Optimization of a Decellularization/Recellularization Strategy for Transplantable Bioengineered Liver

The liver is a complex organ that requires constant perfusion for the delivery of nutrients and oxygen and the removal of waste in order to survive. Efforts to recreate or mimic the liver microstructure via a ground-up approach are essential for liver tissue engineering. A decellularization/recellularization strategy is one of the approaches aiming at the possibility of producing a fully functional organ with in vitro-developed construction for clinical applications to replace failed livers, such as end-stage liver disease (ESLD). However, the complexity of the liver microarchitecture along with the limited suitable hepatic component, such as the optimization of the extracellular matrix (ECM) of the biomaterials, the selection of the seed cells, and development of the liver-specific three-dimensional (3D) niche settings, pose numerous challenges. In this chapter, we have provided a comprehensive outlook on how the physiological, pathological, and spatiotemporal aspects of these drawbacks can be turned into the current challenges in the field, and put forward a few techniques with the potential to address these challenges, mainly focusing on a decellularization-based liver regeneration strategy. We hypothesize the primary concepts necessary for constructing tissue-engineered liver organs based on either an intact (from a naïve liver) or a partial (from a pretreated liver) structure via simulating the natural development and regenerative processes

Synthesis and electrochemical performance of hierarchical Sb2S3 nanorod-bundles for lithium-ion batteries

Uniform hierarchical Sb2S3 nanorod-bundles were synthesised successfully by L-cysteine hydrochloride-assisted solvothermal treatment, and were then characterised by X-ray diffraction, field emission scanning electron microscopy, and high-resolution transmission electron microscopy, respectively. The electrochemical performance of the synthesised Sb2S3 nanorod-bundles was investigated by cyclic voltammetry and galvanostatic charge−discharge technique, respectively. This material was found to exhibit a high initial charge specific capacity of 803 mA h g-1 at a rate of 100 mA g-1, a good cyclability of 614 mA h g-1 at a rate of 100 mA g-1 after 30 cycles, and a good rate capability of 400 mA h g-1 at a rate of 500 mA g-1 when evaluated as an electrode candidate material for lithium-ion batteries

VEGF Is Involved in the Increase of Dermal Microvascular Permeability Induced by Tryptase

Tryptases are predominantly mast cell-specific serine proteases with pleiotropic biological activities and play a critical role in skin allergic reactions, which are manifested with rapid edema and increases of vascular permeability. The exact mechanisms of mast cell tryptase promoting vascular permeability, however, are unclear and, therefore, we investigated the effect and mechanism of tryptase or human mast cells (HMC-1) supernatant on the permeability of human dermal microvascular endothelial cells (HDMECs). Both tryptase and HMC-1 supernatant increased permeability of HDMECs significantly, which was resisted by tryptase inhibitor APC366 and partially reversed by anti-VEGF antibody and SU5614 (catalytic inhibitor of VEGFR). Furthermore, addition of tryptase to HDMECs caused a significant increase of mRNA and protein levels of VEGF and its receptors (Flt-1 and Flk-1) by Real-time RT-PCR and Western blot, respectively. These results strongly suggest an important role of VEGF on the permeability enhancement induced by tryptase, which may lead to novel means of controlling allergic reaction in skin

Survival Fate of Hepatic Stem/Progenitor and Immune Cells in a Liver Fibrosis/Cirrhosis Animal Model and Clinical Implications

This chapter provides novel information about the survival features of hepatic resident stem/progenitor cells (NG2+ HSPs) during liver fibrosis/cirrhotic development. A well-defined diethylnitrosamine (DEN)-induced liver fibrosis/cirrhotic/cancer mouse model was developed to evaluate the fate of the HSPs and its clinical implications. This model possess three time-zones during the disease development: fibrosis (3–5 weeks post-DEN), cirrhosis (6–10 weeks post-DEN), and cancers (up to 10 weeks post-DEN). During this process, the model represents histological patterns similar to those described in humans and shows better survival of the HSPs in the fibrotic zone, which was correlated with inflammatory signals, as compared to the cirrhotic zone. It has also been discovered that immune CD8+ T cells in the fibrotic zone are beneficial in liver fibrosis resolution, suggesting that the fibrotic time zone is important for mobilizing endogenous HSPs and cell-based therapy. As such, we hypothesize that clinical strategies in fibrotic/cirrhotic liver treatment are necessary either in time at the fibrotic phase or to adopt an approach of regulating HSP viability when the disease develops into the cirrhotic phase

Data on a novel liver bioscaffold (rDLS) generated from regenerative liver with activated extracellular matrix for functional liver regeneration

The data presented in this article are related to the original research article entitled “A novel bioscaffold with naturally-occurring extracellular matrix promotes hepatocyte survival and vessel patency in mouse models of heterologous transplantation” (Yang et al., in press) [1]. This article describes a decellularized liver scaffold (DLS) that derived from partial hepatectomy liver (rDLS) which supported primary hepatocyte survival and promoted blood patency, as compared with a conventional scaffold that generated from naïve liver (nDLS). Analysis by immunochemistry and scanning electron microscope (SEM) showed that the vessel network and extracellular matrix (ECM) components were similar to the nDLS. The rDLS could prevent blood clotting after transplanted it in vivo, identified by immunofluorescence staining for the integrin (αIIb, α4) expression and liver transplantation models (mice, pigs) a formed well-blood petency liver lobules. These data indicate that the novel scaffold (rDLS) with naturally-occurring “activated ECM” that may be useful for the implantation in vivo of a bioengineered organoid that is able to exert function long term without clotting in future clinic

Breast Cancer Prevention and Treatment Behaviors in Community-living Women: Latent Class Analysis and Influencing Factors

Background The overall incidence of breast cancer in Chinese women is on the rise, seriously threatening their physical and mental health. Breast cancer prevention and treatment behaviors are critical to the outcomes of affected women in the community. However, these behaviors vary across individuals. And measures should be explored to improve the efficacy of such behaviors. Objective To perform a latent class analysis of breast cancer prevention and treatment behaviors among community-living women, and to explore the associated factors, providing evidence for individualized prevention and management of female breast cancer in the community. Methods A total of 1 355 community-living women were selected from in 15 towns/subdistricts of 5 counties/districts in Yinchuan and Zhongwei cities of Ningxia, China by use of convenience sampling method from November 2019 to August 2020. They were surveyed using a questionnaire consisting of baseline characteristics, and breast cancer prevention and treatment behaviors (relevant questions used are belonging to the part of breast cancer prevention and treatment in the Knowledge, Attitude and Practice of Breast and Cervical Cancer Prevention and Treatment Among Women in Ningxia) . The latent classes of breast cancer prevention and treatment behaviors were presented, and their influencing factors were identified by multivariable logistic regression analysis. Results The survey achieved a response rate of 97.93% (1 327/1 355) .By use of latent class analysis, breast cancer prevention and treatment behaviors of the respondents were classified into four latent classes, including positive prevention and treatment (n=522, 39.34%) , high-risk behaviors plus positive treatment (n=449, 33.83%) , high-risk behaviors plus negative treatment (n=229, 17.26%) , and general prevention and treatment (n=127, 9.57%) . The overall median score of breast cancer prevention and treatment behaviors was 9.00 (7.00, 11.00) points for all respondents. The median score of breast cancer prevention and treatment behaviors was 11.00 (11.00, 12.00) points for respondents with positive prevention and treatment behaviors, 9.00 (8.00, 10.00) points for those with high-risk behaviors plus positive treatment behaviors, 6.00 (5.00, 6.00) points for those with high-risk behaviors plus negative treatment behaviors, and 8.00 (6.00, 9.00) points for those with general prevention and treatment behaviors, with significant difference across the groups (H=1 008.493, P<0.001) . Multivariable Logistic regression analysis showed that, compared with general prevention and treatment behaviors, living in Zhongwei and having a history of childbirth were associated with increased possibility of being classified into positive prevention and treatment behaviors, having health insurance〔urban resident basic medical insurance (URBMI) , commercial health insurance, or other types〕, self-pay treatment, and a history of hormone replacement therapy were associated with increased possibility of being classified into general prevention and treatment behaviors (P<0.05) , having a history of childbirth were associated with increased possibility of being classified into high-risk behaviors plus positive treatment behaviors, having health insurance (URBMI or commercial health insurance) , as well as a history of hormone replacement therapy were associated with increased possibility of being classified into general prevention and treatment behaviors (P<0.05) , and primary education or below, household monthly income per person of 1 000-2 999 yuan were associated with increased possibility of being classified into high-risk behaviors plus negative treatment behaviors, and having URBMI were associated with increased possibility of being classified into general prevention and treatment behaviors (P<0.05) . Conclusion In general, breast cancer prevention and treatment behaviors in this group could be definitely classified, all being performed at a moderate level. To improve the level of breast cancer prevention and treatment behaviors of Ningxia's community-living women, focus should be on those who have high-risk behaviors and negatively seek for treatment. Moreover, the problems in positive breast cancer prevention and treatment behaviors in women with other three classes of behaviors should also be intervened and corrected to improve the outcomes of them

Immunotherapeutic Targeting of NG2/CSPG4 in Solid Organ Cancers

Neuro-glia antigen 2/chondroitin sulfate proteoglycan 4 (NG2/CSPG4, also called MCSP, HMW-MAA, MSK16, MCSPG, MEL-CSPG, or gp240) is a large cell-surface antigen and an unusual cell membrane integral glycoprotein frequently expressed on undifferentiated precursor cells in multiple solid organ cancers, including cancers of the liver, pancreas, lungs, and kidneys. It is a valuable molecule involved in cancer cell adhesion, invasion, spreading, angiogenesis, complement inhibition, and signaling. Although the biological significance underlying NG2/CSPG4 proteoglycan involvement in cancer progression needs to be better defined, based on the current evidence, NG2/CSPG4+ cells, such as pericytes (PCs, NG2+/CD146+/PDGFR-β+) and cancer stem cells (CSCs), are closely associated with the liver malignancy, hepatocellular carcinoma (HCC), pancreatic malignancy, and pancreatic ductal adenocarcinoma (PDAC) as well as poor prognoses. Importantly, with a unique method, we successfully purified NG2/CSPG4-expressing cells from human HCC and PDAC vasculature tissue blocks (by core needle biopsy). The cells appeared to be spheres that stably expanded in cultures. As such, these cells have the potential to be used as sources of target antigens. Herein, we provide new information on the possibilities of frequently selecting NG2/CSPG4 as a solid organ cancer biomarker or exploiting expressing cells such as CSCs, or the PG/chondroitin sulfate chain of NG2/CSPG4 on the cell membrane as specific antigens for the development of antibody- and vaccine-based immunotherapeutic approaches to treat these cancers

Potential of Aromatic Plant-Derived Essential Oils for the Control of Foodborne Bacteria and Antibiotic Resistance in Animal Production: A Review

Antibiotic resistance has become a severe public threat to human health worldwide. Supplementing antibiotic growth promoters (AGPs) at subtherapeutic levels has been a commonly applied method to improve the production performance of livestock and poultry, but the misuse of antibiotics in animal production plays a major role in the antibiotic resistance crisis and foodborne disease outbreaks. The addition of AGPs to improve production performance in livestock and poultry has been prohibited in some countries, including Europe, the United States and China. Moreover, cross-resistance could result in the development of multidrug resistant bacteria and limit therapeutic options for human and animal health. Therefore, finding alternatives to antibiotics to maintain the efficiency of livestock production and reduce the risk of foodborne disease outbreaks is beneficial to human health and the sustainable development of animal husbandry. Essential oils (EOs) and their individual compounds derived from aromatic plants are becoming increasingly popular as potential antibiotic alternatives for animal production based on their antibacterial properties. This paper reviews recent studies in the application of EOs in animal production for the control of foodborne pathogens, summarizes their molecular modes of action to increase the susceptibility of antibiotic-resistant bacteria, and provides a promising role for the application of nanoencapsulated EOs in animal production to control bacteria and overcome antibiotic resistance

Rosemary extract improves egg quality by altering gut barrier function, intestinal microbiota and oviductal gene expressions in late-phase laying hens

Abstract Background Rosemary extract (RE) has been reported to exert antioxidant property. However, the application of RE in late-phase laying hens on egg quality, intestinal barrier and microbiota, and oviductal function has not been systematically studied. This study was investigated to detect the potential effects of RE on performance, egg quality, serum parameters, intestinal heath, cecal microbiota and metabolism, and oviductal gene expressions in late-phase laying hens. A total of 210 65-week-old “Jing Tint 6” laying hens were randomly allocated into five treatments with six replicates and seven birds per replicate and fed basal diet (CON) or basal diet supplemented with chlortetracycline at 50 mg/kg (CTC) or RE at 50 mg/kg (RE50), 100 mg/kg (RE100), and 200 mg/kg (RE200). Results Our results showed that RE200 improved (P < 0.05) Haugh unit and n-6/n-3 of egg yolk, serum superoxide dismutase (SOD) compared with CON. No significant differences were observed for Haugh unit and n-6/n-3 of egg yolk among CTC, RE50, RE100 and RE200 groups. Compared with CTC and RE50 groups, RE200 increased serum SOD activity on d 28 and 56. Compared with CON, RE supplementation decreased (P < 0.05) total cholesterol (TC) level. CTC, RE100 and RE200 decreased (P < 0.05) serum interleukin-6 (IL-6) content compared with CON. CTC and RE200 increased jejunal mRNA expression of ZO-1 and Occludin compared with CON. The biomarkers of cecal microbiota and metabolite induced by RE 200, including Firmicutes, Eisenbergiella, Paraprevotella, Papillibacter, and butyrate, were closely associated with Haugh unit, n-6/n-3, SOD, IL-6, and TC. PICRUSt2 analysis indicated that RE altered carbohydrate and amino acid metabolism of cecal microbiota and increased butyrate synthesizing enzymes, including 3-oxoacid CoA-transferase and butyrate-acetoacetate CoA-transferase. Moreover, transcriptomic analysis revealed that RE200 improved gene expressions and functional pathways related to immunity and albumen formation in the oviductal magnum. Conclusions Dietary supplementation with 200 mg/kg RE could increase egg quality of late-phase laying hens via modulating intestinal barrier, cecal microbiota and metabolism, and oviductal function. Overall, RE could be used as a promising feed additive to improve egg quality of laying hens at late stage of production. Graphical Abstrac