Search Results (79)

Cottonseed meal (CSM) has emerged as an alternative source of protein-based poultry feed because of the increasing cost and scarcity of soybean meal. However, it contains toxic gossypol, which restricts its use. This systematic review examines solid-state fermented CSM’s impact on broiler chickens, focusing on growth performance, carcass traits, and blood parameters. To identify relevant papers, a comprehensive search of Web of Science, Scopus, and PubMed was conducted. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology, peer-reviewed experimental articles published in English up to September 2023 were screened. A total of 60 articles were evaluated over four stages, resulting in 9 articles that met the predefined inclusion and exclusion criteria. The reduction in gossypol content was effective with bacteria like Bacillus subtilis, Aspergillus oryzae, and Aspergillus niger. The content of free gossypol in CSM is significantly reduced after solid-state fermentation using various microorganisms. Fermented CSM increased the body weight gain and feed intake of broilers, while maintaining feed efficiency, and improved growth performance. Fermented CSM included in diets positively affected carcass traits, including increased carcass weight and breast muscle development. It also resulted in decreased fat content and enhanced immune organ development. An improvement in total protein, albumin, and immunoglobulin levels was observed in blood biochemical parameters, suggesting an improved humoral immune response. Depending on the microorganisms used and their concentrations, fermented CSM also had positive effects on cholesterol, triglycerides, and LDL levels. Solid-state fermented CSM can be an effective and sustainable source of protein for broiler chickens. A future research focus should be on long-term effects, underlying mechanisms, economic feasibility, and scalability. In addition, it could be used in novel feed formulations and other livestock species to further enhance animal agriculture. Full article

Gossypol and its derivatives arouse interest due to their broad spectrum of biological activities. Despite its wide potential application, there is no reported example of gossypol derivatives bearing stable radical functional groups. The first gossypol nitroxide hybrid compound was prepared here via formation of a Schiff base. By this approach, synthesis of a gossypol nitroxide conjugate was performed by condensation of gossypol with a 4-amino-TEMPO (4-amino-2,2,6,6-tetramethylpiperidin-1-oxyl) free radical, which afforded the target product in high yield. Its structure was proven by a combination of NMR and EPR spectroscopy, infrared spectroscopy, mass spectrometry, and high-resolution mass spectrometry. In addition, the structure of the gossypol nitroxide was determined by single-crystal X-ray diffraction measurements. In crystals, the paramagnetic Schiff base exists in an enamine–enamine tautomeric form. The tautomer is strongly stabilized by the intra- and intermolecular hydrogen bonds promoted by the resonance of π-electrons in the aromatic system. NMR analyses of the gossypol derivative proved that in solutions, the enamine–enamine tautomeric form prevailed. The gossypol nitroxide at micromolar concentrations suppressed the growth of tumor cells; however, compared to gossypol, the cytotoxicity of the obtained conjugate was substantially lower. Full article

Objective: Gossypol is a natural polyphenolic dialdehyde product that is primarily isolated from cottonseed. It is a racemized mixture of (−)-gossypol and (+)-gossypol that has anti-infection, antimalarial, antiviral, antifertility, antitumor and antioxidant activities, among others. Gossypol optical isomers have been reported to differ in their biological activities and toxic effects. Method: In this study, we performed a metabolomics analysis of rat serum using 1H-NMR technology to investigate gossypol optical isomers’ mechanism of action on uterine fibroids. Network toxicology was used to explore the mechanism of the liver injury caused by gossypol optical isomers. SD rats were randomly divided into a normal control group; model control group; a drug-positive group (compound gossypol acetate tablets); high-, medium- and low-dose (−)-gossypol acetate groups; and high-, medium- and low-dose (+)-gossypol acetate groups. Result: Serum metabolomics showed that gossypol optical isomers’ pharmacodynamic effect on rats’ uterine fibroids affected their lactic acid, cholesterol, leucine, alanine, glutamate, glutamine, arginine, proline, glucose, etc. According to network toxicology, the targets of the liver injury caused by gossypol optical isomers included HSP90AA1, SRC, MAPK1, AKT1, EGFR, BCL2, CASP3, etc. KEGG enrichment showed that the toxicity mechanism may be related to pathways active in cancer, such as the PPAR signaling pathway, glycolysis/glycolysis gluconeogenesis, Th17 cell differentiation, and 91 other closely related signaling pathways. Conclusions: (−)-gossypol acetate and (+)-gossypol acetate play positive roles in the treatment and prevention of uterine fibroids. Gossypol optical isomers cause liver damage through multiple targets and pathways. Full article

Gossypol (GP), a polyphenolic compound in cottonseed, has notable effects on female reproduction and the respiratory system in pigs. This study aimed to discern the alterations in gene expression within swine granulosa cells (GCs) when treated with two concentrations of GP (6.25 and 12.5 µM) for 72 h, in vitro. The analysis revealed significant changes in the expression of numerous genes in the GP-treated groups. A Gene Ontology analysis highlighted that the differentially expressed genes (DEGs) primarily pertained to processes such as the mitotic cell cycle, chromosome organization, centromeric region, and protein binding. Pathway analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) indicated distinct impacts on various pathways in response to different GP concentrations. Specifically, in the GP6.25 group, pathways related to the cycle oocyte meiosis, progesterone-mediated oocyte maturation, and p53 signaling were prominently affected. Meanwhile, in the GP12.5 group, pathways associated with PI3K-Akt signaling, focal adhesion, HIF-1 signaling, cell cycle, and ECM–receptor interaction showed significant alterations. Notably, genes linked to female reproductive function (CDK1, CCNB1, CPEB1, MMP3), cellular component organization (BIRC5, CYP1A1, TGFB3, COL1A2), and oxidation–reduction processes (PRDX6, MGST1, SOD3) exhibited differential expression in GP-treated groups. These findings offer valuable insights into the changes in GC gene expression in pigs exposed to GP. Full article

This study was conducted to investigate and compare the effects of substituting soybean meal (SBM) with untreated cottonseed meal (CSM), fermented CSM (FCSM), or electron beam-irradiated CSM (ICSM) on the growth performance, cecal microbiota, digestive enzyme activity, apparent ileal digestibility (AID), and excreta gas emission of broiler chickens. A total of 384 one-day-old male broiler chickens were randomly assigned to four experimental diets, with eight replicates per diet and 12 birds per replicate, for six weeks. The experimental diets consisted of a control diet based on corn–SBM and three other diets in which 50% of the SBM (control) was substituted with CSM in its raw, irradiated, and fermented forms. The results showed that throughout the entire rearing period, feeding broiler chickens with ICSM significantly increased average daily gain (ADG) and body weight (BW) compared to the CSM diet (p < 0.05). Replacing 50% of SBM with FCSM led to a significant improvement in BW, ADG, and feed conversion ratio (FCR) compared to the CSM and ICSM diets (p < 0.05). Interestingly, no significant differences in BW, ADG, or FCR were observed between birds fed FCSM and those on the control diet (p > 0.05). Birds fed FCSM diets exhibited the lowest pH value in the crop, ileum, and ceca. Substituting SBM with FCSM significantly reduced Escherichia coli and Clostridium spp. counts in the ceca, while enhancing the presence of Lactobacillus spp. (p < 0.05). The AID of protein and ether extract was higher in the FCSM group than in the CSM and ICSM groups (p < 0.05). Compared to the CSM diet, ICSM feeding improved protein digestibility (p < 0.05). Broiler chickens on the FCSM diet exhibited higher intestinal amylase and protease activity than those on the other diets (p < 0.05). Furthermore, feeding diets containing FCSM significantly reduced ammonia emissions compared to the other diets (p < 0.05). Overall, our results indicated that microbial fermentation of CSM is a more effective approach than irradiation for enhancing the nutritional value of CSM. Therefore, FCSM is recommended as a viable alternative protein source that can safely replace up to 50% of SBM in broiler chicken diets, particularly during times of fluctuating SBM prices and availability issues. Full article

The presence of free gossypol (FG) in cottonseed meal (CSM) greatly limits the use of CSM as a high-quality protein feed. Microbial fermentation is an effective method to simultaneously reduce FG and improve the nutritional value of CSM. In this study, using potato dextrose agar containing acetic gossypol as a selective medium and humus soil from cotton fields as the source, we isolated six strains of fungi capable of tolerating FG. With an inoculation ratio of 8% (8 mL × 10⁶ CFU/mL cells or spores in 100 g fermented CSM), 50% moisture content, and a temperature of 30 °C, CSM was fermented for 5 days. The results showed that strain F had the highest FG removal rate at 56.43%, which was identified as Rhodotorula mucilaginosa (R. mucilaginosa) and named R. mucilaginosa TG529. Further optimization revealed that when the fermentation time was extended to 11 days, TG529 achieved a maximum FG removal rate of 73.29%. Compared to the original sample, treatment with TG529 significantly increased the contents of crude protein, acid-soluble protein, and 18 amino acids, while significantly reducing the contents of crude fiber, neutral detergent fiber (NDF), and acid detergent fiber in fermented cottonseed meal (FCSM). Using atmospheric and room temperature plasma for mutagenesis of TG529, it was found that the mutated TG529 significantly increased the contents of acid-soluble protein and phenylalanine in FCSM, significantly reduced the NDF content, and enhanced the FG removal rate to 76.50%. In summary, this study screened and mutagenized a strain of FG detoxifying fungus, R. mucilagnosa TG529, which can effectively reduce the FG content and improve the nutritional value of CSM by solid-state fermentation. Full article

Ruminants exhibit stronger tolerance to gossypol, an anti-nutritional factor, compared to monogastric animals. We transplanted Hu sheep rumen microbiota into male mice to investigate the role of rumen microbiota in animal gossypol tolerance. Thirty specific-pathogen-free (SPF) male C57BL/6 mice were randomly divided into three groups: normal diet (CK group), gossypol diet (FG group), and rumen microbiota transplantation (FMT group, gossypol diet). The pathological changes in the liver and small intestine of the mice, the organ coefficient, and sperm parameters were analyzed. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in the blood and lactate dihydrogen-X (LDH-X) levels in the testicular tissue were also measured. The results showed that body weight, feed intake, sperm concentration, sperm motility, and LDH-X levels in the FMT group increased (p < 0.05) compared with the FG group, while the enzyme activities of ALT, AST, and AST/ALT decreased (p < 0.05). In the FMT group, the injury to liver cells was alleviated, the structure of the small intestine was intact, and the villus height and the ratio of villus height to crypt depth (V/C) were higher than those in the FG group (p < 0.05). And there were no differences in various organ coefficients and sperm deformity rates among the three groups (p > 0.05), but compared with the FG group, mice in the FMT group showed tendencies closer to those in the CK group. Rumen microbiota transplantation relieved the reproductive toxicity and liver damage induced by gossypol in male mice and improved the tolerance of recipient animals to gossypol. Additionally, rumen microbes improved the intestinal structural integrity of recipients. Full article

Several cottonseed varieties are cultivated in different countries. Each variety produces a different amount of gossypol as a natural toxic compound. The rising interest in cottonseed products (oil and feed) increases the demand for establishing simple methods for gossypol detection. Silica gel-based methods are ideal for its isolation, purification, and characterization. Silica gel-based methods are variants and can be used as simple methods for tracking plants’ compounds. In this study, gossypol was isolated, characterized, and purified as gossypol acetic acid in the form of yellow crystals. Methods used for its characterization were TLC, preparative TLC, silica gel column, UV/IR spectrophotometer, and HPLC (robust spherical silica gel). A comparative study between its amount in both the Egyptian and Chinese varieties was performed. Under the experimental conditions, the Egyptian’s cottonseed contains 8.705 gm/kg, while the Chinese’s cottonseed contains 5.395 gm/kg. The TLC used in this study proved to be fast, accurate, and inexpensive. It can be used for gossypol acetic acid evaluation and quantification. Additionally, using TLC as a pre-purification step will give a pre-judgment for the sample’s purity and quality. This step will protect the expensive HPLC silica gel-based column from any unexpected impurities. During each step, the silica gel itself could be simply removed by paper filtration. Collectively, the different silica gel-based methods as well as the other used methods are recommended for better Gossypol acetic acid isolation, purification, and characterization, as well as for maintaining HPLC columns. Full article

Landraces are an important reservoir of genetic variation that can expand the narrow genetic base of cultivated cotton. In this study, quantitative trait loci (QTL) analysis was conducted using an F₂ population developed from crosses between the landrace Hopi and inbred TM-1. A high-density genetic map spanning 2253.11 and 1932.21 cM for the A and D sub-genomes, respectively, with an average marker interval of 1.14 cM, was generated using the CottonSNP63K array. The linkage map showed a strong co-linearity with the physical map of cotton. A total of 21 QTLs were identified, controlling plant height (1), bract type (1), boll number (1), stem color (2), boll pitting (2), fuzz fiber development (2), boll shape (3), boll point (4), and boll glanding (5). In silico analysis of the novel QTLs for boll glanding identified a total of 13 candidate genes. Analysis of tissue-specific expression of the candidate genes suggests roles for the transcription factors bHLH1, MYB2, and ZF1 in gland formation. Comparative sequencing of open reading frames identified early stop codons in all three transcription factors in Hopi. Functional validation of these genes offers avenues to reduce glanding and, consequently, lower gossypol levels in cottonseeds without compromising the defense mechanisms of the plant against biotic stresses. Full article

Solid-State fermentation (SSF) is a valuable process used for the enhancement of the nutritional profile of agro-industrial by-products. The main objective of the present study concerns the exploitation of a mixture consisting of Cottonseed Cake (CSC) and Lathyrus clymenum pericarp (LCP) at a ratio of 80–20% w/w, which was utilized as substrate for the initiated by Pleurotus ostreatus SSF process. The final goal is the improvement of their nutritional value and the parallel reduction in their gossypol content. The obtained results revealed a statistically significant increase (p < 0.05) in protein content by 34.91%, while 1,3-1,6 β-glucans exceeded a 5-fold statistically significant increment (p < 0.05) at Day 11. Furthermore, lignin was reduced significantly (−26.71%) at Day 11. Free gossypol’s presence was lowered by 12.45%, while SSF presented a profound effect concerning the total gossypol level since the latter underwent a statistically significant reduction (p < 0.05) that exceeded 9-fold at Day 11. The study herein highlights SSF’s efficiency as a potential means to reduce free and total gossypol content with a parallel upgrade of its nutritional value. The fermentation outcome reveals its potential as a feed supplement and contributes to the reduction in the environmental footprint within the framework of a circular economy. Full article

Expressions of a wide range of cytoprotective counter-defense genes are mainly regulated by the Keap1-Nrf2-ARE signaling pathway in response to oxidative stress from xenobiotics. Gossypol is the major antiherbivore secondary metabolite of cotton, but how the polyphagous pest Helicoverpa armigera copes with this phytochemical to utilize its favorite host plant cotton remains largely elusive. In this study, we first suppressed the Keap1 gene in newly hatched larvae of cotton bollworm by feeding them the siRNA diet for 4 days. All of the larvae were subsequently fed the artificial diet supplied with gossypol or the control diet for 5 days. We identified that the knockdown of the Keap1 gene significantly decreased larval mortality and significantly increased the percentages of larval survival, reaching the fourth instar, compared with ncsiRNA when exposed to a diet containing gossypol. Three counter-defense genes CYP9A17, CYP4L11 and UGT41B3, which were related to the induction or metabolism of gossypol according to the report before, were all significantly up-regulated after the knockdown of the Keap1 gene. The Antioxidant Response Elements (AREs) were also detected in the promoter regions of the three counter-defense genes above. These data indicate that the suppression of the Keap1 gene activates the Keap1-Nrf2-ARE signaling pathway, up-regulates the expressions of counter-defense genes involved in the resistance of oxidative stress and finally contributes to reducing the susceptibility of gossypol. Our results provide more knowledge about the transcriptional regulation mechanisms of counter-defense genes that enable the cotton bollworm to adapt to the diversity of host plants including cotton. Full article

Cotton is an important plant-based protein. Cottonseed cake, a byproduct of the biodiesel industry, offers potential in animal supplementation, although the presence of the antinutritional sesquiterpenoid gossypol limits utilization. The macrofungus Panus lecomtei offers potential in detoxification of antinutritional factors. Through an enzymatic and proteomic analysis of P. lecomtei strain BRM044603, grown on crushed whole cottonseed contrasting in the presence of free gossypol (FG), this study investigated FG biodegradation over a 15-day cultivation period. Fungal growth reduced FG to levels at 100 μg/g, with a complex adaptive response observed, involving primary metabolism and activation of oxidative enzymes for metabolism of xenobiotics. Increasing activity of secreted laccases correlated with a reduction in FG, with enzyme fractions degrading synthetic gossypol to trace levels. A total of 143 and 49 differentially abundant proteins were observed across the two contrasting growth conditions after 6 and 12 days of cultivation, respectively, revealing a dynamic protein profile during FG degradation, initially related to constitutive metabolism, then later associated with responses to oxidative stress. The findings advance our understanding of the mechanisms involved in gossypol degradation and highlight the potential of P. lecomtei BRM044603 in cotton waste biotreatment, relevant for animal supplementation, sustainable resource utilization, and bioremediation. Full article

Apoptosis signaling controls the cell cycle through the protein–protein interactions (PPIs) of its major B-cell lymphoma 2-associated x protein (BAX) and B-cell lymphoma 2 protein (Bcl-2). Due to the antagonistic function of both proteins, apoptosis depends on a properly tuned balance of the kinetics of BAX and Bcl-2 activities. The utilization of natural polyphenols to regulate the binding process of PPIs is feasible. However, the mechanism of this modulation has not been studied in detail. Here, we utilized atomic force microscopy (AFM) to evaluate the effects of polyphenols (kaempferol, quercetin, dihydromyricetin, baicalin, curcumin, rutin, epigallocatechin gallate, and gossypol) on the BAX/Bcl-2 binding mechanism. We demonstrated at the molecular scale that polyphenols quantitatively affect the interaction forces, kinetics, thermodynamics, and structural properties of BAX/Bcl-2 complex formation. We observed that rutin, epigallocatechin gallate, and baicalin reduced the binding affinity of BAX/Bcl-2 by an order of magnitude. Combined with surface free energy and molecular docking, the results revealed that polyphenols are driven by multiple forces that affect the orientation freedom of PPIs, with hydrogen bonding, hydrophobic interactions, and van der Waals forces being the major contributors. Overall, our work provides valuable insights into how molecules tune PPIs to modulate their function. Full article

Cottonseed meal (CSM) is the major by-product of the cottonseed oil extraction process with high protein content. However, the presence of free gossypol (FG) in CSM severely restricts its utilization in the food and animal feed industries. The development of a biological strategy for the effective removal of FG in CSM has become an urgent need. In this study, three bacterial laccases including CotA from Bacillus licheniformis, CueO from Escherichia coli, and LcLac from Loigolactobacillus coryniformis were heterologously expressed and investigated for their FG degradation ability. The results showed that CotA laccase displayed the highest FG-degrading capacity among the three laccases, achieving 100% FG degradation at 37 °C and pH 7.0 in 1 h without the addition of a redox mediator. Moreover, in vitro and in vivo studies confirmed that the hepatotoxicity of FG was effectively eliminated after oxidative degradation by CotA laccase. Furthermore, the addition of CotA laccase could achieve 87% to 98% FG degradation in defatted CSM within 2 h. In conclusion, CotA laccase can be developed as an effective biocatalyst for the detoxification of FG in CSM. Full article

The plerocercoid of Spirometra mansoni can parasitize both human and animals, resulting in sparganosis. Lactate dehydrogenase (LDH) is an important enzyme in parasites. However, our knowledge of the LDH family in S. mansoni is still inadequate. This work identified 19 new LDH members in S. mansoni. Clustering analysis demonstrated that all SmLDHs were divided into two main groups, which is consistent with the patterns of conserved motif organization. According to RT-qPCR, 2 LDHs were highly expressed in the plerocercoid stage and 17 LDHs were highly expressed in the adult stage. The evolutionary tree showed a high level of diversity of both cestode and trematode LDHs. SmLDHs contained both conserved family members and members in the process of further diversification. rSmLDH has a NAD-binding domain and a substrate-binding domain. The protein was immunolocalized in the epidermis of the pleroceroid and in the tegument, uterus and egg shell of adult worms. The optimum activity for rSmLDH in the pyruvate reduction reaction was found to be pH 4.5 and 37 °C. In the oxidation reaction, optimal values for pH and temperature were 9.0 and 30 °C, respectively. Gossypol was found to be the most powerful inhibitor in both reduction and oxidation reactions. The results provide a basis for the further study of the biological roles of LDHs in S. mansoni and other LDH-containing taxa. Full article