Fermented Ginseng by Modulating Gut Microbiota and Metabolites in Caenorhabditis elegans.

Antioxidative and antiaging abilities of probiotic fermented ginseng (PG) were evaluated in Caenorhabditis elegans (C. elegans). Lifespan and effect on heat stress and acute oxidative stress in C. elegans were significantly enhanced by PG. Antioxidative enzymes such as T-SOD, GSH-PX, CAT were significantly up-regulated, and MDA, ROS and apoptosis levels were significantly down-regulated. At the same time, PG exerted antioxidant and anti-aging activities by reducing the expression of DAF-2 mRNA and increasing the expression of SKN-1 and SOD-3 mRNA in C. elegans. In addition, the mechanism of antioxidative and antiaging activities of PG was explored through gut microbiota sequencing and untargeted metabolomics. The results of gut microbiota indicated that PG could significantly improve the composition and structure of microbes in the gut of C. elegans, and the relative abundance of beneficial bacteria was up-regulated. Untargeted metabolomic results elucidated that PG modulated antioxidant and antiaging activities through neuroactive ligand-receptor interaction, Citrate cycle (TCA cycle), pyruvate metabolism, ascorbate and aldarate metabolism and D-Arginine and D-ornithine metabolism of C. elegans. These results indicated that PG had excellent antioxidant and anti-aging activities, providing research value for the development of functional foods and improvement of aging-related diseases.

Advances and challenges in sexually transmitted infections prevention among men who have sex with men in Asia.

PURPOSE OF REVIEW: This review summarizes recently published research on sexually transmitted infections (STIs) and sexually transmitted diseases (STDs) among men who have sex with men (MSM) in Asia, covering four main areas: prevalence and consequences of STIs/STDs, factors associated with STI risk, strategies and measures of STI prevention, challenges in the prevention of SITs. RECENT FINDINGS: Studies show that STIs among Asian MSM are still prevalent, with the prevalence of STIs varying slightly from country to country. In addition to the number of sexual partners, frequency of condom use, high-risk sexual behaviors, the influence of Confucianism, law, and COVID-19 are also related to STI risk. Social stigma, weak health systems, lack of funding and policy support are the current challenges for STIs prevention. SUMMARY: In the future, new media technologies are encouraged to be used to enhance education and reduce stigma and discrimination against MSM and STIs. Expanding STI screening, strengthening STI knowledge propaganda and education among MSM population, and providing necessary counseling and medical services are main strategies in STI prevention. It is also important to strengthen STI awareness and policy support at the national level.

Serum SALL4 as a predictive biomarker for the prognosis of patients with hepatocellular carcinoma who underwent nonsurgical treatment.

To investigate the role of serum spalt like transcription factor 4 (SALL4) in the hepatocellular carcinoma (HCC) patients with nonsurgical treatment. Serum samples were collected from 101 patients with HCC without surgical treatment, then the SALL4 was detected by enzyme linked immunosorbent assay. According to subsequent treatment, patients were divided into 2 groups, best supportive care (BSC) (58 cases) and nonsurgical anticancer treatment (NSAT) (48 cases). Kaplan-Meier survival analysis and Cox multivariate regression analysis were applied to evaluate the relationship between SALL4 and survival time of 2 groups. In BSC group, there was no significant difference of the survival time between 2 groups (SALL4 < 800 ng/mL or SALL4 ≥ 800 ng/mL) (P = .339). In NSAT group, the survival time of patients with low SALL4 concentration was significantly longer than patients with high SALL4 concentration (P = .005). SALL4 have no predictive effect in BSC patients with HCC. But for patients received NSAT, low SALL4 concentration in serum may indicate longer survival.

APOBEC3B is overexpressed in cervical cancer and promotes the proliferation of cervical cancer cells through apoptosis, cell cycle, and p53 pathway.

Objective: APOBEC3B (A3B), a member of the APOBEC family of cytidine deaminases, has been gradually regarded as a key cancerous regulator. However, its expression and mechanism in cervical cancer (CC) have not been fully elucidated. This study was to investigate its expression pattern and potential mechanism on the cell cycle, as well as HPV oncogenes in CC. Methods: Data from The Cancer Genome Atlas (TCGA) and Gene Expression (GEO) were used to indicate the mRNA expression pattern of A3B in cervical cancer. Western blot assay was used to detect A3B levels in SiHa and Hela cell lines. Immunohistochemistry (IHC) was used to explore A3B protein abundance and sublocation in cervical cancer as well as normal cervical tissues. Based on the Protein atlas (www.proteinatlas.org), A3B expression in the SiHa cell line is lower than in the HeLa cell line. Therefore, the SiHa cell line was used for A3B gene overexpression experiments while the HeLa cell line was used for knockdown experiments. Flow cytometry analysis was used to detect cell apoptosis. Biological function and cancer-related pathways of A3B were conducted using bioinformatics analysis. Results: A3B mRNA was significantly overexpressed in cervical cancer in TCGA-cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), GSE67522, and GSE7803. A3B was more highly expressed in cervical cancers than in high-grade squamous intraepithelial lesions and normal controls. A3B expression was found to be progressively activated during cervical cancer development. IHC results showed that A3B was significantly higher in cervical cancer tissues than in normal cervical tissues. A3B plasmid-mediated overexpression experiments and A3B siRNA-mediated knockdown experiments showed that A3B significantly promotes cell proliferation, migration, cell cycle, and chemoresistance in cervical cancer cells by the p53 pathway. GO and KEGG analyses showed that A3B expression was strikingly associated with cell proliferation, apoptosis, and immune-associated pathways. Conclusions: Taken together, our study implies that A3B promotes cell proliferation, migration, and cell cycle and inhibits cancer cell apoptosis through the p53-mediated signaling pathway. Moreover, A3B could also contribute to chemoresistance in cervical cancer cells. It may be a potential diagnostic biomarker and therapeutic target for chemoresistant cervical cancers.

Influence of Gut Microbiota and Trimethylamine N-Oxide in Patients with Coronary Heart Disease.

In the current study, the gut microbiota of patients with and without coronary heart disease was compared and the relationship between gut microbiota distribution, intending to reveal the role of gut microbiota in the coronary atherosclerosis process, was investigated.This study included 50 patients diagnosed with coronary heart disease (CHD) who received conventional coronary angiography or computed tomography angiography and 50 patients with CHD at Changshu No. 2 People's Hospital, Suzhou, China, from May 2020 to January 2021. Trimethylamine N-oxide (TMAO) level was tested and feces were collected, the DNA of the gut microbiota was extracted, and the distribution by 16SrRNA gene sequencing was obtained from the two groups of patients.Plasma TMAO concentrations were significantly higher in patients with CHD (P < 0.001). In the CHD group, 22 patients with multivessel disease had a higher level of TMAO compared with the 28 patients who had the single-vessel disease (P < 0.001). No difference in the gut microbiota diversity was noted between the two groups (P < 0.001). Patients with CHD had a significantly lower proportion of Bacteroidetes phyla and more proportion of Epsilonbacteraeota phyla. At the genus level, patients with CHD had an increased abundance of Enterococcus, whereas healthy controls had significantly higher levels of Streptococcus. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 2 analysis found that, in the KEGG ORTHOLOGY, the level of choline trimethylamine-lyase gene expression correlated with TMAO production was higher in the fecal microbiome of the CHD group (P < 0.05).Gut microbiota and its product were expected to become a diagnostic marker and a new target for preventing CHD.

Ferroptosis and Its Emerging Role in Pre-Eclampsia.

Iron is essential for cell survival, and iron deficiency is a known risk factor for many reproductive diseases. Paradoxically, such disorders are also more common in cases of iron overload. Here, we evaluated the role of ferroptosis in women's health, particularly focusing on pre-eclampsia (PE). PE is a multisystem disorder and is one of the leading causes of maternal and perinatal morbidity and mortality, especially when the condition is of early onset. Nevertheless, the exact etiological mechanism of PE remains unclear. Interestingly, ferroptosis, as a regulated iron-dependent cell death pathway, involves a lethal accumulation of lipid peroxides and shares some characteristics with PE pathophysiology. In this review, we comprehensively reviewed and summarized recent studies investigating the molecular mechanisms involved in the regulation and execution of ferroptosis, as well as ferroptosis mechanisms in the pathology of PE. We propose that ferroptosis not only plays an important role in PE, but may also become a novel therapeutic target for PE.

The Bioinformatical Identification of Potential Biomarkers in Heart Failure Diagnosis and Treatment.

Background: Heart failure (HF) is defined as the inability of the heart's systolic and diastolic function to properly discharge blood flow from the veins to the heart. The goal of our research is to look into the possible mechanism that causes HF. Methods: The GSE5406 database was used for screening the differentially expressed genes (DEGs). Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction (PPI) network were applied to analyze DEGs. Besides, cell counting Kit-8 (CCK-8) was conducted to observe the knockdown effect of hub genes on cell proliferation. Results: Finally, 377 upregulated and 461 downregulated DEGs came out, enriched in the extracellular matrix organization and gap junction. According to GSEA results, Hoft cd4 positive alpha beta memory t cell bcg vaccine age 18-45 yo id 7 dy top 100 deg ex vivo up, Sobolev t cell pandemrix age 18-64 yo 7 dy dn, and so on were significantly related to gene set GSE5406. 7 hub genes, such as COL1A1, UBB, COL3A1, HSP90AA1, MYC, STAT3 and MAPK1, were selected from PPI networks. CCK-8 indicated silencing of STAT3 promoted the proliferation of H9C2 cells and silencing of UBB inhibited the proliferation of H9C2 cells. Conclusion: Our analysis reveals that COL1A1, UBB, COL3A1, HSP90AA1, MYC, STAT3, and MAPK1 might promote the progression of HF and become the biomarkers for diagnosis and treatment of HF.

The Role of Cancer-Associated Fibroblasts in Ovarian Cancer.

Ovarian cancer is a lethal gynecologic tumor and is generally resistant to conventional treatments. Stable cancer-associated fibroblasts (CAFs) are important cellular components in the ovarian cancer tumor microenvironment and may provide novel resources for future treatment strategies. Different subtypes of CAFs display specific functions in tumor pathogenesis and various CAF markers suggest potential treatment targets, such as FAP and GPR77. Both autocrine and paracrine cytokines play important roles in the CAF activation process and regulate tumor progression. Downstream mediators and pathways, including IL-6, TGF-ß, NF-κB, mitogen-activated protein kinase (MAPK), and AKT/mTOR/(p70S6K), play important roles in the initiation, proliferation, invasiveness, and metastasis of ovarian cancer cells and also participate in angiogenesis, therapeutic resistance, and other biological processes. Several clinical or preclinical trials have targeted stromal fibroblasts and focused on the properties of CAFs to enhance ovarian cancer treatment outcomes. This review concentrates on the origins, subtypes, and activation of CAFs, as well as specific roles of CAFs in regulating tumor development and drug resistance, and aims to provide potential and prospective targets for improving the therapeutic efficacy of ovarian cancer treatment.