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The antiviral response and mechanism of action of KRG extract and ginsenoside Rc, Re, Rf, Rg1, Rg2-20 (R) and -20 (S), Rg3-20 (R) and -20 (S), and Rh2-20 (R) and -20 (S), against the human coronavirus strain OC43 were investigated by using plaque assay, time of addition assay, real-time PCR, and FACS analysis.Virus plaque formation was reduced in KRG extract-treated and HCoV-OC43-infected HCT-8 cells. KRG extract decreased the viral proteins (Nucleocapsid protein and Spike protein) and mRNA (N and M gene) expression, while increased the expression of interferon genes.KRG extract exhibits antiviral activity by enhancing the expression of interferons and can be used in treating infections caused by HCoV-OC43.

A. stechmanniana Besser is a semi-shrub plant indigenous to Mongolia, Central Asia, Russia, and Pakistan. Although A. stechmanniana has been used as folk medicine for inflammation, helminth infection, and tumors, the physiological activities of A. stechmanniana have not been fully experimentally validated. We investigated the anti-inflammatory activities and underlying mechanisms of action of A. stechmanniana on LPS-stimulated murine macrophages. Macrophages treated with A. stechmanniana-methanol extract (As-ME) showed the decreased expression of inducible NO synthase and cyclooxygenase-2 and secretion of NO, prostaglandin E2, and pro-inflammatory cytokines. Furthermore, we found As-ME reduced the phosphorylation of c-Jun N-terminal kinase (JNK), which was accompanied by a decrease in c-Jun in the nucleus, and suppressed the phosphorylation of NF-��B inhibitor �� and the translocation of NF-��B into the nucleus. The results indicated that As-ME possesses anti-inflammatory effects mediated through inhibition of JNK and NF-��B phosphorylation.

Traditional medicinal practices have used natural products such as adaptogens to treat inflammatory, autoimmune, neurodegenerative, bacterial, and viral diseases since the early days of civilization. Panax ginseng Myer is a common herb used in East Asian countries for millennia, especially in Korea, China, and Japan. Numerous studies indicate that ginseng can modulate the immune system and thereby prevent diseases. Although the human immune system comprises many different types of cells, multiple studies suggest that each type of immune cell can be controlled or stimulated by ginseng or its derivatives. Provisional lists of ginseng's potential for use against viruses, bacteria, and other microorganisms suggest it may prove to be a valuable pharmaceutical resource, particularly if higher-quality evidence can be found. Here, we reviewed the role of ginseng as an immune-modulating agent in attempt to provide a valuable starting point for future studies on the herb and the human immune system.

An aqueous extract ofHumulus japonicus(AH) has been documented to ameliorate hypertension and non-alcoholic fatty liver disease (NAFLD). Here, we investigated the effects of an aqueous extract of AH on thermogenesis and palmitate-induced oxidative stress in adipocytes. To verify the effect of AH on browning, we measured the expression levels of specific markers in 3T3-L1 adipocytes using qPCR and Western blotting, respectively. To assess the role of oxidative stress, cells were stained with DCFDA and observed by fluorescence microscopy. AH increased the expression of brown adipose tissue-specific markers. Additionally, it induced fatty acid oxidation and lipolysis and suppressed both lipogenic markers and lipid accumulation. Furthermore, AH ameliorated hydrogen peroxide-induced oxidative stress. Enhanced expression of these markers contributed to fat browning, fatty acid oxidation and lipolysis of 3T3-L1 adipocytesviathe AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor delta (PPARδ) signaling pathways. Moreover, AMPK and PPARδ resulting in protective effects of AH against oxidative stress. In sum, AH could promote the browning, lipolysis and thermogenesis in 3T3-L1 adipocytes and would suppress the hydrogen peroxide-induced oxidative stress and lipogenesis during differentiation. We therefore suggest that AH could be used as a potential candidate for treating obesity and related metabolic disorders.

The purpose of the present study was to investigate the clinical significance of BRCA1/BRCA2 DNA repair associated (BRCA1/BRCA2) gene expression in patients with sporadic gastric cancer (GC) who had received postoperative adjuvant chemotherapy. Breast cancer type 1 and 2 susceptibility protein (BRCA1 and BRCA2) expression and BRCA1/BRCA2 mRNA expression were evaluated using immunohistochemistry (IHC) and in-situ hybridization (ISH) on tissue GC microarray tissues, in addition to reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The results were analyzed for clinicopathological associations. A total of 367 cases of sporadic GC (stages II and III) were subjected to BRCA1 and BRCA2 expression analysis, and for BRCA1 and BRCA2 IHC, 360 cases were informative. A total of 61 cases (16.9%) displayed a loss of BRCA1 and 63 (17.5%) displayed a loss of BRCA2. BRCA1 and BRCA2 ISH results were obtained in 364 cases, of which 98 (26.9%) presented with low expression of BRCA1 mRNA and 148 (40.7%) with low expression of BRCA2 mRNA. In 72 of the 367 cases, BRCA1 and BRCA2 mRNA expression levels were assessed using RT-qPCR, of which 50 (69.4%) and 56 (77.8%) displayed low expression of BRCA1 and BRCA2, respectively. Positive IHC expression of BRCA2 was associated with advanced tumor stage; however, BRCA1 expression was not associated with any clinicopathological parameters. Associations between the RT-qPCR and ISH methods were not significant for either BRCA1 or BRCA2. The results of Kaplan-Meier survival analysis with stage subgrouping revealed no significant differences with regard to survival rate. Of the multivariate analyses, neither BRCA1 nor BRCA2 IHC results were independent prognostic factors. In summary, the present study indicated that BRCA1 and BRCA2, as assessed by IHC, may be used as clinicopathological biomarkers to evaluate the prognosis of sporadic GC.

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a chronic inflammatory disease characterized by intestinal inflammation and epithelial injury. For the treatment of IBD, 5-aminosalicylic acids, corticosteroids, immunomodulators, and biologic agents targeting tumor necrosis factor (TNF)-α, α4β7-integrin, and interleukin (IL)-12/23 have been widely used. Especially, anti-TNF-α antibodies are the first biologic agents that presently remain at the forefront. However, 10-30% of patients resist biologic agents, including anti-TNF-α agents (primary non-responder; PNR), and 20-50% of primary responders develop treatment resistance within one year (secondary loss of response; SLR). Nonetheless, the etiologies of PNR and SLR are not clearly understood, and predictors of response to biologic agents are also not defined yet. Numerous studies are being performed to discover prediction markers of the response to biologic agents, and this review will introduce currently available therapeutic options for IBD, biologics under investigation, and recent studies exploring various predictive factors related to PNR and SLR.

Human breast milk (HBM) is an irreplaceable source of nutrition for early infant growth and development. Breast-fed children are known to have a low prevalence and reduced risk of various diseases, such as necrotizing enterocolitis, gastroenteritis, acute lymphocytic leukemia, and acute myeloid leukemia. In recent years, HBM has been found to contain a microbiome, extracellular vesicles or exosomes, and microRNAs, as well as nutritional components and non-nutritional proteins, including immunoregulatory proteins, hormones, and growth factors. Especially, the milk-derived exosomes exert various physiological and therapeutic function in cell proliferation, inflammation, immunomodulation, and cancer, which are mainly attributed to their cargo molecules such as proteins and microRNAs. The exosomal miRNAs are protected from enzymatic digestion and acidic conditions, and play a critical role in immune regulation and cancer. In addition, the milk-derived exosomes are developed as drug carriers for delivering small molecules and siRNA to tumor sites. In this review, we examined the various components of HBM and their therapeutic potential, in particular of exosomes and microRNAs, towards cancer.

The sense of vision is the primary means by which we gather information from our surroundings, and vision loss, therefore, severely compromises the life of the affected individuals, their families, and society. Loss of vision becomes more frequent with age, and diabetic retinopathy, age-related macular degeneration, cataracts, and glaucoma are the major causes of vision impairment. To find active pharmacological compounds that might prevent or ameliorate the vision-threatening eye diseases, numerous studies have been performed, and some botanical compounds, including those extracted from ginseng, have been shown to possess beneficial effects in the treatment or prevention of common ocular diseases. In this review, we summarize the recent reports investigating the therapeutic effects of ginseng and ginsenosides on diverse ocular diseases and discuss their therapeutic potential. Keywords: Age-related macular degeneration, Cataract, Diabetic retinopathy, Ginseng, Glaucoma

Summary: Background: Exosomes are small extracellular vesicles secreted by various types of cells. Exosomes play an important role in intercellular communication by serving as vehicles for transferring proteins, lipids, mRNAs, microRNAs, and DNAs to recipient cells. This study investigated the role of exosomes in gastric cancer and the aging process by using a large number of human serum samples from young and aged individuals with or without gastric cancer. Methods: The age- and cancer-associated changes in exosome levels and exosomal cytokine content were measured. Exosomes in human serum were isolated by using a total exosome isolation reagent, followed by a quantification of isolated exosomes using a MicroBCA assay. Exosomal cytokines were measured by ELISA. Results: Serum exosome levels are increased by cancer and aging. Exosomal levels of TNF-α and TGF-β are increased, whereas IL-10 levels are reduced in gastric cancer. In addition, the cancer-associated changes in exosomal cytokines remain constant with age, even though aging affects every type of immune cells and immunomodulating factors. Conclusion: Gastric cancer and aging affect serum exosome and exosomal cytokines levels. Future studies would require the analysis of more diverse cytokines in exosomes derived from multiple types of cancer. Keywords: exosome, microvesicle, aging, cancer, cytokine

Motivation Metagenomic sequencing has become a crucial tool for obtaining a gene catalogue of operational taxonomic units (OTUs) in a microbial community. A typical metagenomic sequencing produces a large amount of data (often in the order of terabytes or more), and computational tools are indispensable for efficient processing. In particular, error correction in metagenomics is crucial for accurate and robust genetic cataloging of microbial communities. However, many existing error-correction tools take a prohibitively long time and often bottleneck the whole analysis pipeline. Results To overcome this computational hurdle, we analyzed and exploited the data-level parallelism that exists in the error-correction procedure and proposed a tool named MUGAN that exploits both multi-core central processing units and multiple graphics processing units for co-processing. According to the experimental results, our approach reduced not only the time demand for denoising amplicons from approximately 59 h to only 46 min, but also the overestimation of the number of OTUs, estimating 6.7 times less species-level OTUs than the baseline. In addition, our approach provides web-based intuitive visualization of results. Given its efficiency and convenience, we anticipate that our approach would greatly facilitate denoising efforts in metagenomics studies. Availability and implementation http://data.snu.ac.kr/pub/mugan Supplementary information Supplementary data are available at Bioinformatics online.

Natural compounds from functional foods targeting viruses are considered to have important role for regulating virus-related diseases. Ginsenoside Rg3 is one of the active pharmaceutical components found in Panax ginseng C.A. Meyer which is widely used as a functional food in East Asia. In our present study, we have characterized the antiviral activities of the ginsenoside Rg3 isomers, 20(R)- and 20(S)-ginsenoside Rg3, against murine gammaherpesvirus 68 (MHV-68), a mouse model of human gammaherpesvirus which can cause various malignancies including cancer. We found that both 20(R)- and 20(S)-ginsenoside Rg3 inhibited lytic replication and viral proliferation of MHV-68, although 20(S)-ginsenoside Rg3 was more effective than 20(R)-ginsenoside Rg3. Furthermore, ginsenoside Rg3 isomers efficiently repressed chemically-induced lytic replication of human gammaherpesviruses in EBV-positive BC-3 and KSHV-positive Raji cell lines. Finally, our data showed that ginsenoside Rg3 isomers suppressed the p38 and/or the JNK-associated MAPK signaling pathways, thereby inhibiting viral replication.

Highlights • The emotional public responses to a nation-wide outbreak of Middle East respiratory syndrome (MERS) in Korea was analyzed. • Massive media outlet data was collected during the outbreak. • An intriguing loop of information transfers between the media and the public was discovered. • This method would be helpful for alleviating the unnecessary fear and overreaction of the public regarding infectious diseases., From May to July 2015, there was a nation-wide outbreak of Middle East respiratory syndrome (MERS) in Korea. MERS is caused by MERS-CoV, an enveloped, positive-sense, single-stranded RNA virus belonging to the family Coronaviridae. Despite expert opinions that the danger of MERS might be exaggerated, there was an overreaction by the public according to the Korean mass media, which led to a noticeable reduction in social and economic activities during the outbreak. To explain this phenomenon, we presumed that machine learning-based analysis of media outlets would be helpful and collected a number of Korean mass media articles and short-text comments produced during the 10-week outbreak. To process and analyze the collected data (over 86 million words in total) effectively, we created a methodology composed of machine-learning and information-theoretic approaches. Our proposal included techniques for extracting emotions from emoticons and Internet slang, which allowed us to significantly (approximately 73%) increase the number of emotion-bearing texts needed for robust sentiment analysis of social media. As a result, we discovered a plausible explanation for the public overreaction to MERS in terms of the interplay between the disease, mass media, and public emotions.

Pothos scandens, an edible plant, has been traditionally used for reducing swelling and treating wounds, muscle catches, sprains, bone fractures, blisters, and diarrhea. P. scandens ethanol extract (PSE) was evaluated for its anti-inflammatory potential in lipopolysaccharide-stimulated murine RAW 264.7 cells. Present studies showed that PSE reduced the mRNA expression of inducible nitric oxide synthase and cyclooxygenase-2, followed by a decrease in production of nitric oxide and prostaglandin E2. In addition, the secretion of pro-inflammatory cytokines such as interleukin (IL)-6 and IL-1β was suppressed by PSE treatment. Immunoblotting analyses demonstrated that PSE inhibited the phosphorylation of extracellular signal-regulated kinase and signal transducer and activator of transcription 3 protein, without altering the phosphorylation of inhibitor of κBα, c-Jun N-terminal kinase, and p38 protein kinase. In conclusion, this study demonstrated that P. scandens exhibited anti-inflammatory activity, which might be useful for the development of anti-inflammatory agents.

Breast cancer type 1 susceptibility protein (BRCA1) is a tumor suppressor gene that encodes a nuclear phosphoprotein, which is involved in homologous recombination to repair DNA double strand breaks and maintain genome stability. When BRCA1 is mutated or altered, DNA damage may not be effectively repaired, which leads to DNA replication errors and cancer growth. Accordingly, people carrying a mutation in the BRCA1 gene possess an increased risk of several types of cancer, including breast and ovarian cancer. Previous clinical studies have reported an association between BRCA1 expression level and the incidence of gastric cancer; however, to the best of our knowledge, an in vitro study has not been performed to support these clinical observations. Therefore, the present study evaluated BRCA1 expression levels in gastric cancer cell lines. In addition, the IC50 values of cisplatin and oxaliplatin in each cell line were determined to investigate a potential correlation between BRCA1 expression level and chemosensitivity to platinum agents. The present results revealed that the BRCA1 expression level in gastric cancer is variable and associated with the treatment response to platinum-based chemotherapy. This suggests that BRCA1 may serve as a therapeutic marker for platinum-based chemotherapy in gastric cancer.

The success of gene therapy mainly depends on the carriers for effective gene delivery. A non-viral vector using a cationic block co-polyelectrolyte, PEI-PLA-PEG polyethyleneimine-poly(lactic acid)-poly(ethylene glycol)) was developed as a potential gene carrier. The cationic PEI-PLA-PEG showed less toxicity compared to PEI and formed a gene nanocomplex (termed polyplex) by interaction with plasmid DNA or small interference RNA. The polyplex showed smaller particle size and greater positive zeta potential by increasing the high polymer nitrogen/DNA phosphate ratio. The polyplex with a nitrogen/DNA phosphate ratio of 16 or 32 demonstrated higher gene transfection by fluorescence imaging, flow cytometry measurement, and β-galactosidase activity. In particular, the polyplex with therapeutic histone deacetylase small interference RNA at nitrogen/DNA phosphate ratio 16 showed the most favorable properties with definite tumor growth inhibition. The synthetic PEI-PLA-PEG also showed less toxicity and would, therefore, be a great potential gene carrier, particularly given that small interference RNA delivery does not increase the charge density of small interference RNA due to the formation of a stable complex through conjugation with PLA-PEG.

Background Ginsenosides are the major components of Panax ginseng Meyer, an herbal medicine used for the treatment of various diseases. Different ginsenosides contribute to the biological properties of ginseng, such as antimicrobial, anticancer, and immunomodulatory properties. In this study, we investigated the antiviral effects of 15 ginsenosides and compound K on gammaherpesvirus. Methods The antiviral activity of ginsenosides was examined using the plaque-forming assay and by analyzing the expression of the lytic gene. Results 20( R )-Ginsenoside Rh2 inhibited the replication and proliferation of murine gammaherpesvirus 68 (MHV-68), and its half-maximal inhibitory concentration (IC 50 ) against MHV-68 was estimated to be 2.77 μM. In addition, 20( R )-ginsenoside Rh2 inhibited 12- O -tetradecanoylphorbol-13-acetate (TPA)-induced lytic replication of human gammaherpesvirus in the Kaposi's sarcoma-associated herpesvirus (KSHV)-positive cell line BC3. Conclusion Our results indicate that 20( R )-ginsenoside Rh2 can inhibit the replication of mouse and human gammaherpesviruses, and thus, has the potential to treat gammaherpesvirus infection.

Solanum melongena or eggplant is a species of the nightshade family. According to Korean folk medicine, S. melongena stalk possesses excellent therapeutic effects on warts, burns, and many inflammatory diseases, such as stomatitis, arthritis, and gastritis. In order to investigate the anti-inflammatory effects of S. melongena stalk, an ethanol extract of the stalk was prepared, and fractionated into hexane, dichloromethane, ethyl acetate, n-butanol, and water fractions. The results showed that the ethyl acetate and n-butanol fractions contained high levels of phenol and reduced artificial free radicals. In contrast, the hexane and dichloromethane fractions decreased the production of nitric oxide, pro-inflammatory cytokines, and prostaglandin E2, despite the presence of low levels of phenols implying that other compounds than phenols are involved in anti-inflammatory reactions. The data suggest that S. melongena stalk possesses pharmacological activity and might be useful for development of antiox...

DNA damage causes aging, cancer, and other serious diseases. The comet assay can detect multiple types of DNA lesions with high sensitivity, and it has been widely applied. Although comet assay platforms have improved the limited throughput and reproducibility of traditional assays in recent times, analyzing large quantities of comet data often requires a tremendous human effort. To overcome this challenge, we proposed HiComet, a computational tool that can rapidly recognize and characterize a large number of comets, using little user intervention. We tested HiComet with real data from 35 high-throughput comet assay experiments, with over 700 comets in total. The proposed method provided unprecedented levels of performance as an automated comet recognition tool in terms of robustness (measured by precision and recall) and throughput. HiComet is an automated tool for high-throughput comet-assay analysis and could significantly facilitate characterization of individual comets by accelerating its most rate-limiting step. An online implementation of HiComet is freely available at https://github.com/taehoonlee/HiComet/ .

PurposeTo determine the relationship between two CD24 polymorphisms, rs8734/rs52812045 and rs3838646, and autoimmune disease. DesignMeta-analysis. MethodsThe Medline, EMBASE, Web of Science, and Cochrane Library databases were searched for studies reporting the association between CD24 polymorphisms and autoimmune disease. Two of the authors selected eligible studies and extracted and analyzed the data independently. ResultsCompared with carriers of the C allele (CC, CT, CT+CC), individuals homozygous for the T allele (TT) and heterozygous (CT+TT) at rs8734/rs52812045 have a higher incidence of autoimmune disease, whereas rs3838646 is not associated with autoimmune disease. Subgroup analysis found an increased risk of multiple sclerosis with the TT vs. CC, TT vs. CT, and TT vs. CC+CT alleles. ConclusionThe CD24 polymorphism rs8734/rs52812045 contributes to the development of autoimmune disease. CD24 polymorphism, rs8734/rs52812045 is associated with autoimmune disease.T allele carriers have a higher risk of autoimmune diseases than C allele carriers.CD24 polymorphism, rs3838646 is not associated with autoimmune diseases.

A wide variety of large-scale data has been produced in bioinformatics. In response, the need for efficient handling of biomedical big data has been partly met by parallel computing. However, the time demand of many bioinformatics programs still remains high for large-scale practical uses due to factors that hinder acceleration by parallelization. Recently, new generations of storage devices have emerged, such as NAND flash-based solid-state drives (SSDs), and with the renewed interest in near-data processing, they are increasingly becoming acceleration methods that can accompany parallel processing. In certain cases, a simple drop-in replacement of hard disk drives (HDDs) by SSDs results in dramatic speedup. Despite the various advantages and continuous cost reduction of SSDs, there has been little review of SSD-based profiling and performance exploration of important but time-consuming bioinformatics programs. For an informative review, we perform in-depth profiling and analysis of 23 key bioinformatics programs using multiple types of devices. Based on the insight we obtain from this research, we further discuss issues related to design and optimize bioinformatics algorithms and pipelines to fully exploit SSDs. The programs we profile cover traditional and emerging areas of importance, such as alignment, assembly, mapping, expression analysis, variant calling, and metagenomics. We explain how acceleration by parallelization can be combined with SSDs for improved performance and also how using SSDs can expedite important bioinformatics pipelines, such as variant calling by the Genome Analysis Toolkit (GATK) and transcriptome analysis using RNA sequencing (RNA-seq). We hope that this review can provide useful directions and tips to accompany future bioinformatics algorithm design procedures that properly consider new generations of powerful storage devices., Availability: http://best.snu.ac.kr/pub/biossd; to be published in Briefings in Bioinformatics

Regulatory T cells (Treg cells) are a subpopulation of T cells defined as CD4+Foxp3+CD25+. They mainly function as immunosuppressive T cells by downregulating the induction and proliferation of effector T cells, but also modulate the immune system by maintaining self-tolerance and preventing autoimmune disease. In this study, the regulatory roles of ginsenosides, one of the active components in ginseng, Panax ginseng C. A. Meyer, in Treg cell differentiation were examined. The results demonstrated that ginsenoside Rd induced Treg differentiation by upregulating Foxp3 expression and increased the generation of TGF-β1, IL-10 and IL-35. The data suggest that ginsenoside Rd may be a potential immunomodulating agent or supplement that can be applied for transplantation and autoimmune disorders.

Ilex cornuta, commonly known as Chinese holly, is an evergreen shrub from the family Aquifoliaceae, and it is widely distributed in Korea and China. In folk medicine, the leaves of I. cornuta are used for treatment of several disorders, including weakness of the waist and knees, arthrodynia, headache, acute conjunctivitis, toothache, urticaria, rheumatic arthralgia, and cardiovascular diseases. In this study, we investigated the anti-inflammatory effects of an I. cornuta leaf ethanol extract (ILE) and its underlying mechanisms of action. The anti-inflammatory activities of ILE were evaluated in murine RAW 264.7 macrophages, using lipopolysaccharide (LPS) stimulation. ILE treatment-related changes in the production of nitric oxide (NO), prostaglandin E2 (PGE2), and proinflammatory cytokines were also measured. Finally, the expression of signaling molecules involved in inflammatory reactions was also assessed. Pretreatment of macrophages with ILE attenuated the expression of inducible NO synthase and cyclooxygenase-2, resulting in a decrease in NO and PGE2 production. The secretion of proinflammatory cytokines such as interleukin (IL)-6 and IL-1β was also reduced. Furthermore, ILE reduced extracellular signal-regulated kinases (ERK) phosphorylation, without affecting the inhibitor of kappa Bα and other mitogen-activated protein kinases. Liquid chromatography-tandem mass spectrometry analysis (LC-MS/MS) demonstrated that 1 g of ILE contains 27 mg of kaempferol, 0.3 mg of vanillic acid, and 21 mg of combined amount of isoquercetin and hyperin, among which isoquercetin and kaempferol significantly suppressed IL-6, IL-1β, and PGE2 production. Our results demonstrated that ILE possesses anti-inflammatory effects mediated through inhibition of ERK phosphorylation.

Innate lymphoid cells (ILCs) are a recently defined type of innate-immunity cells that belong to the lymphoid lineage and have lymphoid morphology but do not express an antigen-specific B cell or T-cell receptor. ILCs regulate immune functions prior to the formation of adaptive immunity and exert effector functions through a cytokine release. ILCs have been classified into three groups according to the transcription factors that regulate their development and function and the effector cytokines they produce. Of note, ILCs resemble T helper (Th) cells, such as Th1, Th2, and Th17 cells, and show a similar dependence on transcription factors and distinct cytokine production. Despite their short history in immunology, ILCs have received much attention, and numerous studies have revealed biological functions of ILCs including host defense against pathogens, inflammation, tissue repair, and metabolic homeostasis. Here, we describe recent findings about the roles of ILCs in the pathogenesis of various diseases and potential therapeutic targets.

A "miRNA sponge" is an artificial oligonucleotide-based miRNA inhibitor containing multiple binding sites for a specific miRNA. Each miRNA sponge can bind and sequester several miRNA copies, thereby decreasing the cellular levels of the target miRNA. In addition to developing artificial miRNA sponges, scientists have sought endogenous RNA transcripts and found that long non-coding RNAs, competing endogenous RNAs, pseudogenes, circular RNAs, and coding RNAs could act as miRNA sponges under precise conditions. Here we present a computational approach for the prediction of endogenous human miRNA sponge candidates targeting viral miRNAs derived from pathogenic human viruses. Viral miRNA binding sites were predicted using a newly-developed machine learning-based method, and candidate interactions between miRNAs and sponge RNAs were experimentally validated using luciferase reporter assay, western blot analysis, and flow cytometry. We found that BX649188.1 functions as a potential natural miRNA sponge against kshv-miR-K12-7-3p.

Given the correlation between the deregulation of specific miRNAs and disease onset, it is critical to identify miRNA regulators that effectively control miRNAs involved in the pathogenesis of target diseases. This review provides the latest update on oligonucleotide- and small-molecule-based miRNA regulators, and discusses assays developed to screen for small-molecule regulators.