Synergetic effects of sericin and turmeric on burn wound healing in mice.

Burn wounds are one of the most hazardous issues globally. Silkworm produces a protein called sericin. Sericin assists in wound healing by facilitating the proliferation of keratinocytes and fibroblasts while turmeric is potentially helpful in wound healing because of its antioxidant, anti-inflammatory, and anti-infectious activities. The current study aimed to investigate the synergetic and individual effects of turmeric, sericin, and their nanoparticles on burn wounds in mice. The female mice of 2 months of age (each weighing 29-30 g) were arbitrarily distributed in seven groups. Five mice were added to each group. Burn wounds were induced in mice by using a hot metal rod. Burn wounds were evaluated histologically and morphologically. Turmeric nanoparticles substantially improved the wound contraction area as compared to the negative control group and other treatment groups. The serum level of Glutathione (4.9±0.1umol/L), Catalase (6.0±0.2mmol/ml), Glutathione Peroxidase (183.4±5.1U/L), Superoxide dismutase (194.6±5.1 U/ml) were significantly increased in the turmeric nanoparticles (TNPs) group as compared to the negative control (2.8±0.1umol/L, 3.5±0.1mmol/ml, 87.8±3.0U/L, and 92.0±4.8U/ml respectively). The minimum levels of Malondialdehyde (3.8±0.2mmol/L) were noticed in TNPs group contrary to the negative control (7.4±0.2mmol/L). The restoration of the epidermis was also observed to be faster in TNPs group as compared to all other treatment groups. The histopathological analysis also demonstrated the effectiveness of turmeric, sericin, and their nanoparticles. In conclusion, turmeric, sericin, and their nanoparticles are effective in improving the healing process of burn wounds, but TNPs showed the most effective results as compared to all other treatment groups.

Advanced treatment strategies in breast cancer: A comprehensive mechanistic review.

Breast cancer is a destructive lump type that affects women globally. Despite the availability of multi-directional therapeutic strategies, advanced stages of breast cancer are difficult to treat and impose major healthcare burdens. This situation reinforces the need to identify new potential therapeutic compounds with better clinical features. In this context, different treatment methods were included such as Endocrine therapy, chemotherapy, Radiation therapy, antimicrobial peptide-dependent growth inhibitor, liposome-based drug delivery, antibiotics used as a co-medication, photothermal, immunotherapy, and nano drug delivery systems such as Bombyx mori natural protein sericin and its mediated nanoparticles are promising biomedical agents. They have been tested as an anticancer agent against various malignancies in pre-clinical settings. The biocompatible and restricted breakdown properties of silk sericin and sericin-conjugated nanoparticles made them perfect contenders for a nanoscale drug-delivery system.

Therapeutic Applications of Garlic and Turmeric for the Diabetic Wound Healing in Mice.

Diabetes is involved in delayed wound healing that can be cured by natural products such as garlic, turmeric, and fibroin extracts. Alloxan monohydrate is used for inducing diabetes in mice. The percent wound contraction of garlic (150 mg/ml), turmeric (100 mg/ml), and fibroin (50 mg/ml), individually and in combinations garlic (150 mg/ml) + fibroin (50 mg/ml), turmeric (100 mg/ml) + fibroin (50 mg/ml), garlic (150 mg/ml) + turmeric (100 mg/ml), and garlic (150 mg/ml) + turmeric (100 mg/ml) + fibroin (50 mg/ml) was checked by evaluating the healing time, % wound contraction and histological analysis. The serum level of MMPs (MMP 2, MMP7, MMP 9), pro-inflammatory cytokines (TNF-α, IL-6, IL-8), and TIMPs were evaluated. With the combination of three extracts (Ga+Tu+Fi) garlic (150 mg/ml), turmeric (100 mg/ml) and fibroin (50 mg/ml), wounds healed in 12 days and had 97.3 ± 2.2% wound contraction. While the positive control (polyfax) and diabetic control (saline) wounds healed in 17- and 19-days with wound contraction of 96.7 ± 1.4% and 96.3 ± 1.1%, respectively. Histological analysis showed that the combination of Ga+Tu+Fi exhibited an increase in the growth of collagen fibers, fibroblasts number, and keratinocytes, and lessened inflammation of blood vessels. The combination of Ga+Tu+Fi significantly alleviated the serum concentration of TNF-α (14.2 ± 0.7 pg/ml), IL-6 (10.0 ± 1.0 pg/ml), IL-8 (16.0 ± 1.5 pg/ml), MMP2 (228.0 ± 18.1 pg/ml), MMP7 (271.0 ± 9.9 pg/ml), and MMP9 (141.0 ± 5.3 pg/ml) to diabetic control. The level of TIMPs (193.0 ± 9.1 pg/ml) was increased significantly with respect to diabetic control. We conclude that the combination of these biomaterials possessed high regenerative and healing capabilities and can be an effective remedy in the healing of chronic wounds in diabetic patients.

Organic and inorganic amendments for the remediation of nickel contaminated soil and its improvement on Brassica napus growth and oxidative defense.

In-situ stabilization has been considered an effective way to remediate metal contaminated soil. Thus, pot experiments were undertaken to investigate the effectiveness of multiple stabilization agents such as biochar (BC), mussel shell (MS), zeolite (ZE) and limestone (LS) on the immobilization of Ni, physicochemical features and enzyme activities in polluted soil. Results showed that the sole application of Ni adversely affected the rapeseed growth, photosynthetic pigments, and antioxidative defense. However, the addition of amendments to the contaminated soil significantly reduced Ni bioavailability. The XRD analysis confirmed the formation of Ni related ligands and FTIR showed the presence of hydroxyl, carboxyl and sulfur functional groups, as well as complexation and adsorption of Ni on amendments. Among multiple amendments, biochar significantly enhanced plant biomass attributes and total chlorophyll content. Moreover, addition of amendments also strengthened the antioxidant defense by decreasing Ni induced oxidative stress (H2O2 and O2.-), increased macronutrient availability, reduced Ni uptake and improved soil health. The qPCR analysis showed that the Ni transporters were significantly suppressed by amendments, which is correlated with the lower accumulation of Ni in rapeseed. The present study showed that immobilizing agents, especially biochar, is an effective amendment to immobilize Ni in soil, which restricts its entry into the food chain.

Interactive effects of biochar and mussel shell activated concoctions on immobilization of nickel and their amelioration on the growth of rapeseed in contaminated aged soil.

Mussel shell (MS) and biochar (BC) are commonly used for the remediation of metal contaminated soil. However, less research has been focused to examine the efficacy of their combinations to reduce metal toxicity in crop plants. This study was therefore conducted to investigate the effects of BC, MS and their activated concoctions on the soil properties, enzyme activities and nickel (Ni) immobilization in aged Ni contaminated soil. Moreover, the growth, photosynthetic pigments and anti-oxidative machnery of Brassica napus plants has also been investigated in order to determine amendments efficiency in reducing soil Ni toxicity for plants. The results showed that the application of Ni adversely affected soil health and trigged stress responses by inducing oxidative stress in B. napus. However, the incorporation of amendments reduced the bioavailability of Ni, and the concoctions of BC and MS showed promising results in the immobilization of Ni. Among various combinations of BC and MS, treatment with BC + MS (3:1) significantly reduced Ni uptake, decreased reactive oxygen species (ROS) and enhanced antioxidant defense of B. napus plants. Results showed that amendment's combinations stimulated the transcriptional levels of ROS scavenging enzymes and suppressed the expression level of Ni transporters. The morphological and physical characterization techniques (i.e. SEM, BET, EDS, FTIR and X-ray diffraction analyses) showed that amendment's combinations had relatively higher Ni adsorption capacity, indicating that BC and MS concoctions are efficient immobilizing agents for minimizing Ni availability, preventing oxidative toxicity and promoting growth and biomass production in rapeseed plants under metal stress conditions.

Challenges and prospects for a potential allohexaploid Brassica crop.

The production of a new allohexaploid Brassica crop (2n = AABBCC) is increasingly attracting international interest: a new allohexaploid crop could benefit from several major advantages over the existing Brassica diploid and allotetraploid species, combining genetic diversity and traits from all six crop species with additional allelic heterosis from the extra genome. Although early attempts to produce allohexaploids showed mixed results, recent technological and conceptual advances have provided promising leads to follow. However, there are still major challenges which exist before this new crop type can be realized: (1) incorporation of sufficient genetic diversity to form a basis for breeding and improvement of this potential crop species; (2) restoration of regular meiosis, as most allohexaploids are genetically unstable after formation; and (3) improvement of agronomic traits to the level of "elite" breeding material in the diploid and allotetraploid crop species. In this review, we outline these major prospects and challenges and propose possible plans to produce a stable, diverse and agronomically viable allohexaploid Brassica crop.

Improved physiological defense responses by application of sodium nitroprusside in Isatis cappadocica Desv. under cadmium stress.

Isatis cappadocica is a well-known arsenic-hyperaccumulator, but there are no reports of its responses to cadmium (Cd). Nitric oxide (NO) is a signaling molecule, which induces cross-stress tolerance and mediates several physio-biochemical processes related to heavy metal toxicity. In this study, the effects of Cd and sodium nitroprusside (SNP as NO donor) on the growth, defense responses and Cd accumulation in I. cappadocica were investigated. When I. cappadocica was treated with 100 and 200 µM Cd, there was an insignificant inhibition of shoot growth. However, Cd stress at Cd400 treatment decreased significantly the dry weight of root and shoot by 73 and 38%, respectively, as compared to control. The application of SNP significantly improved the growth parameters and mitigated Cd toxicity. In addition, SNP decreased reactive oxygen species (ROS) production induced by Cd. The increased total thiol and glutathione (GSH) concentrations after SNP application may play a decisive role in maintaining cellular redox homeostasis, thereby protecting plants against oxidative damage under Cd stress. Bovine hemoglobin (Hb as NO scavenger) reduced the protective role of SNP, suggesting a major role of NO in the defensive effect of SNP. Furthermore, the reduction in shoot growth and the increase of oxidative damage were more severe after the addition of Hb, which confirms the protective role of NO against Cd-induced oxidative stress. The protective role of SNP in decreasing Cd-induced oxidative stress may be related to NO production, which can lead to stimulation of the thiols synthesis and improve defense system.

Ursolic Acid Limits Salt-Induced Oxidative Damage by Interfering With Nitric Oxide Production and Oxidative Defense Machinery in Rice.

Crops frequently encounter abiotic stresses, and salinity is a prime factor that suppresses plant growth and crop productivity, globally. Ursolic acid (UA) is a potential signaling molecule that alters physiology and biochemical processes and activates the defense mechanism in numerous animal models; however, effects of UA in plants under stress conditions and the underlying mechanism of stress alleviation have not been explored yet. This study examined the effects of foliar application of UA (100 µM) to mitigate salt stress in three rice cultivars (HZ, 712, and HAY). A pot experiment was conducted in a climate-controlled greenhouse with different salt stress treatments. The results indicated that exposure to NaCl-induced salinity reduces growth of rice cultivars by damaging chlorophyll pigment and chloroplast, particularly at a higher stress level. Application of UA alleviated adverse effects of salinity by suppressing oxidative stress (H2O2, O2-) and stimulating activities of enzymatic and non-enzymatic antioxidants (APX, CAT, POD, GR, GSH, AsA, proline, glycinebutane), as well as protecting cell membrane integrity (MDA, LOX, EL). Furthermore, UA application brought about a significant increase in the concentration of leaf nitric oxide (NO) by modulating the expression of NR and NOS enzymes. It seems that UA application also influenced Na+ efflux and maintained a lower cytosolic Na+/K+ ratio via concomitant upregulation of OsSOS1 and OsHKT1;5 in rice cultivars. The results of pharmacological tests have shown that supply of the NO scavenger (PTI) completely reversed the UA-induced salt tolerance in rice cultivars by quenching endogenous NO and triggering oxidative stress, Na+ uptake, and lipid peroxidation. The PTI application with UA and sodium nitroprusside (SNP) also caused growth retardation and a significant increase in Na+ uptake and oxidative stress in rice cultivars. This suggests that UA promoted salt tolerance of rice cultivars by triggering NO production and limiting toxic ion and reactive oxygen species (ROS) accumulation. These results revealed that both UA and NO are together required to develop a salt tolerance response in rice.

Genome-wide identification and evolution of Dof transcription factor family in cultivated and ancestral cotton species.

The DNA-binding with one finger (Dof) proteins are transcription factors involved in many biological processes in plants. To predict the evolutionary pattern, a genome-wide in-silico analysis of Dof TFs family in diploid (Gossypium arboreum and Gossypium raimondii) and allotetraploid (Gossypium hirsutum and Gossypium barbadense) cotton species were carried out. In G. arboreum, we have identified 58 non-redundant genes encoding Dof proteins renamed as GaDof (G. arboreum Dof), 55 Dof genes were identified in G. raimondii (GrDof), 89 were predicted ffrom G. hirsutum (GhDof) and the highest, 110 Dof genes were identified in G. barbadense (GbDof). The phylogenetic analysis, physical location, gene structure, conserved domain analyses were also investigated for G. arboreum, G. raimondii, and G. hirsutum. The gene expression pattern in G. hirsutum, at different growth stages, revealing the probable involvement of some GhDof genes in growth and development. These genes may improve seed germination and growth in cotton.

Optimization of enhanced microbial production of zinc bacitracin by submerged fermentation technology.

Bacitracin is one of the most important antibiotics used in different biomedical fields. It helps to achieve sizeable amount of foreign exchange due to its use in the poultry feed. The cheap agricultural wastes are readily available for the preparation of fermentation media used for bacitracin production. The microorganisms could be mutated with different chemicals and UV radiation to improve bacitracin production. Thus, the current study was focused on the synthesis of low-cost and effective bacitracin by mutant strains of Bacillus licheniformis, employing the submerged fermentation technique. The bacteria were exposed to the UV irradiation for various time periods ranging from 5 to 40 min. These mutants were named as BLAA-5-BLAA-40. Mutant strain BLAA-25 produced maximum bacitracin, with significantly high activity (142.81 IU/mg) against Klebsiella pneumoniae but less activity against Escherichia coli (115.19 IU/mg). Several fermentation conditions were investigated to optimize bacitracin production. The highest bacitracin yield was obtained by an inoculum size of 10%, fermentation period 48 hr, pH 7, T = 37°C, using soybean meal as a substrate. Among all substrates, cucumber peel was the substrate showing the highest minimum inhibitory concentration (2.3 mg/ml and 2.7 mg/ml against K. pneumoniae and E. coli respectively). A comparison between commercial and experimentally produced Zn bacitracin showed that commercial bacitracin has a low activity (63.2 IU/mg) as compared with experimental bacitracin. Hence, the agro wastes and mutation could be used to increase the synthesis of Zn bacitracin in B. licheniformis.

Oral Intake of EPA:DHA 6:1 by Middle-Aged Rats for One Week Improves Age-Related Endothelial Dysfunction in Both the Femoral Artery and Vein: Role of Cyclooxygenases.

In humans, aging is associated with endothelial dysfunction and an increased risk of venous thromboembolism. Although intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at a ratio of 6:1 by old rats improved the endothelial dysfunction in arteries, the impact on veins remains unclear. Eight-month-old male Wistar rats were either untreated or orally administered corn oil, EPA:DHA 1:1, or EPA:DHA 6:1 (500 mg/kg/d) for seven days. Vascular reactivity was studied by myography. In middle-aged femoral artery rings, acetylcholine caused a partial relaxation at low concentrations and a contractile response at high concentrations, whereas in the old femoral vein only a partial relaxation was observed. The EPA:DHA 6:1 treatment blunted the contractile response to acetylcholine in the middle-aged femoral artery and both EPA:DHA 6:1 and 1:1 increased the relaxation to acetylcholine in the old femoral vein. No such effects were observed with corn oil. Both the non-selective cyclooxygenase inhibitor indomethacin and the COX-1 inhibitor SC-560 increased the relaxation to acetylcholine in the middle-aged femoral artery whereas the COX-2 inhibitor NS-398 increased that in the middle-aged femoral vein. In conclusion, our results indicate that aging is associated with an endothelial dysfunction in the femoral artery and vein, which can be improved by EPA:DHA 6:1 treatment-most likely via a cyclooxygenase-dependent mechanism.

Intake of omega-3 formulation EPA:DHA 6:1 by old rats for 2 weeks improved endothelium-dependent relaxations and normalized the expression level of ACE/AT1R/NADPH oxidase and the formation of ROS in the mesenteric artery.

Omega-3 polyunsaturated fatty acids (PUFAs) including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to protect the cardiovascular system, in part, by stimulating the endothelial formation of nitric oxide (NO). EPA:DHA 6:1 has been identified as a potent omega 3 PUFA formulation to induce endothelium-dependent vasorelaxation and activation of endothelial NO synthase (eNOS). This study examined whether intake of EPA:DHA 6:1 (500 mg/kg/day) for 2 weeks improves an established endothelial dysfunction in old rats (20 months old), and, if so, the underlying mechanism was subsequently determined. In the main mesenteric artery rings, an endothelial dysfunction characterized by a blunted NO component, an abolished endothelium-dependent hyperpolarization component, and increased endothelium-dependent contractile responses (EDCFs) are observed in old rats compared to young rats. Age-related endothelial dysfunction was associated with increased vascular formation of reactive oxygen species (ROS) and expression of eNOS, components of the local angiotensin system, senescence markers, and cyclooxygenase-2 (COX-2), and the downregulation of COX-1. The EPA:DHA 6:1 treatment improved the NO-mediated relaxation, reduced the EDCF-dependent contractile response and the vascular formation of ROS, and normalized the expression level of all target proteins in the old arterial wall. Thus, the present findings indicate that a 2-week intake of EPA:DHA 6:1 by old rats restored endothelium-dependent NO-mediated relaxations, most likely, by preventing the upregulation of the local angiotensin system and the subsequent formation of ROS.

Targeted and stimuli-responsive mesoporous silica nanoparticles for drug delivery and theranostic use.

For cancer therapy, the usefulness of mesoporous silica nanoparticles (MPSNPs) has been widely discussed, likely due to its inorganic nature and excellent structural features. The MPSNPs-based chemotherapeutics have been promisingly delivered to their target sites that help to minimize side effects and improve therapeutic effectiveness. A wide array of studies have been conducted to functionalize drug-loaded MPSNPs using targeting ligands and stimuli-sensitive substances. In addition, anticancer drugs have been precisely delivered to their target sites using MPSNPs, which respond to multi-stimuli. Furthermore, MPSNPs have been extensively tested for their safety and compatibility. The toxicity level of MPSNPs is substantially lower as compared to that of colloidal silica; however, in oxidative stress, they exhibit cytotoxic features. The biocompatibility of MPSNPs can be improved by modifying their surfaces. This article describes the production procedures, functionalization, and applications of biocompatible MPSNPs in drug delivery.

Synergistic effects of chromium and copper on photosynthetic inhibition, subcellular distribution, and related gene expression in Brassica napus cultivars.

Nowadays, modern plant physiology focuses on complex behavior of metal co-contaminants in agrosystems. Keeping this in view, the current study was conducted to investigate the response of two Brassica napus cultivars (Zheda 622 and ZS 758) under co-contamination of copper (Cu2+) and chromium (Cr6+) to observe their effects on plant growth, photosynthetic parameters, and subcellular distribution of these metals in leaves and roots. The results showed that exposure to Cu and Cr causes decline in plant growth, including biomass and plant height. Significant decrease in pigment concentration and the photosynthetic activity [photosynthetic rate (Pn), stomatal conductance (Gs), and transpiration rate (E), maximal quantum yield of photosystem II (Fv/Fm)] in leaves was also observed. Results of subcellular distribution of metals showed that Cu and Cr were predominantly distributed in cell wall and soluble fraction of roots and leaves. Moreover, Cu and Cr in cellular fractions showed a synergistic accumulation pattern under combined metal stress treatment. Both cultivars showed increased levels of reactive oxygen species (ROS), i.e., hydrogen peroxide (H2O2) and superoxide radical (O2•-), and significant modulation in the activities of antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), ascorbate peroxidase (APX)] under Cu/Cr alone or their combined treatments. Similarly, expression levels of defense-related genes, such as BnCat, BnApx, BnPrx, and BnSod, were also generally up-regulated compared with control. Electron micrographs (TEM) of the mesophyll and root tip cells indicated prominent alterations both in cellular and organelle levels. Additionally, Cr was found to be more toxic than Cu but less than their combined effect, as revealed by enhanced production of oxidative stress and a reduction in biomass production and photosynthetic activity. The present results also suggest that cultivar ZS 758 is more resistant to Cu/Cr than Zheda 622, due to better adapted metabolism and maintenance of structural integrity under metal stress.

Dysregulation of c-Jun N-terminal kinase phosphorylation in alcohol dependence.

Alcohol use disorder (AUD) is a chronic, relapsing psychiatric disease characterized by the emergence of negative emotional states and the development of motivational deficits that manifest during alcohol withdrawal. Accordingly, alcohol may be sought after and taken in excessive amounts to alleviate withdrawal-related symptoms. To develop more effective treatments for AUD, it is necessary to identify potential molecular targets that underlie the transition from initial alcohol use to alcohol dependence, and our previous work has implicated a role for potentiated glucocorticoid receptor (GR) signaling in this regard. As a key negative regulator of GR-mediated signaling, the current study first measured c-Jun N-terminal kinase (JNK) phosphorylation in animals following an acute alcohol challenge. We found that JNK phosphorylation (pJNK) was significantly increased in the hippocampus, frontal cortical regions, and striatum of adult male Wistar rats following alcohol challenge, indicating that initial alcohol exposure increases JNK activity across several brain regions. A separate group of adult male Wistar rats were made dependent via chronic, intermittent ethanol vapor exposure and were trained to self-administer alcohol. We found that alcohol-dependent animals consumed significantly more alcohol and escalated their drinking over time compared to non-dependent animals. We then measured alterations in JNK phosphorylation in this alcohol-dependent group during acute withdrawal and found that pJNK was selectively decreased in the dorsal hippocampus, dorsomedial prefrontal cortex, and cingulate cortex. These findings demonstrate that withdrawal from chronic alcohol exposure leads to region-specific deficits in JNK phosphorylation. JNK signaling dysregulation may foster long-lasting behavioral and motivational impairments in alcohol dependence, either as a result of increased GR-mediated stress signaling or via other downstream mechanisms.

Ecotoxicological and Interactive Effects of Copper and Chromium on Physiochemical, Ultrastructural, and Molecular Profiling in Brassica napus L.

Heavy metal accumulation causes huge environmental problems, particularly in agricultural ecosystems which have deteriorative effects on the yield and quality of crops. Individual copper (Cu) and chromium (Cr) effects have been investigated extensively in plants; however, co-contamination of Cu and Cr induced stress on Brassica napus L. is still unclear. In the present experiment, the interactive effects of Cu and Cr were studied in two B. napus cultivars (Zheda 622 and ZS 758). Results showed that the application of Cr was more toxic than Cu, and their combined stress had shown a significant adverse effect on plant growth. Biomass and photosynthetic pigment were decreased remarkably under all metal treatments. Individual treatments of Cu and Cr and their combination cause the accumulation of ROS and lipid peroxidation. Moreover, the activities of antioxidant enzymes and their mRNA transcription levels, such as catalase (CAT), ascorbate peroxidase, glutathione reductase, superoxide dismutase, and peroxidase, were increased, especially when treated with Cr alone or under Cu+Cr combined treatment in both cultivars, except for the CAT activity which was decreased in both leaves and roots of sensitive cultivar Zheda 622 as compared with their respective controls. Additionally, nonenzymatic antioxidants like reduced and oxidized glutathione showed a differential activity pattern in roots and leaves of both cultivars. A more pronounced modification in chloroplast ultrastructure was observed in both cultivars under Cu+Cr treatment followed by Cr and Cu alone treatments. Furthermore, synergistic effects of Cu and Cr were prominent; this may be due to the enhanced metals uptake under combined treatment, which suggests that Cr and Cu interaction is not competitive but is rather additive and genotypic-dependent.

Potential impact of the herbicide 2,4-dichlorophenoxyacetic acid on human and ecosystems.

The herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) is applied directly to aquatic and conventional farming systems to control weeds, and is among the most widely distributed pollutants in the environment. Non-target organisms are exposed to 2,4-D via several ways, which could produce toxic effects depending on the dose, frequency of exposure, and the host factors that influence susceptibility and sensitivity. An increasing number of experimental evidences have shown concerns about its presence/detection in the environment, because several investigations have pointed out its potential lethal effects on non-target organisms. In this review, we critically evaluated the environmental fate and behavior of 2,4-D along with its eco-toxicological effects on aquatic, plants and human life to provide concise assessment in the light of recently published reports. The findings demonstrate that 2,4-D is present in a low concentration in surface water of regions where its usage is high. The highest concentrations of 2,4-D were detected in soil, air and surface water surrounded by crop fields, which suggest that mitigation strategies must be implanted locally to prevent the entry of 2,4-D into the environment. A general public may have frequent exposure to 2,4-D due to its wide applications at home lawns and public parks, etc. Various in vivo and in vitro investigations suggest that several species (or their organs) at different trophic levels are extremely sensitive to the 2,4-D exposure, which may explain variation in outcomes of reported investigations. However, implications for the prenatal exposure to 2,4-D remain unknown because 2,4-D-induced toxicity thresholds in organism have only been derived from juveniles or adults. In near future, introduction of 2,4-D resistant crops will increase its use in agriculture, which may cause relatively high and potentially unsafe residue levels in the environment. The recent findings indicate the urgent need to further explore fate, accumulation and its continuous low level exposure impacts on the environment to generate reliable database which is key in drafting new regulation and policies to protect the population from further exposure.

Salinity reduces 2,4-D efficacy in Echinochloa crusgalli by affecting redox balance, nutrient acquisition, and hormonal regulation.

Distinct salinity levels have been reported to enhance plants tolerance to different types of stresses. The aim of this research is to assess the interaction of saline stress and the use of 2,4-D as a means of controlling the growth of Echinochloa crusgalli. The resultant effect of such interaction is vital for a sustainable approach of weed management and food production. The results showed that 2,4-D alone treatment reduces the chlorophyll contents, photosynthetic capacity, enhanced MDA, electrolyte leakage, and ROS production (H2O2, O2·-) and inhibited the activities of ROS scavenging enzymes. Further analysis of the ultrastructure of chloroplasts indicated that 2,4-D induced severe damage to the ultrastructure of chloroplasts and thylakoids. Severe saline stress (8 dS m-1) followed by mild saline stress treatments (4 dS m-1) also reduced the E. crusgalli growth, but had the least impact as compared to the 2,4-D alone treatment. Surprisingly, under combined treatments (salinity + 2,4-D), the phytotoxic effect of 2,4-D was reduced on saline-stressed E. crusgalli plants, especially under mild saline + 2,4-D treatment. This stimulated growth of E. crusgalli is related to the higher activities of enzymatic and non-enzymatic antioxidants and dynamic regulation of IAA, ABA under mild saline + 2,4-D treatment. This shows that 2,4-D efficacy was affected by salinity in a stress intensity-dependent manner, which may result in the need for greater herbicide application rates, additional application times, or more weed control operations required for controlling salt-affected weed.

2,4-D attenuates salinity-induced toxicity by mediating anatomical changes, antioxidant capacity and cation transporters in the roots of rice cultivars.

Growth regulator herbicides are widely used in paddy fields to control weeds, however their role in conferring environmental stress tolerance in the crop plants are still elusive. In this study, the effects of recommended dose of 2,4-dichlorophenoxyacetic acid (2,4-D)  on growth, oxidative damage, antioxidant defense, regulation of cation transporter genes and anatomical changes in the roots of rice cultivars XS 134 (salt resistant) and ZJ 88 (salt sensitive) were investigated under different levels of saline stress. Individual treatments of saline stress and 2,4-D application induced oxidative damage as evidenced by decreased root growth, enhanced ROS production, more membrane damage and Na+ accumulation in sensitive cultivar compared to the tolerant cultivar. Conversely, combined treatments of 2,4-D and saline stress significantly alleviated the growth inhibition and oxidative stress in roots of rice cultivars by modulating lignin and callose deposition, redox states of AsA, GSH, and related enzyme activities involved in the antioxidant defense system. The expression analysis of nine cation transporter genes showed altered and differential gene expression in salt-stressed roots of sensitive and resistant cultivars. Together, these results suggest that 2,4-D differentially regulates the Na+ and K+ levels, ROS production, antioxidant defense, anatomical changes and cation transporters/genes in roots of rice cultivars.

Withdrawal from Chronic Nicotine Exposure Produces Region-Specific Tolerance to Alcohol-Stimulated GluA1 Phosphorylation.

BACKGROUND: Nicotine use increases alcohol drinking, suggesting that the combination of these drugs may produce synergistic effects in activating reward circuitry. Alternatively, use of either of these drugs may facilitate the development of cross-tolerance to the other to promote intake escalation. METHODS: In this study, adult male Wistar rats were chronically exposed to room air or chronic, intermittent nicotine vapor, which has been shown to produce symptoms of nicotine dependence as evidenced by elevated nicotine self-administration and a host of somatic and motivational withdrawal symptoms. We examined regional neuroadaptations in nicotine-experienced versus nonexperienced animals, focusing on changes in phosphorylation of the AMPA glutamate channel subunit GluA1 in reward-related brain regions as excitatory neuroadaptations are heavily implicated in both alcohol and nicotine addiction. RESULTS: During withdrawal, nicotine exposure and alcohol challenge (1 g/kg) interactively produced neuroadaptations in GluA1 phosphorylation in a brain region-dependent manner. Alcohol robustly increased protein kinase A-mediated phosphorylation of GluA1 at serine 845 in multiple regions. However, this neuroadaptation was largely absent in 3 areas (dorsomedial prefrontal cortex, dorsal striatum, and central amygdala) in nicotine-experienced animals. This interactive effect suggests a molecular tolerance to alcohol-stimulated phosphorylation of GluA1 in the context of nicotine dependence. CONCLUSIONS: Nicotine may modify the rewarding or reinforcing effects of alcohol by altering glutamate signaling in a region-specific manner, thereby leading to increased drinking in heavy smokers.