Bench-to-bedside imaging in brain metastases: a road to precision oncology.

Radiology has seen tremendous evolution in the last few decades. At the same time, oncology has made great strides in diagnosing and treating cancer. Distant metastases of neoplasms are being encountered more often in light of longer patient survival due to better therapeutic strategies and diagnostic methods. Brain metastasis (BM) is a dismal manifestation of systemic cancer. In the present scenario, magnetic resonance imaging (MRI), computed tomography (CT) and positron emission tomography (PET) are playing a big role in providing molecular information about cancer. Lately, molecular imaging has emerged as a stirring arena of dynamic imaging techniques that have enabled clinicians and scientists to noninvasively visualize and understand biological processes at the cellular and molecular levels. This knowledge has impacted etiopathogenesis, detection, personalized treatment, drug development, and our understanding of carcinogenesis. This article offers insight into the molecular biology underlying brain metastasis, its pathogenesis, imaging protocols, and algorithms. It also discusses disease-specific molecular imaging features, focusing on common tumors that spread to the brain, such as lung, breast, colorectal cancer, melanoma, and renal cell carcinoma. Additionally, it covers various targeted treatment options, criteria for assessing treatment response, and the role of artificial intelligence in diagnosing, managing, and predicting prognosis for patients with brain metastases.

Implications of genetic variations, differential gene expression, and allele-specific expression on metformin response in drug-naïve type 2 diabetes.

PURPOSE: Metformin is widely used to treat type 2 diabetes mellitus (T2DM) individuals. Clinically, inter-individual variability of metformin response is of significant concern and is under interrogation. In this study, a targeted exome and whole transcriptome analysis were performed to identify predictive biomarkers of metformin response in drug-naïve T2DM individuals. METHODS: The study followed a prospective study design. Drug-naïve T2DM individuals (n = 192) and controls (n = 223) were enrolled. T2DM individuals were administered with metformin monotherapy and defined as responders and non-responders based on their glycated haemoglobin change over three months. 146 T2DM individuals were used for the final analysis and remaining samples were lost during the follow-up. Target exome sequencing and RNA-seq was performed to analyze genetic and transcriptome profile. The selected SNPs were validated by genotyping and allele specific gene expression using the TaqMan assay. The gene prioritization, enrichment analysis, drug-gene interactions, disease-gene association, and correlation analysis were performed using various tools and databases. RESULTS: rs1050152 and rs272893 in SLC22A4 were associated with improved response to metformin. The copy number loss was observed in PPARGC1A in the non-responders. The expression analysis highlighted potential differentially expressed targets for predicting metformin response (n = 35) and T2DM (n = 14). The expression of GDF15, TWISTNB, and RPL36A genes showed a maximum correlation with the change in HbA1c levels. The disease-gene association analysis highlighted MAGI2 rs113805659 to be linked with T2DM. CONCLUSION: The results provide evidence for the genetic variations, perturbed transcriptome, allele-specific gene expression, and pathways associated with metformin drug response in T2DM.

Primary adrenal plasmablastic lymphoma presenting as lymphomatous meningitis - A diagnostic perplexity.

A rare presentation of primary plasmablastic lymphoma (PBL) of the adrenal gland, as lymphomatous meningitis in a patient living with HIV.

Reuse of poor-quality water for sustainable crop production in the changing scenario of climate.

The availability of freshwater is limited for agriculture systems across the globe. A fast-growing population demands need to enhance the food grain production from a limited natural resources. Therefore, researchers and policymakers have been emphasized on the production potential of agricultural crops in a sustainable manner. On the challenging side, freshwater bodies are shrinking with the pace of time further limiting crop production. Poor-quality water may be a good alternative for fresh water in water scarce areas. It should not contain toxic pollutants beyond certain critical levels. Unfortunately, such critical limits for different pollutants as well as permissible quality parameters for different wastewater types are lacking or poorly addressed. Marginal quality water and industrial effluent used in crop production should be treated prior to application in crop field. Hence, safe reuse of wastewater for cultivation of food material is necessary to fulfil the demands of growing population across the globe in the changing scenario of climate.

Conceptualization of functional single nucleotide polymorphisms of polycystic ovarian syndrome genes: an in silico approach.

PURPOSE: Polycystic ovarian syndrome (PCOS) is a multi-faceted endocrinopathy frequently observed in reproductive-aged females, causing infertility. Cumulative evidence revealed that genetic and epigenetic variations, along with environmental factors, were linked with PCOS. Deciphering the molecular pathways of PCOS is quite complicated due to the availability of limited molecular information. Hence, to explore the influence of genetic variations in PCOS, we mapped the GWAS genes and performed a computational analysis to identify the SNPs and their impact on the coding and non-coding sequences. METHODS: The causative genes of PCOS were searched using the GWAS catalog, and pathway analysis was performed using ClueGO. SNPs were extracted using an Ensembl genome browser, and missense variants were shortlisted. Further, the native and mutant forms of the deleterious SNPs were modeled using I-TASSER, Swiss-PdbViewer, and PyMOL. MirSNP, PolymiRTS, miRNASNP3, and SNP2TFBS, SNPInspector databases were used to find SNPs in the miRNA binding site and transcription factor binding site (TFBS), respectively. EnhancerDB and HaploReg were used to characterize enhancer SNPs. Linkage Disequilibrium (LD) analysis was performed using LDlink. RESULTS: 25 PCOS genes showed interaction with 18 pathways. 7 SNPs were predicted to be deleterious using different pathogenicity predictions. 4 SNPs were found in the miRNA target site, TFBS, and enhancer sites and were in LD with reported PCOS GWAS SNPs. CONCLUSION: Computational analysis of SNPs residing in PCOS genes may provide insight into complex molecular interactions among genes involved in PCOS pathophysiology. It may also aid in determining the causal variants and consequently contributing to predicting disease strategies.

Effect of microwave pre-treatment on quality parameters in Indian mustard.

Demand for edible oil from crops like groundnut, mustard and soybean, is increasing and likely to increase further. In this regard, Indian mustard seeds were treated with microwaves (MW), to investigate the possibility of enhancing oil yield and nutritional content. MW pre-treatment was given to the seeds of two Indian mustard varieties i.e. PM21 (V1) and PDZ1 (V2) for 0, 2, 4 and 6 min (H0, H2, H4 and H6 min respectively). MW treatment with increasing exposure time showed a linear reduction in the glucosinolate and erucic acid content with concomitant increase in oil yield and moisture loss in both the varieties, as evident from correlation and principal component analysis. Antioxidant capacity has increased with the reduction in phytic acid content (1.82) in V2 at 6 min exposure time with respect to untreated control. Free radical scavenging activity was improved with increasing MW treatment in both the varieties. Therefore, from the obtained results, it is advisable to treat mustard seeds with MW before extraction of oil, because it gives a relatively good oil yield, with enhanced nutritional factors. Moreover, microwaving was effective in reducing glucosinolates and erucic acid also.

Mini-implant-supported twin-block appliance: An innovative modification.

Twin block is a commonly used appliance for correction of retrognathic mandible in growing patients. However, it has a drawback of causing lower incisor proclination, which reduces its potential of achieving maximum skeletal effects. Thus, we introduced a novel modification in the present design to facilitate greater anteroposterior effects in skeletal dimension. The aim of the present case reports is to evaluate the efficacy of this modified twin block. Here we present two cases treated with mini-implant-supported twin-block appliance, which successfully controlled the lower incisor position, thereby increasing the envelope for orthopedic correction in class II myofunctional therapy. This modification is useful in growing patients with retruded mandible to achieve maximum skeletal effects.

Medication persistence and risk of fracture among female Medicare beneficiaries diagnosed with osteoporosis.

We examined the relationship between persistent osteoporosis medication use and fracture risk among female Medicare beneficiaries diagnosed with osteoporosis using Medicare claims, 2009-2012. Persistent use was associated with reduced risk of fracture and significantly lower total health care costs in the follow-up period. Results were consistent using different analytical methods. INTRODUCTION: This study aimed to examine the relationship between medication persistence and fracture risk among female Medicare beneficiaries diagnosed with osteoporosis. METHODS: Elderly female Medicare beneficiaries diagnosed with osteoporosis and initiated on osteoporosis medication January 1, 2009-June 30, 2011, were included. Persistent medication use was defined as continuous use (no gap ≥ 60 days) for 1 year or longer. The key outcome was fragility fracture. A difference-in-difference analysis was performed at the log scale of fracture rate using a Poisson regression model with months 1-6 before medication initiation as the pre-initiation period and up to 18 months after as the post-initiation period. Total health care costs were compared using a similar approach. Sensitivity analyses were conducted using different pre- and post-initiation periods. RESULTS: The study included 294,369 patients; 32.9% were persistent osteoporosis medication users and 67.1% non-persistent (< 12 months continuous use). Fracture incidence rates were 16.2 per 100 patient-years pre-initiation and 4.1 post-initiation for persistent users; corresponding rates for non-persistent users were 19.0 and 7.3 per 100 patient-years. The adjusted post-/pre-initiation fracture rate ratios were 0.284 for persistent and 0.411 for non-persistent users. The ratio of the two rate ratios was 0.692 (persistent vs. non-persistent, p < 0.0001), suggesting a significantly greater fracture rate reduction for persistent users. Adjusted cost ratios were significantly lower for persistent users. Sensitivity analyses results were similar. CONCLUSIONS: Persistent use of osteoporosis medications was associated with reduced risk of fracture and significantly lower total health care costs. Payers and patients would benefit from interventions aimed at improving medication persistence.

Rapid analysis of pharmaceutical drugs using LIBS coupled with multivariate analysis.

Type 2 diabetes drug tablets containing voglibose having dose strengths of 0.2 and 0.3 mg of various brands have been examined, using laser-induced breakdown spectroscopy (LIBS) technique. The statistical methods such as the principal component analysis (PCA) and the partial least square regression analysis (PLSR) have been employed on LIBS spectral data for classifying and developing the calibration models of drug samples. We have developed the ratio-based calibration model applying PLSR in which relative spectral intensity ratios H/C, H/N and O/N are used. Further, the developed model has been employed to predict the relative concentration of element in unknown drug samples. The experiment has been performed in air and argon atmosphere, respectively, and the obtained results have been compared. The present model provides rapid spectroscopic method for drug analysis with high statistical significance for online control and measurement process in a wide variety of pharmaceutical industrial applications.

Zero valent metal loaded silica nanoparticles for the removal of TNT from water.

Silica nanoparticles with a surface area of 673.60 m2/g and particle size of 8-12 nm were prepared using aerogel process (AP) followed by super critical drying. Zero valent Fe, Co, Pt, and bimetallic Fe/Pt and Fe/Co were loaded using an incipient wetness impregnation technique and subsequent reduction. Scanning electron microscopy-energy dispersive X-ray (SEM-EDX) and transmission electron microscopy-energy dispersive X-ray (TEM-EDX) characterizations indicated fine dispersion of iron on AP-SiO2 +Fe system. Prepared nanoparticles were evaluated for the adsorptive removal of 2,4,6-trinitrotoluene (TNT) from water. Surface area normalized rate constant values indicated the adsorptive removal potential of prepared nanoparticles to be: AP-SiO2 + Fe/Co > AP-SiO2 + Fe > CM (commercial) SiO2 + Fe > AP-SiO2 + Co > AP-SiO2 + Fe/Pt > AP-SiO2 + Pt. Lower pH helped in accelerating the reactive removal of TNT on zero valent iron loaded silica. AP-SiO2 + Fe/Co system showed the maximum adsorption potential (74 mg/g) after five cycles.

Malignant mixed germ cell tumor of ovary presenting as advanced disease in an adolescent girl.

Mixed germ cell tumors are very rare in young females. Patient survival, preservation of ovarian function and fertility are becoming an important issue. A locally advanced (III), bulky malignant mixed germ cell tumour in a 12-year-old girl presented to the Department of Radiotherapy, Regional Institute of Medical Sciences, Imphal, Manipur, in January 2011 with abdominal distension for one month. On physical examination, there was a large lower abdominal mass approximately 16x 14 cm2. Abdominal and pelvic CTs showed a lobulated 19x 15x10 cm soft tissue attenuation mass lesion in the pelvis extending superoanteriorly to supra-umbilical area. Laboratory investigations revealed increased serum LDH (4,245 IU/ L) and serum P-hCG (105.4 mIU/ml). Ultrasonography (USG)-guided fine needle aspiration cytology (FNAC) from left ovarian mass was suggestive of malignant germ cell tumour. In view of bulky and advanced stage, patient was administered four cycles of neoadjuvant chemotherapy (inj. ifosphamide 1,440 mg, inj. etoposide 90 mg, inj. cisplatin 24 mg for D1 -5, four weekly) followed by left salpingo-oophorectomy with wedge biopsy of right ovary and partial omentectomy, and another two cycles of adjuvant chemotherapy with same regimen. Biopsy tissue histopathology report also confirmed mixed germ cell tumour. Patient was kept on regular follow-up and she has been disease-free for the last four years. The present authors' treatment policy in such bulky and advanced tumor in adolescents is effective.

Potential compounds for the treatment of mitochondrial disease.

INTRODUCTION: Mitochondrial diseases are a group of heterogeneous disorders for which no curative therapy is currently available. Several drugs are currently being pursued as candidates to correct the underlying biochemistry that causes mitochondrial dysfunction. SOURCES OF DATA: A systematic review of pharmacological therapeutics tested using in vitro, in vivo models and clinical trials. Results presented from database searches undertaken to ascertain compounds currently being pioneered to treat mitochondrial disease. AREAS OF AGREEMENT: Previous clinical research has been hindered by poorly designed trials that have shown some evidence in enhancing mitochondrial function but without significant results. AREAS OF CONTROVERSY: Several compounds under investigation display poor pharmacokinetic profiles or numerous off target effects. GROWING POINTS: Drug development teams should continue to screen existing and novel compound libraries for therapeutics that can enhance mitochondrial function. Therapies for mitochondrial disorders could hold potential cures for a myriad of other ailments associated with mitochondrial dysfunction such as neurodegenerative diseases.

Differential expression of virulence genes and role of gyrA mutations in quinolone resistant and susceptible strains of Salmonella Weltevreden and Newport isolated from seafood.

AIMS: To investigate the differential expression of virulence genes and role of gyrA mutations in quinolone resistant and susceptible strains of Salmonella isolated from seafood. METHODS AND RESULTS: Forty Salmonella isolates from seafood were tested for antibiotic sensitivity. Minimal inhibitory concentration (MIC) was determined and two nalidixic acid-resistant isolates, viz Salmonella Weltevreden (SW9) and Salmonella Newport (SN36) were selected for identifying the mechanism of resistance. SW9 showed mutation in the gyrA gene at codon 83 (Ser to Tyr) while SN36 presented at codon 87 (Asp to Asn). Experimental induction of resistance to a sensitive Salm. Newport (SN71) showed point mutation at codon 87 (Asp to Gly) in the gyrA gene, and was designated SN71R. All the isolates resistant to nalidixic acid had a single mutation at different positions in the gyrA gene. However, induction of resistance to a sensitive Salm. Weltevreden (SW30) was exceptional in that it did not show any mutation in the gyrA region. Use of Phe-Arg-ß-naphthylamide (PAßN) also could not reduce MIC below the Clinical and Laboratory Standards Institute guidelines revealing the absence of efflux mediated resistance. Thus, the resistance mechanism in SW30R is unknown. The growth rate of quinolone resistant isolates was slower than the susceptible ones. The resistant isolates showed decreased epithelial cell invasion and intracellular replication. The mRNA expression levels of some of the genes were significantly (P < 0·005) reduced in SN71R compared to the sensitive strain (SN71). CONCLUSIONS: Nalidixic acid-resistant Salmonella strains are associated with lower virulence and pathogenicity than the sensitive strains. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provided valuable information on the difference in the growth, cytotoxicity, infectivity and expression of virulence genes in resistant and susceptible strains. Furthermore, the gyrA mutation was shown to be the main mechanism of quinolone resistance in Salmonella other than the overexpression of efflux pumps or the presence of plasmid mediated quinolone resistance genes.

Emergency surveillance for novel influenza A(H7N9) virus in domestic poultry, feral pigeons and other wild birds in Bhutan.

Following the March 2013 outbreak of novel avian influenza A(H7N9) virus in humans and the subsequent isolation of the virus from chickens, ducks and pigeons in the People's Republic of China, concerns were raised that the H7N9 virus would spread beyond China through the poultry value chain linking to a number of bordering countries. For this reason, a rapid emergency surveillance exercise took place in Bhutan between May and July 2013 with the objective of determining whether influenza A(H7N9) virus was silently circulating in domestic poultryandwild birds in Bhutan.Atotal of 1716 oropharyngeal,tracheal and cloacal swabs together with faecal droppings were collected from poultry, wild birds and feral pigeons throughout the country; these samples included 150 that had been previously collected for surveillance of influenza A(H5N1) virus. Overall, 733 of the samples were tested. A QIAamp Viral RNA Mini K it was used to extract viral RNA from a mix of oropharyngeal, tracheal and cloacal swabs and faecal droppings. The matrix gene of avian influenza type A virus was detected using a specific real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) assay, and positive samples were further tested in RT-PCR for simultaneous detection of the H7 and N9 genes. Among the 733 samples tested, 46 (26 prospective, 20 retrospective) were confirmed positive for influenza A, a prevalence of 6.3% (95% CI: 4.6 to 8.3). The influenza A-positive samples were from areas in the south of Bhutan that had experienced previous outbreaks of highly pathogenic influenza A(H5N1). None of the samples tested positive for H7N9 strains, providing evidence that influenza A(H7N9) virus was not present in the sampled population. A risk-based approach for surveillance of influenza A(H7N9) and H5N1 is recommended in Bhutan, based on the epidemiology of the disease in China and other countries in South and Southeast Asia.

Alterations in lipid and fatty acid composition of the cyanobacterium Scytonema geitleri bharadwaja under water stress.

The composition of the glycerolipids [monogalactosyl diacylglycerol (MGDG), digalactosyl diacylglycerol (DGDG), sulfoquinovosyl diacylglycerol (SQDG) and phosphatidylglycerol (PG)] and alterations in their saturation and unsaturation levels in response to osmotic and matric water potential have been investigated in the cyanobacterium Scytonema geitleri Bharadwaja. The level of MGDG in S. geitleri was high followed by PG, DGDG and SQDG. Whereas, the amount of fatty acids namely palmitic, stearic, oleic, linoleic and linolenic acid were high, arachidic and behenic acid were, however, present in traces in the four glycerolipids. A significant reduction in the level of total lipid as well as individual class lipid was observed in S. geitleri in response to matric water potential to that of its total lipid and individual class lipid in response to osmotic water potential. The levels of polyunsaturated and unsaturated fatty acids also increased in response to matric water potential to that of osmotic water potential.

Presence of T3SS2ß genes in trh⁺ Vibrio parahaemolyticus isolated from seafood harvested along Mangalore coast, India.

UNLABELLED: Vibrio parahaemolyticus is a seafood-borne pathogen autochthonous to the marine and estuarine ecosystem, responsible for gastroenteritis when contaminated raw seafood is consumed. The pathogenicity has been associated with thermostable direct haemolysin (TDH) and TDH-related haemolysin (TRH). Of late, the presence of T3SS2α and T3SS2ß gene clusters has been well documented in clinical isolates of Vibrio parahaemolyticus and known to play an essential role in pathogenesis. However, reports on the presence of T3SSß genes in V. parahaemolyticus isolated from the seafood and/or environmental samples are scanty. In this study, we have identified and analysed the distribution of the T3SS2ß genes in V. parahaemolyticus isolated from seafood harvested along southwest coast of India. Results showed that T3SS2ß genes are solely associated with trh⁺ and tdh⁺ /trh⁺ strains of V. parahaemolyticus. Reverse transcriptase PCR (RT-PCR) showed that the T3SS2ß genes identified in trh⁺ V. parahaemolyticus were transcriptionally active. To our knowledge, this study appears to be the first description on the presence of T3SS2ß-positive V. parahaemolyticus isolated from seafood in India. The study of T3SS2 along with other virulence factors will help in better understanding of the risk of seafood-borne illness due to V. parahaemolyticus. SIGNIFICANCE AND IMPACT OF THE STUDY: T3SSs (α or ß) are the important virulence factors of Vibrio parahaemolyticus that contribute to their pathogenicity in humans. This study demonstrated the presence of T3SS2ß genes in V. parahaemolyticus isolated from the seafood harvested along Mangalore coast. RT-PCR showed that the T3SS2ß genes identified in seafood isolates of V. parahaemolyticus were found to be functional. To the best of our knowledge, this is the first description of T3SS2ß genes in trh⁺ V. parahaemolyticus isolated from seafood in India. The presence of T3SS2 along with other virulence factors such as TDH and/or TRH highlights a potential health risk for seafood consumers.

Cardiovascular risk factors and carotid intima-media thickness with neurocognitive dysfunction in people living with HIV on stable combination anti-retroviral therapy.

The goal of this clinical research was to determine the relationship between carotid intima-media thickness (cIMT), cardiovascular risk factors, and neuro-cognitive function in people living with HIV (PLHIV) and were on stable combination anti-retroviral therapy (cART). This is a cross-sectional study performed at a single center, including 149 patients who visited the anti-retroviral therapy center of our tertiary care hospital. Among the PLHIV of our research, 62.4% had at least one associated cardiovascular risk factor, and 61.1% of them had abnormally high cIMT (≥ 0.9 mm on any one side, p = 0.035). These factors and being the male gender (p = 0.028) were associated with a greater Framingham 10-year risk percentage. Hypercholesterolemia was observed in 30.9% of the PLHIV and a higher body mass index (≥ 25 kg/m2) was found in 26.8% of them. The cognitive impairment was milder in 71.8% of cases and moderate in 9.4% of PLHIV. The Chi-square test revealed that a higher proportion of participants who had lower HDL-C levels (p = 0.045), smokers (p = 0.029), systolic blood pressure ≥ 140 mmHg (p = 0.012), and lower educational status (p = 0.017) had a poorer cognitive performance. In our sample population, a higher prevalence of elevated cIMT, cardiovascular risk factors, and mild and moderate cognitive deficiency was observed in PLHIV, who were on stable cART. However, routine assessment of the neuropsychological functions and management of modifiable risk factors are not performed in our patients. Further exploration of the relationship between cardiovascular risks, cIMT, and cognitive impairment in PLHIV is essential to formulate the guidelines and delay the onset of neurocognitive disorders in these patients.

Electrical excitation of surface plasmons by an individual carbon nanotube transistor.

We demonstrate here the realization of an integrated, electrically driven, source of surface plasmon polaritons. Light-emitting individual single-walled carbon nanotube field effect transistors were fabricated in a plasmonic-ready platform. The devices were operated at ambient conditions to act as an electroluminescence source localized near the contacting gold electrodes. We show that photon emission from the semiconducting channel can couple to propagating surface plasmons developing in the electrical terminals. Our results show that a common functional element can be operated for two different platforms emphasizing thus the high degree of compatibility between state-of-the-art nano-optoelectronics devices and a plasmonic architecture.

Management of plant nutrient dynamics under alkaline soils through graded application of pressmud and gypsum.

An incubation experiment was conducted to monitor the effect of different organic matter inputs with the graded application of gypsum at different time intervals on soil pH, sodium (Na) content and available plant nutrients like nitrogen (N) and sulphur (S) in alkaline soil. The experiment was formulated with nine treatments, i.e. control (T1), recommended dose of fertilizer (RDF) (T2), RDF+Gyp1 (T3), RDF+FYM5+Gyp2 (T4), RDF+FYM10+Gyp1 (T5), RDF+PM5+Gyp2 (T6), RDF+PM10+Gyp1 (T7), RDF+FYM2.5+PM2.5+Gyp2 (T8), RDF+FYM5+PM5+Gyp1 (T9) with three replications. Periodical soil samples were taken at six and twelve months intervals. Results showed that the addition of organic matter reduced the pH and Na content in the soil. More reduction was observed at one year period as compared to six months. The addition of farmyard manure (FYM) and pressmud (PM) at 10 t/ha with gypsum (1 t/ha) improved available N and available S content as compared to organic inputs (5 t/ha) with gypsum (2 t/ha) in soil. Pressmud application with FYM showed better availability of plant nutrients and a reduction of soil pH (8.39 to 7.79) and Na content from 626 to 391 mEq/L in the soil during the incubation period. During the study, the application of treatment T9 (FYM and PM in equal ratio with 1 t/ha gypsum) showed a better availability of available N (175 to 235 kg/ha) and S (15.44 to 23.24 kg/ha) and reduced the active ion concentration of Na. This study is very useful for the management of sodium toxicity, improving soil health and the mineralization rate of organic matter through the application of organic inputs for sustainable crop production.

Citrinin as a potential anti-cancer therapy: A comprehensive review.

Citrinin (CIT) is a polyketide-derived mycotoxin, which is produced by many fungal strains belonging to the gerena Monascus, Aspergillus, and Penicillium. It has been postulated that mycotoxins have several toxic mechanisms and are potentially used as antineoplastic agents. Therefore, the present study carried out a systematic review, including articles from 1978 to 2022, by collecting evidence in experimental studies of CIT antiplorifactive activity in cancer. The Data indicate that CIT intervenes in important mediators and cell signaling pathways, including MAPKs, ERK1/2, JNK, Bcl-2, BAX, caspases 3,6,7 and 9, p53, p21, PARP cleavage, MDA, reactive oxygen species (ROS) and antioxidant defenses (SOD, CAT, GST and GPX). These factors demonstrate the potential antitumor drug CIT in inducing cell death, reducing DNA repair capacity and inducing cytotoxic and genotoxic effects in cancer cells.