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Growing environmental constraints on resources necessitates finding renewable and sustainable means of production. Microalgae provides a promising resource for feedstock in many bio-products and for waste utilization. Microalgae contain a variety of high-value products and are known for their bio-synthesis from waste sources. Increased industrial operations become a sustainable source of wastewater containing nutrient loads; in parallel, energy expenditures imparted to wastewater reclamation deteriorate the environment. To balance this, a circular economy that creates benefits to the environment and increases industrial productivity through planning out pollution/waste and recycling waste and materials back into use is essential. For example, various chemicals in wastewater can be used as sources of nutrient and bio-synthetic inducers in algal biorefining. This review discusses the required technical developments and knowledge gaps across multiple reuse methods for wastewater resources that support public health, industry, and environmental regulatory policies. Furthermore, this review surveys how industrial wastewater can serve as a sustainable resource, with chemical contents as a source of nutrient and substrate for algal cultivation and strategies necessary for biorefinery methods. Wastewaters have noxious contents, but various algal traits are relatively tolerant towards mixed chemicals, in some cases influencing biosynthetic pathways. The chemistry of wastewater varies depending on the stages and processes involved in product manufacturing, this variation require careful planning to ensure that the contents of the wastewater align with the specific targeted uses as a source of micro and macronutrients. [ABSTRACT FROM AUTHOR]

Immunotherapy has emerged as a promising cancer treatment option in recent years. In immune "hot" tumors, characterized by abundant immune cell infiltration, immunotherapy can improve patients' prognosis by activating the function of immune cells. By contrast, immune "cold" tumors are often less sensitive to immunotherapy owing to low immunogenicity of tumor cells, an immune inhibitory tumor microenvironment, and a series of immune-escape mechanisms. Immunogenic cell death (ICD) is a promising cellular process to facilitate the transformation of immune "cold" tumors to immune "hot" tumors by eliciting innate and adaptive immune responses through the release of (or exposure to) damage-related molecular patterns. Accumulating evidence suggests that various traditional therapies can induce ICD, including chemotherapy, targeted therapy, radiotherapy, and photodynamic therapy. In this review, we summarize the biological mechanisms and hallmarks of ICD and introduce some newly discovered and technologically innovative inducers that activate the immune system at the molecular level. Furthermore, we also discuss the clinical applications of combing ICD inducers with cancer immunotherapy. This review will provide valuable insights into the future development of ICDrelated combination therapeutics and potential management for "cold" tumors. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explores alternative methods to combat onion white rot, a destructive disease caused by Sclerotium cepivorum, which poses a significant threat to onion cultivation, leading to substantial yield losses. Traditional fungicides, while effective, raise environmental concerns, prompting a search for eco-friendly alternatives. This research evaluates the efficacy of nanoparticles and chemical inducers in managing the disease. Nanoparticles, including Fe3O4, Cu, and ZnO, exhibit promising results in inhibiting the growth of the pathogen both in vitro and in vivo. Additionally, chemical inducers like salicylic acid show potential in reducing disease incidence and severity while promoting plant growth. This study also includes an assessment of traditional fungicides' inhibitory effects on S. cepivorum. Overall, this research provides valuable insights into eco-friendly strategies for onion white rot management, offering potential solutions to mitigate the impact of this devastating disease on onion crops and the environment. This study investigated the effectiveness of nanoparticles and chemical inducers in managing onion white rot caused by Sclerotium cepivorum. The pathogen severely threatens onion cultivation, resulting in significant yield losses and economic setbacks. Traditional fungicides, though effective, raise environmental concerns, prompting a shift toward eco-friendly alternatives. In this study, four S. cepivorum isolates were utilized, each exhibiting varying degrees of pathogenicity, with the third isolate from Abu-Hamad demonstrating the highest potency. During the in vitro studies, three nanoparticles (NPs) were investigated, including Fe3O4 NPs, Cu NPs, and ZnO NPs, which demonstrated the potential to inhibit mycelial growth, with salicylic acid and Fe3O4 NPs exhibiting synergistic effects. In vivo, these nanoparticles reduced the disease incidence and severity, with Fe3O4 NPs at 1000–1400 ppm resulting in 65.0–80.0% incidence and 80.0–90.0% severity. ZnO NPs had the most positive impact on the chlorophyll content, while Cu NPs had minimal effects. At 1000 ppm, Fe3O4 NPs had variable effects on the phenolic compounds (total: 6.28, free: 4.81, related: 2.59), while ZnO NPs caused minor fluctuations (total: 3.60, free: 1.82, related: 1.73). For the chemical inducers, salicylic acid reduced the disease (10.0% incidence, 25.0% to 10.0% severity) and promoted growth, and it elevated the chlorophyll values and enhanced the phenolic compounds in infected onions. Potassium phosphate dibasic (PDP) had mixed effects, and ascorbic acid showed limited efficacy toward disease reduction. However, PDP at 1400 ppm and ascorbic acid at 1000 ppm elevated the chlorophyll values and enhanced the phenolic compounds. Furthermore, this study extended to traditional fungicides, highlighting their inhibitory effects on S. cepivorum. This research provides a comprehensive comparative analysis of these approaches, emphasizing their potential in eco-friendly onion white rot management. [ABSTRACT FROM AUTHOR]

Growing environmental constraints on resources necessitates finding renewable and sustainable means of production. Microalgae provides a promising resource for feedstock in many bio-products and for waste utilization. Microalgae contain a variety of high-value products and are known for their bio-synthesis from waste sources. Increased industrial operations become a sustainable source of wastewater containing nutrient loads; in parallel, energy expenditures imparted to wastewater reclamation deteriorate the environment. To balance this, a circular economy that creates benefits to the environment and increases industrial productivity through planning out pollution/waste and recycling waste and materials back into use is essential. For example, various chemicals in wastewater can be used as sources of nutrient and bio-synthetic inducers in algal biorefining. This review discusses the required technical developments and knowledge gaps across multiple reuse methods for wastewater resources that support public health, industry, and environmental regulatory policies. Furthermore, this review surveys how industrial wastewater can serve as a sustainable resource, with chemical contents as a source of nutrient and substrate for algal cultivation and strategies necessary for biorefinery methods. Wastewaters have noxious contents, but various algal traits are relatively tolerant towards mixed chemicals, in some cases influencing biosynthetic pathways. The chemistry of wastewater varies depending on the stages and processes involved in product manufacturing, this variation require careful planning to ensure that the contents of the wastewater align with the specific targeted uses as a source of micro and macronutrients.

Hydrocephalus is a disorder caused by excess fluid accumulation in the brain and results in brain damage with consequent cognitive and physical problems. This condition has no cure; the only treatment is brain surgery. Experimental data indicate that P‐glycoprotein (P‐gp) plays a crucial role in the pathogenesis of hydrocephalus due to its function in clearing macromolecules from the brain. Numerous medications frequently used are classified as P‐gp inducers or inhibitors, and comprehending their effects may aid in attaining improved patient outcomes. Therefore, in this single‐center retrospective study, we examined the risk of the need for ventriculoperitoneal shunt placement over 10 years among 4588 adult patients with hydrocephalus not exposed to any P‐gp inhibitors/inducers or exclusively exposed to either P‐gp inhibitors or inducers. Our analysis shows that patients exposed to P‐gp inhibitors had a 3.2 times higher risk of requiring ventriculoperitoneal shunt surgery (P <.0001). In contrast, the relative risk was not significantly affected (P =.07) among those exposed to P‐gp inducers. Our findings indicate the need for caution when prescribing P‐gp inhibitors to patients with hydrocephalus. Additional studies using larger cohorts are required to confirm whether P‐gp inducers in patients with hydrocephalus can mitigate the risk of ventriculoperitoneal shunt. [ABSTRACT FROM AUTHOR]

According to the operation parameters and the design experience parameters, a liquid hydrogen centrifugal pump was developed and tested to meet an application requirement of small flow and high head in cryogenic systems or cryogenic storage tanks. The test results showed that 6 m of hydraulic loss in the pump at the rated condition and the inlet pressure of the cryogenic fluid decreased and fluctuated, which resulted in the pump being prone to cavitation. To improve cavitation resistance and hydraulic efficiency of liquid hydrogen centrifugal pumps, the model was optimized based on the genetic algorithm of MATLAB applying 7 parameters of impeller taken as optimization variables, each sub-objective function was given corresponding weights, and the optimal solution combination at the minimum of the objective function was finally obtained, and an inducer was matched. The results showed that by reducing the angle of the inlet, increasing the diameter of the impeller, and adding an inducer, the cavitation performance of the pump can be improved and the hydraulic loss can be reduced by appropriately reducing the impeller outlet diameter, to improve the head of the pump. A comparison of the performance of the preposition inducer optimized pump with the preliminary pump shows that, at the rated condition point, the head was increased by 4.6 m resulting in an efficiency of 43%. A numerical calculation considered the thermodynamic effect of non-isothermal cryogenic cavitation on the Reynolds-averaged Navier-Stokes combined with the k - ε turbulence model was applied for getting the pump hydrodynamic performances. It was proved that the multi-objective optimization method and preposition inducers were effective, and the calculating results were by experimental data well. Feasibility of the model had been validated to a certain extent. It can bring a high level of pump optimization, integration, and quality to new and existing designs. • A LH 2 centrifugal pump is optimized by the genetic algorithm of MATLAB. • LN 2 centrifugal pump performances are carried out on the cryogenic test platform. • Multi-objective optimization and inducers can improve the LH 2 centrifugal pump. • Numerical model is feasible and prediction performance of LH 2 centrifugal pumps. • Efficiency and anti-cavitation improvement are confirmed by experiments. [ABSTRACT FROM AUTHOR]

Main conclusion: Biphenyl and dibenzofuran phytoalexins are differentially distributed among species of the rosaceous subtribe Malinae, which includes apple and pear, and exhibit varying inhibitory activity against phytopathogenic microorganisms. Biphenyls and dibenzofurans are specialized metabolites, which are formed in species of the rosaceous subtribe Malinae upon elicitation by biotic and abiotic inducers. The subtribe Malinae (previously Pyrinae) comprises approximately 1000 species, which include economically important fruit trees such as apple and pear. The present review summarizes the current status of knowledge of biphenyls and dibenzofurans in the Malinae, mainly focusing on their role as phytoalexins. To date, 46 biphenyls and 41 dibenzofurans have been detected in 44 Malinae species. Structurally, 54 simple molecules, 23 glycosidic compounds and 10 miscellaneous structures were identified. Functionally, 21 biphenyls and 21 dibenzofurans were demonstrated to be phytoalexins. Furthermore, their distribution in species of the Malinae, inhibitory activities against phytopathogens, and structure–activity relationships were studied. The most widely distributed phytoalexins of the Malinae are the three biphenyls aucuparin (3), 2ʹ-methoxyaucuparin (7), and 4ʹ-methoxyaucuparin (9) and the three dibenzofurans α-cotonefuran (47), γ-cotonefuran (49), and eriobofuran (53). The formation of biphenyl and dibenzofuran phytoalexins appears to be an essential defense weapon of the Malinae against various stresses. Manipulating phytoalexin formation may enhance the disease resistance in economically important fruit trees. However, this approach requires an extensive understanding of how the compounds are formed. Although the biosynthesis of biphenyls was partially elucidated, formation of dibenzofurans remains largely unclear. Thus, further efforts have to be made to gain deeper insight into the distribution, function, and metabolism of biphenyls and dibenzofurans in the Malinae. [ABSTRACT FROM AUTHOR]

Autophagy plays a complex impact role in tumor initiation and development. It serves as a double-edged sword by supporting cell survival in certain situations while also triggering autophagic cell death in specific cellular contexts. Understanding the intricate functions and mechanisms of autophagy in tumors is crucial for guiding clinical approaches to cancer treatment. Recent studies highlight its significance in various aspects of cancer biology. Autophagy enables cancer cells to adapt to and survive unfavorable conditions by recycling cellular components. However, excessive or prolonged autophagy can lead to the self-destruction of cancer cells via a process known as autophagic cell death. Unraveling the molecular mechanisms underlying autophagy regulation in cancer is crucial for the development of targeted therapeutic interventions. In this review, we seek to present a comprehensive summary of current knowledge regarding autophagy, its impact on cancer cell survival and death, and the molecular mechanisms involved in the modulation of autophagy for cancer therapy. [ABSTRACT FROM AUTHOR]

This study investigated the effectiveness of nanoparticles and chemical inducers in managing onion white rot caused by Sclerotium cepivorum. The pathogen severely threatens onion cultivation, resulting in significant yield losses and economic setbacks. Traditional fungicides, though effective, raise environmental concerns, prompting a shift toward eco-friendly alternatives. In this study, four S. cepivorum isolates were utilized, each exhibiting varying degrees of pathogenicity, with the third isolate from Abu-Hamad demonstrating the highest potency. During the in vitro studies, three nanoparticles (NPs) were investigated, including Fe3O4 NPs, Cu NPs, and ZnO NPs, which demonstrated the potential to inhibit mycelial growth, with salicylic acid and Fe3O4 NPs exhibiting synergistic effects. In vivo, these nanoparticles reduced the disease incidence and severity, with Fe3O4 NPs at 1000–1400 ppm resulting in 65.0–80.0% incidence and 80.0–90.0% severity. ZnO NPs had the most positive impact on the chlorophyll content, while Cu NPs had minimal effects. At 1000 ppm, Fe3O4 NPs had variable effects on the phenolic compounds (total: 6.28, free: 4.81, related: 2.59), while ZnO NPs caused minor fluctuations (total: 3.60, free: 1.82, related: 1.73). For the chemical inducers, salicylic acid reduced the disease (10.0% incidence, 25.0% to 10.0% severity) and promoted growth, and it elevated the chlorophyll values and enhanced the phenolic compounds in infected onions. Potassium phosphate dibasic (PDP) had mixed effects, and ascorbic acid showed limited efficacy toward disease reduction. However, PDP at 1400 ppm and ascorbic acid at 1000 ppm elevated the chlorophyll values and enhanced the phenolic compounds. Furthermore, this study extended to traditional fungicides, highlighting their inhibitory effects on S. cepivorum. This research provides a comprehensive comparative analysis of these approaches, emphasizing their potential in eco-friendly onion white rot management.

Ferroptosis is a regular cell death pathway that has been proposed as a suitable therapeutic target in cancer and neurodegenerative diseases. Since its definition in 2012, a few hundred ferroptosis modulators have been reported. Based on a literature search, we collected a set of diverse ferroptosis modulators and analyzed them in terms of their structural features and physicochemical and drug-likeness properties. Ferroptosis modulators are mostly natural products or semisynthetic derivatives. In this review, we focused on the abundant subgroup of polyphenolic modulators, primarily phenylpropanoids. Many natural polyphenolic antioxidants have antiferroptotic activities acting through at least one of the following effects: ROS scavenging and/or iron chelation activities, increased GPX4 and NRF2 expression, and LOX inhibition. Some polyphenols are described as ferroptosis inducers acting through the generation of ROS, intracellular accumulation of iron (II), or the inhibition of GPX4. However, some molecules have a dual mode of action depending on the cell type (cancer versus neural cells) and the (micro)environment. The latter enables their successful use (e.g., apigenin, resveratrol, curcumin, and EGCG) in rationally designed, multifunctional nanoparticles that selectively target cancer cells through ferroptosis induction. [ABSTRACT FROM AUTHOR]

This investigation's goal is to assess the effectiveness of eco-friendly treatments, i.e., biocide Blight stop, three natural oil extracts: black seeds, thyme and eucalyptus oils, as well as fungicide Opus 12.5% Sc in reducing powdery mildew infection on susceptible Egyptian barley varieties. These treatments were carried out under greenhouse and field experiments conducted at Giza Experimental Station, Agricultural Research Centre (ARC), during the 2020/21 and 2021/22 growing seasons. All eco-friendly treatments and fungicide reduced disease severity percentage, area under the disease progress curve (AUDPC) and average coefficient of infection (ACI) compared to the control treatment in the two seasons, in addition to increasing yield, total chlorophyll and carotenoids compared to the control treatment. Spraying fungicide Opus provided the most effective treatments, followed by biocide-Blight stop. On the other hand, thyme oil was recorded as having the least effectiveness in comparison to the control treatment during both seasons. [ABSTRACT FROM AUTHOR]

Abstract At present, more than one cell death pathways have been found, one of which is ferroptosis. Ferroptosis was discovered in 2012 and described as an iron-dependent and lipid peroxidation-driven regulated cell death pathway. In the past few years, ferroptosis has been shown to induce tumor cell death, providing new ideas for tumor treatment. In this article, we summarize the latest advances in ferroptosis-induced tumor therapy at the intersection of tumor biology, molecular biology, redox biology, and materials chemistry. First, we state the characteristics of ferroptosis in cells, then introduce the key molecular mechanism of ferroptosis, and describes the relationship between ferroptosis and oxidative stress signaling pathways. Finally, we focused on several types of ferroptosis inducers discovered by scholars, and the application of ferroptosis in systemic chemotherapy, radiotherapy, immunotherapy and nanomedicine, in the hope that ferroptosis can exert its potential in the treatment of tumors.

P-glycoprotein (P-gp) is an important transmembrane ATP-binding cassette (ABC) drug efflux transporter expressed in various human tissues such as the intestines, liver, kidneys, and blood-brain barrier. It limits the intracellular concentration of xenobiotics by pumping them out of the cells, affecting drug pharmacokinetics and therapeutic effects. With its broad substrate specificity, it has the potential to remove a wide range of drugs from Chinese materia medica (CMM), including conventional medicines and active compounds. Increasing evidence hasconfirmed the superior therapeutic effectiveness of CMM in treating a wide range of diseases worldwide, as well as in conjunction with western drugs. As a result, herbal medicine-drug compounds have prompted widespread concern, with the majority of these interactions involving transporters such as P-gp. This review systematically summarizes the inhibition or induction of P-gp expression/function by active CMM compounds and the underlying regulatory mechanisms. It will aid in improving understanding of the synergistic or inhibiting effects associated with transporter P-gp as well as rational safety concerns for using CMM, particularly in combination with drugs.

Biomolecular condensates are compartmentalized communities of biomolecules, which unlike traditional organelles, are not enclosed by membranes. Condensates play roles in diverse cellular processes, are dysfunctional in many disease states, and are often enriched in classically “undruggable” targets. In this review, we provide an overview for how drugs can modulate condensate structure and function by phenotypically classifying them as dissolvers (dissolve condensates), inducers (induce condensates), localizers (alter localization of the specific condensate community members) or morphers (alter the physiochemical properties). We discuss the growing list of bioactive molecules that function as condensate modifiers (c-mods), including small molecules, oligonucleotides, and peptides. We propose that understanding mechanisms of condensate perturbation of known c-mods will accelerate the discovery of a new class of therapies for difficult-to-treat diseases.

Adaptation and microbial attachment mechanisms for the degradation of sulfide ores are mediated by the production of extracellular polymeric substances (EPS) and their role in biofilm formation. EPS production responds to induction mechanisms associated with environmental conditions. In this study, the double induction of EPS with galactose and high ferric iron concentrations in planktonic cells of Acidithiobacillus ferrooxidans, and their attachment on the surface of a polymetallic sulfide ore from Bella Rica-Azuay in Ecuador were evaluated. A. ferrooxidans cells were previously adapted to different concentrations of galactose [0, 0.15, and 0.25% (w/v)], using two ferrous iron concentrations as an energy source (9 and 18 g L-1) in a 9K culture medium. EPS production and its effect on mineral attachment were determined at the time point of maximal growth. The results obtained show a maximum cell attachment of 94.1% within 2 h at 0.15% of galactose and 18 g·L-1 of ferric iron concentration, compared to 71.4% without galactose and 9 g·L-1 of ferric iron. The maximum concentration of EPS was obtained with a 0.25% galactose concentration; however, it did not result in greater attachment compared to 0.15% galactose concentration. Through the combined induction of low galactose concentration and high ferric iron concentration, the percentage of bacterial attachment can be increased and, therefore, a possible increase in the rate of biooxidation and bioleaching could be obtained. [ABSTRACT FROM AUTHOR]

The current work evaluates the production of ligninolytic enzyme optimization via response surface methodology using different inducers: acid cellulignin (CA); MnSO4 (Mn2+); CuSO4·5H2O (Cu2+); veratryl (3, 4-dimethoxybenzyl); alcohol (VA); Tween 80% (T80); and the carbon-to-nitrogen ratio (C/N). A further goal was implementing a fed-batch strategy to produce ligninolytic enzyme extracts from P. sanguineus 2512 using a bubble column reactor (BCR). The best optimized experimental condition in the shake flasks was a 7.5 C/N ratio, 0.025 g/L Cu2+, 1.5 mM Mn2+, 3.0 mM VA and 0.025 mM T80, resulting in 64,580, 9.10 and 80.72 U/L for Laccase (Lac), Manganese (MnP) and Lignin peroxidase (LiP) activities, respectively. In the BCR, three feedings were performed at 24 h intervals on the 6th, 7th and 8th days with a significant increase in Lac (99,600 U/L) and MnP (47.53 U/L) activities on the 8th day and a reduction on the 9th day of cultivation. The LiP activity peak was achieved on the 5th day (416 U/L) of cultivation, decreasing thereafter. Enzyme cocktails concentrated in hollow fiber in the third cultivation batch showed contents of 4 × 105 U/L, 220 U/L and 2.5 g/L for Lac, MnP and total proteins, respectively. The enzymatic cocktail with the highest LiP activity (1200 U/L) was obtained in the first batch. The results showed that the optimization of the biosynthesis of the ligninolytic enzymes provided satisfactory improvement in terms of Lac and MnP production per run. [ABSTRACT FROM AUTHOR]

Adaptation and microbial attachment mechanisms for the degradation of sulfide ores are mediated by the production of extracellular polymeric substances (EPS) and their role in biofilm formation. EPS production responds to induction mechanisms associated with environmental conditions. In this study, the double induction of EPS with galactose and high ferric iron concentrations in planktonic cells of Acidithiobacillus ferrooxidans, and their attachment on the surface of a polymetallic sulfide ore from Bella Rica-Azuay in Ecuador were evaluated. A. ferrooxidans cells were previously adapted to different concentrations of galactose [0, 0.15, and 0.25% (w/v)], using two ferrous iron concentrations as an energy source (9 and 18 g L–1) in a 9K culture medium. EPS production and its effect on mineral attachment were determined at the time point of maximal growth. The results obtained show a maximum cell attachment of 94.1% within 2 h at 0.15% of galactose and 18 g⋅L–1 of ferric iron concentration, compared to 71.4% without galactose and 9 g⋅L–1 of ferric iron. The maximum concentration of EPS was obtained with a 0.25% galactose concentration; however, it did not result in greater attachment compared to 0.15% galactose concentration. Through the combined induction of low galactose concentration and high ferric iron concentration, the percentage of bacterial attachment can be increased and, therefore, a possible increase in the rate of biooxidation and bioleaching could be obtained.

Autophagy plays a complex impact role in tumor initiation and development. It serves as a double-edged sword by supporting cell survival in certain situations while also triggering autophagic cell death in specific cellular contexts. Understanding the intricate functions and mechanisms of autophagy in tumors is crucial for guiding clinical approaches to cancer treatment. Recent studies highlight its significance in various aspects of cancer biology. Autophagy enables cancer cells to adapt to and survive unfavorable conditions by recycling cellular components. However, excessive or prolonged autophagy can lead to the self-destruction of cancer cells via a process known as autophagic cell death. Unraveling the molecular mechanisms underlying autophagy regulation in cancer is crucial for the development of targeted therapeutic interventions. In this review, we seek to present a comprehensive summary of current knowledge regarding autophagy, its impact on cancer cell survival and death, and the molecular mechanisms involved in the modulation of autophagy for cancer therapy.

The term ferroptosis refers to a peculiar type of programmed cell death (PCD) mainly characterized by extensive iron-dependent lipid peroxidation. Recently, ferroptosis has been suggested as a potential new strategy for the treatment of several cancers, including breast cancer (BC). In particular, among the BC subtypes, triple negative breast cancer (TNBC) is considered the most aggressive, and conventional drugs fail to provide long-term efficacy. In this context, our study's purpose was to investigate the mechanism of ferroptosis in breast cancer cell lines and reveal the significance of heme oxygenase (HO) modulation in the process, providing new biochemical approaches. HO's effect on BC was evaluated by MTT tests, gene silencing, Western blot analysis, and measurement of reactive oxygen species (ROS), glutathione (GSH) and lipid hydroperoxide (LOOH) levels. In order to assess HO's implication, different approaches were exploited, using two distinct HO-1 inducers (hemin and curcumin), a well-known HO inhibitor (SnMP) and a selective HO-2 inhibitor. The data obtained showed HO's contribution to the onset of ferroptosis; in particular, HO-1 induction seemed to accelerate the process. Moreover, our results suggest a potential role of HO-2 in erastin-induced ferroptosis. In view of the above, HO modulation in ferroptosis can offer a novel approach for breast cancer treatment. [ABSTRACT FROM AUTHOR]

Laccases are one of many groups of inducible enzymes produced by the filamentous fungus, Botrytis cinerea during colonisation of host plant tissues. While the processes involved in laccase induction are not fully understood, Cupric ions (e.g. CuSO4) and gallic acid (GA) have been reported as laccase inducers. This study investigates laccases activities and the expression of three laccase genes (BcLCC1, BcLCC2, BcLCC3) in three B. cinerea isolates grown in laccase-inducing medium (LIM) supplemented with CuSO4 and GA. Laccase activity in culture filtrates with CuSO4 increased after 48 h of growth in LIM at 24°C. The induction of BcLCC2 transcription was greatest at a concentration of 0.6 mM CuSO4, concentrations greater than 0.6 mM inhibited fungal growth. In contrast, no laccase induction was observed in the presence of GA. Liquid chromatography-mass spectroscopy (NanoLC ESI MS/MS) analysis confirmed the presence of a 63.4 kDa protein, the BcLCC2 isoform in the culture filtrate with 0.6 mM CuSO4. Analysis of mRNA transcripts further showed BcLCC3 was also inducible and the expression of BcLCC2 and BcLCC3 was isolate-dependent. In conclusion, CuSO4 induces a 63.4 kDa laccase in B. cinerea by induced transcription of the BcLCC2 gene.

Ferroptosis is a regular cell death pathway that has been proposed as a suitable therapeutic target in cancer and neurodegenerative diseases. Since its definition in 2012, a few hundred ferroptosis modulators have been reported. Based on a literature search, we collected a set of diverse ferroptosis modulators and analyzed them in terms of their structural features and physicochemical and drug-likeness properties. Ferroptosis modulators are mostly natural products or semisynthetic derivatives. In this review, we focused on the abundant subgroup of polyphenolic modulators, primarily phenylpropanoids. Many natural polyphenolic antioxidants have antiferroptotic activities acting through at least one of the following effects: ROS scavenging and/or iron chelation activities, increased GPX4 and NRF2 expression, and LOX inhibition. Some polyphenols are described as ferroptosis inducers acting through the generation of ROS, intracellular accumulation of iron (II), or the inhibition of GPX4. However, some molecules have a dual mode of action depending on the cell type (cancer versus neural cells) and the (micro)environment. The latter enables their successful use (e.g., apigenin, resveratrol, curcumin, and EGCG) in rationally designed, multifunctional nanoparticles that selectively target cancer cells through ferroptosis induction.

At present, more than one cell death pathways have been found, one of which is ferroptosis. Ferroptosis was discovered in 2012 and described as an iron-dependent and lipid peroxidation-driven regulated cell death pathway. In the past few years, ferroptosis has been shown to induce tumor cell death, providing new ideas for tumor treatment. In this article, we summarize the latest advances in ferroptosis-induced tumor therapy at the intersection of tumor biology, molecular biology, redox biology, and materials chemistry. First, we state the characteristics of ferroptosis in cells, then introduce the key molecular mechanism of ferroptosis, and describes the relationship between ferroptosis and oxidative stress signaling pathways. Finally, we focused on several types of ferroptosis inducers discovered by scholars, and the application of ferroptosis in systemic chemotherapy, radiotherapy, immunotherapy and nanomedicine, in the hope that ferroptosis can exert its potential in the treatment of tumors. [ABSTRACT FROM AUTHOR]

3β, 7α, 15α-Trihydroxyandrost-5-en-17-one (7α, 15α-diOH-DHEA) is a key intermediate in the synthesis of drospirenone, the active ingredient of female oral contraceptive " Yasmin". In order to increase the molar yield of the target product 7α, 15α-diOH-DHEA, we studied the effect of cytochrome P450 (CYP450) inducers on the biotransformation of dehydroepiandrosterone (DHEA) to 7α, 15α-diOH-DHEA by Gibberella intermedia CA3-1 was investigated. Results show that as the inducers of CYP450, hexane, DHEA and benzene could significantly increase the molar yield of 7α, 15α-diOH-DHEA. Among them, benzene was the best inducer. On the basis of the above work, an induction process was established as follows; the seed culture that entered the rapid growth period (inoculation for 24 h) was inoculated into a fresh transformation medium at 10% inoculation amount. Benzene 0. 8% (V/V) was added for induction after 12 h of transformation, and then 8 g/L of DHEA was added to the transformation medium at the end of the logarithmic period (transformation for 24 h). With the above induction conditions, biotransformation was carried out in a 5-L fermenter. Compared with the process without the addition of benzene, the content of CYP450 was increased by 43%, the molar yield of 7α, 15α-diOH-DHEA reached 68. 7%±1. 37%,and the conversion period was shortened by 8 h. Our findings provede for a basis for the industrial production of 7α, 15α-diOH-DHEA. [ABSTRACT FROM AUTHOR]

Protein dimerization plays a key role in many biological processes. Most cellular events such as enzyme activation, transcriptional cofactor recruitment, signal transduction, and even pathogenic pathways are significantly regulated via protein-protein interactions. Understanding and controlling the molecular mechanisms that regulate protein dimerization is crucial for biomedical applications. The limitations of engineered protein dimerization provide an opportunity for molecular chemistry to induce dimerization of protein in biological events. In this review, molecular control over dimerization of protein and activation in this respect are discussed. The well known molecule glue-based approaches to induced protein dimerization provide powerful tools to modulate the functionality of dimerized proteins and are shortly highlighted. Subsequently metal ion, nucleic acid and host-guest chemistry are brought forward as novel approaches for orthogonal control over dimerization of protein. The specific focus of the review will be on host-guest systems as novel, robust and versatile supramolecular approaches to modulate the dimerization of proteins, using functional proteins as model systems.

Necroptosis, a genetically programmed form of necrotic cell death, serves as an important pathway in human diseases. As a critical cell-killing mechanism, necroptosis is associated with cancer progression, metastasis, and immunosurveillance. Targeting necroptosis pathway by small molecule modulators is emerging as an effective approach in cancer therapy, which has the advantage to bypass the apoptosis-resistance and maintain antitumor immunity. Therefore, a better understanding of the mechanism of necroptosis and necroptosis modulators is necessary to develop novel strategies for cancer therapy. This review will summarize recent progress of the mechanisms and detecting methods of necroptosis. In particular, the relationship between necroptosis and cancer therapy and medicinal chemistry of necroptosis modulators will be focused on.

Introduction Luteolin is one of the most important flavonoids, which release from seeds during the first four hours of imbibition. On the other hand, at present, salinity is one of the most important factors in reducing crop production. The results of some studies show that the use of external flavonoids increases expression of nod genes, yield and nodulation in some legumes species under stress conditions. Therefore, this experiment was conducted with the aim of investigating the effect of luteolin and alfalfa seed exudates external inducers on the expression of Rhizobium nod gene and the yield and nodulation of alfalfa in normal and salinity condition. Materials and Methods We studied the effect of luteolin on the induction of nod genes in R. Meliloti carrying a plasmid with a translational fusion between R. Meliloti nodA and lacZ of Escherichia coli, and the expression activity was measured by β-galactosidase activity. Luteolin strongly induced the expression of nod genes inhibitory effects. We further studied the effect of luteolin and Seed exudate on alfalfa (Medicago sativa L.) yield and nodulation under optimal and salinity condition. One greenhouse was conducted to determine whether the pre-incubation of Rhizobium meliloti with luteolin and application of luteolin and seed exudate directly on to the seed surface can increase alfalfa nodulation and yield. The factorial experiment was arranged based on randomized complete block design, with three replications. Treatments were two cultivars, two bacterial strains (Sensitive and resistant strains), two levels of salt (0 and 15 dS.m-1 of NaCl) and two levels of application of inducers along with control. Results and Discussion The results from this experiment clearly indicated that inoculation of alfalfa seeds with luteolin and seed exudate increase alfalfa nodulation (47%) and yield (30%) significantly under salinity condition that these treats affect on traits more under normal condition. But significant effect was not observed on chlorophyll content. In this experiment a significant difference was not observed between the control and pre-incubation of R. meliloti. Also, salinity increased proline four times compared to normal condition. Luteolin and seed exudates increased proline 1.66 and 1.35 times respectively in salinity condition, but under normal condition they did not have significant effect. Salinity increased the content of sodium in the leaves (7 times) and roots (8.5 times) and decreased the content of potassium 29% and 24% in these organs of the plant, respectively, that, luteolin and seed exudate partially moderated these changes. Conclusions The results of this experiment indicated that luteolin and seed exudate can be used as exogenous inducers to improve the growth and nodulation of alfalfa under salinity and normal condition. Flavonoid inducers act in low concentration, and their negative effects relate to reduced germination and growth. In general, it seems that the application of flavonoid inducers is more suitable to improve nodulation, but the direct application of them in agriculture should be used only in specified cases and when flavonoids are as a limiting factor.

Immunotherapy has emerged as a promising cancer treatment option in recent years. In immune "hot" tumors, characterized by abundant immune cell infiltration, immunotherapy can improve patients' prognosis by activating the function of immune cells. By contrast, immune "cold" tumors are often less sensitive to immunotherapy owing to low immunogenicity of tumor cells, an immune inhibitory tumor microenvironment, and a series of immune-escape mechanisms. Immunogenic cell death (ICD) is a promising cellular process to facilitate the transformation of immune "cold" tumors to immune "hot" tumors by eliciting innate and adaptive immune responses through the release of (or exposure to) damage-related molecular patterns. Accumulating evidence suggests that various traditional therapies can induce ICD, including chemotherapy, targeted therapy, radiotherapy, and photodynamic therapy. In this review, we summarize the biological mechanisms and hallmarks of ICD and introduce some newly discovered and technologically innovative inducers that activate the immune system at the molecular level. Furthermore, we also discuss the clinical applications of combing ICD inducers with cancer immunotherapy. This review will provide valuable insights into the future development of ICD-related combination therapeutics and potential management for "cold" tumors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Han, Tian, Zhai and Zhang.)

Human cytochrome P450 enzymes (CYPs) are heme-containing monooxygenases. This superfamily of drug-metabolizing enzymes is responsible for the metabolism of most drugs and other xenobiotics. The inhibition of CYPs may lead to drug–drug interactions and impair the biotransformation of drugs. CYP inducers may decrease the bioavailability and increase the clearance of drugs. Based on the freely available databases ChEMBL and PubChem, we have collected over 70,000 records containing the structures of inhibitors and inducers together with the IC50 values for the inhibitors of the five major human CYPs: 1A2, 3A4, 2D6, 2C9, and 2C19. Based on the collected data, we developed (Q)SAR models for predicting inhibitors and inducers of these CYPs using GUSAR and PASS software. The developed (Q)SAR models could be applied for assessment of the interaction of novel drug-like substances with the major human CYPs. The created (Q)SAR models demonstrated reasonable accuracy of prediction. They have been implemented in the web application P450-Analyzer that is freely available via the Internet.

The current work evaluates the production of ligninolytic enzyme optimization via response surface methodology using different inducers: acid cellulignin (CA); MnSO4 (Mn2+); CuSO4·5H2O (Cu2+); veratryl (3, 4-dimethoxybenzyl); alcohol (VA); Tween 80% (T80); and the carbon-to-nitrogen ratio (C/N). A further goal was implementing a fed-batch strategy to produce ligninolytic enzyme extracts from P. sanguineus 2512 using a bubble column reactor (BCR). The best optimized experimental condition in the shake flasks was a 7.5 C/N ratio, 0.025 g/L Cu2+, 1.5 mM Mn2+, 3.0 mM VA and 0.025 mM T80, resulting in 64,580, 9.10 and 80.72 U/L for Laccase (Lac), Manganese (MnP) and Lignin peroxidase (LiP) activities, respectively. In the BCR, three feedings were performed at 24 h intervals on the 6th, 7th and 8th days with a significant increase in Lac (99,600 U/L) and MnP (47.53 U/L) activities on the 8th day and a reduction on the 9th day of cultivation. The LiP activity peak was achieved on the 5th day (416 U/L) of cultivation, decreasing thereafter. Enzyme cocktails concentrated in hollow fiber in the third cultivation batch showed contents of 4 × 105 U/L, 220 U/L and 2.5 g/L for Lac, MnP and total proteins, respectively. The enzymatic cocktail with the highest LiP activity (1200 U/L) was obtained in the first batch. The results showed that the optimization of the biosynthesis of the ligninolytic enzymes provided satisfactory improvement in terms of Lac and MnP production per run.

Field study was conducted to evaluate the capability of two neonicotinoids as seed treatment to alleviate the negative effects of water deficit on cotton plants. The effect of water-deficit reflected in a significant decrease in plant height, leaf area, chlorophyll content index, photosynthesis (parameter Fv/Fm), also a significant induction in antioxidant enzyme activity and proline content was obtained, while Protein content was slightly changed. A reduction ranged between 38.7-44.1 in the obtained seed cotton/plant occurred as a result of water-deficit. The two neonicotinoids had a phytotonic effect on the cotton plant with a significant increase in both morphological and physiological parameters. A reduction in antioxidant enzymes activity and proline content was observed with the two compounds. Both of them succeeded to maintain cotton yield stability (less than 7% reduction) under water-deficit condition (19.4%). The results reflected the capability of the tested neonicotinoids to mitigate the adverse effects of water deficit on cotton plant. [ABSTRACT FROM AUTHOR]

This review addresses the function of the protein-transporter glycoprotein-P (Pgp, ABCB1 protein) and the expression of its encoding gene MDR1/mdr1 throughout the gestational period in humans and animals. We discuss the relationship between the transporter function and the hormone fluctuations during pregnancy. We cite studies on the association between the MDR1/mdr1 gene polymorphisms and the hemato-placental barrier permeability for Pgp substrates, as well as fetal malformations. Under a separate section, drugs commonly used in pregnant women are characterized in terms of their roles as substrates, inducers or inhibitors of the Pgp transporter.

Autophagy is a process that degrades and recycles superfluous organelles or damaged cellular contents. It has been found to have dual functions in renal cell carcinoma (RCC). Many autophagy-related proteins are regarded as prognostic markers of RCC. Researchers have attempted to explore synthetic and phytochemical drugs for RCC therapy that target autophagy. In this review, we highlight the importance of autophagy in RCC and potential treatments related to autophagy.

Laccases are one of many groups of inducible enzymes produced by the filamentous fungus, Botrytis cinerea during colonisation of host plant tissues. While the processes involved in laccase induction are not fully understood, Cupric ions (e.g. CuSO4) and gallic acid (GA) have been reported as laccase inducers. This study investigates laccases activities and the expression of three laccase genes (BcLCC1, BcLCC2, BcLCC3) in three B. cinerea isolates grown in laccase-inducing medium (LIM) supplemented with CuSO4 and GA. Laccase activity in culture filtrates with CuSO4 increased after 48 h of growth in LIM at 24°C. The induction of BcLCC2 transcription was greatest at a concentration of 0.6 mM CuSO4, concentrations greater than 0.6 mM inhibited fungal growth. In contrast, no laccase induction was observed in the presence of GA. Liquid chromatography-mass spectroscopy (NanoLC ESI MS/MS) analysis confirmed the presence of a 63.4 kDa protein, the BcLCC2 isoform in the culture filtrate with 0.6 mM CuSO4. Analysis of mRNA transcripts further showed BcLCC3 was also inducible and the expression of BcLCC2 and BcLCC3 was isolate-dependent. In conclusion, CuSO4 induces a 63.4 kDa laccase in B. cinerea by induced transcription of the BcLCC2 gene. [ABSTRACT FROM AUTHOR]

Background/aim: Ferroptosis refers to an iron-dependent mechanism of regulated cell death that is attributable to lipid peroxidation. Ferroptosis has been documented as a therapeutic target for various solid cancers; nonetheless, its implication in leukemia remains ambiguous. Therefore, this study aimed at investigating the impact of ferroptosis inducers and inhibitors on in vitro leukemia cell line proliferation., Materials and Methods: Six leukemia cell lines, including acute myeloid leukemia (AML)-derived MV4-11, THP-1, HL-60, and U-937, and T-lymphoblastic leukemia (T-ALL)-derived Jurkat and KOPT-K1 with activating NOTCH1 mutations, were assessed. Erastin, which interrupts cystine uptake and depletes intracellular glutathione, and RAS-selective lethal 3 (RSL3), which suppresses glutathione peroxidase 4 (GPX4), were employed as ferroptosis inducers. Lipid peroxidation-arresting ferrostatin-1 and deferoxamine were used as ferroptosis inhibitors. Cells were cultured with these compounds and cell proliferation was assessed using a colorimetric assay. Additionally, signaling protein expression was monitored using immunoblotting, and the outcome of GPX4 knockdown was evaluated., Results: Ferroptosis inducers suppressed proliferation in all cell lines except THP-1 for Erastin and THP-1 and Jurkat for RSL3. Although the ferroptosis inhibitors did not affect cell proliferation, they rescued inducer-mediated growth suppression. Ferroptosis inducers impeded MYC and cyclin D3 expression in certain cell lines and NOTCH1 signaling in T-ALL cells. GPX4 knockdown and RSL3 treatment interrupted MYC and cyclin D3 expression, respectively, in four cell lines., Conclusion: Ferroptosis inducers may serve as potential candidates for novel molecular therapy against AML and T-ALL., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Ferroptosis, a newly described type of iron-dependent programmed cell death that is distinct from apoptosis, necroptosis, and other types of cell death, is involved in lipid peroxidation (LP), reactive oxygen species (ROS) production, and mitochondrial dysfunction. Accumulating evidence has highlighted vital roles for ferroptosis in multiple diseases, including acute kidney injury, cancer, hepatic fibrosis, Parkinson’s disease, and Alzheimer’s disease. Therefore, ferroptosis has become one of the research hotspots for disease treatment and attracted extensive attention in recent years. This review mainly summarizes the relationship between ferroptosis and various diseases classified by the system, including the urinary system, digestive system, respiratory system, nervous system. In addition, the role and molecular mechanism of multiple inhibitors and inducers for ferroptosis are further elucidated. A deeper understanding of the relationship between ferroptosis and multiple diseases may provide new strategies for researching diseases and drug development based on ferroptosis.

Necroptosis, a genetically programmed form of necrotic cell death, serves as an important pathway in human diseases. As a critical cell-killing mechanism, necroptosis is associated with cancer progression, metastasis, and immunosurveillance. Targeting necroptosis pathway by small molecule modulators is emerging as an effective approach in cancer therapy, which has the advantage to bypass the apoptosis-resistance and maintain antitumor immunity. Therefore, a better understanding of the mechanism of necroptosis and necroptosis modulators is necessary to develop novel strategies for cancer therapy. This review will summarize recent progress of the mechanisms and detecting methods of necroptosis. In particular, the relationship between necroptosis and cancer therapy and medicinal chemistry of necroptosis modulators will be focused on. Targeting necroptosis pathway by small molecule modulators is emerging as an effective approach in cancer therapy Image 1. [ABSTRACT FROM AUTHOR]

The induction of resistance (IR) in plants by natural products has been the subject of several studies, these being activated by eliciting molecules of biotic or abiotic origin. Elicitors activate resistance mechanisms such as pathogenesis-related proteins (PRP's), which act to protect plants by preventing pathogen development. The present study aims to verify the activation of PRP's (peroxidase, catalase, polyphenoloxidase and β-glucanase) in pyre corn plants (Zea mays) treated with different concentrations (0%, 0.5%, 1%, 1.5%, 3% and 5%) of the commercial biofertilizer Microgeo®. Analyzing the PRP's enzymes, it was observed that the Microgeo® activated and increased the activity of these enzymes and that this induction is more related to the activation time, but not to the concentration used. [ABSTRACT FROM AUTHOR]

As well as cellulose and hemicelluloses, rice straw contains phenolic acids. The simultaneous production of monosaccharides and phenolic acids could improve the value of rice straw. In this study, it was confirmed that Penicillium decumbens produces more ferulic acid esterase (FAE) than other cellulase-producing fungi. Cellulose, destarched wheat bran (DSWB), and rice straw were used as carbon sources. Little phenolic acid was released by cellulose- and DSWB-based enzymes during the saccharification of rice straw, whereas rice straw was a favorable carbon source for the simultaneous production of cellulase and FAE. High-performance liquid chromatography showed that during enzyme production, phenolic acids were released from rice straw, and ball-milling affected this release of phenolic acids. Small amounts of phenolic acids induced FAE production. Although the enzymes produced with rice straw showed lower FAE activity than those produced with DSWB, phenolic acids were produced efficiently during the saccharification of rice straw in response to the synergistic effects of cellulase and FAE. Therefore, we suggest that the production of enzymes by P. decumbens on rice straw as the sole carbon source will allow the production of more valuable products from rice straw, making the utilization of rice straw more economic. Image 1 [ABSTRACT FROM AUTHOR]

Cell lysate of Escherichia coli strain BL21 showed significant D-glucose isomerase activity. The rate of glucose conversion was increased up to 40% when cells were induced with 1% D-xylose. E. coli BL21 xylose isomerase (ECXI-BL21) was purified to homogeneity, up to 1.9-fold with overall 10.88% enzyme yield by heat shock, salting out and electro-elution. The molecular mass of ECXI-BL21 was estimated as 43.9 kDa on SDS-PAGE. pHopt. and Topt. of the enzyme were calculated as 7.0 and 50 °C, respectively. Activation energy (Ea) of ECXI-BL21 was 45 kJ/mol. Enzyme was stable from 30 to 55 °C and at pH range 6.0–8.0. ECXI-BL21(holo) was activated by 10 mM magnesium (35%), 0.5 mM cobalt (20%) and manganese (25%), and 0.5/10 mM Mn2+/Mg2+ (50%) and Co2+/Mg2+ (30%) as compared to ECXI-BL21(apo). Catalytic affinity (Km) of ECXI-BL21 for D-glucose was calculated as 0.82 mM, while maximum velocity (Vmax) of the reaction D-glucose(aldo) ⇌ D-fructose(keto) was 108 μmol/mg/min. D-fructose formed was identified on silica gel plate. This thermophilic enzyme, Tm = 75 °C, has great potential for high fructose syrup production used in food and soft drink industries. [ABSTRACT FROM AUTHOR]

The present investigation deals with the purification of extracellular tyrosinase produced by Trichoderma reesei and Trichoderma harzianum and the characterization of putative inducers and inhibitors on the enzyme activity. Tyrosinase enzyme from T. reesei and T. harzianum was purified to homogeneity using ammonium sulphate precipitation (85%) followed by DEAE-cellulose, and phenyl Sepharose. SDS-PAGE exhibited a single band of 45 and 65 kDa for the purified tyrosinase from T. reesei and T. harzianum, respectively. The influence of guaiacol, catechol, vanillin, caffeic acid, syringaldazine and p-coumaric acid on purified enzyme was tested. Tyrosinase produced by the two Trichoderma species displayed a dose-dependent response toward all tested inducers. The effect of kojic acid, cinnamic acid, sodium azide, benzaldehyde and potassium cyanide was assayed at pH 5.0 in presence of monophenolic substrate (p-coumaric acid) and diphenolic substrate (caffeic acid). KCN and kojic acid were the powerful inhibitors on the tyrosinase-monophenolase and diphenolase activities from the investigated Trichoderma, respectively. The rate of tyrosinase activity showed a pseudo-firstorder reaction kinetics and was proportional to the inhibitor concentration. The results reveal the possibility of using the inducers of tyrosinase to increase its activity. [ABSTRACT FROM AUTHOR]

Objective: To estimate associations between contraceptive failures and concomitant CYP3A4-inducing medications by route of administration.Study Design: Comparison of unintended pregnancy outcomes within U.S. Food and Drug Administration's Adverse Event Reporting System by couse of CYP3A4-inducing drugs and route of administration for levonorgestrel and etonogestrel/desogestrel.Results: Among 14,504 levonorgestrel case reports, the reporting odds ratio (ROR) was increased for oral (ROR = 4.2 [3.0-5.7]), implants (ROR = 8.0 [5.8-11.0]), but not intrauterine (ROR = 0.9 [0.6-1.3]) levonorgestrel products. For 9348 etonogestrel/desogestrel case reports, oral and vaginal products were not associated with contraceptive failure. Etonogestrel containing implants (ROR = 4.9 [4.1-5.9]) were associated with increased contraceptive failure.Conclusion: Levonorgestrel containing combination oral products and implants containing levonorgestrel or etonogestrel were prone to CYP3A4-inducing drug-drug interactions that may increase contraceptive failures.Implications: The progestin components of hormonal contraceptives are susceptible to drug-drug interactions, but this susceptibility is influenced by route of administration. This study provides evidence from an Adverse Event Reporting System that CYP3A4-inducing medications increase the risk of unintended pregnancy for oral and implant contraceptives but not intrauterine or vaginal devices. [ABSTRACT FROM AUTHOR]

Sugarcane crop is important to sugar-energy industry. Thus, the aim of this study was to evaluate yield and technological quality of Sugarcane juice obtained from the SP81-3250 variety following exogenous spraying of resistance inducers. The experiment consisted of a randomized block design with four replicates per treatment: salicylic acid (0, 5, 10, 20, and 40 µM) and acibenzolar-S-methyl (0, 0.2, 0.4, 0.8 and 1.6 g 100 L-1). The resistance inducers were sprayed using CO2-pressurized sprayer. Sugarcane tillage was harvested thirty-days after the spraying of resistance inducers and stalks were milled for juice samples extraction, in which were evaluated the following parameters: °Brix, Pol, purity, reducing sugars (RS), total reducing sugars (TRS), theoretical sugar recoverable (TSR), fi bres and yields of sugar and stalks. Obtained data was submitted to following statistical tests (P < 0.05): Shapiro-Wilk's normality, Fisher's variance, regression, and Pearson's linear correlation. Results showed that quadratic trends rejected null hypothesis for almost all parameters. Salicylic acid levels till 10 µM increased °Brix, Pol, purity, TRS, TSR contents and sugar and stalks yield. However, 20 and 40 µM showed negative effects on juice technological quality and agronomic performance. Therefore, the elicitors improved photosynthetic characteristics and sugarcane physiological maturation. It was concluded that salicylic acid and acibenzolar-S-methyl levels till 10 µM and 0.8 g 100 L-1, respectively, are recommendable to management of SP81-3250 variety. [ABSTRACT FROM AUTHOR]

Little is known regarding the management of direct oral anticoagulants (DOACs) in patients with enzyme-inducing drugs (EID). The use of EID may lead to sub-therapeutic concentrations of DOACs and to treatment failure. Thus, many patients on EIDs cannot benefit from the advantages of DOACs. This was a retrospective study, evaluating the management of hospitalized patients with DOACs. Characteristics of hospitalized patients with a prescription for DOACs, with and without EIDs, were summarized and evaluated, and management strategies addressing the potential interaction were documented, including the use of DOAC concentration monitoring. During the period evaluated, 1596 hospitalized patients with prescriptions for DOACs were identified. Most patients received apixaban (n = 1227, 77%), followed by rivaroxaban (240, 15%), and dabigatran (129, 8%). Twenty-two patients (1.4%) had concomitant EIDs. Demographic and clinical characteristics of hospitalized patients with DOACs were similar in those receiving EID and those not. Management strategies included stopping DOAC or EID (41%), and DOAC dose increase (14%). During management of these interactions, DOAC concentrations were measured for 11 of 22 patients and were below the 5th percentile of expected concentration for six of these patients. The management of patients with DOAC concentration measurement differed significantly from those without (p = 0.005), as they were much less likely to have one of the medications stopped and more often had the DOACs' dose increased. Among hospitalized patients with DOACs, EIDs are not rare. DOAC concentrations are often low in the presence of EIDs. DOAC concentration monitoring may be useful in settings requiring both DOAC and EIDs. [ABSTRACT FROM AUTHOR]

A high incidence of positive results is obtained with in vitro genotoxicity tests, which do not correlate with the in vivo negative results in many cases. To address this issue, the metabolic profile of rat liver 9000 × g supernatant fraction (S9) pretreated with phenobarbital (PB) and 5,6-benzoflavone (BNF) was characterized. Furthermore, the in vitro micronucleus tests of 10 compounds were performed with PB-BNF-induced rat S9. PB-BNF increased cytochrome P450 (CYP) activity and CYP1A1, CYP1A2, CYP2B1/2, CYP2C6, CYP3A1, and CYP3A2 expression in rat S9, whereas it decreased CYP2C11 and CYP2E1 expression. PB-BNF-induced S9 enhanced the micronucleus induction (MI) of benzo[a]pyrene (BaP), cyclophosphamide (CPA), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine hydrochloride (PhIP), which are metabolized by CYP1A1, CYP2C6, and CYP1A2, respectively. In contrast, coumarin and chlorpheniramine showed MI with PB-BNF-induced S9 despite the fact that they show negative results in the in vivo studies. Furthermore, diclofenac, piroxicam, lansoprazole, and caffeine showed MI regardless of the enzyme induction by PB-BNF, whereas phenacetin did not show MI. These results indicate that PB-BNF-induced rat S9 is effective in detecting the genotoxic potential of promutagens, such as BaP, CPA, and PhIP, but not of coumarin and chlorpheniramine, probably due to the differences in the in vitro and in vivo metabolic profile and its exposure levels of the drugs. [ABSTRACT FROM AUTHOR]