Reprogramming human urine cells into intestinal organoids with long-term expansion ability and barrier function.

Generation of intestinal organoids from human somatic cells by reprogramming would enable intestinal regeneration, disease modeling, and drug screening in a personalized pattern. Here, we report a direct reprogramming protocol for the generation of human urine cells induced intestinal organoids (U-iIOs) under a defined medium. U-iIOs expressed multiple intestinal specific genes and showed resembling gene expression profiles to primary small intestines. U-iIOs can be stably long-term expanded and further differentiated into more mature intestinal lineage cells with high expression of metallothionein and cytochrome P450 (CYP450) genes. These specific molecular features of U-iIOs differ from human pluripotent stem cells derived intestinal organoids (P-iIOs) and intestinal immortalized cell lines. Furthermore, U-iIOs exhibit intestinal barriers indicated by blocking FITC-dextran permeation and uptaking of the specific substrate rhodamine 123. Our study provides a novel platform for patient-specific intestinal organoid generation, which may lead to precision treatment of intestinal diseases and facilitate drug discovery.

Circulating white blood cell traits and prolonged night shifts: a cross-sectional study based on nurses in Guangxi.

This study aimed to elucidate the effects of long day and night shifts on immune cells in a population of nurses. This cross-sectional study in December 2019 was based on a group of nurses. 1568 physically healthy caregivers were included, including 1540 women and 28 men. 1093 nurses had long-term shift work (working in a rotating system for > 1 year). The receiver operating characteristic curve, Ensemble Learning, and Logistic regression analyses were used to evaluate factors related to long-term shift work. The night shift group nurses had significantly higher MPV, PLCR, and WBC and significantly lower BASO%, ELR, MCHC, PLR, RDW-CV, and RDW-SD (P < 0.01). ROC curves showed that WBC, PLR, ELR, RDW_CV, and BASO% were more related to the night shift. Ensemble Learning, combined with the LASSO model, finally filtered out three indicators of night shifts related to ELR, WBC, and RDW_SD. Finally, logistic regression analysis showed that the nurses' night shift situation greatly influenced two peripheral blood ELR and WBC indicators (ELR: log (OR) = - 3.9, 95% CI: - 5.8- - 2.0; WBC: log (OR) = 0.25, 95% CI: 0.18-0.32). Finally, we showed that, unlike WBC, the relative riskiness of ELR showed opposite results among junior nurses and middle-senior nurses (log (OR) 6.5 (95% CI: 1.2, 13) and - 7.1 (95% CI: - 10, - 3.8), respectively). Our study found that prolonged night shifts were associated with abnormal WBC and ELR, but after strict age matching, WBC remained significantly different. These findings help to confirm that COVID-19 and tumorigenesis (e.g., breast cancer) are significantly associated with circadian rhythm disruption. However, more detailed studies are needed to confirm this.

Peripheral blood lipid and liver and kidney function test results in long-term night shift nurses: a cross-sectional study in South China.

Purpose: This study aimed to elucidate the effects of long-term day and night shifts on liver function and lipid metabolism in a group of nurses. Methods: This cross-sectional study in December 2019 was based on a group of nurses. A total of 1,253 physically healthy caregivers were included, including 1231 women and 22 men. A total of 886 nurses had long-term shift work (working in a rotating system for >1 year). The receiver operating characteristic (ROC) curve and logistic regression analyses were used to evaluate factors related to long-term shift work. Results: We observed differences in liver and kidney indicators between the non-night and night shift groups. The ROC curve revealed that CHO (AUC: 62.4%), LDLC (AUC: 62%), and GLUO (AUC: 61.5%) were more related to the night shift. Logistic regression analysis showed that night shift work was associated significantly with CREA (log (OR) = -0.02, 95% CI: -0.04 to -0.01), CHO (log (OR) = -0.38, 95% CI: -0.67 to -0.09), and GLUO (log (OR) = -0.35, 95% CI: -0.56 to -0.17). This correlation was observed only for CHO and LDHC (CHO: log (OR) = -0.55, 95% CI: -0.98 to -0.12; LDLC: log (OR) = 0.83, 95% CI: 0.32, 1.4) after age standardization. After using propensity score matching, we did not find evidence to support that the indicators differed between night and non-night shift groups. Conclusion: Our study observed an association of long-term night work with abnormal liver and kidney function and dyslipidemia, but the difference was not significant after strict age matching. Although these findings may support interventions for long-term night shift nurses, more detailed studies are needed to confirm.

A Comprehensive Review on Metal Catalysts for the Production of Cyclopentanone Derivatives from Furfural and HMF.

The catalytic transformation of biomass-based furan compounds (furfural and HMF) for the synthesis of organic chemicals is one of the important ways to utilize renewable biomass resources. Among the numerous high-value products, cyclopentanone derivatives are a kind of valuable compound obtained by the hydrogenation rearrangement of furfural and HMF in the aqueous phase of metal-hydrogen catalysis. Following the vast application of cyclopentanone derivatives, this reaction has attracted wide attention since its discovery, and a large number of catalytic systems have been reported to be effective in this transformation. Among them, the design and synthesis of metal catalysts are at the core of the reaction. This review briefly introduces the application of cyclopentanone derivatives, the transformation mechanism, and the pathway of biomass-based furan compounds for the synthesis of cyclopentanone derivatives. The important progress of metal catalysts in the reaction since the first report in 2012 up to now is emphasized, the characteristics and catalytic performance of different metal catalysts are introduced, and the critical role of metal catalysts in the reaction is discussed. Finally, the future development of this transformation process was prospected.

The RXFP2-PLC/PKC signaling pathway mediates INSL3-induced regulation of the proliferation, migration and apoptosis of mouse gubernacular cells.

BACKGROUND: Testicular hypoplasia can affect the sexual and reproductive ability in adulthood, and even increase the risk of cancer. Abnormal development of the gubernaculum is one of the important factors of testicular hypoplasia. Therefore, a study of the structure and function of the gubernaculum is an important but neglected new breakthrough point for investigating the normal/abnormal development of the testis. Previous findings showed that Insulin like factor 3 (INSL3) is a key factor regulating the growth of gubernaculum, however, the mechanism by which INSL3 acts on the gubernaculum remains unknown. Therefore, we probed the mechanism associated with INSL3-induced the proliferation, migration, and apoptosis of gubernacular cells in mice. METHODS: A culture cell model of neonatal mice gubernaculum is established by INSL3 intervention. We blocked PLC/PKC signaling pathway with U73122 pretreat to investigate the role of the PLC/PKC signaling pathway. The changes of cell proliferation, migration, and apoptosis were detected by molecular biological methods. In addition, the levels of PCNA and F-action were detected by immunofluorescence and western blotting. RESULTS: We found that INSL3 can promote the proliferation and migration of gubernacular cells and inhibit their apoptosis, meanwhile, INSL3 significantly up-regulated PLC/PKC protein phosphorylation. However, treatment with the PLC/PKC signaling pathway inhibitor U73122 significantly inhibited these effects of INSL3. Besides, we found that INSL3 could up-regulate the protein expression level of PCNA and F-actin, while the PCNA and F-actin expression was significantly weakened after U73122 pretreatment. CONCLUSIONS: This research revealed that INSL3 binding to RXFP2 may up-regulate the expression levels of PCNA and F-actin by activating the PLC/PKC signaling pathway to promote the proliferation and migration of gubernacular cells. It suggests that the RXFP2-PLC/PKC axis may serve as a novel molecular mechanism by which INSL3 regulates growth of the gubernaculum.

Delivery of Nanoparticles across the Intestinal Epithelium via the Transferrin Transport Pathway.

The aim of this study was to probe whether the transferrin (Tf) transport pathway can be exploited for intestinal delivery of nanoparticles. Tf was adsorbed on 100 nm model polystyrene nanoparticles (NP), followed by size characterisation of these systems. Cell uptake of Tf and Tf-adsorbed NP was investigated in intestinal epithelial Caco-2 cells cultured on multi-well plates and as differentiated polarised monolayers. Tf-NP demonstrated a remarkably higher cell uptake compared to unmodified NP in both non-polarised (5-fold) and polarised cell monolayers (16-fold difference). Application of soluble Tf significantly attenuated the uptake of Tf-NP. Notably, Tf-NP displayed remarkably higher rate (23-fold) of epithelial transport across Caco-2 monolayers compared to unmodified NP. This study therefore strongly suggests that the Tf transport pathway should be considered as a candidate biological transport route for orally-administered nanomedicines and drugs with poor oral bioavailability.

Biogenic Synthesis of Novel Functionalized Selenium Nanoparticles by Lactobacillus casei ATCC 393 and Its Protective Effects on Intestinal Barrier Dysfunction Caused by Enterotoxigenic Escherichia coli K88.

Selenium (Se) is an essential element for human and animal health. Biogenic selenium nanoparticles (SeNPs) by microorganism possess unique physical and chemical properties and biological activities compared with inorganic Se and organic Se. The study was conducted to investigate the mainly biological activities of SeNPs by Lactobacillus casei ATCC 393 (L. casei 393). The results showed that L. casei 393 transformed sodium selenite to red SeNPs with the size of 50-80 nm, and accumulated them intracellularly. L. casei 393-SeNPs promoted the growth and proliferation of porcine intestinal epithelial cells (IPEC-J2), human colonic epithelial cells (NCM460), and human acute monocytic leukemia cell (THP-1)-derived macrophagocyte. L. casei 393-SeNPs significantly inhibited the growth of human liver tumor cell line-HepG2, and alleviated diquat-induced IPEC-J2 oxidative damage. Moreover, in vivo and in vitro experimental results showed that administration with L. casei 393-SeNPs protected against Enterotoxigenic Escherichia coli K88 (ETEC K88)-caused intestinal barrier dysfunction. ETEC K88 infection-associated oxidative stress (glutathione peroxidase activity, total superoxide dismutase activity, total antioxidant capacity, and malondialdehyde) was ameliorated in L. casei 393-SeNPs-treated mice. These findings suggest that L. casei 393-SeNPs with no cytotoxicity play a key role in maintaining intestinal epithelial integrity and intestinal microflora balance in response to oxidative stress and infection.

Preparation, characteristics and antioxidant activity of polysaccharides and proteins-capped selenium nanoparticles synthesized by Lactobacillus casei ATCC 393.

Selenium (Se) is an essential element nutrient for human and animal health. Biogenic selenium nanoparticles (SeNPs) by microorganism possesses unique physical and chemical properties and biological activities compared to inorganic selenium and organic selenium. The study was conducted to establish a green, efficient and low-cost biotechnology for biogenic synthesis of SeNPs by Lactobacillus casei ATCC 393 (L. casei 393), and investigate its characteristics and antioxidant activities in vitro. The results showed that L. casei 393 transforms sodium selenite to SeNPs under anaerobic conditions. Moreover, 50-80 nm SeNPs were accumulated in the intracellular L. casei 393. The whole bacteria present distinct bright red color. SeNPs were isolated and characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy dispersive X-ray spectrometry (EDX), X-ray photoelectron spectroscopy (XPS), and fourier transform infrared spectroscopy (FT-IR). The results showed that the extracted SeNPs were capped by proteins and polysaccharides. Extracted biogenic SeNPs by L. casei 393 at a concentration less than 25 µg Se/mL had no cytotoxicity on the growth and proliferation of human normal epithelial cell (NCM460). The toxicity order of different selenium forms was: Sodium selenite > Selenium methionine > SeNPs synthesized by L. casei 393. Moreover, biogenic SeNPs by L. casei 393 induced HepG2 cells apoptosis via caspase cascade signaling and endocytosis of SeNPs. Moreover, SeNPs alleviated diquat or hydrogen peroxide (H2O2)-caused oxidative damage in intestinal epithelial cells, and reduced malondialdehyde (MDA) concentration and increased glutathione peroxidase (GPx) activity in culture medium. The findings suggest that biomolecules capped-SeNPs synthesized by probiotic L. casei 393 possess significant antioxidant and anticancer activities, and probiotic bacteria can provide a better alternative to synthesize biogenic elemental selenium particles with potential applications as anticancer and antioxidant agents.

Recombinant expressed vasoactive intestinal peptide analogue ameliorates TNBS-induced colitis in rats.

AIM: To investigate the modulatory effect of recombinant-expressed vasoactive intestinal peptide (VIP) analogue (rVIPa) on trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. METHODS: Forty-eight rats were randomized into six groups: normal control group (Control), model control group (TNBS), ethanol treatment group (ETOH), and VIP treatment groups with different dosage (rVIPa1nmol, rVIPa2nmol, rVIPa4nmol). Diarrhea and bloody stool were observed. Colonic damage was evaluated histologically. The levels of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), myeloperoxidase (MPO) and endotoxin in colonic tissue and serum were determined by enzyme-linked immunosorbent assay (ELISA). The expression of occludin, ZO-1, Toll-like receptor 4 (TLR4), and nuclear factor-kappa B p65 (NF-κB p65), IκBα, and p-IκBα were detected by Western blot. RESULTS: Administration with 2 nmol rVIPa prevented TNBS-induced necrosis, hyperemia, swelling, inflammation, etc., pathologic changes observed in the inner surface of colon in experimental rats. Moreover, rVIPa significantly decreased colonic TNF-α level (P < 0.001), MPO activity (P < 0.001) and serum endotoxin level (P < 0.01), and remarkably increased colonic IL-10 content (P < 0.001) in rats with TNBS-induced colitis. Furthermore, compared to the TNBS-induced colitis group, 2 nmol rVIPa treatment up-regulated the levels of occludin (P < 0.05) and ZO-1 (P < 0.05), NF-κB p65 (P < 0.01) and IκBα (P < 0.001), and down-regulated the levels of TLR4. CONCLUSION: rVIPa ameliorates TNBS-induced colonic injury and inflammation and effectively protected the intestinal mucosal barrier function in rats. The mechanism may be related to TLR4/NF-κB-mediated signaling pathway. rVIPa could be used as a new alternative therapy for intestinal inflammatory disorders.