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The term "liver disease" refers to any hepatic condition that leads to tissue damage or altered hepatic function and can be induced by virus infections, autoimmunity, inherited genetic mutations, high consumption of alcohol or drugs, fat accumulation, and cancer. Some types of liver diseases are becoming more frequent worldwide. This can be related to increasing rates of obesity in developed countries, diet changes, higher alcohol intake, and even the coronavirus disease 2019 (COVID-19) pandemic was associated with increased liver disease-related deaths. Although the liver can regenerate, in cases of chronic damage or extensive fibrosis, the recovery of tissue mass is impossible, and a liver transplant is indicated. Because of reduced organ availability, it is necessary to search for alternative bioengineered solutions aiming for a cure or increased life expectancy while a transplant is not possible. Therefore, several groups were studying the possibility of stem cells transplantation as a therapeutic alternative since it is a promising strategy in regenerative medicine for treating various diseases. At the same time, nanotechnological advances can contribute to specifically targeting transplanted cells to injured sites using magnetic nanoparticles. In this review, we summarize multiple magnetic nanostructure-based strategies that are promising for treating liver diseases.

The transplantation world changed significantly following the introduction of immunosuppressants, with millions of people saved. Several physicians have noted that liver recipients that do not take their medication for different reasons became tolerant regarding kidney, heart, and lung transplantations at higher frequencies. Most studies have attempted to explain this phenomenon through unique immunological mechanisms and the fact that the hepatic environment is continuously exposed to high levels of pathogen-associated molecular patterns (PAMPs) or non-pathogenic microorganism-associated molecular patterns (MAMPs) from commensal flora. These components are highly inflammatory in the periphery but tolerated in the liver as part of the normal components that arrive via the hepatic portal vein. These immunological mechanisms are discussed herein based on current evidence, although we hypothesize the participation of neuroendocrine-immune pathways, which have played a relevant role in autoimmune diseases. Cells found in the liver present receptors for several cytokines, hormones, peptides, and neurotransmitters that would allow for system crosstalk. Furthermore, the liver is innervated by the autonomic system and may, thus, be influenced by the parasympathetic and sympathetic systems. This review therefore seeks to discuss classical immunological hepatic tolerance mechanisms and hypothesizes the possible participation of the neuroendocrine-immune system based on the current literature.

Background: Flaxseed oil (FO) is an alpha linolenic acid source important for growth and body development. However, there is little literature on the role of FO in critical stages of bone development and formation., Objective: This study evaluated the influence of a diet containing FO on rat femurs., Methods: After birth, mothers and pups were divided into control and flaxseed groups (n = 6 pups each) fed diets containing 7% soybean oil (C) or 7% FO. At 21 days, pups were weaned and separated from the mothers, and control or experimental diets were continued. At 67 days, the following were analyzed: osteocalcin and osteoprotegerin (OPG) levels, bone mineral density (BMD) and content, and bone area; the dimension, BMD, head radiodensity, and biomechanical proprieties of the right femur; and histomorphometric parameters of the left femur., Results: Compared to the C group, the FO group presented ( p  < 0.05) a lower body mass (-3.7%) and medullary area (-10.1%) and higher osteocalcin (+36.7%), OPG (+52.5%), femur width (+3.8%), absolute mass (+2.3%), femur BMD (+3.6%), head radiodensity (+6.1%), maximum force (+7.4%), breaking strength (+17.3), and cortical thickness (+7.0)., Conclusion: The FO diet contributed to femur quality in healthy male Wistar rats.

One of the limitations in organ, tissue or cellular transplantations is graft rejection. To minimize or prevent this, recipients must make use of immunosuppressive drugs (IS) throughout their entire lives. However, its continuous use generally causes several side effects. Although some IS dose reductions and withdrawal strategies have been employed, many patients do not adapt to these protocols and must return to conventional IS use. Therefore, many studies have been carried out to offer treatments that may avoid IS administration in the long term. A promising strategy is cellular microencapsulation. The possibility of microencapsulating cells originates from the opportunity to use biomaterials that mimic the extracellular matrix. This matrix acts as a support for cell adhesion and the syntheses of new extracellular matrix self-components followed by cell growth and survival. Furthermore, by involving the cells in a polymeric matrix, the matrix acts as an immunoprotective barrier, protecting cells against the recipient's immune system while still allowing essential cell survival molecules to diffuse bilaterally through the polymer matrix pores. In addition, this matrix can be associated with IS, thus diminishing systemic side effects. In this context, this review will address the natural biomaterials currently in use and their importance in cell therapy.

Rational synthesis and simple methodology for the purification of large (35-45 nm in lateral size) and flat (1.0-1.5 nm of height) nitrogen-doped graphene oxide quantum dots (GOQDs) are presented. The methodology allows robust metal-free and acid-free preparation of N-GOQDs with a yield of about 100% and includes hydrothermal treatment of graphene oxide with hydrogen peroxide and ammonia. It was demonstrated that macroscopic impurities can be separated from N-GOQD suspension by their coagulation with 0.9% NaCl solution. Redispersible in water and saline solutions, particles of N-GOQDs were characterized using tip-enhanced Raman spectroscopy (TERS), photoluminescent, XPS, and UV-VIS spectroscopies. The size and morphology of N-GOQDs were studied by dynamic light scattering, AFM, SEM, and TEM. The procedure proposed allows nitrogen-doped GOQDs to be obtained, having 60-51% of carbon, 34-45% of oxygen, and up to 7.2% of nitrogen. The N-GOQD particles obtained in two hours of synthesis contain only pyrrolic defects of the graphene core. The fraction of pyridine moieties grows with the time of synthesis, while the fraction of quaternary nitrogen declines. Application of TERS allows demonstration that the N-GOQDs consist of a graphene core with an average crystallite size of 9 nm and an average distance between nearest defects smaller than 3 nm. The cytotoxicity tests reveal high viability of the monkey epithelial kidney cells Vero in the presence of N-GOQDs in a concentration below 60 mg L -1 . The N-GOQDs demonstrate green luminescence with an emission maximum at 505 nm and sedimentation stability in the cell culture medium., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

The liver is a multifaceted organ; its location and detoxifying function expose this organ to countless injuries. Acute-on-chronic failure liver (ACLF) is a severe syndrome that affects the liver due to acute decompensation in patients with chronic liver disease. An infection environment, ascites, increased liver enzymes and prothrombin time, encephalopathy and fast-evolving multiorgan failure, leading to death, usually accompany this. The pathophysiology remains poorly understand. In this context, animal models become a very useful tool in this regard, as understanding; the disease may be helpful in developing novel therapeutic methodologies for ACLF. However, although animal models display several similarities to the human condition, they do not represent all ACLF manifestations, resulting in significant challenges. An initial liver cirrhosis framework followed by the induction of an acute decompensation by administering lipopolysaccharide and D-GaIN, potentiating liver damage supports the methodologies applied to induce experimental ACLF. The entire methodology has been described mostly for rats. Nevertheless, a quick PubMed database search indicates about 30 studies concerning ACFL models and over 1000 regarding acute liver failure models. These findings demonstrate the clear need to establish easily reproducible ACFL models to elucidate questions about this quickly established and often fatal syndrome., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Microencapsulation is a widely studied cell therapy and tissue bioengineering technique, since it is capable of creating an immune-privileged site, protecting encapsulated cells from the host immune system. Several polymers have been tested, but sodium alginate is in widespread use for cell encapsulation applications, due to its low toxicity and easy manipulation. Different cell encapsulation methods have been described in the literature using pressure differences or electrostatic changes with high cost commercial devices (about 30,000 US dollars). Herein, a low-cost device (about 100 US dollars) that can be created by commercial syringes or 3D printer devices has been developed. The capsules, whose diameter is around 500 µm and can decrease or increase according to the pressure applied to the system, is able to maintain cells viable and functional. The hydrogel porosity of the capsule indicates that the immune system is not capable of destroying host cells, demonstrating that new studies can be developed for cell therapy at low cost with microencapsulation production. This device may aid pre-clinical and clinical projects in low- and middle-income countries and is lined up with open source equipment devices.

Background and Aims: Acute liver failure (ALF) is a severe syndrome with an elevated mortality rate, ranging from 40 to 80 %. Currently, liver transplantation is the only definitive treatment for these patients and new therapies aiming to treat ALF include artificial organs implant and stem cells therapy, for example. However, a major limitation of liver donors exists. Living donor liver transplantation (LDLT), split liver transplantation (SLT), and domino liver transplantation (DLT) are some of the available alternatives to treat ALF patients, but these do not reduce the number of patients on waiting lists. Herein, we discuss domino hepatocyte transplantation (DHT) using livers that would not meet transplantation criteria., Methods: We conducted a literature search on PubMed/Medline using acute liver failure, liver transplantation, hepatocyte transplantation, and domino liver transplantation as key words., Results: New sources of biochemically functional hepatocytes and therapeutic treatments, in parallel to organ transplantation, may improve liver injury recovery and decrease mortality rates. Moreover, the literature reports hepatocyte transplantation as a therapeutic alternative for organ shortage. However, a major challenge remains for a wide clinical application of hepatocytes therapy, i.e., the availability of sufficient amounts of cells for transplantation. Ideally, hepatocytes isolated from livers rejected for transplantation may be a promising alternative for this problem., Conclusion: Our review suggests that DHT may be an excellent strategy to increase cell supplies for hepatocyte transplantation.

Introduction: intake of diets with high saturated fat may produce deleterious effects on bone mineralization. Lifestyle changes help reduce the bone loss observed in osteoporosis. Resveratrol, present in grape juice and red wine, has osteogenic and osteoinductive effects, being potentially beneficial for bone health., Objective: to evaluate the effects of red grape juice, red wine and resveratrol consumption on bone parameters in Wistar rats submitted to a high-fat diet and physical training., Method: female Wistar rats, with 90 days of age, were divided into five groups and followed up for 60 days: a) control group; b) high-fat group; c) grape juice group; d) red wine group; and e) resveratrol group. The different groups of animals performed a physical training protocol. Animal's weight and consumption were monitored weekly. After 60 days, femoral dimensions, bone mineral density (BMD) and bone mineral content (BMC) were evaluated., Results: there was no difference in body mass; however, all groups consuming the high-fat diet had higher consumption (p < 0.05). RWG presented a greater distance between the epiphyses, femoral mass and BMC (p < 0.05). RWG and RG presented greater mean diaphysis point width and BMD (p < 0.05)., Conclusion: the results suggest that the bioactive compounds present in red wine and resveratrol solution together with regular exercise were able to promote beneficial effects on bone health, even when associated with a high saturated fat diet.

Cryopreservation of hepatocytes is a crucial step in the implementation of cell therapy for treating certain liver diseases. In the present study we investigated the effect of the some disaccharides on the cryopreservation of rat hepatocytes. Liver cells were frozen in media in the presence or absence of low concentrations of Me 2 SO (5% Me 2 SO) supplemented with varying concentrations of disaccharides (sucrose, glucose and trehalose). After 7 days of cryopreservation, the hepatocytes were thawed and viability was measure by exclusion of trypan blue and by the MTT technique, as well as by determining albumin production. Among the investigated disaccharides and concentrations, 0.2 M trehalose showed the best overall outcome. Compared to the use of Me 2 SO alone, significant improvement in post-thaw cell viability was observed. The new solution may reduce Me 2 SO side effects on patients and improve the viability and quality of cryopreserved hepatocytes., (Copyright © 2017 Elsevier Inc. All rights reserved.)