Hepatocellular carcinoma (HCC) is the most common subtype of liver cancer, and assessing its histopathological grade requires visual inspection by an experienced pathologist. In this study, the histopathological H&E images from the Genomic Data Commons Databases were used to train a neural network (inception V3) for automatic classification. According to the evaluation of our model by the Matthews correlation coefficient, the performance level was close to the ability of a 5-year experience pathologist, with 96.0% accuracy for benign and malignant classification, and 89.6% accuracy for well, moderate, and poor tumor differentiation. Furthermore, the model was trained to predict the ten most common and prognostic mutated genes in HCC. We found that four of them, including CTNNB1, FMN2, TP53, and ZFX4, could be predicted from histopathology images, with external AUCs from 0.71 to 0.89. The findings demonstrated that convolutional neural networks could be used to assist pathologists in the classification and detection of gene mutation in liver cancer.

Classification and mutation prediction based on histopathology H&E images in liver cancer using deep learning

Medicinal mushrooms are higher fungi with additional nutraceutical attributes having low fat content and a trans-isomer of unsaturated fatty acids along with high fibre content, triterpenes, phenolic compounds, sterols, eritadenine and chitosan. They are considered as the unmatched source of healthy foods and drugs. They have outstanding attractive taste, aroma and nutritional value, so are considered as functional food, which means they are beneficial to the body not only in terms of nutrition but also for improved health. Medicinal mushrooms and their extract have a large number of bioactive components called secondary metabolites. The presence of polysaccharide β-glucans or polysaccharide–protein complexes content in mushroom extract have great therapeutic applications in human health as they possess many properties such as anti-diabetic, anti-cancerous, anti-obesity, immunomodulatory, hypocholesteremia, hepatoprotective nature along with anti-aging. The present review focuses on the comprehensive account of the medicinal properties of various medicinal mushrooms. This will further help the researchers to understand the metabolites and find other metabolites as well from the mushrooms which can be used for the potential development of the drugs to treat various life-threatening diseases.

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Medicinal mushroom: boon for therapeutic applications

Long non-coding RNAs (lncRNAs) have been known to partake in the development and the immune escape of hepatocellular carcinoma (HCC). The initial microarray analysis of GSE115018 expression profile revealed differentially expressed lncRNA fetal-lethal non-coding developmental regulatory RNA (FENDRR) in HCC. Therefore, this study's main purpose was to explore the mechanism of tumor suppressor lncRNA FENDRR in regulating the immune escape of HCC cells. Notably, it was further validated through this study that lncRNA FENDRR competitively bound to microRNA-423-5p (miR-423-5p), and miR-423-5p specifically targeted growth arrest and DNA-damage-inducible beta protein (GADD45B). The effects that lncRNA FENDRR and miR-423-5p have on the cell proliferation and apoptosis, the immune capacity of regulatory T cells (Tregs), and the tumorigenicity of HCC cells were examined through overexpressing or the knocking down of lncRNA FENDRR and miR-423-5p both in vitro and in vivo. Subsequently, lncRNA FENDRR and GADD45B were revealed to have poor expressions in HCC. Meanwhile, miR-423-5p was highly expressed in HCC. Importantly, overexpressed lncRNA FENDRR and downregulated miR-423-5p diminished cell proliferation and tumorigenicity, and promoted apoptosis in HCC cells, thus regulating the immune escape of HCC mediated by Tregs. Taken conjointly, lncRNA FENDRR inhibited the Treg-mediated immune escape of HCC cells by upregulating GADD45B by sponging miR-423-5p.

Long Non-coding RNA FENDRR Acts as a miR-423-5p Sponge to Suppress the Treg-Mediated Immune Escape of Hepatocellular Carcinoma Cells

Mushrooms have been valued as food and health supplements by humans for centuries. They are rich in dietary fiber, essential amino acids, minerals, and many bioactive compounds, especially those related to human immune system functions. Mushrooms contain diverse immunoregulatory compounds such as terpenes and terpenoids, lectins, fungal immunomodulatory proteins (FIPs) and polysaccharides. The distributions of these compounds differ among mushroom species and their potent immune modulation activities vary depending on their core structures and fraction composition chemical modifications. Here we review the current status of clinical studies on immunomodulatory activities of mushrooms and mushroom products. The potential mechanisms for their activities both in vitro and in vivo were summarized. We describe the approaches that have been used in the development and application of bioactive compounds extracted from mushrooms. These developments have led to the commercialization of a large number of mushroom products. Finally, we discuss the problems in pharmacological applications of mushrooms and mushroom products and highlight a few areas that should be improved before immunomodulatory compounds from mushrooms can be widely used as therapeutic agents.

Immunomodulatory Effects of Edible and Medicinal Mushrooms and Their Bioactive Immunoregulatory Products.

This article reviews mushrooms with anti-breast cancer activity. The mushrooms covered which are better known include the following: button mushroom Agaricus bisporus, Brazilian mushroom Agaricus blazei, Amauroderma rugosum, stout camphor fungus Antrodia camphorata, Jew’s ear (black) fungus or black wood ear fungus Auricularia auricula–judae, reishi mushroom or Lingzhi Ganoderma lucidum, Ganoderma sinense, maitake mushroom or sheep’s head mushroom Grifola frondosa, lion’s mane mushroom or monkey head mushroom Hericium erinaceum, brown beech mushroom Hypsizigus marmoreus, sulfur polypore mushroom Laetiporus sulphureus, Lentinula edodes (shiitake mushroom), Phellinus linteus (Japanese “meshimakobu,” Chinese “song gen,” Korean “sanghwang,” American “black hoof mushroom”), abalone mushroom Pleurotus abalonus, king oyster mushroom Pleurotus eryngii, oyster mushroom Pleurotus ostreatus, tuckahoe or Fu Ling Poria cocos, and split gill mushroom Schizophyllum commune. Antineoplastic effectiveness in human clinical trials and mechanism of anticancer action have been reported for Antrodia camphorata, Cordyceps sinensis, Coriolus versicolor, Ganoderma lucidum, Grifola frondosa, and Lentinula edodes.

Mushroom extracts and compounds with suppressive action on breast cancer: evidence from studies using cultured cancer cells, tumor-bearing animals, and clinical trials.

Molecular mechanistic insight of hepatitis B virus mediated hepatocellular carcinoma.

Diabetes and obesity are the most frequently found disease worldwide. Several factors are responsible for obesity, i.e., imbalance in energy expenditure, environmental factors, feeding habit, lifestyle, etc., which can also be responsible for type 2 diabetes mellitus. There are several synthetic drugs available to combat these diseases which have some side effects on sufferers. Therefore, people are shifting towards inexpensive, effective, widely available natural and herbal medicines. Edible mushrooms, which have been used from ancient time to cure these diseases, contain anti-oxidant, fibers, triterpenoids, alkaloid, and other phytochemicals. Comatin, β-glucan, Tremellastin, and Lentinan KS-2 are active chemicals of mushrooms which show great effect on diabetes mellitus and obesity by modulating either cellular function or biochemical pathways. Here, in this review, we have discussed the potential role of edible mushrooms and its biochemicals in control of diabetes and obesity. Using Bioinformatics, we can find the specific targets of theses biochemicals, so that these can be more effective.

Role of edible mushroom as a potent therapeutics for the diabetes and obesity

The Indian system of medicine - Ayurveda says "When diet is wrong, medicine is of no use. When diet is correct, medicine is of no use". In this context, mushroom constitutes one of the major resources for nutraceuticals. Biomolecules of mushrooms have attracted the attention of researchers around the globe due to their proven healthy attributes. They have a plenitude of health-giving properties and these range from immunomodulatory, antiviral, antibacterial, antifungal, antioxidant, anti-inflammatory, antitumor, anticancer, anti-HIV, antidiabetic, anticholesterolic to antiarthritic activities.Mushrooms contain both primary and secondary metabolites. The primary metabolites provide energy while the secondary metabolite exhibits medicinal properties. Hence, the mushroom can be a recipe for human wellness and will play a significant role in fighting COVID-19 pandemics and other infectious diseases.The key findings suggested in this paper refer to the exploration of health and the healing traits of biomolecules of mushrooms. This article reviews the current status of the medicinal attributes of mushrooms and their biomolecules in different diseases such as cardiovascular, diabetes, reproductive diseases, cancer, and neurodegenerative diseases. The global malnutrition-related morbidity and mortality among children under five and lactating women presents a frightening picture and also a black spot on the human face. Malnutrition is responsible for more ill-health than any other cause. Mushrooms as a rich source of bioactive compounds can be claimed as "Best from the Waste" since they grow on the most abundant organic wastes of the Earth, the lignocellulosic substrate, and 'Best of the Rest' because they are excellent nutraceutical resources.

Biomolecules of mushroom: a recipe of human wellness.

Background The antidiabetic effects of the Pleurotus fossulatus on liver and kidney were unexplored. The present study assessed the vital effects of P. fossulatus aqueous extract (PFA-extract) on liver and kidney function in diabetic rats model. Methods The albino Wistar rats were divided into five groups with six animals in each. Group, I, II, and III were normal, diabetic, and drug control, respectively, and groups IV and V were test groups. As treatment dose, group II received saline, and group III (drug control) received metformin in 100 mg/kg of body weight as a standard drug. Whereas, group IV (D1) and V (D2) were test groups, received PFA-extract in 250 mg/kg, and 500 mg/kg of body weight, respectively. The changes in body weight, blood glucose level (BGL), lipid profile, liver, and kidney biochemical parameters were evaluated. Results The PFA-extract dose at 500 mg/kg in D2 groups showed very good effects. The body weight was recovered by 97.9% and blood glucose level (BGL) was reduced to 53% in the D2 group. For the lipid profile, total cholesterol (TC), triglyceride (TG), and high-density lipoprotein (HDL) were estimated in blood plasma and their values were 92.31±3.788, 80.85±8.962, and 31.35±1.781, respectively. PFA-extract improved the liver function for which aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were evaluated and recorded to their normal range in D2 group which were 132.01±5.553, 58.63±4.390, and 143.26±2.423, respectively. For the kidney function test, creatinine (CRT), blood urea nitrogen (BUN), and uric acid were evaluated and in the D2 group, it was significantly reduced ie, 0.656±0.0707, 15.13±1.463, and 6.27±0.325, respectively. Conclusion These attributes of PFA-extract make it a potential natural agent to provide protection to the liver and kidney and also reduce the BGL and control the total lipid in type 1 diabetes condition.

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Sushil K. Dubey

Papers

Molecular mechanistic insight of hepatitis B virus mediated hepatocellular carcinoma.

Role of edible mushroom as a potent therapeutics for the diabetes and obesity

Biomolecules of mushroom: a recipe of human wellness.

Effect of Pleurotus fossulatus Aqueous Extract on Biochemical Properties of Liver and Kidney in Streptozotocin-Induced Diabetic Rat

Antidiabetic Potential of Medicinal Mushrooms