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Citrinin (CTN) has been reported to induce renal failure and structural damage, but its nephrotoxic effects and mechanisms are not fully understood. Therefore, we established a model by orally administering CTN (0, 1.25, 5, or 20 mg/kg) to mice for 21 consecutive days. Histological and biochemical analyses revealed that CTN caused structural damage to renal tubules, increased inflammatory cell infiltration, and elevated levels of serum markers of renal function (creatinine, urea, and uric acid). Moreover, mRNA transcript levels of the inflammatory factors TNF-α, IL-1β, and IL-6 were increased, indicating the occurrence of an inflammatory response. Furthermore, exposure to CTN induced renal oxidative stress by decreasing antioxidant GSH levels, antioxidant enzyme (SOD, CAT) activities, and increasing oxidative products (ROS, MDA). In addition, CTN increased the expression of proteins associated with endoplasmic reticulum (ER)stress and apoptotic pathways. ER stress has been shown to be involved in regulating various models of kidney disease, but its role in CTN-induced renal injury has not been reported. We found that pretreatment with the ER stress inhibitor 4-PBA (240 mg/kg, ip) alleviated CTN-induced oxidative stress, NF-κB pathway mediated inflammatory response, and apoptosis. Interestingly, 4-PBA also partially alleviated renal structural damage and dysfunction. Thus, ER stress may be a novel target for the prevention and treatment of CTN-induced renal injury. [Display omitted] • Citrinin causes renal failure and tubule damage. • Citrinin induces ER stress-mediated oxidative stress, inflammatory response, and apoptosis. • Inhibition of endoplasmic reticulum stress alleviates citrinin-induced nephrotoxicity. [ABSTRACT FROM AUTHOR]

Citrinin (CTN) is a mycotoxin commonly found in contaminated foods and feed, posing health risks to both humans and animals. However, the mechanism by which CTN damages the intestine remains unclear. In this study, a model of intestinal injury was induced by administering 1.25 mg/kg and 5 mg/kg of CTN via gavage for 28 consecutive days in 6-week-old Kunming mice, aiming to explore the potential mechanisms underlying intestinal injury. The results demonstrate that CTN can cause structural damage to the mouse jejunum. Additionally, CTN reduces the protein expression of Claudin-1, Occludin, ZO-1, and MUC2, thereby disrupting the physical and chemical barriers of the intestine. Furthermore, exposure to CTN alters the structure of the intestinal microbiota in mice, thus compromising the intestinal microbial barrier. Meanwhile, the results showed that CTN exposure could induce excessive apoptosis in intestinal cells by altering the expression of proteins such as CHOP and GRP78 in the endoplasmic reticulum and Bax and Cyt c in mitochondria. The mitochondria and endoplasmic reticulum are connected through the mitochondria-associated endoplasmic reticulum membrane (MAM), which regulates the membrane. We found that the expression of bridging proteins Fis1 and BAP31 on the membrane was increased after CTN treatment, which would exacerbate the endoplasmic reticulum dysfunction, and could activate proteins such as Caspase-8 and Bid, thus further inducing apoptosis via the mitochondrial pathway. Taken together, these results suggest that CTN exposure can cause intestinal damage by disrupting the intestinal barrier and inducing excessive apoptosis in intestinal cells. [Display omitted] • CTN destroys both the physical and chemical barriers in the intestine. • Ingestion of CTN alters the structure of the intestinal microbiota. • CTN mediates enterocyte apoptosis through the endoplasmic reticulum and mitochondria. • MAM plays a crucial role in CTN-induced apoptosis of intestinal cells. [ABSTRACT FROM AUTHOR]

Biogenic amines (BAs) are often involved in human pathologies such as hypersensitivity symptoms. This research studied the effect of exogenous tannic acid (ETA) supplementation at various concentrations (0–20 mg/mL) on BA and mycotoxin citrinin levels in monascal soybean (MSB) and conducted a metabolomics analysis to estimate the metabolites in MSB. Addition of 20 mg/mL ETA decreased BA and citrinin levels in MSB after 25 days of fermentation by > 1.76 and >2.46 fold, respectively compared to the treatment without ETA addition. After 10 days of fermentation, the number of enterococci in MSB after treatment of >10 mg/mL ETA decreased by a minimum of 1.33 log CFU/g. ETA promoted large amounts of monacolin K, Monascus pigments, and free amino acids (FAAs) in MSB. A heatmap-HCA revealed that the 20 mg/mL ETA treatment was optimal, as confirmed by the VIP score and PCA. During MSB fermentation, seven notable metabolic pathways were identified as 1. phenylalanine metabolism, 2. arginine and proline metabolism, 3. phenylalanine, tyrosine, and tryptophan biosynthesis, 4. arginine biosynthesis, 5. histidine metabolism, 6. tryptophan metabolism, and 7. tyrosine metabolism. Supplementation of ETA in soybean substrate led to reduced BA and citrinin levels in MSB. The metabolomics analysis provide a better understanding of metabolite correlations, especially FAA formation and BA biosynthesis. [Display omitted] • 20 mg/mL ETA increased glucosamine level in MSB by 100 % compared to the control. • The amount of monacolin K and citrinin remarkably increased during the death phase. • Total BA and citrinin levels in MSB from ETA treatments decreased by > 1.2 fold. • Heatmap-HCA confirmation revealed the discrimination of 20 mg/mL ETA treatment. • Seven notable metabolic pathways of FAAs in MSB were identified. [ABSTRACT FROM AUTHOR]

[Display omitted] • Five new compounds were isolated from the sponge-derived fungus Penicillium sp. SCSIO41303. • Extensive NMR spectroscopic analysis, ECD calculation and X-ray crystallography data were used to elucidate new structures. • Compounds 2 and 11 exhibited enzyme inhibition activity against PL with IC 50 values of 24.62 and 7.15 μg/mL, respectively. Four new N -methyl-4-quinolones (1 – 4) and a new citrinin dimer derivative (10) with fourteen known compounds (5 – 9 , 11 – 19) were isolated from the sponge-derived fungus Penicillium sp. SCSIO41303. Their structures and absolute configurations were elucidated by extensive spectroscopic analysis, electronic circular dichroism (ECD) calculation, and X-ray single-crystal diffraction. Most of the isolated compounds were evaluated for their cytotoxic, antibacterial, anti-virus, and enzyme inhibitory activities against acetylcholinesterase (AChE), and pancreatic lipase (PL). Compounds 2 and 11 exhibited enzyme inhibition activity against PL with IC 50 values of 24.6 and 7.2 μg/mL, respectively. Besides, compound 11 showed enzyme inhibition activity against AChE with IC 50 value of 16.5 μg/mL. Compound 15 showed moderate inhibition activities with 52.2% at the concentration of 50 μg/mL against PL and antibacterial activity against Staphylococcus aureus displaying diameter of about 10 mm. [ABSTRACT FROM AUTHOR]

This study focuses on the identification and characterization of bioactive components and mycotoxins in Monascus red biopigment in order to prove its health beneficial attributes and safety as a biocolorant. The total phenols, flavonoids, and condensed tannin contents were observed within the range of 3.25–62.70 μgGAE/g, 2.20–52.04 μgQUE/g, and 2.59–30.18 μgCE/g of a sample in 1 μg/mL to 640 μg/mL concentrations of red biopigment, respectively. The iron-chelating activity of red biopigment was additionally observed to vary from 2.44 to 67.15 μg, which was equivalent to the EDTA with an increasing biopigment concentration from 1 μg/mL to 640 μg/mL. The extracted biopigment was found to be citrinin-free via the HPLC analysis. Moreover, the aflatoxin content in the biopigment was recorded within permissible limits. The Monascus red biopigment has a significant number of bioactive properties, such as antioxidants and ion scavenging components. The present investigation would significantly boost the use of Monascus natural biopigment as potential bio-colorants in the production of natural, healthy, and non-toxic foods. • The red biopigment was used for qualitative evaluation of different bioactive components. • Total phenols, flavonoid, tannin and ion chelation showed dependency on biopigment concentration. • Safety of biopigment was ensured by absence of citrinin and presence aflatoxins within lawful range. [ABSTRACT FROM AUTHOR]

Monascus pigment (MP) is a safe and natural microbial coloring agent. MP and red yeast rice (RYR) play an important role in the food industry. In this study, a citrinin-free Monascus puprureus MS-12 with high MP production was generated using dual mutagenesis of atmospheric and room-temperature plasma and heavy ion beam irradiation. The fermentation characteristics of eight rice substrates for solid-state fermentation (SSF) were compared to produce a premium RYR. Indica rice was the optimal fermentation substrate (MP = 4526 U/g in RYR), followed by japonica rice (MP = 3556 U/g). The MP value was <1000 U/g using other substrates (red, brown and black rice) for fermentation. RT-qPCR results demonstrated that the expression levels of MP synthesis- and the glycolysis-related genes of the mutant strain were upregulated compared with those of the parental strain, with MpigA exhibiting a 1.70-fold increase, while the relative expression levels of citrinin synthesis-related genes were downregulated; citE was downregulated 7.84-fold. In comparison to M. purpureus MS-12 mRNA levels using indica rice as the fermentation substrate during SSF, genes for MP, citrinin biosynthesis, and glycolysis resulted in the downregulation of other substrates. Our results show that colored and glutinous rice are unsuitable for RYR preparation via SSF. The maximum MP value was obtained using indical rice as the fermentation substrate, resulting from the upregulated expression levels of the pigment biosynthesis gene cluster and glycolytic pathway. [Display omitted] • Citrinin-free M. purpureus MS-12 with high MP production was obtained. • Characteristics of different rice substrates for SSF were compared. • Indica rice is the most suitable fermentation substrate for RYR production. [ABSTRACT FROM AUTHOR]

Monascus pigments (MPs) are a series of high-quality natural edible pigments produced by Monascus spp. , which possess a variety of biological functions such as antioxidation, antibacterial, regulating cholesterol, anti-inflammatory, anti-cancer and antitumor. MPs have been widely used in food, medicine, cosmetics, chemical and dyes industries as functionally active ingredients. However, a mycotoxin named citrinin produced by some strains of Monascus restricts the application of MPs. It is proposed that there was a confusing relationship between the biosynthesis of MPs and citrinin. Therefore, a comprehensive understanding of the relationship can be used to develop strategies aimed at a selective production of MPs. In the present review, the discovery of MPs and citrinin, and common-used strategies for regulating their production are sorted. The possible links and controversies on synthetic pathways and productions between MPs and citrinin are also proposed and discussed. We hope this review contributes to a comprehensive understanding of the relationship between the biosynthesis of MPs and citrinin. [ABSTRACT FROM AUTHOR]

Abstract The ability of a strain to produce citrinin was analysed in the growth inhibition zone using HPLC and UHPLC–MS. A total of 12 Penicillium citrinum strains isolated from Liupao tea were inoculated onto tea leaves and their capability for citrinin production were studied using different water content (15–45%) and temperatures (15–40 °C). The results provided a theoretical base for the safe manufacture of Liupao tea. Five strains of P. citrinum produced a clear growth inhibition zone with diameters of 11–22 mm. The citrinin contents in the liquid cultures of the 12 strains of P. citrinum ranged from 0.03 to 14.5 μg/mL. The citrinin contents of the teas with initial water content of 15 and 25% and those inoculated with P. citrinum were below the limit of detection during the fermentation. The citrinin content of the teas with initial water contents of 35 and 45% at 25 °C increased rapidly at first and then decreased during the fermentation. Similarly, the citrinin contents of the teas at 15 and 25 °C rapidly increased and then decreased. Meanwhile, P. citrinum was unable to produce citrinin at 35 and 40 °C. The optimum conditions were 45% water and 25 °C, generating the highest citrinin yield of 181 ng/g, which was higher than the limit of 50 ng/g citrinin in red yeast rice that can cause harm to human health. The highest citrinin yield in tea fermented for 50 days was 34.8 ng/g for stored teas with proper conditions. Therefore, storing teas with a low water content and temperature can reduce the content of citrinin. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

Abstract Monascus species produce useful secondary metabolite, Monascus pigments (MPs). They are widely used in food industry as a color intensifier, food additives and nitrite substitute in the meat product. MPs are also reported to have the potential for therapeutic use and used as a dye in cosmetic and textile industries. This paper reviews the production, composition, bioactivity, utilization of MPs, the citrinin and methods of eliminating citrinin from MPs were also discussed. MPs possess antioxidant properties, immunosuppressive properties, teratogenicity, and antimicrobial. Notwithstanding all these useful characteristics, it has been discovered that Monascus species co-produce citrinin and current studies on Monascus focus on how to minimize or eliminate citrinin from the useful pigment to improve quality and safety, several methods have been developed, including, detoxification of citrinin, regulation of gene, manipulation of fermentation conditions and use of nanoparticles for production of citrinin free MPs. [ABSTRACT FROM AUTHOR]

The specific immune-reaction between the anti-citrinin antibody immobilized on the surface of magnetic/silica core–shell (MSCS) and the citrinin–Rho123–BSA conjugate brings the Rho123 fluorophore as an acceptor and the QDs as a donor in close spatial proximity and causes FRET for occurring upon photo-excitation of the QDs. The novelties of this study include: (1) immobilization of the MSCS; (2) large amount of the immobilized QDs, and (3) immobilization of a large amount of Rho123 on the BSA macromolecule. Cd/Te QDs were synthesized by the simultaneous reduction of cadmium chloride and tellurium in the presence of sodium borohydride. Magnetic nanoparticles were synthesized using FeSO 4 and FeCl 3 . The prepared magnetic nanoparticles shelled by silica using tetraethoxysilane in the presence of ammonia. Transmission electron microscopy (TEM) analysis was used for investigating shape and monodispersity of the nanoparticles. EDC/NHS was used as a cross linking agent for immobilization of the QDs, conjugation of citrinin to amino groups of BSA, labeling of BSA with Rho123 and also for immobilization of the amino-functionalized MSCS on the immobilized QDs. Immobilization of the anti-citrinin antibody on the surface of the amino-functionalized MSCS was performed by Schiff-base mechanism. By using these three effective strategies, sensitivity of the designed nanobiosensor was incredibly enhanced as a very low limit of detection (up to 0.1 pM). The feasibility of this technique was tested by the detection of citrinin in the spiked human serum. Results showed that there was a linear correlation between the decreased fluorescence intensity of the Rho123 and increased fluorescence intensity of the QDs with increasing concentration of citrinin in the spiked samples in the range of 1–6 pM. According to obtained results, we conclude that this highly sensitive detection scheme is a easy, quick and impressive method that can be used in optical-based nanosensors. [ABSTRACT FROM AUTHOR]

Citrinin (CIT) is one of by-products by Monascus fermentation with known nephrotoxicity. Except dihydro-citrinone, no other metabolites including the possible metabolic pathways have been found in vivo metabolism. In this study, we applied ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) to analyze and identify potential CIT metabolites in the human cytochrome 450 (P450) subtype system. Four new metabolites with liver microsomes incubation were first found, namely 3-hydroxy-citrinin (M1), 4,5-ene-citrinin (M2), 5-hydroxymethyl-citrinin (M3), and 7-hydroxy-citrinin (M4). We also found the distinguished levels of the four metabolites with the incubation of various P450 subtypes. According to the results of molecular docking prediction, it showed the metabolic correlation of CYP3A4 with M1, CYP1A2, CYP2C9, and CYP2D6 with M2, M3, and M4. The maximum level of M1 metabolite was found in the incubation with liver microsome and P450 subtypes. Moreover, M1 and M4 metabolites were found in mice's duodenum, jejunum, ileum, liver, kidney, and hippocampus, but not M2 and M3. These results indicated the mediation of citrinin metabolism by P450s. It also suggested the concentration differences of metabolites with the incubation of different P450 subtypes. [Display omitted] • First found four new citrinin metabolites with incubation of liver microsome. • Found the metabolic pathway of citrinin with P450 mediation. • Found citrinin and metabolites M1 and M4 in in vivo metabolic systems. [ABSTRACT FROM AUTHOR]

Citrinin, a mycotoxin existing in fruits, has nephrotoxicity, hepatotoxicity and embryotoxicity. The effects of citrinin on Leydig cell development in prepuberty remains unclear. Male Sprague-Dawley rats were gavaged with 0, 1, 2.5, and 5 mg/kg citrinin from postnatal days 21–28. Citrinin at 5 mg/kg significantly decreased serum testosterone levels, while increasing serum LH and FSH levels. Citrinin at 1–5 mg/kg markedly downregulated Hsd17b3 and HSD17B3 expression, while upregulating Srd5a1 (SRD5A1) and Akr1c14 (AKR1C14) expression at 2.5 and/or 5 mg/kg. Citrinin at 5 mg/kg also significantly increased PCNA-labeling index in Leydig cells. Citrinin at 5 mg/kg significantly raised testicular MDA amount, whiling at 2.5 and 5 mg/kg downregulating SOD1 and SOD2 expression. Citrinin at 5 mg/kg markedly decreased the ratio of Bcl2 to Bax, in consistent with the increased apoptosis in Leydig cells judged by TUNEL assay. Enzymatic assay revealed that citrinin inhibited rat testicular HSD3B1 activity at 100 µM and HSD17B3 activity at 10–100 μM. Citrinin at 50 μM and higher also induced reactive oxygen species (ROS) and apoptosis of R2C cell line. In conclusion, citrinin inhibits Leydig cell development at multiple levels via different mechanisms and oxidative stress partially plays a role. [Display omitted] • CTN lowers serum testosterone level after in vivo exposure from postnatal day 21–28. • CTN inhibits the enzymes activity of steroidogenesis in prepuberty Leydig cells. • CTN promotes the enzymes activity of testosterone metabolism in prepuberty Leydig cells. • CTN stimulates proliferation of Leydig cell during prepuberty. • CTN induced the apoptosis of Leydig cell by enhancing reactive oxygen species. [ABSTRACT FROM AUTHOR]

Monascus species are traditional edible and medicinal filamentous fungi with a very long history in East Asia, but their sparse production of asexual spores (conidia) limits their large-scale industrial application. Previous studies have revealed that the flbA ortholog plays a negative role in the conidiation of Monascus ruber M7. FlbA, together with FlbB, FlbC, FlbD, FlbE, and FluG, were shown to be upstream development activators (UDAs) in the asexual development pathway in the model fungus Aspergillus nidulans. In the present study, homologs of these UDAs in M. ruber M7 were identified and functionally characterized. Disruption of MrflbB , MrflbD , and MrflbE delayed and decreased conidiation in M7, whereas the deletion of MrflbC or MrfluG resulted in no detectable change in sporulation. Deletion of MrflbA not only increased conidial number but also postponed sexual development in M7. Furthermore, the deletion of some UDAs also affected the production of secondary metabolites, particularly citrinin, whose yields were dramatically decreased in the Δ MrflbC and Δ MrflbA mutants. These findings provide new insights and opportunities to further explore the asexual development mechanism and modify the conidial production in Monascus spp. • Upstream development activators have been characterized in Monascus ruber M7. • The deletion of MrflbC impeded citrinin production. • MrflbB , MrflbD , and MrflbE had conserved conidial roles in M7 as found in Aspergillus nidulans. • MrflbA balanced sexual and asexual development in M. ruber M7. • The deletion of MrfluG showed no effect on conidiation in M. ruber M7. [ABSTRACT FROM AUTHOR]

For centuries, Monascus purpureus pigments have been used traditionally as a natural food colorant in Asian countries. However, this way is not practical to use in different products due to the production of citrinin by Monascus sp. Co-culture of Monascus purpureus and Saccharomyces cerevisiae is one of the biological ways which significantly reduces citrinin. In this research, the live cells of S. cerevisiae at three concentrations of 103, 104, and 105 cells/mL were used on the 8th, 11th, and 13th days of the M. purpureus fermentation. Analysis of Citrinin and measurement of pigments absorbance were conducted by HPLC and spectrophotometry, respectively. The result indicated that the addition of live cells of S. cerevisiae to Monascus culture improves pigments production and reduces citrinin. Yellow intracellular pigment on day 8 of fermentation at 105 cells/mL yeast cell with the absorbance of 18.40 AU revealed the highest absorbance which was more than three times greater than the control one (5.54 AU). The HPLC results demonstrated that citrinin content at 105 cells/mL live yeast cell on the 13th day of Monascus fermentation (0.9 ppm) was five fold less than its content in the control (4.43 ppm). Above all, results proved that the co-culture of M. purpureus and S.cerevisiae can play an important role to produce not only more portions of pigments but also can warrant more safety. • Impacts of coculture of S. cerevisiae and M. purpureus in different levels were screened. • Addition of S. cerevisiae to Monascus culture improves pigments production and reduces citrinin. • The highest absorbance of Yellow intracellular pigment on day 8 of fermentation was obtained. • Citrinin portion on the 13th day of Monascus fermentation was fivefold less than the control. [ABSTRACT FROM AUTHOR]

The article provides information on a study which examined the prevalence of moulds in cheddar and processed cheese from organized dairies and Roquefort and Swiss cheese from private dairies. Topics covered include the materials used and methods applied in the study, the yeast and mould counts in Cheddar, Roqueforty, Swiss and Processed cheese and the isolates of moulds that were identified in the study.

The article investigates the effects of feeding broiler chicken with sublethal dose of the mycotoxins citrinin (CTN) and aflatoxin (AF). Results of the experiments showed that body weight gain in chicken in both CTN and AF-fed groups were significantly decreased from second week onward compared to the control group. Lower feed consumption was also noted in the CTN and AF groups compared to the control group.

Citrinin, a secondary metabolite, can pose serious risks to the environment and organisms, but its hepatotoxic mechanisms are still unclear. Histopathological and ultrastructural results showed that citrinin-induced liver injury in Kunming mice, and the mechanism of citrinin-induced hepatotoxicity was studied in L02 cells. Firstly, citrinin mades L02 cell cycle arrest in G2/M phase by inhibition of cyclin B1, cyclin D1, cyclin-dependent kinases 2 (CDK2), and CDK4 expression. Secondly, citrinin inhibits proliferation and promotes apoptosis of L02 cells via disruption of mitochondria membrane potential, increase Bax/Bcl-2 ration, activation of caspase-3, 9, and enhance lactate dehydrogenase (LDH) release. Then, citrinin inhibits superoxide dismutase (SOD) activity and increases the accumulation of malondialdehyde (MDA) and reactive oxygen species (ROS), resulting oxidative damage in L02 cells; upregulates the protein expression of binding immunoglobulin protein (Bip), C/EBP homologous protein (CHOP), PKR-like ER kinase (PERK) and activating transcription factor6 (ATF6), inducing ER stress in L02 cells; increases the phosphorylation of AMP-activated protein kinase (AMPK) and decreases the content of adenosine-triphosphate (ATP), activating AMPK pathway in L02 cells. Eventually, pretreatment with NAC, an ROS inhibitor, alleviates citrinin-induced cell cycle G2/M arrest and apoptosis by inhibiting ROS-mediated ER stress; pretreatment with 4-PBA, an ER stress inhibitor, reversed ER stress and p-AMPK; pretreatment with dorsomorphin, an AMPK inhibitor, decreases citrinin-induced cell cycle G2/M arrest and apoptosis. In summary, citrinin induces cell cycle arrest and apoptosis to aggravate liver injury by activating ROS-ER stress-AMPK signaling pathway. [Display omitted] • Citrinin induces hepatocytes damage by aggravating oxidative stress in vivo and in vitro. • Citrinin induces G2/M arrest and apoptosis of hepatocytes through ROS-mediated ER-stress. • Inhibition of AMPK can relieve G2/M arrest and apoptosis of hepatocytes induced by ER-stress. [ABSTRACT FROM AUTHOR]

Traditionally, Monascus fermented rice has developed as functional food for cholesterol lowering agent due to its secondary metabolite, monacolin K, was found to inhibit the biosynthesis of cholesterol. The formation of secondary metabolite in solid substrates fermentation is influenced by cultivation environment. Objective of the research was to study the influences of solid substrates in Monascus fermentation for production of anticholesterol agent, monacolin K with minimal citrinin content (M/C). The research aimed to select the best substrate on Monascus fermentation for better production of monacolin K. On this study we used waste tofu, gadung ( Dioscorea hispida ) and rice as the solid substrates. The fermentation was carried out by cultivation Monascus purpureus HD001 on dried substrates and incubated at 30 o C for 14 days. Monacolin K was extracted with ethanol 95%, at 60 o C, shaked at 110 rpm for two hours. The content of monacolin, citrinin and pigment in extracts was measured by spectrophotometric method and monacolin K was analyzed by HPLC method. The results showed that the highest M/C ratio was found on Monascus fermented waste tofu (M/C=4.4) with monacolin K content was 1,620 μg g -1 . However, the highest monacolin K content was found on Monascus fermented rice was 7,000 μg g -1 . Rice as the substrate of Monascus fermentation can produce monakolin K 4.6 times higher compared to gadung ( Dioscorea hispida ). [ABSTRACT FROM AUTHOR]

Monascus pigments, which are produced by various species of Monascus, often have been used as a natural colourant and as traditional natural food additives, especially in Southern China, Japan and Southeastern Asia. The limitation of wide using Monascus pigment is attributed to one of its secondary metabolites named citrinin. The aim of this study was to investigate the influence of pigment and citrinin production via submerged fermentation (SmF) and solid-state fermentation (SF) from rice (Oryza sativa L.) by Monascus purpureus AS3.531. The optimal fermentation temperature and pH were significantly different for pigment production through different fermentation mode (35 °C, pH 5.0 for SF and 32 °C, pH 5.5 for SmF, respectively). Adding 2% (w/v) of glycerol in the medium could enhance the pigment production. On the optimized condition, although the concentration of citrinin produced by SmF (19.02 ug/g) increased more than 100 times than that by SF (0.018 ug/g), the pigment yield by SmF (7.93 U/g/g) could be comparable to that by SF (6.63 U/gig). Those indicate us that fermentation mode seems to be the primary factor which influence the citrinin yield and secondary factor for pigment production. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To Isolate, purify, characterize, and evaluate the bioactive compounds from the sponge-derived fungus Penicillium sp. FF001 and to elucidate its structure. Methods: The fungal strain FF001 with an interesting bioactivity profile was isolated from a marine Fijian sponge Melophlus sp. Based on conidiophores aggregation, conidia development and mycelia morphological characteristics, the isolate FF001 was classically identified as a Penicillium sp. The bioactive compound was identified using various spectral analysis of UV, high resolution electrospray ionization mass spectra, 1H and 13C NMR spectral data. Further minimum inhibitory concentrations (MICs) assay and brine shrimp cytotoxicity assay were also carried out to evaluate the biological properties of the purified compound. Results: Bioassay guided fractionation of the EtOAc extract of a static culture of this Penicillium sp. by different chromatographic methods led the isolation of an antibacterial, anticryptococcal and cytotoxic active compound, which was identified as citrinin (1). Further, citrinin (1) is reported for its potent antibacterial activity against methicillin-resistant Staphylococcus aureus (S. aureus), rifampicin-resistant S. aureus, wild type S. aureus and vancomycin-resistant Enterococcus faecium showed MICs of 3.90, 0.97, 1.95 and 7.81 μg/mL, respectively. Further citrinin (1) displayed significant activity against the pathogenic yeast Cryptococcus neoformans (MIC 3.90 μg/mL), and exhibited cytotoxicity against brine shrimp larvae LD50 of 96 μg/mL. Conclusions: Citrinin (1) is reported from sponge associated Penicillium sp. from this study and for its strong antibacterial activity against multi-drug resistant human pathogens including cytotoxicity against brine shrimp larvae, which indicated that sponge associated Penicillium spp. are promising sources of natural bioactive metabolites. [Copyright &y& Elsevier]

Abstract: This study investigated the effects of citrinin (CTN) on male mouse reproductive organs. Adult male mice were exposed to intraperitoneal injection of CTN at 0–6.25mg/kg body weight daily for 7 days, and then mated with sexually mature untreated female mice. Reproductive organ relative weights, semen quality, serum testosterone concentrations and fertility of treated mice were assessed. CTN significantly increased relative weights of the testes, epididymis, seminal vesicle and preputial gland, increased the number of abnormal spermatozoa and decreased the number of live spermatozoa. A significantly lower pregnancy rate was observed when females were mated with CTN-exposed males. The histological results indicated that distance of testicular seminiferus tubule increased. The sperm count and serum testosterone concentrations were significantly reduced in a dose-dependent manner in mice treated with CTN. The results suggest that CTN has adverse effects on the reproductive system of adult male mice. [Copyright &y& Elsevier]

The article presents a study of the effects of citrinin (CIT) and endosulfan toxicity on the immune response of pregnant Wistar rats. The study uses delayed type hypersensitivity to assess the cell-mediated immune response against ovalbumin and lymphocyte transformation test (LTT). Results suggest that simultaneous exposure CIT and endosulfan are potential immunosuppressants and their effect was enhanced when combined in pregnant Wistar rats.

The present study was undertaken to find out the individual and combined effects of citrinin (CTN) (5 ppm) and aflatoxin (AF) (0.5 ppm) on serum lipid profile in broiler chicken, by feeding the toxins from 0 to 6 weeks of age. Significant (P<0.05) increase in the serum triglycerides, very low density lipoproteins and total cholesterol/ high density lipoprotein ratio and significant (P<0.05) decrease in the total cholesterol, high density lipoproteins and low density lipoproteins were observed in the mycotoxin fed birds. The CTN+AF combined toxicity had more effect. However, AF seemed to play a major role and the combined effect due to CTN was less than additive. [ABSTRACT FROM AUTHOR]

Objective: To prepare artificial antigens and anti-citrinin egg yolk-derived immunoglobulin (IgY) to build an enzyme-linked immunosorbent assay (ELISA) for citrinin (CTN). Methods: CTN was conjugated with bovine serum albumin (BSA), ovalbumin (OVA) with formaldehyde condensation method to prepare artificial antigens and identified by ultraviolet (UV) spectrometry and Infrared (IR) spectrometry. Artificial antigens for CTN and anti-CTN IgY were purified with polyethylene glycol two-step precipitation method and identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). ELISA with IgY was established. Cross-reactivity of IgY with various structural similarities to CTN and possible co-occurrence with CTN in agricultural commodities were studied. Results: UV and IR absorption spectra suggested that CTN was correlated with the carrier protein of BSA or OVA. SDS-PAGE patterns showed that the anti-CTN IgY was almost pure with a molecular weight of approximate 100 KD. The indirect competitive ELISA showed that the detection limit of CTN was 10 ng·mL−1, with a good linearity ranging 20-640 ng·mL−1. Conclusion: Artificial antigens of CTN can be successfully synthesized. The established ELISA can be used to determine CTN-contaminated samples. [Copyright &y& Elsevier]

Objective To obtain the full-length cDNA of a novel gene (named yp05) associated with citrinin production-related genes in Monascus auranriacus. Methods Total RNA was extracted from mycelium, 3′ and 5′ cDNA end of yp05 gene was amplified using smartTM trace cDNA amplification kit, and the full-length cDNA of a novel gene (named yp05) was obtained from the electronic assembly of 3-RACE and 5′- RACE products. Results This yp05 gene was 787 bp including a 597 bp open reading frame (ORF) and encoded a deduced protein with 199 amino acid residues, and the amino acid sequence of this protein was found similar with the sequences of many fungal manganese-superoxide dismutases in the GenBank with the aid of BLASTp. The transcription of yp05 gene in Monascus strains was analyzed with the aid of Northern blotting. The transcription of yp05 gene was only detected in Monascus strains, provided that citrinin was produced. Conclusion The transcription of yp05 gene belongs to differential expression genes of citrinin yielded from Monascus and has no correlation with the biosynthesis pathway of red pigments. [ABSTRACT FROM AUTHOR]

Objective To construct a tag expression library of Monascus aurantiacus that could produce citrinin maximally on the thirteenth (0.966 mg/mL) day in the submerged culture. Methods Total RNA was extracted from the mycelium, cDNA was synthesized using the SuperScript choice system, and then, a SAGE library was successfully constructed according to the MicroSAGE method. Results Five hundred and ninety eight clones were obtained in SAGE library, and 120 clones were picked out randomly for identification and sequencing purpose. Eighty nine clones had positive inserts, 26 clones had no inserts and the remaining 5 clones had no site of NlaIII enzyme in inserts. There were seven repeated clones. Conclusion With the aid of SAGE2000 software, 901 tags were obtained from 89 clones, representing 686 unique transcripts. Six unique tags of them belong to highly expressed genes (Number of tags⩾10) and 143 unique tags to moderately expressed genes (repeat tags⩾2). [ABSTRACT FROM AUTHOR]

Hongqu is a fermented product of Monascus species, which is widely used as food or food additives in Southeast Asian countries. The contamination of citrinin in Hongqu has caused controversy about its safety. So control of citrinin has always been an important issue of Hongqu products. In current study, we isolated a putative histone acetyltransferase named MrGcn5 and explored its regulatory function on citrinin production. The results showed the citrinin content of MrGcn5 null strain dramatically reduced in the late growth period. Even the citrinin content was as low as 21 % of the wild-type strain, and RT-qPCR experiment suggested that the expression level of genes involving in citrinin synthesis was significantly attenuated in MrGcn5 null strain. With regard to the asexual and sexual development, the conidia germination rate was significantly accelerated in MrGcn5 null strain in the vegetative growth phase, but the number of ascospores was 41.9 % less than the wild-type strain. RT-qPCR revealed the expression level of the homologs to flbA-flbE , fluG and wetA in Aspe r gillus had changed to some extent in MrGcn5 null strain. Meanwhile, there was no significant effects on the growth, nutrition adaption and Monascus azaphilone pigments production. Taken together, these characteristics of MrGcn5 make it very suitable for targeted improvement to reduce citrinin production in fermentation process. • MrGcn5 regulates both asexual and sexual development. • MrGcn5 positively regulates the mycotoxin production in the late growth period. • MrGcn5 affects expression level of genes involving in citrinin synthesis. [ABSTRACT FROM AUTHOR]

In Saudi Arabia, table olives are widely consumed as appetizers, pickles, and food additives. Many food-borne fungal pathogens such as Penicillium specie have ability to survive on prepared and preserved green table olives. Penicillium polonicum , an important mycotoxin producer, is much more frequently found in cereals, peanuts, onions, dried meats, citrus fruits and recently in frozen food. The aim of this study was to determine, identify and characterize the occurrence of mycotoxin producing Penicillium species from retail green table olives purchased in the Saudi Arabia markets and used for human consumption. Our results revealed that Penicillium expansum , P. citrinum , P. verrucosum and P. polonicum were isolated form all samples. P. polonicum was the only species that able to grow producing vegetative and reproductive structures in refrigerators. The qualitative determination of citrinin, penicillic acid and cyclopiazonic acid is positive in all investigated samples. This study provides insight into the presence of toxigenic P. polonicum not only as a mould but also as a source of toxic metabolites that produced inside food products. Thus, the application of prevention actions should be attained. Furthermore, P. polonicum is reported here for first time as both an inhabitant and a pathogen on green table olives. [ABSTRACT FROM AUTHOR]

The article reports on a study of tissue residues of Citrinin (CTN) and Aflatoxin (AF) in broiler chickens (BC) in India in 2014. Feeding CTN and AF to 0-6 week-aged BC showed tissue residue levels higher than the CTN permissible level in the feedstuff. This poses a potential health threat to both humans and animals.