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Adult acne vulgaris affects up to 43–51% of individuals. While there are numerous treatment options for acne including topical, oral, and energy-based approaches, benzoyl peroxide (BPO) is a popular over the counter (OTC) treatment. Although BPO monotherapy has a long history of efficacy and safety, it suffers from several disadvantages, most notably, skin irritation, particularly for treatment naïve patients. In this prospective, randomized, controlled, split-face study, we evaluated the comparative efficacy, safety, and tolerability of a novel 3-step azelaic acid, salicylic acid, and graduated retinol regimen versus a common OTC BPO-based regimen over 12 weeks. A total of 37 adult subjects with self-reported mild to moderate acne vulgaris were recruited. A total of 21 subjects underwent a 2-week washout period and completed the full study with 3 dropping out due to product irritation from the BPO routine, and 13 being lost to follow-up. Detailed tolerability surveys were conducted at Week 4. Additional surveys on tolerability and product preferences were collected monthly, at Week 4, Week 8, and Week 12. A blinded board-certified dermatologist objectively scored the presence and type of acne lesions (open or closed comedones, papules, pustules, nodules, and cysts) at baseline, Week 4, Week 8, and Week 12. Patients photographed themselves and uploaded the images using personal mobile phones. Detailed Week 4 survey results showed across 25 domains of user-assessed product performance, the novel routine outperformed the BPO routine in 19 (76%) which included domains in preference (e.g. “I would use this in the future) and performance (“my skin improved” and “helped my acne clear up faster”). Users of the novel routine reported less facial redness, itching, and burning, though differences did not reach statistical significance. In terms of efficacy, both products performed similarly, reducing total acne lesions by 36% (novel routine) and 40% (BPO routine) by Week 12. Overall, accounting for user preferences and tolerability the novel routine was more preferred than the BPO routine in 79% of domains (22/28). Differences in objective acne lesion reduction were not statistically significant (p = 0.97). In a randomized split-face study, a 3-step azelaic acid, salicylic acid, and graduated retinol regimen delivered similar acne lesion reduction, fewer user dropouts, greater user tolerability, and higher use preference compared to a 3-step BPO routine based in a cohort of participants with mild-to-moderate acne vulgaris.

Cryotherapy is widely used for the treatment of cutaneous warts in primary care. However, evidence favours salicylic acid application. We compared the effectiveness of these treatments as well as a wait-and-see approach. Consecutive patients with new cutaneous warts were recruited in 30 primary care practices in the Netherlands between May 1, 2006, and Jan. 26, 2007. We randomly allocated eligible patients to one of three groups: cryotherapy with liquid nitrogen every two weeks, self-application of salicylic acid daily or a wait-and-see approach. The primary outcome was the proportion of participants whose warts were all cured at 13 weeks. Analysis was on an intention-to-treat basis. Secondary outcomes included treatment adherence, side effects and treatment satisfaction. Research nurses assessed outcomes during home visits at 4, 13 and 26 weeks. Of the 250 participants (age 4 to 79 years), 240 were included in the analysis at 13 weeks (loss to follow-up 4%). Cure rates were 39% (95% confidence interval [CI] 29%-51%) in the cryotherapy group, 24% (95% CI 16%-35%) in the salicylic acid group and 16% (95% CI 9.5%-25%) in the wait-and-see group. Differences in effectiveness were most pronounced among participants with common warts (n = 116): cure rates were 49% (95% CI 34%-64%) in the cryotherapy group, 15% (95% CI 7%-30%) in the salicylic acid group and 8% (95% CI 3%-21%) in the wait-and-see group. Cure rates among the participants with plantar warts (n = 124) did not differ significantly between treatment groups. For common warts, cryotherapy was the most effective therapy in primary care. For plantar warts, we found no clinically relevant difference in effectiveness between cryotherapy, topical application of salicylic acid or a wait-and-see approach after 13 weeks. (ClinicalTrial.gov registration no. ISRCTN42730629)

Beneficial root endophytes such as Trichoderma spp. can reduce infections by parasitic nematodes through triggering host defences. Little is currently known about the complex hormone signalling underlying the induction of resistance. In this study, we investigated whether Trichoderma modulates the hormone signalling network in the host to induce resistance to nematodes. We investigated the role and the timing of the jasmonic acid (JA)- and salicylic acid (SA)-regulated defensive pathways in Trichoderma-induced resistance to the root knot nematode Meloidogyne incognita. A split-root system of tomato (Solanum lycopersicum) was used to study local and systemic induced defences by analysing nematode performance, defence gene expression, responsiveness to exogenous hormone application, and dependence on SA and JA signalling of Trichoderma-induced resistance. Root colonization by Trichoderma impeded nematode performance both locally and systemically at multiple stages of the parasitism, that is, invasion, galling and reproduction. First, Trichoderma primed SA-regulated defences, which limited nematode root invasion. Then, Trichoderma enhanced JA-regulated defences, thereby antagonizing the deregulation of JA-dependent immunity by the nematodes, which compromised galling and fecundity. Our results show that Trichoderma primes SA- and JA-dependent defences in roots, and that the priming of responsiveness to these hormones upon nematode attack is plastic and adaptive to the parasitism stage.

Salicylic acid (SA) is a phytohormone that plays important roles in many aspects of plant life, notably in plant defenses against pathogens. Key mechanisms of SA signal transduction pathways have now been uncovered. Even though details are still missing, we understand how SA production is regulated and which molecular machinery is implicated in the control of downstream transcriptional responses. The NPR1 pathway has been described to play the main role in SA transduction. However, the mode of SA perception is unclear. NPR1 protein has been shown to bind SA. Nevertheless, NPR1 action requires upstream regulatory events (such as a change in cell redox status). Besides, a number of SA-induced responses are independent from NPR1. This shows that there is more than one way for plants to perceive SA. Indeed, multiple SA-binding proteins of contrasting structures and functions have now been identified. Yet, all of these proteins can be considered as candidate SA receptors and might have a role in multinodal (decentralized) SA input. This phenomenon is unprecedented for other plant hormones and is a point of discussion of this review.

Canola, a vital oilseed crop, is grown globally for food and biodiesel. With the enormous demand for growing various crops, the utilization of agriculturally marginal lands is emerging as an attractive alternative, including brackish-saline transitional lands. Salinity is a major abiotic stress limiting growth and productivity of most crops, and causing food insecurity. Salicylic acid (SA), a small-molecule phenolic compound, is an essential plant defense phytohormone that promotes immunity against pathogens. Recently, several studies have reported that SA was able to improve plant resilience to withstand high salinity. For this purpose, a pot experiment was carried out to ameliorate the negative effects of sodium chloride (NaCl) on canola plants through foliar application of SA. Two canola varieties Faisal (V1) and Super (V2) were assessed for their growth performance during exposure to high salinity i.e. 0 mM NaCl (control) and 200 mM NaCl. Three levels of SA (0, 10, and 20 mM) were applied through foliar spray. The experimental design used for this study was completely randomized design (CRD) with three replicates. The salt stress reduced the shoot and root fresh weights up to 50.3% and 47% respectively. In addition, foliar chlorophyll a and b contents decreased up to 61–65%. Meanwhile, SA treatment diminished the negative effects of salinity and enhanced the shoot fresh weight (49.5%), root dry weight (70%), chl. a (36%) and chl. b (67%). Plants treated with SA showed an increased levels of both enzymatic i.e. (superoxide dismutase (27%), peroxidase (16%) and catalase (34%)) and non-enzymatic antioxidants i.e. total soluble protein (20%), total soluble sugar (17%), total phenolic (22%) flavonoids (19%), anthocyanin (23%), and endogenous ascorbic acid (23%). Application of SA also increased the levels of osmolytes i.e. glycine betaine (31%) and total free proline (24%). Salinity increased the concentration of Na + ions and concomitantly decreased the K + and Ca 2+ absorption in canola plants. Overall, the foliar treatments of SA were quite effective in reducing the negative effects of salinity. By comparing both varieties of canola, it was observed that variety V2 (Super) grew better than variety V1 (Faisal). Interestingly, 20 mM foliar application of SA proved to be effective in ameliorating the negative effects of high salinity in canola plants.

WRKY transcription factors (TFs) have been mainly associated with plant defense, but recent studies have suggested additional roles in the regulation of other physiological processes. Here, we explored the possible contribution of two related group III WRKY TFs, WRKY70 and WRKY54, to osmotic stress tolerance. These TFs are positive regulators of plant defense, and co-operate as negative regulators of salicylic acid (SA) biosynthesis and senescence. We employed single and double mutants of wrky54 and wrky70, as well as a WRKY70 overexpressor line, to explore the role of these TFs in osmotic stress (polyethylene glycol) responses. Their effect on gene expression was characterized by microarrays and verified by quantitative PCR. Stomatal phenotypes were assessed by water retention and stomatal conductance measurements. The wrky54wrky70 double mutants exhibited clearly enhanced tolerance to osmotic stress. However, gene expression analysis showed reduced induction of osmotic stress-responsive genes in addition to reduced accumulation of the osmoprotectant proline. By contrast, the enhanced tolerance was correlated with improved water retention and enhanced stomatal closure. These findings demonstrate that WRKY70 and WRKY54 co-operate as negative regulators of stomatal closure and, consequently, osmotic stress tolerance in Arabidopsis, suggesting that they have an important role, not only in plant defense, but also in abiotic stress signaling.

Salicylic acid (SA) is an important plant hormone with a critical role in plant defense against pathogen infection. Despite extensive research over the past 30 year or so, SA biosynthesis and its complex roles in plant defense are still not fully understood. Even though earlier biochemical studies suggested that plants synthesize SA from cinnamate produced by phenylalanine ammonia lyase (PAL), genetic analysis has indicated that in Arabidopsis, the bulk of SA is synthesized from isochorismate (IC) produced by IC synthase (ICS). Recent studies have further established the enzymes responsible for the conversion of IC to SA in Arabidopsis. However, it remains unclear whether other plants also rely on the ICS pathway for SA biosynthesis. SA induces defense genes against biotrophic pathogens, but represses genes involved in growth for balancing defense and growth to a great extent through crosstalk with the growth-promoting plant hormone auxin. Important progress has been made recently in understanding how SA attenuates plant growth by regulating the biosynthesis, transport, and signaling of auxin. In this review, we summarize recent progress in the biosynthesis and the broad roles of SA in regulating plant growth during defense responses. Further understanding of SA production and its regulation of both defense and growth will be critical for developing better knowledge to improve the disease resistance and fitness of crops.

Salicylic acid (SA) is an important plant hormone that is best known for mediating host responses upon pathogen infection. Its role in plant defense activation is well established, but its biosynthesis in plants is not fully understood. SA is considered to be derived from two possible pathways; the ICS and PAL pathway, both starting from chorismate. The importance of both pathways for biosynthesis differs between plant species, rendering it hard to make generalizations about SA production that cover the entire plant kingdom. Yet, understanding SA biosynthesis is important to gain insight into how plant pathogen responses function and how pathogens can interfere with them. In this review, we have taken a closer look at how SA is synthesized and the importance of both biosynthesis pathways in different plant species.

Leaf senescence is a highly coordinated, complicated process involving the integration of numerous internal and environmental signals. Salicylic acid (SA) and reactive oxygen species (ROS) are two well-defined inducers of leaf senescence whose contents progressively and interdependently increase during leaf senescence via an unknown mechanism. Here, we characterized the transcription factor WRKY75 as a positive regulator of leaf senescence in Arabidopsis thaliana. Knockdown or knockout of WRKY75 delayed age-dependent leaf senescence, while overexpression of WRKY75 accelerated this process. WRKY75 transcription is induced by age, SA, H2O2, and multiple plant hormones. Meanwhile, WRKY75 promotes SA production by inducing the transcription of SA INDUCTION-DEFICIENT2 (SID2) and suppresses H2O2 scavenging, partly by repressing the transcription of CATALASE2 (CAT2). Genetic analysis revealed that the mutation of SID2 or an increase in catalase activity rescued the precocious leaf senescence phenotype evoked by WRKY75 overexpression. Based on these results, we propose a tripartite amplification loop model in which WRKY75, SA, and ROS undergo a gradual but self-sustained rise driven by three interlinking positive feedback loops. This tripartite amplification loop provides a molecular framework connecting upstream signals, such as age and plant hormones, to the downstream regulatory network executed by SA- and H2O2-responsive transcription factors during leaf senescence.

Salicylic acid (SA) is a plant hormone that is critical for resistance to pathogens 1 – 3 . The NPR proteins have previously been identified as SA receptors 4 – 10 , although how they perceive SA and coordinate hormonal signalling remain unknown. Here we report the mapping of the SA-binding core of Arabidopsis thaliana NPR4 and its ligand-bound crystal structure. The SA-binding core domain of NPR4 refolded with SA adopts an α-helical fold that completely buries SA in its hydrophobic core. The lack of a ligand-entry pathway suggests that SA binding involves a major conformational remodelling of the SA-binding core of NPR4, which we validated using hydrogen–deuterium-exchange mass spectrometry analysis of the full-length protein and through SA-induced disruption of interactions between NPR1 and NPR4. We show that, despite the two proteins sharing nearly identical hormone-binding residues, NPR1 displays minimal SA-binding activity compared to NPR4. We further identify two surface residues of the SA-binding core, the mutation of which can alter the SA-binding ability of NPR4 and its interaction with NPR1. We also demonstrate that expressing a variant of NPR4 that is hypersensitive to SA could enhance SA-mediated basal immunity without compromising effector-triggered immunity, because the ability of this variant to re-associate with NPR1 at high levels of SA remains intact. By revealing the structural mechanisms of SA perception by NPR proteins, our work paves the way for future investigation of the specific roles of these proteins in SA signalling and their potential for engineering plant immunity. Structural determination of the salicylic-acid-binding core of Arabidopsis NPR4 sheds light on the mechanisms through which this plant hormone interacts with its receptors, providing insights that are of potential use in engineering enhanced immunity.