The Potential Role of Intestinal Stem Cells and Microbiota for the Treatment of Colorectal Cancer.

Colorectal cancer is a global health concern with high incidence and mortality rates. Conventional treatments like surgery, chemotherapy, and radiation therapy have limitations in improving patient survival rates. Recent research highlights the role of gut microbiota and intestinal stem cells in maintaining intestinal health and their potential therapeutic applications in colorectal cancer treatment. The interaction between gut microbiota and stem cells influences epithelial self-renewal and overall intestinal homeostasis. Novel therapeutic approaches, including immunotherapy, targeted therapy, regenerative medicine using stem cells, and modulation of gut microbiota, are being explored to improve treatment outcomes. Accordingly, this chapter provides an overview of the potential therapeutic applications of gut microbiota and intestinal stem cells in treating colorectal cancer.

Comparison of the effects of preservation methods on structural, biological, and mechanical properties of the human amniotic membrane for medical applications.

Amniotic membrane (AM), the innermost layer of the placenta, is an exceptionally effective biomaterial with divers applications in clinical medicine. It possesses various biological functions, including scar reduction, anti-inflammatory properties, support for epithelialization, as well as anti-microbial, anti-fibrotic and angio-modulatory effects. Furthermore, its abundant availability, cost-effectiveness, and ethical acceptability make it a compelling biomaterial in the field of medicine. Given the potential unavailability of fresh tissue when needed, the preservation of AM is crucial to ensure a readily accessible and continuous supply for clinical use. However, preserving the properties of AM presents a significant challenge. Therefore, the establishment of standardized protocols for the collection and preservation of AM is vital to ensure optimal tissue quality and enhance patient safety. Various preservation methods, such as cryopreservation, lyophilization, and air-drying, have been employed over the years. However, identifying a preservation method that effectively safeguards AM properties remains an ongoing endeavor. This article aims to review and discuss different sterilization and preservation procedures for AM, as well as their impacts on its histological, physical, and biochemical characteristics.

The wonders of stem cells therapeutic application towards chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a respiratory condition characterized by its heterogeneous nature, progressive course, and significant impact on individuals' quality of life. It is a prevalent global health issue affecting a substantial number of individuals and can pose life-threatening complications if left unmanaged. The development and course of COPD can be influenced by a range of risk factors, including genetic predisposition and environmental exposures. Nevertheless, as researchers adopt a more comprehensive and expansive viewpoint of therapeutic techniques, the associated obstacles become more apparent. Indeed, a definitive medication for COPD that reliably leads to symptom alleviation has not yet been discovered. Therefore, the limitations of conventional therapy methods prompted researchers to focus on the advancement of novel procedures, potentially leading to significant outcomes. In contemporary times, the field of regenerative medicine and cell therapy has presented unprecedented opportunities for the exploration of innovative treatments for COPD, owing to the distinctive attributes exhibited by stem cells. Hence, it is imperative to provide due consideration to preclinical investigations and notable characteristics of stem cells as they serve as a means to comprehensively comprehend the fundamental mechanisms of COPD and uncover novel therapeutic strategies with enhanced efficacy for patients.

Laboratory methods: A concise review and update for COVID-19 diagnosis.

Since late December 2019, coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been rapidly spread across the globe. The early, safe, sensitive, and accurate diagnosis of viral infection is required to decrease and control contagious infection and improve public health surveillance. The diagnosis generally is made by detecting SARS-CoV-2-related agents, including a range of nucleic acid detection-based, immunoassay-based, radiographic-based, and biosensor-based methods. This review presents the progress of various detection tools for diagnosing COVID-19 and addresses the advantages and restrictions of each detection method. Given that diagnosis of a contagious various like SARS-COV-2 can improve patient survival rates and break the transmission chain, there is no surprise that significant efforts should be made to reduce the limitations of tests that lead to false-negative results and to develop a substantial test for COVID-19 diagnosis.

Brown adipose tissue and alzheimer's disease.

Alzheimer's disease (AD), the most common type of senile dementia, is a chronic neurodegenerative disease characterized by cognitive dysfunction and behavioral disability. The two histopathological hallmarks in this disease are the extraneuronal accumulation of amyloid-ß (Aß) and the intraneuronal deposition of neurofibrillary tangles (NFTs). Despite this, central and peripheral metabolic dysfunction, such as abnormal brain signaling, insulin resistance, inflammation, and impaired glucose utilization, have been indicated to be correlated with AD. There is solid evidence that the age-associated thermoregulatory deficit induces diverse metabolic changes associated with AD development. Brown adipose tissue (BAT) has been known as a thermoregulatory organ particularly vital during infancy. However, in recent years, BAT has been accepted as an endocrine organ, being involved in various functions that prevent AD, such as regulating energy metabolism, secreting hormones, improving insulin sensitivity, and increasing glucose utilization in adult humans. This review focuses on the mechanisms of BAT activation and the effect of aging on BAT production and signaling. Specifically, the evidence demonstrating the effect of BAT on pathological mechanisms influencing the development of AD, including insulin pathway, thermoregulation, and other hormonal pathways, are reviewed in this article.

DNA Damage Responses, the Trump Card of Stem Cells in the Survival Game.

Stem cells, as a group of undifferentiated cells, are enriched with self-renewal and high proliferative capacity, which have attracted the attention of many researchers as a promising approach in the treatment of many diseases over the past years. However, from the cellular and molecular point of view, the DNA repair system is one of the biggest challenges in achieving therapeutic goals through stem cell technology. DNA repair mechanisms are an advantage for stem cells that are constantly multiplying to deal with various types of DNA damage. However, this mechanism can be considered a trump card in the game of cell survival and treatment resistance in cancer stem cells, which can hinder the curability of various types of cancer. Therefore, getting a deep insight into the DNA repair system can bring researchers one step closer to achieving major therapeutic goals. The remarkable thing about the DNA repair system is that this system is not only under the control of genetic factors, but also under the control of epigenetic factors. Therefore, it is necessary to investigate the role of the DNA repair system in maintaining the survival of cancer stem cells from both aspects.

Application of Biocompatible Scaffolds in Stem-Cell-Based Dental Tissue Engineering.

Tissue engineering as an important field in regenerative medicine is a promising therapeutic approach to replace or regenerate injured tissues. It consists of three vital steps including the selection of suitable cells, formation of 3d scaffolds, and adding growth factors. Mesenchymal stem cells (MSCs) and embryonic stem cells (ESCs) are mentioned as two main sources for this approach that have been used for the treatment of various types of disorders. However, the main focus of literature in the field of dental tissue engineering is on utilizing MSCs. On the other hand, biocompatible scaffolds play a notable role in this regenerative process which is mentioned to be harmless with acceptable osteoinductivity. Their ability in inhibiting inflammatory responses also makes them powerful tools. Indeed, stem cell functions should be supported by biomaterials acting as scaffolds incorporated with biological signals. Naturally derived polymeric scaffolds and synthetically engineered polymeric/ceramic scaffolds are two main types of scaffolds regarding their materials that are defined further in this review. Various strategies of tissue bioengineering can affect the regeneration of dentin-pulp complex, periodontium regeneration, and whole teeth bioengineering. In this regard, in vivo/ex vivo experimental models have been developed recently in order to perform preclinical studies of dental tissue engineering which make it more transferable to be used for clinic uses. This review summarizes dental tissue engineering through its different components. Also, strategies of tissue bioengineering and experimental models are introduced in order to provide a perspective of the potential roles of dental tissue engineering to be used for clinical aims.

How to establish infrastructures to achieve more efficient regenerative medicine?

The field of regenerative medicine (RM) as an innovative technology has the ability to affect the healthcare system. It develops a variety of techniques through stem cell biology, genetics, bioengineering, biomaterial science, and tissue engineering to replace or restore the role of lost, disabled, or aging cells in the human body. However, the field's proficiency has still been underwhelming at the clinical trial level. This could be due to the innovation of such technologies, as well as their incredible nature. Therefore, managing the infrastructure framework for the safe and efficient application of the aforementioned field of science would help in the process of progress. In this context, the current review focuses on how to establish infrastructures for more effective RM.

Critical roles of cytokine storm and bacterial infection in patients with COVID-19: therapeutic potential of mesenchymal stem cells.

The severe acute respiratory syndrome coronavirus 2 has been a shocking disaster for healthcare systems worldwide since December 2019. This virus can affect all systems of the body and its symptoms vary from a simple upper respiratory infection to fatal complications including end-organ damage. On the other hand, the normal immune system plays a pivotal role in the recovery of infectious diseases such as COVID-19. However, occasionally, exaggerated immune system inflammation and an excessive synthesis of cytokines, known as a "cytokine storm," can deteriorate the patient's clinical condition. Secondary bacterial co-infection is another problem in COVID-19 which affects the prognosis of patients. Although there are a few studies about this complication, they suggest not using antibiotics commonly, especially broad-spectrum ones. During this pandemic, various approaches and therapeutics were introduced for treating COVID-19 patients. However, available treatments are not helpful enough, especially for complicated cases. Hence, in this era, cell therapy and regenerative medicine will create new opportunities. Therefore, the therapeutic benefits of mesenchymal stem cells, especially their antimicrobial activity, will help us understand how to treat COVID-19. Herein, mesenchymal stem cells may stop the immune system from becoming overactive in COVID-19 patients. On the other side, the stem cells' capacity for repair could encourage natural healing processes.

Introducing Matrix Metalloproteinases as Crucial Targets for Intra-articular Laser Therapy in Patients with Synovial Fluid of Knee Osteoarthritis.

Background: Many elder people have knee osteoarthritis (OA). The patients are faced with pain and disability in movement. Given the challenging lifestyle of the patients, finding an efficient therapy approach is necessary. Since low-level laser therapy applies to the treatment of many diseases, it seems it can be a suitable option for the treatment of knee OA. The present study aimed to evaluate the molecular mechanism of laser therapy on knee OA via a protein expression change study. Methods: The present study examines the gene expression profile of patients with OA in the knee using bioinformatics. The protein expression change profile of synovial fluid of knee OA patients is extracted from the literature and is analyzed based on the rate of expression and interactions between the differentially expressed proteins (DEPs). The results are compared with the DEPs of similar tissue of the treated knee OA patients (from published documents) after laser therapy. Results: Apolipoprotein B (APOB) and matrix metallopeptidase 2 (MMP2) were determined as the hub bottlenecks of the protein-protein interaction (PPI) network of synovial fluid of knee OA patients. MMP2, complement 5, transthyretin, and apolipoprotein A-1 from laser-treated patients were related to the PPI network of knee OA patients. The reduction of Interleukin-6 activity was highlighted as a critical event as a function of laser on the human body. Conclusion: In conclusion, it was noted that the main phenomenon associated with laser therapy-induced improvement in the condition of knee OA patients is the downregulation of MMP2.

Systematic Analysis of Protein-Protein and Gene-Environment Interactions to Decipher the Cognitive Mechanisms of Autism Spectrum Disorder.

Autism spectrum disorder (ASD), a heterogeneous neurodevelopmental disorder resulting from both genetic and environmental risk factors, is manifested by deficits in cognitive function. Elucidating the cognitive disorder-relevant biological mechanisms may open up promising therapeutic approaches. In this work, we mined ASD cognitive phenotype proteins to construct and analyze protein-protein and gene-environment interaction networks. Incorporating the protein-protein interaction (PPI), human cognition proteins, and connections of autism-cognition proteins enabled us to generate an autism-cognition network (ACN). With the topological analysis of ACN, important proteins, highly clustered modules, and 3-node motifs were identified. Moreover, the impact of environmental exposures in cognitive impairment was investigated through chemicals that target the cognition-related proteins. Functional enrichment analysis of the ACN-associated modules and chemical targets revealed biological processes involved in the cognitive deficits of ASD. Among the 17 identified hub-bottlenecks in the ACN, PSD-95 was recognized as an important protein through analyzing the module and motif interactions. PSD-95 and its interacting partners constructed a cognitive-specific module. This hub-bottleneck interacted with the 89 cognition-related 3-node motifs. The identification of gene-environment interactions indicated that most of the cognitive-related proteins interact with bisphenol A (BPA) and valproic acid (VPA). Moreover, we detected significant expression changes of 56 cognitive-specific genes using four ASD microarray datasets in the GEO database, including GSE28521, GSE26415, GSE18123 and GSE29691. Our outcomes suggest future endeavors for dissecting the PSD-95 function in ASD and evaluating the various environmental conditions to discover possible mechanisms of the different levels of cognitive impairment.

Current advances and challenges in COVID-19 vaccine development: from conventional vaccines to next-generation vaccine platforms.

The world is grappling with an unprecedented public health crisis COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2. Due to the high transmission/mortality rates and socioeconomic impacts of the COVID-19, its control is crucial. In the absence of specific treatment, vaccines represent the most efficient way to control and stop the pandemic. Many companies around the world are currently making efforts to develop the vaccine to combat COVID-19. This review outlines key strategies for generating SARS-CoV-2 vaccine candidates, along with the mechanism of action, advantages, and potential limitations of each vaccine. The use of nanomaterials and nanotechnology for COVID-19 vaccines development will also be discussed.

Diagnostic of Cytokeratin-19 Gene Expression in Iranian Breast Cancer Patients.

Sentinel lymph node (SLN) biopsy is currently the recommended procedure for axillary staging in clinically node-negative early breast cancer at diagnosis. The present study aimed to identify Cytokeratin-19 (CK19) gene profiles that accurately predicted the outcome of breast cancer patients. Fifty tumor samples from breast cancer patients were analyzed for the expression of the CK19 gene using quantitative PCR. Also, normal breast tissues (N = 50) were taken from the same patients that had undergone partial or total mastectomy. This gene signature was confirmed based on tumor's stage, grade, and estrogen receptor (ER) status, using conditional logistic regression. Based on these findings, the negative reported lymph nodes for metastasis had micrometastasis in significant values. There was a significant difference between normal and cancer samples in  CK19 expression. In this sentinel node evaluation, the relationship of this gene with tumor characteristics needs to be established and discussed finding a clear role for this gene in tumor outcome.

The Fingerprints of Biomedical Science in Internal Medicine.

With the development of numerous advances in science and technologies, medical science has also been updated. Internal medicine is one of the most valuable specialized fields of medical sciences that review a broad range of diseases. Herein, the internal medicine specialist (internist) is obliged to do diagnostic measures to evaluate disease signs and symptoms. In recent times, biomedical sciences as the new emergence science (including cellular and molecular biology, genetics, nanobiotechnology, bioinformatics, biochemistry, etc.) have been capable of providing more specific diagnostic methods together with techniques for better understanding the mechanism of the disease and the best diseases modeling and offering proper therapies. Accordingly, the authors have tried to review the link between biomedical sciences and medicine, particularly internal medicine.

Metabolomics Signatures of SARS-CoV-2 Infection.

For a very long time, viral infections have been considered as one of the most important causes of death and disability around the world. Through the viral infection, viruses as small pathogens enter the host cells and use hosts' biosynthesis machinery to replicate and collect infectious lineages. Moreover, they can modify hosts' metabolic pathways in order to their own purposes. Nowadays (in 2019-2020), the most famous type of viral infection which was caused by a novel type of coronavirus is called COVID-19 disease. It has claimed the lives of many people around the world and is a very serious threat to health. Since investigations of the effects of viruses on host metabolism using metabolomics tools may have given focuses on novel appropriate treatments, in the current review the authors highlighted the virus-host metabolic interactions and metabolomics perspective in COVID-19.

Severe Acute Respiratory Syndrome Coronavirus 2 Induces Hepatocyte Cell Death, Active Autophagosome Formation and Caspase 3 Up-Regulation in Postmortem Cases: Stereological and Molecular Study.

This research investigated the histopathological changes in the tissue of the lung, heart and liver, hepatocyte cell death, autophagy, and the apoptosis inductions in the postmortem cases. Since December 2019, coronavirus disease 2019 (COVID-19) has become a significant global health concern. In order to clarify the changes in tissues of the lung, heart and liver by COVID-19, samples were taken from five patients who died of COVID-19 and five control cases, and the pathological changes in the lung, liver, and heart tissue were studied by X-ray, computed tomography, histological studies, and stereological analysis. The formation of hyaline membranes, alveolar wall edema, and fibrin exudate was seen on histological analysis of the lungs in the COVID-19 group. Stereological analysis illustrated the number of hepatocytes, volume of the sinusoid, and volume of the liver have been decreased, however the pathological changes in the heart tissue were not observed. Serum levels of alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, and angiotensin-converting enzyme significantly increased. Real-time PCR results showed that the Bcl2, Caspase3, ATG5, and LC3 decreased while the Bax increased. COVID-19 causes fibrotic changes in the lung tissue and hepatocyte mortality in the liver tissue. Besides, it elevates the level of apoptosis and autophagy markers.

Looking at time dependent differentiation of mesenchymal stem cells by culture media using MALDI-TOF-MS.

Mesenchymal stem cells (MSCs) are multipotent cells which are popular in human regenerative medicine. These cells can renew themselves and differentiate into several specialized cell types including osteoblasts, adipocytes, and chondrocytes under physiological and experimental conditions. MSCs can secret a lot of components including proteins and metabolites. These components have significant effects on their surrounding cells and also can be used to characterize them. This characterization of multipotent MSCs plays a critical role in their therapeutic potential. The metabolic profile of culture media verified by applying matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF-MS) techniques. Also, the differentiation and development of MSCs have monitored through culture media metabolome or secretome (secreted metabolites). Totally, 24 potential metabolites were identified. Between them 12 metabolites are unique to BM-MSCs and 5 metabolites are unique to AD-MSCs. Trilineage differentiation including chondrocytes, osteoblasts, and adipocytes, as well as metabolites that are being differentiated, have been shown in different weeks. In the present study, the therapeutic effects of MSCs analyzed by decoding the metabolome for MSCs secretome via metabolic profiling using MALDI-TOF-MS techniques.

Healing effect of acellular fish skin with plasma rich in growth factor on full-thickness skin defects.

Acellular skin as a scaffold has a good potential to regenerate or repair damaged tissues. Growth factors such as Plasma Rich in Growth Factor (PRGF) as a rich source of active proteins can accelerate tissue regeneration. In this study, an acellular scaffold derived from fish skin with growth factors was used to repair full-thickness skin defects in a rat model. Cellular results demonstrated that epithelial cells adhere well to acellular scaffolds. The results of animal studies showed that the groups treated with acellular scaffold and growth factor have a high ability to close and heal wounds on the 28th day after surgery. Histological and staining results showed that in the treated groups with scaffold and growth factor, an epidermal layer was formed with some skin appendages similar to normal skin. Overall, such scaffolds with biological agents can cause an acceptable synergistic effect on skin regeneration and wound healing.

Coronavirus: proteomics analysis of chicken kidney tissue infected with variant 2 (IS-1494)-like avian infectious bronchitis virus.

Avian infectious bronchitis virus is one of the most important gammacoronaviruses, which causes a highly contagious disease. In this study, we investigated changes in the proteome of kidney tissue of specific-pathogen-free (SPF) chickens that were infected with an isolate of the nephrotropic variant 2 genotype (IS/1494/06) of avian coronavirus. Twenty 1-day-old SPF White Leghorn chickens were randomly divided into two groups, each comprising 10 chickens, which were kept in separate positive-pressure isolators. Chickens in group A served as a virus-free control group up to the end of the experiment, whereas chickens in group B were inoculated with 0.1 ml of 104.5 EID50 of the IBV/chicken/Iran/UTIVO-C/2014 isolate of IBV, and kidney tissue samples were collected at 2 and 7 days post-inoculation (dpi) from both groups. Sequencing of five protein spots at 2 dpi and 22 spots at 7 dpi that showed differential expression by two-dimensional electrophoresis (2DE) along with fold change greater than 2 was done by MS-MALDI/TOF/TOF. Furthermore, the corresponding protein-protein interaction (PPI) networks at 2 and 7 dpi were identified to develop a detailed understanding of the mechanism of molecular pathogenesis. Topological graph analysis of this undirected PPI network revealed the effect of 10 genes in the 2 dpi PPI network and nine genes in the 7 dpi PPI network during virus pathogenesis. Proteins that were found by 2DE analysis and MS/TOF-TOF mass spectrometry to be down- or upregulated were subjected to PPI network analysis to identify interactions with other cellular components. The results show that cellular metabolism was altered due to viral infection. Additionally, multifunctional heat shock proteins with a significant role in host cell survival may be employed circuitously by the virus to reach its target. The data from this study suggest that the process of pathogenesis that occurs during avian coronavirus infection involves the regulation of vital cellular processes and the gradual disruption of critical cellular functions.

Toward finding the difference between untreated celiac disease and COVID-19 infected patients in terms of CD4, CD25 (IL-2 Rα), FOXP3 and IL-6 expressions as genes affecting immune homeostasis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is defined as an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 and celiac disease (CD) is one of the autoimmune multiorgan diseases, which can be accompanied by an increased risk of viral infections. CD patients, especially untreated subjects, may be at greater risk of infections such as viral illnesses. Interleukin (IL)-6, CD4, CD25, and FOXP3 are known as genes affecting immune homeostasis and relate to the inflammation state. This study aimed to compare the expression levels of aforementioned genes in peripheral blood samples of CD and severe COVID-19 patients. METHODS: Sixty newly diagnosed CD patients with median age (mean ± SD) of 35.40 ± 24.12 years; thirty confirmed severe COVID-19 patients with median age (mean ± SD) of 59.67 ± 17.22, and 60 healthy subjects with median age (mean ± SD) of 35.6 ± 13.02 years; were recruited from March to September 2020. Fresh whole blood samples were collected, total RNA was obtained and cDNA synthesis was carried out. RNA expression levels of IL-6, CD4, CD25, and FOXP3 genes were assessed using real-time quantitative RT-PCR according to the 2-∆∆Ct formula. Statistical analysis was performed using SPSS (V.21) and GraphPad, Prism (V.6). RESULTS: While increased expression of CD4, CD25, and FOXP3 was observed in CD patients compared to the control group (p = 0.02, p = 0.03, and p < 0.0001 respectively) and COVID-19 patients group (p < 0.0001 for all of them), their expression levels in COVID-19 patients decreased compared to controls (p < 0.0001, p = 0.01, p = 0.007, respectively). Increased IL-6 expression was observed in both groups of patients compared to controls (p < 0.0001 for both of them). CONCLUSIONS: Although untreated CD patients may be at greater risk of developing into severe COVID-19 if they are infected by SARS-CoV-2 virus (due to their high expression of IL-6), increased expression of anti-inflammatory markers in these patients may be beneficial for them with the ability of reducing the severity of COVID-19 disease, which needs to be proven in future studies involving celiac patients infected with COVID-19.