Smart Bioinks for the Printing of Human Tissue Models

3D bioprinting has tremendous potential to revolutionize the field of regenerative medicine by automating the process of tissue engineering. A significant number of new and advanced bioprinting technologies have been developed in recent years, enabling the generation of increasingly accurate models of human tissues both in the healthy and diseased state. Accordingly, this technology has generated a demand for smart bioinks that can enable the rapid and efficient generation of human bioprinted tissues that accurately recapitulate the properties of the same tissue found in vivo. Here, we define smart bioinks as those that provide controlled release of factors in response to stimuli or combine multiple materials to yield novel properties for the bioprinting of human tissues. This perspective piece reviews the existing literature and examines the potential for the incorporation of micro and nanotechnologies into bioinks to enhance their properties. It also discusses avenues for future work in this cutting-edge field.

WASH Practices and Its Association With Disease and Nutritional Status of Under Five Children: Evidence From Rural Bangladesh

This study aimed to assess knowledge and practice of caregivers and its relationship to the disease and nutritional status of children under five years of age in rural areas of Sylhet, Bangladesh. A total of 110 households having 6 to 59 months aged children was selected by simple random method from ten rural communities of three Upazila of Sylhet during September 2019 to February 2020. Descriptive statistics were used to assess the WASH knowledge & practice and multivariate chi-square analyses were performed to assess associations among diseases & nutritional status with WASH following a structured questionnaire. The study found a significant association of WASH with childhood disease and nutritional status, and 65% of children were found to be in a diseased state and 35% of children were found to be in a disease-free state within the last six months. The findings sketched that mother with poor wash knowledge and practice was at greater risk for disease outbreaks, disease frequency and duration. The highest incidence of diarrhea was 17% in children aged 12 to 23 months. Significant effect of WASH was also found in children nutrition status, that was reflected in the ratio of stunted, underweight and wasted children. Integrated convergent work focusing on the provision of clean water within the household, stop open defecation, promotion of hand washing, behavior change and poverty alleviation is needed to improve the situation. Health, nutrition and livelihood programs should be uninterrupted, and mothers or caregivers should be encouraged to participate in these programs.

Drug-Repositioning Approaches Based on Medical and Life Science Databases

Drug repositioning is a drug discovery strategy in which an existing drug is utilized as a therapeutic agent for a different disease. As information regarding the safety, pharmacokinetics, and formulation of existing drugs is already available, the cost and time required for drug development is reduced. Conventional drug repositioning has been dominated by a method involving the search for candidate drugs that act on the target molecules of an organism in a diseased state through basic research. However, recently, information hosted on medical information and life science databases have been used in translational research to bridge the gap between basic research in drug repositioning and clinical application. Here, we review an example of drug repositioning wherein candidate drugs were found and their mechanisms of action against a novel therapeutic target were identified via a basic research method that combines the findings retrieved from various medical and life science databases.

Validation of mRNAs in Early Diagnosis and Treatment of Hepatocellular Carcinoma

Poor and late diagnosis of HCV is main the cause of liver cancer. MicroRNAs are non-coding molecules that are involved in regulation of a variety of functions happening in the cell, in healthy and diseased state. Dysregulation of microRNAs is observed in different diseases, especially in liver cancer like hepatocellular carcinoma. The available detection methods detect HCC at a late stage. There is a need to find novel biomarkers for diagnosis at an earlier stage to minimize chances of liver cancer. Circulating microRNAs are novel and minimal invasive markers for early detection of HCV based hepatocellular carcinoma. In this review, the current progress on the potential role of miRNA as biomarkers for detection of HCC and therapeutic targets are summarized. We concluded that the expression of microRNAis upregulated in the patients of hepatocellular carcinoma when compared with the healthy ones. In-depth studies of miRNA in patients of HCC as genetic biomarkers will improve the diagnosis. It will also improve the prognosis of early stage HCC patients. This will also help in identifying a suitable and effective therapeutic targets so as to reduce the chances of failure of chemotherapy.

Emerging role of MyomiRs as Biomarkers and Therapeutic Targets in Skeletal Muscle Diseases

Several chronic diseases lead to skeletal muscle loss and a decline in physical performance. MicroRNAs (miRNA) are small, non-coding RNAs, which has exhibited its role in the development and diseased state of the skeletal muscle. miRNA regulates gene expression by binding to the 3' untranslated region of its target mRNA. Due to the robust stability in biological fluids, miRNAs are ideal candidate as biomarker. These miRNAs provide a novel avenue in strengthening our awareness and knowledge about the factors governing skeletal muscle functions such as, development, growth, metabolism, differentiation and cell proliferation. It also helps in understanding the therapeutic strategies in improving or conserving skeletal muscle health. This review outlines the evidence regarding the present knowledge on the role miRNA as a potential biomarker in skeletal muscle diseases and their exploration might be a unique and potential therapeutic strategy for various skeletal muscle disorders.

The origin and role of the renal stroma

ABSTRACT The postnatal kidney is predominantly composed of nephron epithelia with the interstitial components representing a small proportion of the final organ, except in the diseased state. This is in stark contrast to the developing organ, which arises from the mesoderm and comprises an expansive stromal population with distinct regional gene expression. In many organs, the identity and ultimate function of an epithelium is tightly regulated by the surrounding stroma during development. However, although the presence of a renal stromal stem cell population has been demonstrated, the focus has been on understanding the process of nephrogenesis whereas the role of distinct stromal components during kidney morphogenesis is less clear. In this Review, we consider what is known about the role of the stroma of the developing kidney in nephrogenesis, where these cells come from as well as their heterogeneity, and reflect on how this information may improve human kidney organoid models.

MitoCellPhe reveals mitochondrial morphologies in single fibroblasts and clustered stem cells

Mitochondria are dynamic organelles that differ significantly in their morphologies across cell types, reflecting specific cellular needs and stages in development. Despite the wide biological significance in disease and health, delineating mitochondrial morphologies in complex systems remains challenging. Here, we present the Mitochondrial Cellular Phenotype (MitoCellPhe) tool developed for quantifying mitochondrial morphologies and demonstrate its utility in delineating differences in mitochondrial morphologies in a human fibroblast and human induced pluripotent stem cell (hiPSC) line. MitoCellPhe generates 24 parameters, allowing for a comprehensive analysis of mitochondrial structures and importantly allows for quantification to be performed on mitochondria in images containing single cells or clusters of cells. With this tool, we were able to validate previous findings that show networks of mitochondria in healthy fibroblast cell lines and a more fragmented morphology in hiPSCs. Using images generated from control and diseased fibroblasts and hiPSCs, we also demonstrate the efficacy of the toolset in delineating differences in morphologies between healthy and the diseased state in both stem cell (hiPSC) and differentiated fibroblast cells. Our results demonstrate that MitoCellPhe enables high-throughput, sensitive, detailed and quantitative mitochondrial morphological assessment and thus enables better biological insights into mitochondrial dynamics in health and disease

The Microbiome as a Potential Target for Therapeutic Manipulation in Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers and is projected to be the second most common cause of cancer-related death by 2030, with an overall 5-year survival rate between 7% and 9%. Despite recent advances in surgical, chemotherapy, and radiotherapy techniques, the outcome for patients with PDAC remains poor. Poor prognosis is multifactorial, including the likelihood of sub-clinical metastatic disease at presentation, late-stage at presentation, absence of early and reliable diagnostic biomarkers, and complex biology surrounding the extensive desmoplastic PDAC tumour micro-environment. Microbiota refers to all the microorganisms found in an environment, whereas microbiome is the collection of microbiota and their genome within an environment. These organisms reside on body surfaces and within mucosal layers, but are most abundantly found within the gut. The commensal microbiome resides in symbiosis in healthy individuals and contributes to nutritive, metabolic and immune-modulation to maintain normal health. Dysbiosis is the perturbation of the microbiome that can lead to a diseased state, including inflammatory bowel conditions and aetiology of cancer, such as colorectal and PDAC. Microbes have been linked to approximately 10% to 20% of human cancers, and they can induce carcinogenesis by affecting a number of the cancer hallmarks, such as promoting inflammation, avoiding immune destruction, and microbial metabolites can deregulate host genome stability preceding cancer development. Significant advances have been made in cancer treatment since the advent of immunotherapy. The microbiome signature has been linked to response to immunotherapy and survival in many solid tumours. However, progress with immunotherapy in PDAC has been challenging. Therefore, this review will focus on the available published evidence of the microbiome association with PDAC and explore its potential as a target for therapeutic manipulation.

Quantifying Mitochondrial Dynamics in Patient Fibroblasts with Multiple Developmental Defects and Mitochondrial Disorders

Mitochondria are dynamic organelles that undergo rounds of fission and fusion and exhibit a wide range of morphologies that contribute to the regulation of different signaling pathways and various cellular functions. It is important to understand the differences between mitochondrial structure in health and disease so that therapies can be developed to maintain the homeostatic balance of mitochondrial dynamics. Mitochondrial disorders are multisystemic and characterized by complex and variable clinical pathologies. The dynamics of mitochondria in mitochondrial disorders is thus worthy of investigation. Therefore, in this study, we performed a comprehensive analysis of mitochondrial dynamics in ten patient-derived fibroblasts containing different mutations and deletions associated with various mitochondrial disorders. Our results suggest that the most predominant morphological signature for mitochondria in the diseased state is fragmentation, with eight out of the ten cell lines exhibiting characteristics consistent with fragmented mitochondria. To our knowledge, this is the first comprehensive study that quantifies mitochondrial dynamics in cell lines with a wide array of developmental and mitochondrial disorders. A more thorough analysis of the correlations between mitochondrial dynamics, mitochondrial genome perturbations, and bioenergetic dysfunction will aid in identifying unique morphological signatures of various mitochondrial disorders in the future.