Recalling the reported toxicity assessment of deoxynivalenol, mitigating strategies and its toxicity mechanisms: Comprehensive review.

Mycotoxins frequently contaminate a variety of food items, posing significant concerns for both food safety and public health. The adverse consequences linked to poisoning from these substances encompass symptoms such as vomiting, loss of appetite, diarrhea, the potential for cancer development, impairments to the immune system, disruptions in neuroendocrine function, genetic damage, and, in severe cases, fatality. The deoxynivalenol (DON) raises significant concerns for both food safety and human health, particularly due to its potential harm to vital organs in the body. It is one of the most prevalent fungal contaminants found in edible items used by humans and animals globally. The presence of harmful mycotoxins, including DON, in food has caused widespread worry. Altered versions of DON have arisen as possible risks to the environment and well-being, as they exhibit a greater propensity to revert back to the original mycotoxins. This can result in the buildup of mycotoxins in both animals and humans, underscoring the pressing requirement for additional investigation into the adverse consequences of these modified mycotoxins. Furthermore, due to the lack of sufficient safety data, accurately evaluating the risk posed by modified mycotoxins remains challenging. Our review study delves into conjugated forms of DON, exploring its structure, toxicity, control strategies, and a novel animal model for assessing its toxicity. Various toxicities, such as acute, sub-acute, chronic, and cellular, are proposed as potential mechanisms contributing to the toxicity of conjugated forms of DON. Additionally, the study offers an overview of DON's toxicity mechanisms and discusses its widespread presence worldwide. A thorough exploration of the health risk evaluation associated with conjugated form of DON is also provided in this discussion.

Pathological effects of feeding aflatoxin-contaminated feed on immune status and reproductive performance of juvenile white leghorn males and its mitigation with ∝-tocopherol and Moringa oleifera.

This study was planned to detect the adverse pathological consequences of aflatoxin B1 in White Leghorn (WLH) layer breeder males. Eight-week-old male layer cockerels were separated into six experimental categories: A group was kept as negative control, offered with normal feed only; group B was fed with 400 ppb amount of aflatoxin, while groups F and D fed with normal feed and supplemented with vitamin E 100 ppm and 1% Moringa oleifera, respectively, whereas groups E and C were fed with 400 ppb aflatoxin containing feed and ameliorated with vitamin E 100 ppm and 1% Moringa oleifera, respectively. This study was continued for 2 months and immunologic disorders and reproductive parameters were observed during the trial. To find out immunological status lymphoproliferative response to phytohemagglutinin-P (PHA-P), antibody titers against sheep red blood cells (SRBCs) and carbon clear assay were performed by collecting samples from five birds from each group. The whole data was measured by ANOVA test, and group means were compared by DMR test by using M-Stat C software. Regarding the reproductive status, spermatogenesis, blood testosterone level, testes weight, testes histology, sperm motility, and morphology were negatively affected by aflatoxins, but these deviations positively ameliorated by vitamin E and Moringa. Vitamin E and Moringa found advantageous in boosting the immune status of affected bird. All the immunological parameters including antibody titers against sheed red blood cells, lymphoproliferative response to avian tuberculin and phagocytic potential of macrophages were suppressed by AFB1 however in control, Moringa and vitamin E groups these immunological responses were significantly higher.

Therapeutic potential of natural antisense transcripts and various mechanisms involved for clinical applications and disease prevention.

Antisense transcription, a prevalent occurrence in mammalian genomes, gives rise to natural antisense transcripts (NATs) as RNA molecules. These NATs serve as agents of diverse transcriptional and post-transcriptional regulatory mechanisms, playing crucial roles in various biological processes vital for cell function and immune response. However, when their normal functions are disrupted, they can contribute to human diseases. This comprehensive review aims to establish the molecular foundation linking NATs to the development of disorders like cancer, neurodegenerative conditions, and cardiovascular ailments. Additionally, we evaluate the potential of oligonucleotide-based therapies targeting NATs, presenting both their advantages and limitations, while also highlighting the latest advancements in this promising realm of clinical investigation.Abbreviations: NATs- Natural antisense transcripts, PRC1- Polycomb Repressive Complex 1, PRC2- Polycomb Repressive Complex 2, ADARs- Adenosine deaminases acting on RNA, BDNF-AS- Brain-derived neurotrophic factor antisense transcript, ASOs- Antisense oligonucleotides, SINEUPs- Inverted SINEB2 sequence-mediated upregulating molecules, PTBP1- Polypyrimidine tract binding protein-1, HNRNPK- heterogeneous nuclear ribonucleoprotein K, MAPT-AS1- microtubule-associated protein tau antisense 1, KCNQ1OT- (KCNQ1 opposite strand/antisense transcript 1, ERK- extracellular signal-regulated kinase 1, USP14- ubiquitin-specific protease 14, EGF- Epidermal growth factor, LSD1- Lysine Specific Demethylase 1, ANRIL- Antisense Noncoding RNA in the INK4 Locus, BWS- Beckwith-Wiedemann syndrome, VEGFA- Vascular Endothelial Growth component A.

Attenuative effects of tamarixetin against polystyrene microplastics-induced hepatotoxicity in rats by regulation of Nrf-2/Keap-1 pathway.

Polystyrene microplastics (PS-MPs) are environmental contaminants due to their potential to induce damages in multiple organs specifically liver. Tamarixetin (TMT) is a naturally occurring flavonoid present in Tamarix ramosissima plant that exhibits multiple pharmacological properties. Therefore, the present research was designed to evaluate the palliative role of TMT against PS-MPs instigated liver dysfunction in rats. The exposure to PS-MPs reduced the expressions of nuclear factor erythroid 2-related factor 2 and antioxidant genes, while increasing the expression of Kelch-like ECH-associated protein 1. PS-MPs exposed rats exhibited considerably (p < .05) higher alkaline phosphatase (ALP), aspartate aminotransferase (AST) as well as alanine aminotransferase (ALT) contents. Additionally, PS-MPs treatment resulted in a notable decrease in anti-oxidants activity, that is, glutathione S-transferase (GST), superoxide dismutase (SOD), heme oxygenase-1 (HO-1), glutathione reductase (GSR), glutathione peroxidase (GPx), catalase (CAT) and glutathione (GSH) content, whereas upregulating reactive oxygen species (ROS) and malondialdehyde (MDA) contents. Moreover, PS-MPs intoxication noticeably increased (p < .05) the inflammatory indices (interleukin-1ß [IL-1ß], nuclear factor kappa B [NF-κB], interleukin-6 [IL-6], tumor necrosis factor-α [TNF-α] levels, and cyclooxygenase-2 [COX-2] activity). Besides, Caspase-3 and Bax expressions were upregulated and Bcl-2 expression was decreased after PS-MPs exposure. Additionally, the histomorphological examination revealed notable hepatic damage in PS-MPs treated group. However, TMT treatment substantially (p < .05) recovered all the PS-MPs-induced damages and histopathological changes. Taken together, it can be deduced that TMT might be used as a pharmacological agent to ameliorate hepatic damage.

Unraveling the combined deleterious effects of ochratoxin A and atrazine upon broiler's health: Toxicopathological, serum biochemical and immunological perspectives.

Atrazine, a herbicide, is used for eradication of broad-leaved herbs in corn crop; and ochratoxins, particularly ochratoxin A (OTA), are major pollutants of poultry diet. Existence of both of these hazardous chemicals as residues is obvious as elucidated by various epidemiological findings. The present study was designed to investigate toxicopathological, serum biochemical and immunological alterations incurred by atrazine alone and/or, in combination with OTA in broilers. For this purpose, one-day old broiler chicks (n = 180) were purchased from a local hatching unit and were fed two levels of atrazine (50 and 150 mg/kg) and one level of OTA (100 µg/kg) in different combinations. Results of this experiment showed a significant reduction in feed intake, body weight gain, relative organ weights, serum total protein, albumin and globulin while there was a significant increase in urea and creatinine levels, decreased antibody response to sheep red blood cells, reduced lymphoproliferative response and phagocytic capacity in groups given OTA and atrazine individually in feed and these effects became more pronounced when atrazine was given in combination with OTA suggesting synergistic effects of both toxicants for each other.

Aflatoxins associated oxidative stress and immunological alterations are mitigated by dietary supplementation of Pichia kudriavzevii in broiler chicks.

Mycotoxins are the secondary metabolites of certain toxigenic fungi which pose severe health stress in humans, animals and poultry. Certain biological agents and components are used to adsorb mycotoxins in poultry industry which provide promising results in this regard. Pichia kudriazevii (PK), a novel yeast, has the ability to enhance the immune status of poultry chicks. The present study was designed to investigate the ameliorative potential of PK against aflatoxins associated immunosuppression and oxidative stress in broiler chicks. 180-one day old broiler chicks were equally divided into six groups and given different combinations of aflatoxins (300 and 600 µg/kg) and PK (1 g/kg). Parameters studied were antibody response to sheep red blood cells, lymphoproliferative response to PHA-P; phagocytic response by carbon clearance assay system, total antioxidant capacity and total oxidant status of chicks. Results of this experiment confirmed the immunomodulation and antioxidant capacity of PK against 300 µg/kg aflatoxin level. However such amelioration was partial when PK was used with 600 µg/kg aflatoxins. Moreover, the exact ratio of aflatoxin: PK to cause such amelioration still needs to be investigated.

Frequency of pregnant women who accept HIV screening using rapid detection test and factors associated with acceptance.

To assess the frequency of pregnant women who accept HIV screening using rapid detection test and factors associated with acceptance we undertook a cross-sectional study conducted from July to December 2018. Women aged 20-45 years, who were pregnant and planned to deliver at the facility, were included. Women were counseled and offered about Human Immunodeficiency virus (HIV) screening. A total of 718 women were included in the study. The screening was accepted by 32.3% of women. Six women tested positive in the study giving a seroprevalence of 0.8% in the population studied. Acceptance of counseling and screening varied significantly with age range, educational status, socioeconomic status, and employment status. Women aged 30 years and above (p = 0.023) and women with higher education (p < 0.001) were more likely to refuse counselling. Similarly, employed women (p = 0.041) and women of higher socioeconomic class (p = 0.039) refused counselling. However, when logistic regression was conducted, only educational status (p < 0.001) and occupational status (p = 0.039) were significantly associated with acceptance of counseling and screening. The acceptance of counselling and testing for HIV in antenatal care attendees was low. Women of higher educational status and having some employment refused counselling and testing more commonly.

Advanced glycation end products (AGEs), protein aggregation and their cross talk: new insight in tumorigenesis.

Protein glycation and protein aggregation are two distinct phenomena being observed in cancer cells as factors promoting cancer cell viability. Protein aggregation is an abnormal interaction between proteins caused as a result of structural changes in them after any mutation or environmental assault. Protein aggregation is usually associated with neurodegenerative diseases like Alzheimer's and Parkinson's, but of late, research findings have shown its association with the development of different cancers like lung, breast and ovarian cancer. On the contrary, protein glycation is a cascade of irreversible nonenzymatic reaction of reducing sugar with the amino group of the protein resulting in the modification of protein structure and formation of advanced glycation end products (AGEs). These AGEs are reported to obstruct the normal function of proteins. Lately, it has been reported that protein aggregation occurs as a result of AGEs. This aggregation of protein promotes the transformation of healthy cells to neoplasia leading to tumorigenesis. In this review, we underline the current knowledge of protein aggregation and glycation along with the cross talk between the two, which may eventually lead to the development of cancer.

Dietary L-carnitine and vitamin-E; a strategy to combat ochratoxin-A induced immunosuppression.

This study aimed to evaluate the effect of dietary ochratoxin A (OA), in the presence and absence of L-carnitine (LC) and vitamin E (VE), on the humoral immune responses of White Leghorn cockerels (WLC). One-day old white male Leghorn chicks were divided into 12 groups, having 20 birds each and were offered ration contaminated with OA (1.0 or 2.0 mg/kg feed) alone and concurrently with LC (1.0 g/kg) and/or VE (0.2 g/kg), for 42 days. The humoral immune responses were accessed by lymphoproliferative response to avian tuberculin, in-vivo phagosomes activity to carbon particles and antibody response to the sheep red blood cells (SRBCs). The dietary addition of OA alone suppressed the humoral immune responses, however, the exposure of birds to 1.0 mg/kg OA in the presence of LC and/or VE showed a significant reduction in OA induced immunotoxicity. This protective response was absent in the birds fed 2.0 mg/kg OA in the presence and absence of LC and/or VE. Histopathological and morphometric examination of the bursa of Fabricius exhibited a decrease in the severity and frequency of OA induced lesions in the presence of dietary LC and/or VE. The use of LC and VE as dietary supplement, can effectively overcome OA (≤1.0 mg/kg) induced immunosuppression.

Pathological effects of concurrent administration of aflatoxin B1 and fowl adenovirus-4 in broiler chicks.

The current study was designed to investigate pathological effects of fowl adenovirus in broilers exposed to aflatoxin B1. Fowl Adenovirus-4 (FAdV-4) infection is remerging in all types of poultry birds in Pakistan. Poultry feed contamination with mycotoxin (aflatoxin) is another important global issue. A total of 125-day old broiler birds were divided into six equal groups. Group A served as control. B and C groups were administered with aflatoxin B1 (AFB1) 100 and 200 µg/kg feed. Group D was infected with FAdV-4, while groups E and F administered with both AFB1 (100 & 200 µg/kg) along with FAdV-4. These birds were monitored for clinical signs and mortality. Feed intake, body weight (BW), relative organ weights and gross & histopathological lesions were recorded. The highest mortality was observed in group F (FAdV-4 + AFB1 200 µg/kg feed) and the lowest mortality was observed in group B (AFB1 100 µg/kg feed). Body weights of all the groups were significantly (p < 0.05) lower as compared with control group. Relative weight of liver and kidneys in groups E and F were significantly higher as compared with control. Grossly, liver was swollen, anemic with round margins in groups D, E and F. Kidneys were also swollen with whitish areas indicating dead tissue. Microscopically intranuclear inclusion bodies were observed in group D-F. The hepatic parenchyma was also indicating necrotic changes along with vacuolar degeneration. In renal parenchyma, acute tubular necrosis was observed in groups C, E and F. It was concluded that AFB1 intoxication lead to dose dependent changes in liver and kidneys. Severity of the changes was increased in interactive groups of AFB1 with FAdV-4. Therefore, feed should be regularly monitored for AFB1 levels and day old chicks for vertically transmitted FAdV-4 to prevent losses.

Effects of feeding bentonite clay upon ochratoxin A-induced immunosuppression in broiler chicks.

A presence of mycotoxins in feed is one of the most alarming issues in the poultry feed industry. Ochratoxins, produced by several Aspergillus and Penicillium species, are important mycotoxin regarding the health status of poultry birds. Ochratoxins are further classified into to several subtypes (A, B, C, etc) depending on their chemical structures, but ochratoxin A (OTA) is considered the most important and toxic. Bentonite clay, belonging to phyllosilicates and formed from weathering of volcanic ashes, has adsorbent ability for several mycotoxins. The present study was designed to study the effects of bentonite clay upon OTA-induced immunosuppression in broiler chicks. For this, 480 day-old broiler chicks were procured from a local hatchery and then different combinations of OTA (0.15, 0.3, or 1.0 mg/kg) and bentonite clay (5, 10, and 20 g/kg) were incorporated into their feed. At 13, 30, and 42 days of age, parameters such as antibody responses to sheep red blood cells, in situ lymphoproliferative responses to mitogen (PHA-P), and in situ phagocytic activity (i.e., via carbon clearance) were determined respectively. The results indicated there was a significant reduction of total antibody and immunoglobulin titres, lymphoproliferative responses, and phagocytic potential in OTA-treated birds, suggesting clear immunosuppression by OTA in birds in a dose-dependent manner. These results were also significantly lower in all combination groups (OTA with bentonite clay), suggesting few to no effects of feeding bentonite clay upon OTA- induced alterations in different immune parameters.

Amelioration of Ochratoxin A-induced immunotoxic effects by silymarin and Vitamin E in White Leghorn cockerels.

Silymarin (SL) is the bioactive extract of the plant Silybum marianum and Vitamin E (VE) is an important anti-oxidant. The present study was designed to evaluate potential ameliorative effects of SL and VE against Ochratoxin A (OTA)-induced immunotoxic effects in White Leghorn cockerels. One day-old birds were divided into 12 groups (20 birds/group) and fed basal diets amended with OTA (1.0 or 2.0 mg/kg) alone or in combination with SL (10 g/kg) and/or VE (200 mg/kg) for 42 days. Immunological in situ responses, including antibody formation against sheep red blood cells (7 and 14 days after both primary and booster injections), lymphoproliferative responses to avian tuberculin (30 days of age), and mononuclear phagocytic system function (i.e. by clearance of injected carbon particles) assay (42 days of age), were assessed. Results suggested that silymarin and Vitamin E alone or in combination ameliorated the immunotoxic effects induced by 1.0 mg OTA/kg but could not significantly impact on the effect from ingestion of 2.0 mg OTA/kg. The results of the present study suggested that both SL and VE possess an ability to ameliorate OTA-induced immunotoxicity in chicks. However, it remains to be determined whether/what SL:OTA or VE:OTA ratios are required to assure such mitigation of OTA-induced immunotoxicities.