Synthesis and evaluation of pyridine-3-carboxamide analogs as effective agents against bacterial wilt in tomatoes.

This study focused on developing novel pyridine-3-carboxamide analogs to treat bacterial wilt in tomatoes caused by Ralstonia solanacearum. The analogs were synthesized through a multistep process and their structures confirmed using spectroscopy. Molecular docking studies identified the most potent analog from the series. A specific analog, compound 4a, was found to significantly enhance disease resistance in tomato plants infected with R. solanacearum. The structure-activity relationship analysis showed the positions and types of substituents on the aromatic rings of compounds 4a-i strongly influenced their biological activity. Compound 4a, with a chloro group at the para position on ring C and hydroxyl group at the ortho position on ring A, was exceptionally effective against R. solanacearum. When used to treat seeds, the analogs displayed remarkable efficacy, especially compound 4a which had specific activity against bacterial wilt pathogens. Compound 4a also promoted vegetative and reproductive growth of tomato plants, increasing seed germination and seedling vigor. In plants mechanically infected with bacteria, compound 4a substantially reduced the percentage of infection, pathogen quantity in young tissue, and disease progression. The analogs were highly potent due to their amide linkage. Molecular docking identified the best compounds with strong binding affinities. Overall, the strategic design and synthesis of these pyridine-3-carboxamide analogs offers an effective approach to targeting and controlling R. solanacearum and bacterial wilt in tomatoes.

Empagliflozin Ameliorates Bleomycin-Induced Pulmonary Fibrosis in Rats by Modulating Sesn2/AMPK/Nrf2 Signaling and Targeting Ferroptosis and Autophagy.

Pulmonary fibrosis (PF) is a life-threatening disorder that severely disrupts normal lung architecture and function, resulting in severe respiratory failure and death. It has no definite treatment. Empagliflozin (EMPA), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has protective potential in PF. However, the mechanisms underlying these effects require further elucidation. Therefore, this study aimed to evaluate the ameliorative effect of EMPA against bleomycin (BLM)-induced PF and the potential mechanisms. Twenty-four male Wister rats were randomly divided into four groups: control, BLM treated, EMPA treated, and EMPA+BLM treated. EMPA significantly improved the histopathological injuries illustrated by both hematoxylin and eosin and Masson's trichrome-stained lung tissue sections, as confirmed by electron microscopic examination. It significantly reduced the lung index, hydroxyproline content, and transforming growth factor ß1 levels in the BLM rat model. It had an anti-inflammatory effect, as evidenced by a decrease in the inflammatory cytokines' tumor necrosis factor alpha and high mobility group box 1, inflammatory cell infiltration into the bronchoalveolar lavage fluid, and the CD68 immunoreaction. Furthermore, EMPA mitigated oxidative stress, DNA fragmentation, ferroptosis, and endoplasmic reticulum stress, as evidenced by the up-regulation of nuclear factor erythroid 2-related factor expression, heme oxygenase-1 activity, glutathione peroxidase 4 levels, and a decrease in C/EBP homologous protein levels. This protective potential could be explained on the basis of autophagy induction via up-regulating lung sestrin2 expression and the LC3 II immunoreaction observed in this study. Our findings indicated that EMPA protected against BLM-induced PF-associated cellular stress by enhancing autophagy and modulating sestrin2/adenosine monophosphate-activated protein kinase/nuclear factor erythroid 2-related factor 2/heme oxygenase 1 signaling.

Green synthesis of MgO nanoparticles and its antibacterial properties.

Magnesium oxide nanostructured particles (NP) were prepared using a simple solution combustion technique using different leaf extracts such as Mangifera indica (Mango - Ma), Azadirachta indica (Neem-Ne), and Carica papaya (Papaya-Pa) as surfactants. The highly crystalline phase of MgO nanostructures was confirmed by PXRD and FTIR studies for 2 h 500°C calcined samples. To analyze the characteristics of obtained material-MaNP, NeNP, and PaNP for dosimetry applications, thermoluminescence (TL) studies were carried out for Co-60 gamma rays irradiated samples in the dose range 10-50 KGy; PaNP and NeNP exhibited well-defined glow curve when compared with MaNP samples. In addition, it was observed that the TL intensity decreases, with increase in gamma dose and the glow peak temperature is shifted towards the higher temperature with the increase in heating rate. The glow peak was segregated using glow curve deconvolution and thermal cleaning method. Kinetic parameters estimated using Chen's method, trap depth (E), and frequency factor (s) were found to be 0.699, 7.408, 0.4929, and 38.71, 11.008, and 10.71 for PaNP, NeNP, and MaNP respectively. The well-resolved glow curve, good linear behavior in the dose range of 10-50, KGy, and less fading were observed in PaNP as compared with MaNP and NeNP. Further, the antibacterial activity was checked against human pathogens such as Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. A visible zone of clearance was observed at 200 and 100 µg/mL by the PaNP and NeNP, indicating the death of colonies by the nanoparticles. Therefore, PaNP nanomaterial is a potential phosphor material for dosimetry and antibacterial application compared to NeNP and MaNP.

Coagulation Profile in COVID-19 Patients and its Relation to Disease Severity and Overall Survival: A Single-Center Study.

Objectives: This study aims to investigate hemostatic changes in patients with coronavirus disease (COVID-19) and their relationship to disease severity and survival. Methods: This study included 284 patients with COVID-19 who attended the Security Forces Hospital, Makkah, Saudi Arabia between October 2020 and March 2021, and retrospectively reviewed their demographic, radiological, and laboratory findings. The coagulation profile was assayed at the time of diagnosis for platelet counts using an automated hematology analyzer; Sysmex XN2000 while international normalized ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen, D-dimer, factor VIII, ristocetin cofactor (RiCoF), and von Willebrand factor antigen (VWF-Ag) were measured by Stago kits on a Stago automated coagulation analyzer (STA Compact Max®). Results: In this study, 32.3% of the cases had severe disease, while 8.8% of the cases died. D-dimer, factor VIII, and RiCoF were the only independent predictors of disease severity, with factor VIII and RiCoF having significantly higher areas under the curve (AUCs) than D-dimer (all p < 0.001). Furthermore, age, aPTT, and factor VIII were associated with an increased risk of mortality in multivariate Cox regression analysis, with factor VIII having a higher AUC of 0.98 than aPTT with an optimal cut-off value of >314 IU/dl in predicting mortality. Cases with factor VIII levels >314 IU/dl, compared to those with factor VIII levels <314 IU/dl, were associated with a significantly shorter mean overall survival time (20.08 vs. 31.35 days, p < 0.001), a lower survival rate (30.3% vs. 99.2%, p < 0.001), and a 16.62-fold increased mortality risk. Conclusion: RiCoF is a novel predictor of disease severity in COVID-19, while factor VIII is confirmed as a predictor of severity and mortality in COVID-19 patients and is associated with lower overall survival and increased mortality risk.

Prognostic relevance of combined IDH1 and NPM1 mutations in the intermediate cytogenetic de novo acute myeloid leukemia.

Despite the great advance in treatment, cytogenetically normal Acute myeloid leukemia (CN-AML) is still a challenging entity. The discovery of IDH1 mutation in AML together with the frequent co-mutations; NPM1 and FLT3-ITD throughs a new insight into the pathogenesis and outcome of CN-AML. Recently, there has been an increasing number of recurring mutations in other genes for which the forecasting effect is still required. Despite the large number of risk variables established, there are relatively few prognostic indicators that can help in treatment decisions in AML patients. This study aimed at recording the frequency of IDH1 and NPM1 mutations in newly diagnosed AML and, dual clinicopathological significance. IDH1 and NPM1 mutations were analyzed using High-Resolution Melting curve analysis PCR in 78 newly diagnosed AML patients; 30 pediatric and 48 adult AML patients. IDH1 mutation was detected in 6 out of the 48 adult AML cases (12.5%) and all of them had intermediate cytogenetic prognostic stratification. 5/6 mutant IDH1 patients showed NPM1 co-mutation (P-value= 0.008). Mutant IDH1 patients showed significant resistance to induction therapy (P-value <0.001) and even those who achieved complete remission were relapsed later. Within the intermediate cytogenetic group, the IDH1 mutated patients had short overall survival (HR 12.9, 95% CI (3.1- 53.45) and event-free survival (HR 15.7, 95% CI (2.99-82.72) and P-value <0.001). IDH1 mutation is closely linked to the intermediate cytogenetic stratified group and in particular old age patients and has a great impact on their survival.

Role of BAALC Gene in Prognosis of Acute Lymphoblastic Leukemia in Egyptian Children.

Acute lymphoblastic leukemia (ALL) is characterized by excess bone marrow lymphoblast cell production. Brain and Acute Leukemia Cytoplasmic gene (BAALC gene) is a recently identified gene on chromosome 8q22.3. The aim of this work was to study the role of BAALC gene in prognosis of ALL in Egyptian children. This study was conducted on 60 children with ALL who were admitted in Oncology Unit in the period from January 2012 to March 2015 including 36 males and 24 females with mean age of 8.74 ± 2.66 years. For all patients the following were done: Full history taking, thorough clinical examination and laboratory investigations including: complete blood count, LDH, bone marrow aspiration, cytochemistry, immunophenotyping, FISH technique for detection of t(12;21) and t(9;22) and assessment of BAALC gene expression by PCR in bone marrow aspirate mononuclear cells at diagnosis before chemotherapy. Positive BAALC gene expression was found in 36 patients (60%) and negative expression in 24 patients (40%). Positive BAALC gene expression group includes 14 males and 22 females with mean age at presentation of 8.45 ± 2.77 years while negative BAALC gene expression group includes 18 males and 6 females with mean age at presentation of 8.61 ± 2.44 years with no significant differences between positive and negative BAALC gene expression groups regarding age, sex, clinical presentations, WBCs and platelets counts, hemoglobin and LDH levels, peripheral blood and BM blast cell counts, immunophenotyping and chromosomal translocations including t(12;21) and t(9;22). There were significant differences in disease outcome between positive and negative BAALC gene expression groups with higher rate of relapse and death and lower rate of complete remission, disease free survival (DFS) and overall survival (OS) in positive BAALC gene expression group compared with negative group (p = 0.028). Multivariate analyses for overall survival and disease free survival shows significant role of BAALC gene expression in OS and DFS. BAALC expression might represent an additional prognostic marker in children with ALL and should be routinely assessed at diagnosis for better prognostic assessment.