P53/NANOG balance; the leading switch between poorly to well differentiated status in liver cancer cells

Enforcing a well-differentiated state on cells requires tumor suppressor p53 activation as a key player in apoptosis induction and well differentiation. In addition, recent investigations showed a significant correlation between poorly differentiated status and higher expression of NANOG. Inducing the expression of NANOG and decreasing p53 level switch the status of liver cancer cells from well differentiated to poorly status. In this review, we highlighted p53 and NANOG cross-talk in hepatocellular carcinoma (HCC) which is regulated through mitophagy and makes it a novel molecular target to attenuate cancerous phenotype in the management of this tumor

Platelet-Rich Plasma in Regenerative Medicine: Possible Applications in Management of Burns and Post-Burn Scars: A Review

Contribution of platelets in tissue regeneration and their possible application in regenerative medicine, which is primarilymediated via secretion of granular components following platelet activation, has been well established in the recent decades.Therefore, platelet rich plasma (PRP), as a portion of plasma with higher concentrations of platelets than the baseline level,is now an attractive therapeutic option in various medical fields mainly for tissue repair and regeneration following injuries.Burn injuries are devastating trauma with high rate of morbidities affecting several aspects of the patient’s life. They requirea long-time medical care and high costs. However, even following the best treatment procedures, post-burn scars areinevitable consequence of burn healing process. Therefore, development of new treatment modalities for both burn healingand prevention of post-burn scar establishment seems to be necessary. Regarding the well-known role of PRP in woundhealing, here we aimed to provide a comprehensive insight in the possible application of PRP as an adjuvant therapy forthe management of burn injuries and subsequent scars. In terms of the following keywords (individually or in combination),original/review articles were searched in PubMed, Scopus, and Google Scholar databases from 2009 to 2021: platelet richplasma, PRP therapy, platelet biology, platelet function, burn healing, burn scar, scar formation, burn management, woundhealing, regenerative medicine. All type of articles or book chapters in English language and relevant data were included inthis review. This review initially focused on PRP, its mechanisms of action, preparation methods, and available sources. Then,pathophysiology of burns and subsequent scars were discussed. Finally, their current conventional therapeutic modalities andimplication of PRP in their healing process were highlighted

Review on Kidney-Liver Crosstalk: Pathophysiology of Their Disorders

Kidney-liver crosstalk plays a crucial role in normal and certain pathological conditions. In pathologic states, bothrenal-induced liver damage and liver-induced kidney diseases may happen through these kidney-liver interactions.This bidirectional crosstalk takes place through the systemic conditions that mutually influence both the liver andkidneys. Ischemia and reperfusion, cytokine release and pro-inflammatory signaling pathways, metabolic acidosis,oxidative stress, and altered enzyme activity and metabolic pathways establish the base of this interaction betweenthe kidneys and liver. In these concomitant kidney-liver diseases, the survival rates strongly correlate with earlyintervention and treatment of organ dysfunction. Proper care of a nephrologist and hepatologist and the identificationof pathological conditions using biomarkers at early stages are necessary to prevent the complications induced by thiscomplex and potentially vicious cycle. Therefore, understanding the characteristics of this crosstalk is essential forbetter management. In this review, we discussed the available literature concerning the detrimental effects of kidneyfailure on liver functions and liver-induced kidney diseases

The Sera miRNA Pattern in Patients Inflammatory Bowel Disease

Inflammatory bowel disease comprising Crohn's disease and ulcerative colitis presents with periods of flares and remission. Many reports have identified different dysregulated miRNAs in patients with IBD. Finding new biomarkers in IBD patients can help to launch a novel non-invasive approach for diagnosis and prognosis for patients with UC and CD. This study aimed to evaluate the plasma expression pattern of the miRNAs panel in IBD patients compared to healthy individuals. 73 plasma samples were included; 58 patients with IBD (33 individuals in flare and 25 in remission phase) and 15 healthy controls were enrolled in the study. The miRNA expression was measured by qRT-PCR using miScript SYBR Green PCR Kit (QIAGEN). Our results showed the expression level of miR-16-5P was significantly increased in the active phase compared to the inactive phase (P=0.0138) and in CD patients compared to UC patients (P=0.0216). There was a significant difference in the expression of miR-29a in Crohn's patients compared to healthy subjects (P=0.04). Measuring the expression of mir-106a; a significant increase was observed compared to healthy individuals (P=0.03) and patients with CD (P=0.0143) in proportion of UC patients’ group. The miR-126 expression significantly increased in patients with active disease compared to patients in the inactive phase (P=0.0413) and healthy controls (P=0.0492). This study showed evidence for differential expression levels of plasma panel of miR-16, miR-29a, miR-106a, and miR-126 in IBD patients compare to healthy individuals. We illustrate that miRNAs in plasma correlate with disease activity and can be used as a practical and non-invasive biomarker for early diagnosis and monitoring of the treatment protocol

Disulfiram-Loaded Niosomes Reduces Cancerous Phenotypes in Oral Squamous Cell Carcinoma Cells

Objective: Surgery and chemotherapy are the most common therapeutic strategies proposed for oral squamous cellcarcinoma (OSCC). However, some of the disadvantages associated with the current methods like unwanted sideeffects and poor drug response lead the scientist to seek for novel modalities and delivery approaches to enhance theefficacy of treatments. The study aimed to assess the effectiveness of disulfiram (DSF)-loaded Niosomes on cancerousphenotypes of the OSCC cells.Materials and Methods: In this experimental study, an optimum formulation of DSF-loaded Niosomes was developedfor the treatment of OSCC cells to reduce drug doses and improve the poor stability of DSF in the OSCC environment.The design expert software was utilized to optimize the particles in terms of size, polydispersity index (PDI), andentrapment effcacy (EE).Results: Acidic pH increased the release rate of DSF from these formulations. The size, PDI, and EE of Niosomeswere more stable at 4°C compared to 25°C. The results indicated that DSF-loaded Niosomes could induce apoptosis(P=0.019) in the OSCC cells compared to the control group. Moreover, it could reduce colony formation ability(P=0.0046) and also migration capacity of OSCC cells (P=0.0015).Conclusion: Our findings indicated that the application of proper dose of DSF-loaded Niosomes (12.5 μg/ml) increasesapoptosis, decreases colony formation capacity and declines the migration ability of OSCC cells

Subcutaneous Injection of Allogeneic Adipose-Derived Mesenchymal Stromal Cells in Psoriasis Plaques: Clinical Trial Phase I

Objective: Mesenchymal stromal cells (MSCs) play immunomodulatory role in various autoimmune diseases. Previouspre-clinical and clinical studies have shown that MSCs could be a therapeutic modality for psoriasis. However, themechanisms of treatment and its possible side effects are under investigation. In this study, the safety and probableefficacy of injecting allogeneic adipose-derived mesenchymal stromal cells (ADSCs) in psoriatic patients were evaluated.Materials and Methods: In this phase I clinical study with six months of follow-up, total number of 1×106 or 3×106cells/cm2 of ADSCs were injected into the subcutaneous tissue of each plaque as a single dose in three males and twofemales (3M/2F) with a mean age of 32.8 ± 8.18. The primary outcome was safety. Changes in clinical and histologicalindexes, the number of B and T lymphocytes in local and peripheral blood, and serum levels of inflammatory cytokineswere assessed. Paired t test was used to compare variables at two time points (baseline and six months after injection)and repeated measures ANOVA test was utilized for variables at three time points in follow-up visits.Results: No major adverse effects such as burning, pain, itching, or any systemic side effects were observed followingADSCs injection, and the lesions showed slight to considerable improvement after injection. The mRNA expressionlevels of pro-inflammatory factors were reduced in the dermis of the patients after injection. The increased expressionlevel of Foxp3 transcription factor in the patient blood samples suggested modulation of inflammation after ADMSCsadministration. Six months after the intervention, no major side effects were reported, but skin thickness, erythema, andscaling of the plaques, as well as the PASI score, were decreased in majority of patients.Conclusion: Our study suggested that ADSC injection could be considered as a safe and effective therapeuticapproach for psoriatic plaques (registration number: IRCT20080728001031N24)

Galactosylation of rat natural scaffold for MSC differentiation into hepatocyte-like cells: A comparative analysis of 2D vs. 3D cell culture techniques

The liver plays a crucial role in drug detoxification, and the main source of liver transplants is brain-dead patients. However, the demand for transplants exceeds the available supply, leading to controversies in selecting suitable candidates for acute liver diseases. This research aimed to differentiate mesenchymal stem cells (MSCs) into hepatocyte-like cells using galactosylated rat natural scaffolds and comparing 2-D and 3-D cell culture methods. The study involved isolating and culturing Wharton's jelly cells from the umbilical cord, examining surface markers and adipogenic differentiation potential of MSCs, and culturing mesenchymal cells on galactosylated scaffolds. The growth and proliferation of stem cells on the scaffolds were evaluated using the MTT test, and urea synthesis was measured in different culture environments. Changes in gene expression were analyzed using real-time PCR. Flow cytometry results confirmed the presence of specific surface antigens on MSCs, indicating their identity, while the absence of a specific antigen indicated their differentiation into adipocytes. The MTT test revealed higher cell attachment to galactosylated scaffolds compared to the control groups. Urea secretion was observed in differentiated cells, with the highest levels in cells cultured on galactosylated scaffolds. Gene expression analysis showed differential expression patterns for OCT-4, HNF1, ALB, AFP, and CYP genes under different conditions. The findings indicated that hepatocyte-like cells derived from 3D cultures on galactosylated scaffolds exhibited superior characteristics compared to cells in other culture conditions. These cells demonstrated enhanced proliferation, stability, and urea secretion ability. The study also supported the differentiation potential of MSCs derived from Wharton's jelly umbilical cord into liver-like cells

Immune regulation and therapeutic application of T regulatory cells in liver diseases

CD4+ CD25+ FOXP3+ T regulatory cells (Tregs) are a subset of the immunomodulatory cell population that can inhibit both innate and adaptive immunity by various regulatory mechanisms. In hepatic microenvironment, proliferation, plasticity, migration, and function of Tregs are interrelated to the remaining immune cells and their secreted cytokines and chemokines. In normal conditions, Tregs protect the liver from inflammatory and auto-immune responses, while disruption of this crosstalk between Tregs and other immune cells may result in the progression of chronic liver diseases and the development of hepatic malignancy. In this review, we analyze the deviance of this protective nature of Tregs in response to chronic inflammation and its involvement in inducing liver fibrosis, cirrhosis, and hepatocellular carcinoma. We will also provide a detailed emphasis on the relevance of Tregs as an effective immunotherapeutic option for autoimmune diseases, liver transplantation, and chronic liver diseases including liver cancer.SCOPUS: re.jinfo:eu-repo/semantics/publishe

In vitro Generated Hepatocyte- like cells: a Novel Tool in Regenerative Medicine and Drug Discovery

Hepatocyte-like cells (HLCs) generated from various human pluripotent stem cells (hPSCs), mostly induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) or direct cell conversion and also other stem cells like gestational tissues stem cells and mesenchymal stromal cells; provide potential cell sources for biomedical applications. Liver transplantation is the gold standard treatment for patients with end stage liver disease, but there are many practical limits, mostly insufficient number of donated healthy livers. Meanwhile the number of patients to receive a liver organ transplant for a better life is increasing. In this regard, HLCs may provide an adequate cell source to overcome these shortages. New molecular engineering approaches such as CRISPR/Cas systen with iPSCs technology provid the basic principles of gene correction for monogenic inherited metabolic liver diseases as another application of HLCs. It has shown that HLCs could replace primary human hepatocytes in drug discovery and hepatotoxicity tests. However, generation of fully functional HLCs is still a big challenge; research groups have been trying to improve current differentiation protocols to achieve better HLCs according to morphology and function of cells. Large-scale generation of functional HLCs in bioreactors could make a new window in producing enough hepatocytes for treating end-stage liver patients as well as other biomedical applications such as drug studies. In this review, regarding the biomedical value of hepatocyte-like cells, we focus on the current and efficient approaches for generating hepatocyte- like cells in vitro and discuss about their applications in regenerative medicine and drug discovery

Metabolic hallmarks of liver regeneration.

Despite the crucial role of cell metabolism in biological processes, particularly cell division, metabolic aspects of liver regeneration are not well defined. Better understanding of the metabolic activity governing division of liver cells will provide powerful insights into mechanisms of physiological and pathological liver regeneration. Recent studies have provided evidence that metabolic response to liver failure might be a proximal signal to initiate cell proliferation in liver regeneration. In this review, we highlight how lipids, carbohydrates, and proteins dynamically change and orchestrate liver regeneration. In addition, we discuss translational studies in which metabolic intervention has been used to treat chronic liver diseases (CLDs)