Design, synthesis and biological evaluation of 5H-[1,2,4]triazino[5,6-b]indole derivatives bearing a pyridinocycloalkyl moiety as iron chelators.

The avidity of cancer cells for iron highlights the potential for iron chelators to be used in cancer therapy. Herein, we designed and synthesized a novel series of 5H-[1,2,4]triazino[5,6-b]indole derivatives bearing a pyridinocycloalkyl moiety using a ring-fusion strategy based on the structure of an iron chelator, VLX600. The antiproliferative activity evaluation against cancer cells and normal cells led to the identification of compound 3k, which displayed the strongest antiproliferative activity in vitro against A549, MCF-7, Hela and HepG-2 with IC50 values of 0.59, 0.86, 1.31 and 0.92 µM, respectively, and had lower cytotoxicity against HEK293 than VLX600. Further investigations revealed that unlike VLX600, compound 3k selectively bound to ferrous ions, but not to ferric ions, and addition of Fe2+ abolished the cytotoxicity of 3k. Flow cytometry assays demonstrated that 3k arrested the cell cycle at the G1 phase and induced significant apoptosis in A549 cells in dose and time-dependent manners, corresponding to JC-1 staining assay results. Western blot analysis of Bcl-2, Bax and cleaved caspase-3 proteins further provided evidences that induction of apoptosis by 3k in A549 cells might be at least via the mitochondria pathway. These above results highlight that 3k is a valuable lead compound that deserves further investigation as an iron chelator for the treatment of cancer.

Current status of cancer starvation therapy.

Conventional therapies for malignant tumors have limitations and disadvantages. In recent years, the cancer starvation therapy has emerged which intends to deprive cancer cells of nutritional supply. There are several approaches to"starve" cancer cells: to intervene tumor angiogenesis by targeted inhibition of angiogenic factors or their receptors and integrins; to block the blood supply of cancer cells by embolizing or compressing blood vessels; to intervene metabolic process of cancer cells by inhibition of the signal pathways of mitochondrial serine-glycine-one earbon metabolism, glycolysis and amino acid metabolism; cancer starvation therapy can be employed with oxidation therapy, chemotherapy, sonodynamic therapy, anti-autophagy therapy or other therapies to achieve synergistic effects. This article reviews the research progress of cancer starvation therapy in recent years and discusses the existing problems.

Critical thinking and regional gray matter volume interact to predict representation connection in scientific problem solving.

Representation connection (RC) is a stable ability that significantly predicts the accuracy of scientific innovation problem solving while critical thinking has been strongly related to problem solving. However, the neural mechanisms underlying this relationship have not been assessed. Using voxel-based morphometry (VBM) and scientific innovation problem solving materials, we investigated the correlation between RC and regional gray matter volume (rGMV) in healthy young participants. We found that RC was positively correlated with rGMV in the right superior temporal gyrus (STG) and in a cluster in the left medial frontal gyrus (MFG). These results indicate that increased rGMV in the right STG may lead to the ability to overcome misdirection more easily, which may result in better semantic integration of the "certain construction" of heuristic prototypes. Increased rGMV in the left MFG may be associated with forming novel associations and retrieving matched unsolved technical problems from memory. Further analysis revealed that the interaction between critical thinking and rGMV predicted RC in insightful problem solving, and found that higher rGMV was correlated with higher RC in participants with lower cognitive maturity, but not in participants with higher cognitive maturity. These findings suggest that rGMV could interact with cognitive maturity to modulate RC in insightful problem solving.

NUBPL, a novel metastasis-related gene, promotes colorectal carcinoma cell motility by inducing epithelial-mesenchymal transition.

Nucleotide binding protein-like, NUBPL, is an assembly factor for human mitochondrial complex I, which is the biggest member of the mitochondrial respiratory chain. However, the relationship between NUBPL and carcinoma progression remains unknown. In this study, NUBPL was characterized for its role in colorectal cancer (CRC) and the underlying molecular mechanisms. Data (n = 197) from the Oncomine database revealed that mRNA levels of NUBPL were remarkably overexpressed in CRC tissues compared with normal tissues. In addition, immunohistochemical analysis of 75 pairs of CRC and non-tumor tissues showed that the expression level of NUBPL was significantly higher in CRC tissues, and its expression level was positively associated with lymph node metastasis (P = 0.028) and advanced staging (P = 0.030). Expression of NUBPL in metastatic lymph nodes of CRC patients was also detected by immunohistochemical staining and high expression levels of NUBPL were observed. Overexpression of NUBPL significantly promoted the migration and invasion ability of CRC cell lines SW480 and SW620, whereas knockdown of NUBPL lead to an opposite effect. Our further study found that NUBPL could induce epithelial-mesenchymal transition (EMT), characterized by downregulation of epithelial markers (E-cadherin) and upregulation of mesenchymal markers (N-cadherin and vimentin). Moreover, NUBPL was able to activate ERK, which is believed to promote EMT and tumor metastasis. Inhibition of ERK suppressed the NUBPL-induced changes in EMT and cell motility. These data showed that NUBPL plays a vital role in CRC migration and invasion by inducing EMT and activating ERK. It might be a novel therapeutic target for CRC.

Increased Eps15 homology domain 1 and RAB11FIP3 expression regulate breast cancer progression via promoting epithelial growth factor receptor recycling.

Recent research indicates that the C-terminal Eps15 homology domain 1 is associated with epithelial growth factor receptor-mediated endocytosis recycling in non-small-cell lung cancer. The aim of this study was to determine the clinical significance of Eps15 homology domain 1 gene expression in relation to phosphorylation of epithelial growth factor receptor expression in patients with breast cancer. Primary breast cancer samples from 306 patients were analyzed for Eps15 homology domain 1, RAB11FIP3, and phosphorylation of epithelial growth factor receptor expression via immunohistochemistry. The clinical significance was assessed via a multivariate Cox regression analysis, Kaplan-Meier curves, and the log-rank test. Eps15 homology domain 1 and phosphorylation of epithelial growth factor receptor were upregulated in 60.46% (185/306) and 53.92% (165/306) of tumor tissues, respectively, as assessed by immunohistochemistry. The statistical correlation analysis indicated that Eps15 homology domain 1 overexpression was positively correlated with the increases in phosphorylation of epithelial growth factor receptor ( r = 0.242, p < 0.001) and RAB11FIP3 ( r = 0.165, p = 0.005) expression. The multivariate Cox proportional hazard model analysis demonstrated that the expression of Eps15 homology domain 1 alone is a significant prognostic marker of breast cancer for the overall survival in the total, chemotherapy, and human epidermal growth factor receptor 2 (-) groups. However, the use of combined expression of Eps15 homology domain 1 and phosphorylation of epithelial growth factor receptor markers is more effective for the disease-free survival in the overall population, chemotherapy, and human epidermal growth factor receptor 2 (-) groups. Moreover, the combined markers are also significant prognostic markers of breast cancer in the human epidermal growth factor receptor 2 (+), estrogen receptor (+), and estrogen receptor (-) groups. Eps15 homology domain 1 has a tumor suppressor function, and the combined marker of Eps15 homology domain 1/phosphorylation of epithelial growth factor receptor expression was identified as a better prognostic marker in breast cancer diagnosis. Furthermore, RAB11FIP3 combines with Eps15 homology domain 1 to promote the endocytosis recycling of phosphorylation of epithelial growth factor receptor.

A meta-analysis of neuroimaging studies on divergent thinking using activation likelihood estimation.

In this study, an activation likelihood estimation (ALE) meta-analysis was used to conduct a quantitative investigation of neuroimaging studies on divergent thinking. Based on the ALE results, the functional magnetic resonance imaging (fMRI) studies showed that distributed brain regions were more active under divergent thinking tasks (DTTs) than those under control tasks, but a large portion of the brain regions were deactivated. The ALE results indicated that the brain networks of the creative idea generation in DTTs may be composed of the lateral prefrontal cortex, posterior parietal cortex [such as the inferior parietal lobule (BA 40) and precuneus (BA 7)], anterior cingulate cortex (ACC) (BA 32), and several regions in the temporal cortex [such as the left middle temporal gyrus (BA 39), and left fusiform gyrus (BA 37)]. The left dorsolateral prefrontal cortex (BA 46) was related to selecting the loosely and remotely associated concepts and organizing them into creative ideas, whereas the ACC (BA 32) was related to observing and forming distant semantic associations in performing DTTs. The posterior parietal cortex may be involved in the semantic information related to the retrieval and buffering of the formed creative ideas, and several regions in the temporal cortex may be related to the stored long-term memory. In addition, the ALE results of the structural studies showed that divergent thinking was related to the dopaminergic system (e.g., left caudate and claustrum). Based on the ALE results, both fMRI and structural MRI studies could uncover the neural basis of divergent thinking from different aspects (e.g., specific cognitive processing and stable individual difference of cognitive capability).

An illustrated heuristic prototype facilitates scientific inventive problem solving: A functional magnetic resonance imaging study.

Many scientific inventions (SI) throughout history were inspired by heuristic prototypes (HPs). For instance, an event or piece of knowledge similar to displaced water from a tub inspired Archimedes' principle. However, the neural mechanisms underlying this insightful problem solving are not very clear. Thus, the present study explored the neural correlates used to solve SI problems facilitated by HPs. Each HP had two versions: a literal description with an illustration (LDI) and a literal description with no illustration (LDNI). Thirty-two participants were divided randomly into these two groups. Blood oxygenation level-dependent fMRI contrasts between LDI and LDNI groups were measured. Greater activity in the right middle occipital gyrus (RMOG, BA19), right precentral gyrus (RPCG, BA4), and left middle frontal gyrus (LMFG, BA46) were found within the LDI group as compared to the LDNI group. We discuss these results in terms cognitive functions within these regions related to problem solving and memory retrieval.

Reduced ING4 Expression Is Associated with the Malignancy of Human Bladder.

INTRODUCTION: Inhibitor of growth 4 (ING4) is a tumor suppressor. However the role of ING4 in human bladder malignancy is unknown. In this study, ING4 expression in human bladder cancer and its potential effects were studied. MATERIALS AND METHODS: ING4 expression in 47 human bladder cancer tissues and paired adjacent normal tissues was detected by Western blotting, quantitative reverse transcription-polymerase chain reaction, and immunohistochemistry. The migration and cell cycle progression of SV-HUC-1 and T24 cells with aberrant ING4 expression were examined. RESULTS: ING4 protein and mRNA were significantly decreased in bladder cancer tissues. ING4 protein level was significantly lower in the group of patients over 50 years of age. ING4 knockdown caused more rapid cell migration and increased the population of SV-HUC-1 and T24 cells in the G2-M phase. CONCLUSION: Our data suggest a close connection between aberrant ING4 expression and the carcinogenesis of human bladder cells. ING4 may be a potential target for bladder cancer chemotherapy.

Bullying Victimization and Malevolent Creativity in Rural Adolescents: The Longitudinal Mediational Role of Hostile Attribution.

Extensive research has documented bully victimization as a pivotal risk factor contributing to aggressive behaviors among adolescents. Particularly, the negative outcome of increased aggressive behaviors may be exacerbated when the aggressive actions are novel and difficult to detect. The present study aims to explore the complex relationships between cyberbullying and school bullying victimization and malevolent creativity and the potential mediating role of hostile attribution using two-wave longitudinal data. The present study analyzed data from 262 rural adolescents. The results revealed that cyberbullying victimization significantly predicted malevolent creativity, whereas school bullying victimization did not. Hostile attribution served as a mediator in the relationship between cyberbullying victimization and malevolent creativity in the longitudinal models. These findings provide significant implications for mitigating the negative influence of bullying victimization on the emergence of malevolent creativity in rural adolescents.

Exosomal EphA2 promotes tumor metastasis of triple-negative breast cancer by damaging endothelial barrier.

Many evidences show that exosomes play an important role in cancer development, invasion and metastasis. This study is based on the need to explore exosomal protein that promote breast cancer metastasis. We found that tyrosine kinase EphA2 was enriched in Triple-negative breast cancer -derived exosomes and it could disrupt the endothelial monolayer barrier through downregulating tight junction proteins of endothelial cells. These mechanisms were confirmed by in vivo experiments. After periodical injection of exosomal EphA2 into mice caudal vein, we found increased vascular permeability and breast cancer metastases in distant organs, and this phenomenon decreased dramatically after exosomal EphA2 knockdown. This study provides a new mechanism of exosome promoting breast cancer metastasis and suggests a new therapeutic target for the prevention and treatment of breast cancer metastasis.

DJ-1 may contribute to metastasis of non-small cell lung cancer.

Lung cancer is a leading cause of cancer-related death, about 40% human non-small cell lung cancer (NSCLC) patients showed lymph node involvements. However, the precise mechanism for the metastasis is still not fully understood. This study was to analyze the potential molecular mechanism for lung cancer metastasis. In the current study, proteomics analysis by two-dimensional electrophoresis (2-DE) was performed first to identify the differentially expressed protein between the higher metastasis lung adenocarcinoma cell line Anip973 and the lower metastasis lung adenocarcinoma cell line AGZY83-a. We confirmed the result by RT-PCR, immunoblotting and immunocytochemistry analyses in these two cell lines. Then we examined the expression of the differentially expressed protein in tumor tissues of NSCLC patients by immunoblotting and immunohistochemistry analyses. Using 2-DE analysis, we have identified DJ-1 was expressed higher in the higher metastasis Anip973 compared to the parental cell line AGZY83-a, that was confirmed by RT-PCR, immunoblotting and immunocytochemistry analyses. In NSCLC patients' tumor tissues study, immunoblotting data showed that, DJ-1 expression level was significantly higher in 72.2% (13/18) of NSCLC tissue samples compared to that in paired normal lung tissues (P = 0.044). Immunohistochemistry analysis demonstrated increased DJ-1 expression in 85 NSCLC tumor tissue samples compared with 7 normal lung tissue samples (P = 0.044). DJ-1 expression was also found to be significantly correlated with cancer lymphatic metastasis (P = 0.039). DJ-1 might contribute to the metastasis of NSCLC.

Regional gray matter volume mediates the relationship between neuroticism and depressed emotion.

The underlying psychological mechanism of the effect of neuroticism on depressed emotion has been widely studied. However, the neural mechanism of this relationship remains unclear. Therefore, the present study aimed to apply voxel-based morphometry (VBM) to explore the neural mechanism of the relationship between depressed emotion and neuroticism in healthy and young participants through longitudinal tracking research. The behavioral results showed that neuroticism was positively related to depressed emotion at T1 and T2 (6 months later). The VBM analysis revealed that neuroticism positively associated with the gray matter volume (GMV) in the dorsal medial prefrontal cortex (dmPFC). Mediation analysis was conducted to investigate the neural basis of the association between depressed emotion and neuroticism. The mediation result revealed that GMV of the dmPFC partially mediates the relationship between neuroticism and depressed emotion at T1 but not T2. Together, these findings suggest that the gray matter volume of dmPFC could may affect the relationship between depressed emotion and neuroticism.

E2F1 Affects the Therapeutic Response to Neoadjuvant Therapy in Breast Cancer.

This study is aimed at screening genes for predicting the sensitivity response and favorable outcome of neoadjuvant therapy in breast cancer. We downloaded neoadjuvant therapy genetic data of breast cancer and separated it into the pathological complete response (pCR) group and the non-pCR group. Differential expression analysis was performed to select the differentially expressed genes (DEGs). After that, we investigated the enriched biological processes and pathways of DEGs. Then, core up/down protein-protein interaction (PPI) network was, respectively, constructed to identify the hub genes. A transcription factor-target gene regulation network was built to screen core transcription factors (TFs). We found one upregulated DEG (KLHDC7B) and four downregulated DEGs (TFF1, LOC440335, SLC39A6, and MLPH) overlapped in three datasets. All DEGs were mainly enriched in pathways related to DNA biosynthesis, cell cycle, immune response, metabolism, and angiogenesis. The hub genes were KRT18, IL7R, HIST1H1A, and E2F1. The core TFs were HOXA9, SPDEF, FOXA1, E2F1, and PGR. RT-qPCR suggested that E2F1 was overexpressed in MCF-7, but HOXA9 was low-expressed. Western blot suggested that the MAPK signal pathway was inhibited in MCF-7/ADR. That is to say, some genes and core TFs can predict the sensitivity response of neoadjuvant therapy in breast cancer. And E2F1 may be involved in the process of drug resistance by regulating the MAPK signaling pathway. These might be useful as sensitive genes for the efficacy evaluation of neoadjuvant chemotherapy in breast cancer.

The Impact of Emotional Intelligence on Domain-Specific Creativity: The Mediating Role of Resilience and the Moderating Effects of Gratitude.

Creativity incorporates both domain-general and domain-specific ideas. While previous studies have explored the impact of emotional intelligence (EI) on creativity in both domains, a consensus has not been reached, and the mechanism is currently unclear. In the present study, we examined which aspect of creativity EI was most strongly associated with in a group of undergraduates. Moreover, we explored the moderated mediation effect between EI and domain-specific creativity. In Study 1, 532 undergraduates completed questionnaires measuring EI, convergent and divergent creative thinking, and creative achievement. The results revealed that the most reliable positive correlations were between EI and domain-specific creativity. In Study 2, 926 undergraduates completed measurements of EI, resilience, gratitude, and creative achievement. The results revealed that resilience mediates the relationship between EI and creative achievement. Furthermore, gratitude moderated the indirect effect of EI on creative achievement through resilience. The indirect effect of EI on creative achievement was stronger for high-gratitude individuals than for low-gratitude individuals. This orientation and other results are discussed. Overall, our findings add further nuance to the relationship between EI and creativity in different domains. This study serves as a basis for other contributions aligned with these concepts.

The oriental armyworm genome yields insights into the long-distance migration of noctuid moths.

The oriental armyworm, Mythimna separata, is known for its long-distance seasonal migration and environment-dependent phase polymorphisms. Here, we present a chromosome-level genome reference and integrate multi-omics, functional genetics, and behavioral assays to explore the genetic bases of the hallmark traits of M. separata migration. Gene family comparisons show expansion of gustatory receptor genes in this cereal crop pest. Functional investigation of magnetoreception-related genes and associated flight behaviors suggest that M. separata may use the geomagnetic field to guide orientation in its nocturnal flight. Comparative transcriptome characterizes a suite of genes that may confer the observed plasticity between phases, including genes involved in protein processing, hormone regulation, and dopamine metabolism. We further report molecular signatures that underlie the dynamic regulation of a migratory syndrome coordinating reproduction and flight. Our study yields insights into environment-dependent developmental plasticity in moths and advances our understanding of long-distance migration in nocturnal insect pests.

Will the patient's double eyelid shape be like that of the surgeon performing the procedure? A study of surgeons' aesthetics in East Asian Blepharoplasty.

BACKGROUND: No reports of the potential areas of surgeons' aesthetics in blepharoplasty. AIMS: To explore the association between the surgeons' own double eyelid morphology and their aesthetics and surgical outcome. METHODS: An investigation of 1605 patients was carried collecting the data of double eyelid shape, based on which to propose a preliminary double eyelid classification for analyzing the aesthetics of surgeons. Ten double eyelid surgical cases were randomly collected from each surgeon according to the inclusion criteria, whose double eyelid shape, ideal shape, the selection tendency of surgical approach, most cared factor during surgery, and design concept of eyelid shape were collected. Structural equation modeling (SEM) was performed to assess the association between participants' double eyelid shape, aesthetics, and blepharoplasty outcome. RESULTS: Fifty-three double eyelid surgeons were enrolled for study, whose double eyelids shapes mostly were obviously fan-shaped (37.74%) and low-parallel eyelid (26.42%), and the ideal shapes were obviously fan-shaped (41.51%) and high-parallel eyelid (24.53%). 54.72% of the subjects preferred to use the full-incisional method. 45.28% cared for long-term outcome most. Regarding blepharoplasty outcome style, 49.06% of the subjects preferred obviously fan-shaped type and 24.53% for high-parallel type. SEM showed that aesthetics rank increased by 0.692 points for surgeons' shape (P < .001), and surgical outcome rank increased by 0.861 points for aesthetics (P < .001). However, their eyelid shape had no direct contribution to surgical outcome (P = .96). CONCLUSIONS: The findings indicated that surgeons' double eyelid shape positively affected their aesthetics, which affected their surgical outcomes further, but their double eyelid shape failed to affect the surgical outcomes directly.

Down-regulation of ING4 is associated with initiation and progression of lung cancer.

AIMS: Tumour suppressor ING4 is one of ING family genes, which are involved in cell cycle arrest, gene transcription regulation, DNA repair and apoptosis. ING4 inhibition has been reported in various tumours, including gliomas, breast tumours, and stomach adenocarcinoma. The aim was to evaluate ING4 expression in lung cancers. METHOD AND RESULTS: By immunohistochemistry of 246 lung tumour tissues, reduced ING4 nuclear and cytoplasmic expression were both revealed in lung cancer and associated with tumour grade. Interestingly, compared with normal tissues, we found more tumours with ING4 expression in the cytoplasm higher than in the nucleus. Nuclear ING4 inhibition correlated with the tumour stage and lymph node metastasis. Consistent with these findings, semiquantitative reverse transcriptase-polymerase chain reaction and Western blotting demonstrated decreased ING4 mRNA and expression in 100% (50/50) tumour tissues. Furthermore, ING4 expression was lower in grade III than in grades I-II tumours. Reduced ING4 mRNA correlated with lymph node metastasis. CONCLUSIONS: Our results indicate that overall inhibition of ING4 expression and ING4 expression higher in cytoplasm than in nucleus of tumour cells may be involved in the initiation and progression of lung cancers, and thus, analysis for ING4 expression may be useful as a clinical diagnostic and prognostic tool for lung cancer.

Reduced expression and novel splice variants of ING4 in human gastric adenocarcinoma.

ING4, a new member of the ING (inhibitor of growth) family of tumour suppressor genes, has been found to be deleted or down-regulated in gliomas, breast tumours, and head and neck squamous cell carcinomas. The goal of the present study was to investigate whether the expression and alternative splicing of ING4 transcripts are involved in the initiation and progression of stomach adenocarcinoma. ING4 mRNA and protein expression was examined in gastric adenocarcinoma tissues and human gastric adenocarcinoma cell lines by RT-PCR, real-time RT-PCR, tissue microarray immunohistochemistry, and western blot analysis. Alterations in ING4 transcripts were determined through sequence analysis of ING4 cDNA. Our data showed that ING4 mRNA and protein were dramatically reduced in stomach adenocarcinoma cell lines and tissues, and significantly less in female than in male patients. We also found that reduced ING4 mRNA expression correlated with the stage of the tumour. Interestingly, by sequence analysis, we discovered five novel aberrantly spliced variant forms of ING4_v1 and ING4_v2. These variants cause a codon frame-shift and, eventually, deletion of the NLS or PHD domain contributing to the mislocalization of p53 and/or HAT/HDAC complexes and, subsequently, altered gene expression in gastric adenocarcinoma. These results suggest that attenuated and aberrant ING4 expression may be involved in the initiation and progression of stomach adenocarcinoma.

RUNX3 inhibits cell proliferation and induces apoptosis by TGF-beta-dependent and -independent mechanisms in human colon carcinoma cells.

BACKGROUND: Genes involved in the TGF-beta signaling pathway are often altered in several types of cancers. The TGF-beta-resistant human colon cancer cell line HT-29 has inactivated TbetaRII and deficient expression of RUNX3 and Smad4, which are involved in the TGF-beta signaling pathway. METHODS: Western blot and immunocytochemistry were performed to confirm gene expression, the MTT assay to detect cell growth, flow cytometry to investigate the cell cycle and the TUNEL to detect cell apoptosis. RESULTS: In the absence of TGF-beta, Bim was upregulated, cell growth was inhibited and apoptosis was induced. TGF-beta treatment did not affect RUNX3 expression; however, the increase in Bim expression was significant and time dependent. Interestingly, Smad4 but not Smad2/3 was also upregulated upon exposure to TGF-beta. This was not the case after TGF-beta treatment of parent HT-29 cells. As expected, TGF-beta further inhibited cell growth and induced apoptosis in HT-29/RUNX3+ cells. CONCLUSION: Our data demonstrate that RUNX3 is involved in TGF-beta-dependent and -independent cell growth inhibition and apoptosis induction pathways.

Probiotics as antifungal agents: Experimental confirmation and future prospects.

Fungal burden throughout the world is very high and it keeps escalating due to increasing numbers of immunocompromised individuals. In contrast, the drugs used in management of fungal infections are so few some with high toxicity. Furthermore, highly resistant fungal pathogens are emerging for example Candida auris, Candida glabrata, Candida gullemondii and Aspergillus species among others. Thus now, more than ever, there is a need for combined efforts and an all round search for possible solutions to curb these problems. Therefore, the role of probiotics in management of fungal infections is indispensable. In fact, the antimicrobial activity of probiotics has been screened with promising results against microbial pathogens. Although, recent reports indicated that probiotics may also contribute to protect against fungal infections, the research done in checking antifungal activity of probiotics has used varied technology. This calls for harmonization of the methods used to screen and confirm the antimicrobial activity of probiotics and other candidate microorganisms. We therefore sought to address issues of disparity in probiotic research and their outcomes. Thus this paper is in order as it comprehensively reviews' publications, provides a summary of the methods and future prospects of probiotics as antifungal agents.