Advances in crosstalk among innate immune pathways activated by mitochondrial DNA.

Mitochondria are not only the power plant for intracellular oxidative phosphorylation and ATP synthesis, but also involved in cell proliferation, differentiation, signaling and apoptosis. Recent studies have shown that mitochondria play an important role in other pathophysiological functions in addition to cellular energy metabolism. Mitochondria release mitochondrial DNA (mtDNA) as a damage-associated molecular pattern (DAMP) to activate Toll-like receptor 9 (TLR9), NOD-, LRR-, and pyrin domain-containing 3 (NLRP3) inflammasome and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) innate immune signaling pathways against foreign pathogenic microorganisms. The innate immune response not only promotes antimicrobial immune defense and regulates antiviral signaling, but their overactivation also induces the onset and progression of inflammatory diseases. In this paper, we review the role of mtDNA in the activation of innate immune signaling pathways and the crosstalk among innate immune signaling pathways activated by mtDNA, providing clues for the study of inflammatory diseases caused by mtDNA cytoplasmic translocation.

Effects of chitosan molecular weight and mass ratio with natural blue phycocyanin on physiochemical and structural stability of protein.

Phycocyanin (PC), an algae-extracted colorant, has extensive applications for its water-solubility and fresh blue shade. When PC is added to acidified media, dispersions are prone to aggregate and decolorize into cloudy systems. For palliating this matter, chitosan with high, medium, and low molecular weights (HMC, MMC, and LMC) were adopted in PC dispersions, and their protective effects were compared based on physiochemical stabilities. The optimal mass ratio between chitosan and PC was identified as 1:5 based on preliminary evaluations and was supported by the higher ζ-potential (31.0-32.1 mV), lower turbidity (39.6-43.6 NTU), and polyacrylamide gel electrophoresis results. Through interfacial and antioxidant capacity analyses, LMC was found to display a higher affinity to PC, which was also confirmed by SEM images and the maximum increase in transition temperature of their complex (155.70 °C) in DSC measurements. The mechanism of electrostatic interaction reinforced by hydrophobic effects and hydrogen bonding was elucidated by FT-IR and Raman spectroscopy. Further comprehensive stability evaluations revealed that, without light exposure, LMC kept PC from internal secondary structure to external blueness luster to the maximum extent. While with light exposure, LMC was not so flexible as HMC, to protect chromophores from attack of free radicals.

MiR-150-5p contributes to unexplained recurrent spontaneous abortion by targeting VEGFA and downregulating the PI3K/AKT/mTOR signaling pathway.

PURPOSE: The purpose of this study is to investigate the function of miR-150-5p in URSA. METHOD: Twenty-six chorionic villous tissues were collected to examine the expression of miR-150-5p and VEGFA by using quantitative polymerase chain reaction (qPCR) and western blot assay, respectively. Transwell assay was conducted to assess the migration and invasion ability of trophoblast cells. The dual-luciferase reporter assay was applied to determine the relationship between miR-150-5p and VEGFA in vitro. Relevant signaling pathway protein expression level was measured via western blot assay. Signaling transduction inhibitor LY294002 was used to block PI3K/AKT/mTOR signaling pathway. Finally, in vivo the effect of miR-150-5p on embryonic absorption rate was evaluated in mice. RESULTS: Clinical samples revealed that miR-150-5p expression was significantly elevated in the villous tissues and serum of URSA patients. Moreover, the overexpressing of miR-150-5p could inhibit both HTR-8/SVneo cell and JAR cell migration, invasion, and restrained PI3K/AKT/mTOR signaling pathway by targeting VEGFA in vitro. This inhibitory effect of miR-150-5p could be reversed by overexpressing the gene of vascular epithelial growth factor A (VEGFA). In contrary, inhibition of miR-150-5p significantly enhanced migration, invasion ability of both HTR-8/SVneo and JAR cells, and also could stimulate PI3K/AKT/mTOR signaling pathway. This promoting effect of miR-150-5p could be ameliorated by LY294002 (PI3K inhibitor). Finally, after miR-150-5p overexpression in vivo, the embryo resorption rate in pregnant mice was increased significantly. CONCLUSIONS: Overall, these findings imply that miR-150-5p is among the key factors that regulate the pathogenesis of URSA.

Application of a new multi-element integrated teaching mode based on bite-sized teaching, flipped classroom, and MOOC in clinical teaching of obstetrics and gynaecology.

CONTEXT: Effective clinical medical student education includes attention to teaching approaches. This study assessed the impact of a new multi-element teaching mode that utilizes Bite-Sized Teaching, flipped classroom, and MOOC on learner perception in an Obstetrics and gynaecology clerkship. METHODS: A Two-stage crossover design study was conducted of a multi-element teaching mode compared to traditional teaching mode in an academic year. Participants included Ninety-six medical students practicing obstetrics and gynecology in our hospital, randomly divided into two groups respectively underwent multi-element teaching mode and traditional teaching mode. After each semester, a final test (including theoretical and clinical practical test) was conducted.When an academic year was completed, post intervention survey assessed learner perceptions of the intervention. RESULT: In order to comprehensively test students' performance after study, we take theoretical and practical examinations. The theoretical examination mainly tests students' grasp of basic knowledge points, while the practical examination focuses on the examination of students' diagnosis and treatment of diseases. There were statistically significant differences both in the theoretical and clinical practical scores between the new multi-element integrated teaching mode and the traditional teaching mode, specifically as follows: In the end of first semester, the theoretical scores of the two groups were respective 43.75 ± 3.42 vs. 42.07 ± 2.90, and clinic practical test scores were respective 44.93 ± 2.42 vs. 43.37 ± 2.52; In the end of second semester, the theoretical scores of the two groups were respective 44.30 ± 2.69 vs. 42.25 ± 3.39, and clinic practical test scores were respective 43.79 ± 2.25 vs. 41.93 ± 2.80.(p < 0.05). The results of questionnaires demonstrated that 80.21% of the students showed preference for the new multi-element integrated teaching mode comparing to traditional teaching methods. CONCLUSION: The new multi-element integrated teaching mode is well accepted by the students and can improve the students' mastery of knowledge, and can improve the students' clinical comprehensive ability. The new multi-element integrated teaching mode is shown more preference than traditional teaching mode in the teaching of Obstetrics and Gynaecology. Further long term study is needed carried out to consolidate our conclusion. The new multi-element integrated teaching mode may have positive effects on clinical teaching of Obstetrics and Gynaecology.

Extraction, identification and application of gliadin from gluten: Impact of pH on physicochemical properties of unloaded- and lutein-loaded gliadin nanoparticles.

In the present study, high purity gliadin was extracted from gluten by the marginally modified Osborne method and the effect of different pHs in the aqueous ethanol on the physicochemical properties of unloaded gliadin nanoparticles (UGNs) and lutein-loaded gliadin nanoparticles (LGNs) was investigated. The results revealed that the formation of UGNs and LGNs at diverse pHs was driven by a conjunction of hydrogen bonding, electrostatic interactions and hydrophobic effects, but their dominant roles varied at different pHs. pH also significantly impacted the surface hydrophobicity, secondary structure and aromatic amino acid microenvironment of UGNs and LGNs. LGNs at pH 5.0 and at pH 9.0 exhibited better loading capacity and could reach 9.7884 ± 0.0006 % and 9.7360 ± 0.0017 %, respectively. These two samples also had greater photostability and thermal stability. Half-lives of LGNs at pH 5.0 were 2.185 h and 54.579 h, respectively. Half-lives of LGNs at pH 9.0 were 2.937 h and 49.159 h, respectively. LGNs at pH 5.0 and LGNs at pH 9.0 also had higher bioaccessibility of lutein, with 15.98 ± 0.04 % and 15.27 ± 0.03 %, respectively. These findings yielded precious inspirations for designing innovative lutein delivery system.

Effects of Bifidobacterium BL21 and Lacticaseibacillus LRa05 on gut microbiota in type 2 diabetes mellitus mice.

Gut dysbiosis causes damage to the intestinal barrier and is associated with type 2 diabetes mellitus (T2DM). We tested the potential protective effects of probiotic BL21 and LRa05 on gut microbiota in type 2 diabetes mellitus mice and determined whether these effects were related to the modulation of gut microbiota.Thirty specific pathogen-free C57BL/6J mice were randomly allocated to three groups-the (CTL) control group, HFD/STZ model (T2DM) group, and HFD/STZ-probiotic intervention (PRO) group-and intragastrically administered strains BL21 and LRa05 for 11 weeks. The administration of strains BL21 and LRa05 significantly regulated blood glucose levels, accompanied by ameliorated oxidative stress in mice. The BL21/LRa05-treated mice were protected from liver, cecal, and colon damage. Microbiota analysis showed that the cecal and fecal microbiota of the mice presented significantly different spatial distributions from one another. Principal coordinate analysis results indicated that both T2DM and the BL21/LRa05 intervention had significant effects on the cecal contents and fecal microbiota structure. In terms of the fecal microbiota, an abundance of Akkermansia and Anaeroplasma was noted in the PRO group. In terms of the cecal content microbiota, enrichment of Akkermansia, Desulfovibrio, Bifidobacterium, Lactobacillus, and Limosilactobacillus was noted in the PRO group. The probiotics BL21 and LRa05 prevent or ameliorate T2DM by regulating the intestinal flora and reducing inflammation and oxidative stress. Our results suggest that BL21 and LRa05 colonize in the cecum. Thus, BL21/LRa05 combined with probiotics having a strong ability to colonize in the colon may achieve better therapeutic effects in T2DM. Our study illustrated the feasibility and benefits of the combined use of probiotics and implied the importance of intervening at multiple intestinal sites in T2DM mice.

Sustained ameliorative effect of Lactobacillus acidophilus LA85 on dextran sulfate sodium-induced colitis in mice.

Ulcerative colitis (UC) is a type of inflammatory bowel disease associated with immune system dysfunction caused by gut dysbiosis. This study aimed to investigate the alleviating effect of Lactobacillus acidophilus LA85 on colitis and its underlying mechanism using mouse models of dextran sulfate sodium (DSS)-induced UC. The UC mouse models were established by treating C57BL/6J male mice with 2.5% (w/v) DSS in drinking water for 7 days. These mice received supplementation with either L. acidophilus LA85 (1 × 109 colony-forming units/day) or 200 µL of sterile water once daily (LA85-treated and UC model mice, respectively). The disease activity index (DAI), colon length, and histological changes in the colons of mice were then analyzed at Day 21, and the effects of L. acidophilus LA85 on the gut microbiota and serum inflammatory cytokines were also investigated. Compared with the UC model mice, L. acidophilus LA85-treated UC mice showed significant reductions in a variety of colitis symptoms, including weight loss, the DAI score, colon shortening, and colon tissue damage. Lactobacillus acidophilus LA85 supplementation also significantly decreased the serum concentrations of tumor necrosis factor α and interleukin-6 while increasing the serum concentration of IL-10. Furthermore, LA85 supplementation improved the diversity and composition of the gut microbiota, both of which had been decreased by DSS. In particular, L. acidophilus LA85-treated UC mice showed higher relative abundances of Akkermansia and Romboutsia than the UC model mice. These results demonstrate that L. acidophilus LA85 can alleviate inflammatory diseases of the intestine, such as inflammatory bowel disease, by regulating immune responses and restoring the gut microbiota. PRACTICAL APPLICATION: Ulcerative colitis is a type of inflammatory bowel disease caused by imbalance of gut microbiota. This study showed that L. acidophilus LA85 can alleviate DSS-induced colitis in mice through regulation of inflammatory cytokines, protection of intestinal barrier, and regulation of specific gut microbiota. L. acidophilus LA85 is a promising probiotic candidate for the treatment of UC.

A novel clinical prediction model of severity based on red cell distribution width, neutrophil-lymphocyte ratio and intra-abdominal pressure in acute pancreatitis in pregnancy.

BACKGROUND: Acute pancreatitis in pregnancy (APIP) with a high risk of death is extremely harmful to mother and fetus. There are few models specifically designed to assess the severity of APIP. Our study aimed to establish a clinical model for early prediction of severity of APIP. METHODS: A retrospective study in a total of 188 patients with APIP was enrolled. The hematological indicators, IAP (intra-abdominal pressure) and clinical data were obtained for statistical analysis and prediction model construction. RESULTS: According to univariate and multivariate logistic regression analysis, we found that red cell distribution width (RDW), neutrophil-lymphocyte ratio (NLR) and Intra-abdominal pressure (IAP) are prediction indexes of the severity in APIP (p-value < 0.05). Our novel clinical prediction model was created by based on the above three risk factors and showed superior predictive power in primary cohort (AUC = 0.895) and validation cohort (AUC = 0.863). A nomogram for severe acute pancreatitis in pregnancy (SAPIP) was created based on the three indicators. The nomogram was well-calibrated. CONCLUSION: RDW, NLR and IAP were the independent risk factors of APIP. Our clinical prediction model of severity in APIP based on RDW, NLR and IAP with predictive evaluation is accurate and effective.

Nanostructured lipid carriers (NLCs) stabilized by natural or synthetic emulsifiers for lutein delivery: Improved physicochemical stability, antioxidant activity, and bioaccessibility.

This study investigated the impacts of individual emulsifiers on the physicochemical stability, antioxidant ability, and in vitro digestion behavior of lutein-loaded nanostructured lipid carriers (NLCs). NLCs particles stabilized by ethyl lauroyl arginate, rhamnolipid, or tea saponin were fabricated by high-pressure microfluidization method. Differential scanning calorimetry and X-ray diffraction results confirmed the regulatory effect of emulsifiers on the crystallization behavior of NLCs. NLCs stabilized by rhamnolipid presented higher encapsulation efficiency (94.73%) for lutein than those stabilized by tea saponin (90.39%) or ethyl lauroyl arginate (88.86%). Meanwhile, the stability of embedded lutein during storage or photothermal treatments was greatly enhanced. Individual emulsifiers, together with lutein, endowed NLCs with excellent antioxidant capacity. During in vitro digestion, rhamnolipid-stabilized NLCs showed the slowest release of free fatty acids (50.87%) and provided an optimal sustained release for lutein with relatively high bioaccessibility (23.01%).

Application of online teaching mode combining case studies and the MOOC platform in obstetrics and gynecology probation teaching.

OBJECTIVE: To explore the application effect of the clinical basic integration teaching mode constructed by case studies and the MOOC platform in obstetrics and gynecology internship teaching in the face of public health emergencies. METHODS: One hundred ten clinical medical students of grade 2020 were selected as the experimental group, and 110 clinical medical students of grade 2021 were selected as the control group. The experimental group adopted the online teaching mode combined with case studies and the MOOC platform, while the control group adopted the offline traditional probation teaching method. Comprehensive test and questionnaire were used to evaluate and compare the teaching effect of the two groups of students. RESULTS: The experimental group was found to be superior to the control group in the quality assessment of complete medical record writing and the ability assessment of diagnosis and analysis of typical obstetrics and gynecology cases (P < 0. 05). However, the score of professional knowledge was lower than that of the control group (P < 0. 05). The results of questionnaire survey showed that the satisfaction of the experimental group in stimulating learning interest, enhancing problem solving ability, enhancing communication and clinical thinking ability, enhancing team cooperation awareness and independent innovation ability was higher than that of the control group (P < 0.01). The satisfaction of teacher-student interaction was also better (P < 0.05). However, in terms of strengthening theoretical understanding, the satisfaction of the experimental group was lower than that of the control group, but with no significant difference (P > 0.05). CONCLUSION: During the epidemic period, we designed a new online teaching mode, which can be applied to the probation teaching of obstetrics and gynecology. In our study, compared with traditional offline teaching, the new online teaching mode could improve students' ability of case writing and case analysis. However, more teaching practice is needed to complete this online teaching mode.

A study on the effect of symbiotic fermented milk products on human gastrointestinal health: Double-blind randomized controlled clinical trial.

Several studies have claimed that the consumption of fermented dairy products can improve human gastrointestinal (GI) health. However, the numbers of systematic clinic trials are limited. In this study, a yogurt containing both probiotics and prebiotics was developed and a double-blind randomized controlled clinical trial was carried out to evaluate the effect of the product on human gastrointestinal health in three different aspects: (1) the effect on functional constipation (FC) and functional diarrhea (FD); (2) the effect on gastrointestinal (GI) tract immune system; and (3) the changes in GI tract microbiota. Participants who suffered FC or FD were randomized into three groups (n = 66 each group): the first group was treated with fermented milk with Lactobacillus plantarum ST-III (7 mg/kg) and inulin (1.5%), the second group was treated with L. plantarum ST-III (7 mg/kg) and inulin (1.0%), and the third group (control group) was treated without probiotics and prebiotics. Half of the participants stopped the treatment after 14 days and the rest of the group continued the trial to the full 28 days. The fecal samples of participants were analyzed regarding their short-chain fatty acids (SCFAs), secretory immunoglobulin A (sIgA), and microbiota. A survey on GI tract health was conducted and the Bristol stool scale was recorded. The results showed that the consumption of the symbiotic yogurt for 14 days and 28 days can both improve the digestive system, with the continual consumption of product containing L. plantarum ST-III (7 mg/kg) and inulin (1.5%) for 28 days showing the most significance. The consumption of this product may be used as a potential functional food.

Protective effects of Lacticaseibacillus rhamnosus Hao9 on dextran sulphate sodium-induced ulcerative colitis in mice.

AIMS: Some probiotics used as food additives or food supplements had an anti-inflammatory effect. We tested the potential protective effects of probiotic Lacticaseibacillus rhamnosus Hao9 (Hao9) in mice with dextran sulphate sodium (DSS)-induced ulcerative colitis (UC) and determined whether these effects were related to the modulation of gut microbiota and amelioration of inflammation. METHODS AND RESULTS: Ulcerative colitis mouse model was established by feeding mice with 2.5% (w/v) DSS in drinking water for 7 days. We analysed the disease activity index (DAI), colon length and histological changes in the colon. In addition, we investigated the effects of Hao9 (1 × 109 colony forming unit/day) and curcumin (CUR) (200 mg/kg/day) on gut microbiota and serum inflammatory cytokines. In this study, CUR was used as a positive control. The results showed that both Hao9 and CUR effectively reduced body mass loss and DAI, restored colon length, alleviated colonic pathological variations and reduced histological scores compared with the UC group. Hao9 reduced the serum concentrations of proinflammatory cytokines (tumour necrosis factor alpha, interleukin [IL]-6 and IL-1ß) and increased the concentration of the anti-inflammatory cytokine IL-10. In addition, Hao9 promoted the growth of Faecalibaculum and Romboutsia in the gut and helped to maintain intestinal homeostasis. CONCLUSIONS: Hao9 had a protective effect against DSS-induced colitis, and the mechanisms underlying Hao9 may involve controlling inflammation and maintaining host micro-ecological balance. This study provided experimental evidence for the application of Hao9 in the treatment of ulcerative colitis and suggested that Hao9 may be a promising candidate as a dietary supplement against colitis. SIGNIFICANCE AND IMPACT OF THE STUDY: The comparison of probiotics and prebiotics in terms of therapeutic efficacy in UC helps us to understand their different patterns of regulation of intestinal microbiota.

Bifidobacterium BLa80 mitigates colitis by altering gut microbiota and alleviating inflammation.

This study was conducted to explore the therapeutic effect of the probiotic Bifidobacterium animalis subsp. lactis BLa80 on inflammatory bowel disease. A model of ulcerative colitis (UC) was induced in C57BL/6 mice by administering of 2.5% dextran sulphate sodium (DSS) for 8 days. After developing UC, some mice were treated via intragastric administration of BLa80 at a dose of 109 colony-forming units to assess the preventive effects of BLa80 on DSS-induced UC. Compared with non-treated UC model mice, BLa80-treated mice had reduced colon shortening and improvements in colonic tissue structure. Treatment with BLa80 also decreased the serum concentrations of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin (IL) 6 and IL-17 in mice. 16S rRNA gene sequencing revealed that BLa80 increased gut microbial diversity in mice and modulated UC-associated imbalances in the gut microbiota. BLa80 selectively promoted the growth of beneficial bacteria, including Romboutsia and Adlercreutzia, the abundances of which were negatively correlated with concentration of cellular inflammatory factors. In summary, the study results demonstrated that pretreatment with B. lactis BLa80 reduced intestinal inflammation and altered the gut microbiota, implying that BLa80 is a promising probiotic strain with potential therapeutic function in UC.

Improvement of stability and bioaccessibility of ß-carotene by curcumin in pea protein isolate-based complexes-stabilized emulsions: Effect of protein complexation by pectin and small molecular surfactants.

The impact of different complexes on the properties of ß-carotene-loaded emulsions was investigated by measuring the droplet size, encapsulation efficiency, droplet morphology, and physical stability. The photo and thermal stability of ß-carotene and its bioaccessibility during digestion were also analyzed. Comparing to the emulsions stabilized by other complexes, the emulsion stabilized by the high methoxyl pectin-rhamnolipid-pea protein isolate-curcumin (HMP-Rha-PPI-Cur) complex had the smallest droplet size (17.53 ± 0.15 µm) and the maximum encapsulation efficiency for curcumin (90.33 ± 0.03 %) and ß-carotene (92.16 ± 0.01 %). The emulsion stabilized by the HMP-Rha-PPI-Cur complex exhibited better physical stability against creaming. The retention rate of ß-carotene in the HMP-Rha-PPI-Cur complex-stabilized emulsion was 17.75 ± 0.02 and 33.64 ± 0.02 % after UV irradiation and thermal treatment. The HMP-Rha-PPI-Cur complex-stabilized emulsion also had a higher level of free fatty acid released (43.67 %) and higher bioaccessibility of ß-carotene (32.35 ± 0.02 %).

Lacticaseibacillus rhamnosus Hao9 exerts antidiabetic effects by regulating gut microbiome, glucagon metabolism, and insulin levels in type 2 diabetic mice.

Introduction: Type 2 diabetes mellitus (T2DM) is a metabolic disease that has led to a significant global public health burden. Methods: In this work, we investigated the effects of Lacticaseibacillus rhamnosus Hao9 on T2DM in mice with high-fat diet- and streptozotocin (STZ)-induced diabetes (diabetic mice) and explored the underlying mechanisms. Results: We found that 109 colony forming units (CFUs) of Hao9 per day significantly reduced fasting blood glucose and insulin levels (p < 0.001) in diabetic mice. Moreover, Hao9 enhanced liver antioxidant capacity and significantly decreased glucose-6-phosphatase and phosphoenolpyruvate carboxykinase expression in the livers of diabetic mice (p < 0.001). Hao9 also reduced the serum concentrations of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNFα), interleukin-1ß (IL1ß), and IL6 (p < 0.05) and improved intestinal barrier function in diabetic mice. The composition of the gut microbiome was modulated by Hao9, with an increased abundance of Roseburia, Eubacterium, and Lacticaseibacillus, and decreased abundance of Escherichia/Shigella. Notably, Lacticaseibacillus was detected at both weeks 5 and 12 post-treatment, suggesting sustained colonization of the gut by Hao9. Discussion: The supplementation of Hao9 improved gut microbiota, glucose metabolism, and insulin levels significantly in T2DM mice. That means Hao9 contributes to improving T2DM symptoms with its potential beneficial effects. Therefore, Hao9 is a promising dietary supplement for the treatment of T2DM.

Enhanced stability and controlled gastrointestinal digestion of ß-carotene loaded Pickering emulsions with particle-particle complex interfaces.

In this study, we used large, rigid, and hydrophilic zein-propylene glycol alginate composite particles (ZPCPs) and small, soft, and hydrophobic whey protein microgel (WPM) particles to synergistically stabilize a Pickering emulsion for delivery of ß-carotene. The photothermal stability and storage stability of ß-carotene were improved with the combined use of different particles. Microstructural observations showed that ZPCPs were effectively adsorbed at the oil/water interface despite the substantial interparticle gaps. WPM particles could swell and stretch on the interface due to their deformable structure, thereby forming an interfacial layer of flattened particles to cover a large surface area. The interfacial structure and macroscopic properties of Pickering emulsions were modulated by adjusting the mass ratio and addition sequence of different particles. The combination of ZPCPs and WPM delayed the lipolysis during gastrointestinal digestion. Through controlling the composition of the complex interface, the free fatty acid (FFA) release rate of Pickering emulsions in the small intestinal phase was reduced from 15.64% to 9.03%. When ZPCPs were used as the inner layer and WPM as the outer layer and the mass ratio of ZPCPs to WPM was 4 : 1, the Pickering emulsion showed the best stability and ß-carotene bioaccessibility. The Pickering emulsion with particle-particle complex interfaces could be applied in foods and pharmaceuticals for the purpose of enhanced stability, delayed lipolysis or sustained nutrient release.

Microbiome Profiling Using Shotgun Metagenomic Sequencing Identified Unique Microorganisms in COVID-19 Patients With Altered Gut Microbiota.

COVID-19 is mainly associated with respiratory distress syndrome, but a subset of patients often present gastrointestinal (GI) symptoms. Imbalances of gut microbiota have been previously linked to respiratory virus infection. Understanding how the gut-lung axis affects the progression of COVID-19 can provide a novel framework for therapies and management. In this study, we examined the gut microbiota of patients with COVID-19 (n = 47) and compared it to healthy controls (n = 19). Using shotgun metagenomic sequencing, we have identified four microorganisms unique in COVID-19 patients, namely Streptococcus thermophilus, Bacteroides oleiciplenus, Fusobacterium ulcerans, and Prevotella bivia. The abundances of Bacteroides stercoris, B. vulgatus, B. massiliensis, Bifidobacterium longum, Streptococcus thermophilus, Lachnospiraceae bacterium 5163FAA, Prevotella bivia, Erysipelotrichaceae bacterium 6145, and Erysipelotrichaceae bacterium 2244A were enriched in COVID-19 patients, whereas the abundances of Clostridium nexile, Streptococcus salivarius, Coprococcus catus, Eubacterium hallii, Enterobacter aerogenes, and Adlercreutzia equolifaciens were decreased (p < 0.05). The relative abundance of butyrate-producing Roseburia inulinivorans is evidently depleted in COVID-19 patients, while the relative abundances of Paraprevotella sp. and the probiotic Streptococcus thermophilus were increased. We further identified 30 KEGG orthology (KO) modules overrepresented, with 7 increasing and 23 decreasing modules. Notably, 15 optimal microbial markers were identified using the random forest model to have strong diagnostic potential in distinguishing COVID-19. Based on Spearman's correlation, eight species were associated with eight clinical indices. Moreover, the increased abundance of Bacteroidetes and decreased abundance of Firmicutes were also found across clinical types of COVID-19. Our findings suggest that the alterations of gut microbiota in patients with COVID-19 may influence disease severity. Our COVID-19 classifier, which was cross-regionally verified, provides a proof of concept that a set of microbial species markers can distinguish the presence of COVID-19.

Effect of MiR-375 Regulates YAP1 on the Invasion, Apoptosis, and Epithelial-Mesenchymal Transition of Cervical Cancer HeLa Cells.

Yes-associated protein 1 (YAP1) is an important signaling pathway activator molecule. Studies have shown that it is involved in the occurrence of malignant tumors. This study identified a microRNA (miR/miRNA) targeting the 3' untranslated region (3″ utr) of the YAP1 gene and evaluated its biological impact on human cervical cancer cells and related molecular mechanisms. qPCR and western blotting were used to detect the levels of miR-375 and YAP1 in HeLa cells. TargetScan software was used to identify the binding sites of YAP1 and miR-375. The MTT method was used to determine the viability of HeLa cells transfected with miR-375 mimic and YAP1 interference vector, the Transwell chamber experiment was used to detect the invasion of HeLa cells after transfection, the apoptosis of HeLa cells after transfection was detected by flow cytometry, and the western blotting was used to detect the epithelial mesenchymal transition (EMT) of HeLa cells after transfection. The expression of miR-375 in HeLa cells was significantly lower than that of normal control cervical cells, and the expression of YAP1 in HeLa cells was significantly higher than that of normal control cervical cells. TargetScan analysis showed that miR-375 was bound to the 3' UTR of YAP1. qPCR and western blot analysis showed that transfection of miR-375 mimics inhibited YAP1 expression in HeLa cells. Transfection of miR-375 mimic and YAP1 interference vector inhibited HeLa cell invasion and EMT and promoted HeLa cell apoptosis. These findings indicate that miR-375 inhibits the malignant development of human cervical cancer cells by regulating the expression of YAP1.

Zein Colloidal Particles and Cellulose Nanocrystals Synergistic Stabilization of Pickering Emulsions for Delivery of ß-Carotene.

In this study, we utilized different types of particles to stabilize ß-carotene-loaded Pickering emulsions: spherical hydrophobic zein colloidal particles (ZCPs) (517.3 nm) and rod-shaped hydrophilic cellulose nanocrystals (CNCs) (115.2 nm). Either of the particles was incapable of stabilizing Pickering emulsions owing to their inappropriate wettability. When the mass ratio of ZCPs and CNCs was 1:4, the Pickering emulsion showed the best physical and photothermal stability. Compared to the ZCP-stabilized Pickering emulsion (9.29%), the retention rate of ß-carotene in the Pickering emulsion costabilized by ZCPs and CNCs was increased to 60.23% after 28 days of storage at 55 °C. Confocal microscopy and cryoscanning electron microscopy confirmed that different types of particles could form a multilayered structure or induce the formation of an interparticle network. Furthermore, the complexation of ZCPs and CNCs delayed the lipolysis of the emulsion during in vitro digestion. The free fatty acid (FFA) release rate of Pickering emulsions in the small intestinal phase was reduced from 19.46 to 8.73%. Accordingly, the bioaccessibility of ß-carotene in Pickering emulsions ranged from 9.14 to 27.25% through adjusting the mass ratio and addition sequence of distinct particles at the interface. The Pickering emulsion with the novel particle-particle complex interface was designed in foods and pharmaceuticals for purpose of enhanced stability, delayed lipolysis, or sustained nutrient release.

Development of curcumin loaded core-shell zein microparticles stabilized by cellulose nanocrystals and whey protein microgels through interparticle interactions.

Novel multilayered core-shell microparticles were developed to deliver curcumin using positively charged zein microparticles coated with negatively charged cellulose nanocrystals (CNCs) and positively charged whey protein microgels (WPMs) at pH 4. Different levels of WPMs (0.10%-1.50%, w/v) were utilized to regulate the structure, stability, and in vitro digestion of curcumin loaded zein-CNC core-shell microparticles. The size of zein-CNC-WPM core-shell microparticles ranged from 2087.7 to 2928.2 nm. The electrostatic attraction and hydrogen bonding were mainly involved in the assembly of the core-shell microparticles through particle-particle interactions. The microstructure of the core-shell microparticles was dependent on the level of the WPM. When its appropriate level was adopted (0.50%-1.00%, w/v), the WPM formed a protective shell for zein-CNC-WPM core-shell microparticles. The retention rate of curcumin in the core-shell microparticles increased by 47.56% and 32.79% during light and thermal treatment, respectively. Excess microgels facilitated the bridging aggregation and formation of a network structure on the particle surface, which further reduced their stability and greatly restricted the curcumin release. The potential of nanosized protein microgels was explored to stabilize and modulate the physicochemical properties of multilayered core-shell microparticles through interparticle interactions.