PTI-ETI synergistic signal mechanisms in plant immunity.

Plants face a relentless onslaught from a diverse array of pathogens in their natural environment, to which they have evolved a myriad of strategies that unfold across various temporal scales. Cell surface pattern recognition receptors (PRRs) detect conserved elicitors from pathogens or endogenous molecules released during pathogen invasion, initiating the first line of defence in plants, known as pattern-triggered immunity (PTI), which imparts a baseline level of disease resistance. Inside host cells, pathogen effectors are sensed by the nucleotide-binding/leucine-rich repeat (NLR) receptors, which then activate the second line of defence: effector-triggered immunity (ETI), offering a more potent and enduring defence mechanism. Moreover, PTI and ETI collaborate synergistically to bolster disease resistance and collectively trigger a cascade of downstream defence responses. This article provides a comprehensive review of plant defence responses, offering an overview of the stepwise activation of plant immunity and the interactions between PTI-ETI synergistic signal transduction.

Recent contributions of pyridazine as a privileged scaffold of anticancer agents in medicinal chemistry: An updated review.

Pyridazine, as a privileged scaffold, has been extensively utilized in drug development due to its multiple biological activities. Especially around its distinctive anticancer property, a massive number of pyridazine-containing compounds have been synthesized and evaluated that target a diverse array of biological processes involved in cancer onset and progression. These include glutaminase 1 (GLS1) inhibitors, tropomyosin receptor kinase (TRK) inhibitors, and bromodomain containing protein (BRD) inhibitors, targeting aberrant tumor metabolism, cell signal transduction and epigenetic modifications, respectively. Pyridazine moieties functioned as either core frameworks or warheads in the above agents, exhibiting promising potential in cancer treatment. Therefore, the review aims to summarize the recent contributions of pyridazine derivatives as potent anticancer agents between 2020 and 2024, focusing mainly on their structure-activity relationships (SARs) and development strategies, with a view to show that the application of the pyridazine scaffold by different medicinal chemists provides new insights into the rational design of anticancer drugs.

EZH2 serves as a promising therapeutic target for fibrosis.

Fibrosis affects the function of many organs and tissues, and its persistent development can lead to tissue sclerosis and cancer, even leading to death further. Recent studies suggested that enhancer of zeste homolog 2 (EZH2), a major regulator of epigenetic repression, played an important role in the occurrence and development of fibrosis through gene silencing or transcriptional activation. As the most studied and powerful pro-fibrotic cytokine closely related to EZH2, TGF-ß1 was primarily involved in the regulation of fibrosis along with the typical Smads and non-Smads signaling pathways. In addition, EZH2 inhibitors demonstrated inhibitory effects in several types of fibrosis. This review summarized the relationship underlying the action of EZH2, TGF-ß1/Smads, and TGF-ß1/non-Smads with fibrosis and described the research progress of EZH2 inhibitors in the treatment of fibrosis.

Histone deacetylase 6 as a novel promising target to treat cardiovascular disease.

Histone deacetylase 6 (HDAC6) belongs to a class of epigenetic targets that have been found to be a key protein in the association between tumors and cardiovascular disease. Recent studies have focused on the crucial role of HDAC6 in regulating cardiovascular diseases such as atherosclerosis, myocardial infarction, myocardial hypertrophy, myocardial fibrosis, hypertension, pulmonary hypertension, and arrhythmia. Here, we review the association between HDAC6 and cardiovascular disease, the research progress of HDAC6 inhibitors in the treatment of cardiovascular disease, and discuss the feasibility of combining HDAC6 inhibitors with other therapeutic agents to treat cardiovascular disease.

Histone deacetylases (HDACs) as the promising immunotherapeutic targets for hematologic cancer treatment.

Bone marrow transplantation is regarded as the most effective immunotherapy for hematologic cancer, but it generally faces difficulties in matching. Aberrant expression of histone deacetylases (HDACs) is closely related to the occurrence and development of hematological cancer. Recent studies suggested that HDACs might play a critical role in initiating anti-cancer immune response or enhancing anti-cancer immunotherapy. Besides, combining HDAC inhibition and immunotherapy could prevent immunotherapy resistance in some degree and reach an extended treatment window. This review summarized the relationship between HDACs and immune and described the current understanding of HDACs in immunotherapy for hematologic cancer.

Genome-wide analysis of autophagy-related gene family and PagATG18a enhances salt tolerance by regulating ROS homeostasis in poplar.

Autophagy is the process by which intracellular components are delivered to lysosomes or vacuoles for degradation and recycling, which can promote the tolerance of organisms to biotic/abiotic stresses. However, autophagy-related genes (ATG) are not well studied in woody plants. Here, 48 ATG genes were identified in the poplar genome and divided into 14 subfamilies according to the phylogenetic tree. Collinearity analysis showed that 26 pairs of genes were derived by segmental duplication in poplars. The isogenous gene pairs of the ATG family between P. trichocarpa and other six species were analyzed by synteny analysis. Moreover, the ATG promoters contain a large number of phytohormone response elements and stress-response elements. Both phytohormone and salt treatments can induce the expression of PagATG18 subfamily genes. Overexpression of PagATG18a significantly improved the salt tolerance of poplar and reducing the oxidative damage of the membrane. Further research verified that PagATG18a interacted with the light-harvesting complex LHCB1 and APX2, indicating PagATG18a might be involved in regulating photosynthesis and antioxidant activity under stress. This study provides valuable information for further research on the functional characteristics of ATG genes in poplar and the theoretical basis for poplar stress resistance breeding.

Bioinformatic Analysis and Translational Validation of Psoriasis Candidate Genes for Precision Medicine.

Background: Psoriasis is a recurrent, chronic, inflammation- and immune-mediated skin disease with multiple causative factors. However, the genetic markers associated with recurrence have not yet been fully elucidated. Accordingly, in this study, we aimed to identify markers associated with the recurrence of psoriasis. Methods: We analyzed differentially expressed genes to determine which targets were associated with the recurrence of psoriasis and used these data to construct a protein-protein interaction network using Cytoscape software. The results were then validated by analysis of core targets using Gene Expression Omnibus (GEO) datasets and clinical samples. Functional enrichment analysis was used to explore the potential mechanisms mediating the recurrence of psoriasis. Results: We screened out six core targets that played important roles in recurrence of psoriasis, and validation of GEO datasets and clinical samples showed that the expression levels of five core targets were higher in patients with psoriasis than in healthy individuals. Functional enrichment analysis revealed that the cell cycle and oocyte meiosis signaling pathways were involved in the recurrence of psoriasis. Conclusion: Our findings provided insights into the mechanisms mediating the onset and recurrence of psoriasis.

Prediction and verification of the effect of psoriasis on coronary heart disease based on artificial neural network.

Background and objectives: Psoriasis is an independent risk factor for coronary heart disease. It is important for predicting the complications of coronary heart disease in patients with psoriasis. Methods: In this study, related cases were collected from the case system of Qingdao University, and commonly used laboratory indicators were extracted. Artificial neural network (ANN) and logistics regression analysis were used to learn to distinguish psoriasis patients, coronary heart disease patients, and psoriasis patients with coronary heart disease. We identified independent risk factors for coronary heart disease in psoriasis patients that exacerbate coronary heart disease symptoms in patients with psoriasis. Findings: Analysis shows that the accuracy of the ANN model was higher than 79%. It was determined that age, chlorinated, phosphorus, magnesium, low-density lipoprotein, triglycerides, high density lipoprotein and total cholesterol are independent risk factors for coronary heart disease in patients with psoriasis. Similarly, gender, age, chlorinated, magnesium, triglycerides, and high density lipoprotein are risk factors that exacerbate coronary heart disease symptoms in patients with psoriasis. Interpretation: The presented approach is a valuable tool for identifying psoriasis patients, coronary heart disease patients, and psoriasis patients with coronary heart disease. It can also serve as a support tool clinicians in the diagnostic process, by providing an outstanding support in the diagnostics prevention of coronary heart disease in psoriasis.

[Effects of bio-glass in subgingival scaling and root planing].

OBJECTIVE: To evaluate the effect of locally applied bio-glass on the teeth hypersentivity and periodontal recovery after subgingival scaling and root planing. METHODS: In this double blind study, 60 patients with chronic periodontitis were included and were randomly divided into four groups of 15 patients: bio-glass powder and bio-glass paste group (Po+Pa), bio-glass powder group (Po), bio-glass paste group (Pa) and control group. Powder was applied in pockets after subgingival scaling and root planning (SRP) and paste was used as toothpaste for 6 weeks. Periodontal indices and the severity of tooth hypersensitivity were recorded. RESULTS: Obvious mitigation of tooth hypersensitivity was observed in bio-glass powder or paste applied patients within the fist three weeks after SRP. Only few patients presented teeth hypersensitivity in the 6th week after SRP. In the 6th week after SRP, bleeding index significantly decreased in bio-glass powder or paste applied patients. More pocket depth and clinical attachment level reduction was found in bio-glass powder applied patients. Application of bio-glass powder or paste improved clinical attachment level in the 3rd month after SRP. CONCLUSION: The hypersensitivity after subgingival scaling could be relieved without any treatment in 6 weeks, while the bio-glass powder and the 7% bio-glass paste could reduce the prevalence and the severity of it. Further more, bio-glass also improved the clinical outcomes of subgingival scaling via its bacteriostatic action.

[Association between periodontitis and preterm low birth weight].

There were increasing studies on the association of periodontitis with preterm low birth weight (PLBW) in the recent 10 years. PLBW is associated with about half of all perinatal mortality. Known factors which could induce PLBW include smoking, genetics, alcohol, prenatal care, nutrition, urinary tract infections, However, there are still about 25% of PLBW cases occur with etiology unknown. Many evidences supported the association between periodontitis and PLBW. Periodontitis is a risk factor of PLBW, but the mechanism is unclear. Current theory suggests that periodontal inflammation adversely affects pregnancy outcomes by one or two mechanisms. First, women with periodontal disease may experience more frequent and severe bacteremia than periodontally healthy women. As a result, the uterine cavity may become exposed to or colonized by periodontal bacteria or their byproducts (e.g. lipopolysaccharides). Once they reach the maternal-fetal unit, oral bacteria may elicit an inflammatory cascade that leads to preterm labor. A second putative mechanism does not require oral bacteria to colonize the uterine cavity. Rather, cytokines generated within the diseased periodontal tissue may enter the systemic circulation and precipitate a similar cascade, again leading to spontaneous preterm labor and birth. Therefore, oral health instruction and periodontal treatment may decrease the infection of periodontal pathogens and reduce the risk of PLBW. For the present, the best advice for a woman who contemplate pregnancy is effective brushing for two times per day and regular periodontal treatment.

[Comparison of treatment effect between periodontal subgingival scaling with the special series of ultrasonic inserts and Gracey curette].

OBJECTIVE: To compare the special series of ultrasonic inserts with Gracey curettes in the effectiveness and efficiency for non-surgical periodontal treatment. METHODS: A total of 30 patients with moderate to advanced chronic periodontal disease were treated with both ultrasonic inserts (ultrasonic group) and Gracey curettes (Gracey group) according to a prospective, randomized, controlled, one-blind, "split-mouth" design. Twenty-six cases were available for the whole follow-up period. Plaque index (PLI), bleeding index(BI), probing depth (PD), attachment loss (AL) were evaluated before and 6 weeks after treatment. Treatment time was recorded. The severity of pain during treatment and teeth sensitivity after treatment were evaluated by the visual analogue scale (VAS). Differences in clinical parameters were analyzed with the Wilcoxon signed ranks test and Mann and Whitney U-test. RESULTS: No significant differences in any of the clinical parameters were observed at baseline between the two groups. The mean value of PD, BI, PLI, AL decreased in both ultrasonic group and Gracey group. At moderately deep site (initial PD between 4 mm and 5 mm), PD [M(Q(25), Q(75))] changed in the ultrasonic group from 4.0 (4.0, 4.5) mm to 3.0 (3.0, 3.0) mm (P < 0.001) and in the Gracey group from 4.0 (4.0, 5.0) mm to 3.0(3.0, 3.0) mm (P < 0.001). At deep sites (initial PD ≥ 6 mm) PD [M(Q(25), Q(75))] changed in the ultrasonic group from 7.0(6.0, 7.0) mm to 5.0(4.0, 7.0) mm (P < 0.001) and in the Gracey group from 7.0 (6.0, 7.0) mm to 5.0(4.0, 6.0) mm(P < 0.001). In the furcation area, PD [M(Q(25), Q(75))] changed from 5.0(4.0, 7.0) mm to 3.0(3.0, 5.0) mm (P < 0.001) in both Gracey group and ultrasonic group. However, the average time of active instrumentation was (2.41 ± 0.61) min/tooth in the ultrasonic scaling and (2.71 ± 0.61) min/tooth in the Gracey curette (P < 0.001). VAS scores [M(Q(25), Q(75))] of pain during treatment was 5.0(3.0, 6.7) in the ultrasonic group and 5.9 (4.9, 8.0) in the Gracey group (P = 0.001). VAS scores [M(Q(25), Q(75))] of sensitivity after treatment was 4.0 (1.8, 6.0) in the ultrasonic group and 4.9 (2.0, 8.0) in the Gracey group (P = 0.043). CONCLUSIONS: Treatment with the special series of ultrasonic inserts was as effective as the Gracey curette during initial therapy period in all clinical parameters measured and has the advantage of being quicker.