Exploring and clinical validation of prognostic significance and therapeutic implications of copper homeostasis-related gene dysregulation in acute myeloid leukemia.

The patterns and biological functions of copper homeostasis-related genes (CHRGs) in acute myeloid leukemia (AML) remain unclear. We explored the patterns and biological functions of CHRGs in AML. Using independent cohorts, including TCGA-GTEx, GSE114868, GSE37642, and clinical samples, we identified 826 common differentially expressed genes. Specifically, 12 cuproptosis-related genes (e.g., ATP7A, ATP7B) were upregulated, while 17 cuproplasia-associated genes (e.g., ATOX1, ATP7A) were downregulated in AML. We used LASSO-Cox, Kaplan-Meier, and Nomogram analyses to establish prognostic risk models, effectively stratifying patients with AML into high- and low-risk groups. Subgroup analysis revealed that high-risk patients exhibited poorer overall survival and involvement in fatty acid metabolism, apoptosis, and glycolysis. Immune infiltration analysis indicated differences in immune cell composition, with notable increases in B cells, cytotoxic T cells, and memory T cells in the low-risk group, and increased monocytes and neutrophils in the high-risk group. Single-cell sequencing analysis corroborated the expression characteristics of critical CHRGs, such as MAPK1 and ATOX1, associated with the function of T, B, and NK cells. Drug sensitivity analysis suggested potential therapeutic agents targeting copper homeostasis, including Bicalutamide and Sorafenib. PCR validation confirmed the differential expression of 4 cuproptosis-related genes (LIPT1, SLC31A1, GCSH, and PDHA1) and 9 cuproplasia-associated genes (ATOX1, CCS, CP, MAPK1, SOD1, COA6, PDK1, DBH, and PDE3B) in AML cell line. Importantly, these genes serve as potential biomarkers for patient stratification and treatment. In conclusion, we shed light on the expression patterns and biological functions of CHRGs in AML. The developed risk models provided prognostic implications for patient survival, offering valuable information on the regulatory characteristics of CHRGs and potential avenues for personalized treatment in AML.

Usnic acid as potential inhibitors of BCL2 and P13K protein through network pharmacology-based analysis, molecular docking and molecular dynamic simulation.

Usnic acid (UA) lately piqued the interest of researchers for its extraordinary biological characteristics, including anticancer activity. Here, the mechanism was clarified through network pharmacology,molecular docking and molecular dynamic simulation. Sixteen proteins were selected through network pharmacology study as they are probable to interact with UA. Out of these proteins, 13 were filtered from PPI network analysis based on their significance of interactions (p < 0.05). KEGG pathway analysis has also aided us in determining the three most significant protein targets for UA, which are BCL2, PI3KCA and PI3KCG. Therefore molecular docking and molecular dynamic (MD) simulations throughout 100 ns were performed for usnic acid onto the three proteins mentioned. However, UA's docking score in all proteins is lower than their co-crystalised ligand, especially for BCL2 (-36.5158 kcal/mol) and PI3KCA (-44.5995 kcal/mol) proteins. The only exception is PI3KCG which has comparable results with the co-crystallised ligand with (-41.9351 kcal/mol). Furthermore, MD simulation has also revealed that usnic acid does not stay fit in the protein throughout the simulation trajectory for PI3KCA protein evident from RMSF and RMSD plots. Nevertheless, it still poses good ability in inhibiting BCL2 and PI3KCG protein in MD simulation. In the end, usnic acid has exhibited good potential in the inhibition of PI3KCG proteins, rather than the other proteins mentioned. Thus further study on structural modification of usnic acid could enhance the ability of usnic acid in the inhibition of PI3KCG as anti-colorectal and anti-small cell lung cancer drug candidate.Communicated by Ramaswamy H. Sarma.

The efficacy of deep learning based LSTM model in forecasting the outbreak of contagious diseases.

The coronavirus disease that outbreak in 2019 has caused various health issues. According to the WHO, the first positive case was detected in Bangladesh on 7th March 2020, but while writing this paper in June 2021, the total confirmed, recovered, and death cases were 826922, 766266 and 13118, respectively. Due to the emergence of COVID-19 in Bangladesh, the country is facing a major public health crisis. Unfortunately, the country does not have a comprehensive health policy to address this issue. This makes it hard to predict how the pandemic will affect the population. Machine learning techniques can help us detect the disease's spread. To predict the trend, parameters, risks, and to take preventive measure in Bangladesh; this work utilized the Recurrent Neural Networks based Deep Learning methodologies like LongShort-Term Memory. Here, we aim to predict the epidemic's progression for a period of more than a year under various scenarios in Bangladesh. We extracted the data for daily confirmed, recovered, and death cases from March 2020 to August 2021. The obtained Root Mean Square Error (RMSE) values of confirmed, recovered, and death cases indicates that our result is more accurate than other contemporary techniques. This study indicates that the LSTM model could be used effectively in predicting contagious diseases. The obtained results could help in explaining the seriousness of the situation, also mayhelp the authorities to take precautionary steps to control the situation.

Potential bioactive phytochemicals, antioxidant properties and anticancer pathways of Nymphaea nouchali

Objective: To investigate bioactive phytochemicals and antioxidant activities of Nymphaea nouchali and to explore its anticancer pathways by a network pharmacology approach.Methods: Using a spectrophotometer and high-performance liquid chromatography-diode array detector (HPLC-DAD), we quantified bioactive phytochemicals in methanolic extract of Nymphaea nouchali tuber. The extracts were investigated for in vitro antioxidant properties. Targets of these bioactive phytochemicals were predicted and anticancer-associated pathways were analyzed by a network pharmacology approach. Moreover, we identified the predicted genes associated with cancer pathways and the hub genes in the protein-protein interaction network of predicted genes. Results: Quantitative results indicated the total phenolics, total flavonoids, and total proanthocyanidins in the methanolic extract of Nymphaea nouchali tuber. HPLC-DAD analysis showed rutin (39.44 mg), catechin (39.20 mg), myricetin (30.77 mg), ellagic acid (11.05 mg), gallic acid (3.67 mg), vanillic acid (0.75 mg), rosmarinic acid (4.81 mg), p-coumaric acid (3.35 mg), and quercetin (0.90 mg) in 1 g of dry extract. The extract showed the radical scavenging activities of 2, 2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) and N,N-dimethyl-p-phenylenediamine. By using network pharmacology, we predicted 130 target genes associated with cancer pathways. The top hub genes (IL6, AKT1, EGFR, JUN, PTGS2, MAPK3, CASP3, and CXCL8) were also identified, which were associated with cancer pathways and interacted with bioactive phytochemicals of the methanolic extract of Nymphaea nouchali tuber. Conclusions: Our study provides insights into the mechanism of anticancer activities of the methanolic extract of Nymphaea nouchali tuber.

Clinical and Laboratory Characteristics of an Acute Chikungunya Outbreak in Bangladesh in 2017.

From April to September 2017, Bangladesh experienced a huge outbreak of acute Chikungunya virus infection in Dhaka. This series describes the clinical and laboratory features of a large number of cases (690; 399 confirmed and 291 probable) suffered during that period. This observational study was carried out at Dhaka Medical College Hospital, Bangladesh. The median age of the patients at presentation was 38 years (IQR 30-50) with a male (57.3%) predominance. Hypertension and diabetes were the most common comorbidities. The mean (±SD) duration of fever was 3.7 (±1.4) days. Other common manifestations were arthralgia (99.2%), maculopapular rash (50.2%), morning stiffness (49.7%), joint swelling (48.5%), and headache (37.6%). Cases were confirmed by anti-chikungunya IgG (173; 43.3%), IgM (165; 42.3%), and reverse transcription polymerase chain reaction (44; 11.0%). Important laboratory findings include high erythrocyte sedimentation rate (156; 22.6%), raised serum glutamic pyruvic transaminase (73; 10.5%), random blood sugar (54; 7.8%), leukopenia (72; 10.4%), thrombocytopenia (41; 5.9%), and others. The oligo-articular (453; 66.1%) variety of joint involvement was significantly more common compared with the poly-articular (237; 34.5%) variety. Commonly involved joints were the wrist (371; 54.1%), small joints of the hand (321; 46.8%), ankle (251; 36.6%), knee (240; 35.0%), and elbow (228; 33.2%). Eleven cases were found to be complicated with neurological involvement and two of them died. Another patient died due to myocarditis. Public health experts, clinicians, and policymakers could use the results of this study to construct the future strategy tackling chikungunya in Bangladesh and other epidemic countries.

Characterization of immunomodulatory activities of honey glycoproteins and glycopeptides.

Recent evidence suggests an important role for natural honey in modulating immune response. To identify active components responsible, this study investigated the immunomodulatory properties of glycoproteins and glycopeptides fractionated from Ziziphus honey. Honey proteins/peptides were fractionated by size exclusion chromatography into five peaks with molecular masses in the range of 2-450 kDa. The fractionated proteins exhibited potent, concentration-dependent inhibition of reactive oxygen species production in zymosan-activated human neutrophils (IC50 = 6-14 ng/mL) and murine macrophages (IC50 = 2-9 ng/mL). Honey proteins significantly suppressed the nitric oxide production by LPS-activated murine macrophages (IC50 = 96-450 ng/mL). Moreover, honey proteins inhibited the phagocytosis latex bead macrophages. The production of pro-inflammatory cytokines IL-1ß and TNF-α by human monocytic cell line in the presence of honey proteins was analyzed. Honey proteins did not affect the production of IL-1ß; however, TNF-α production was significantly suppressed. These findings indicated that honey glycoproteins and glycopeptides significantly interfere with molecules of the innate immune system.

Retinal microvascular structure and function in patients with risk factors of atherosclerosis and coronary artery disease.

OBJECTIVE: Retinal microvascular signs are markers of cardiovascular disease risk. There are limited data, on relationships between retinal microvascular signs and retinal microvascular endothelial function. We sought to determine the relationship of retinal vascular signs with retinal microvascular endothelial function in patients with or at high risk of coronary artery disease. METHODS: Participants with atherosclerosis risk factors and coronary disease (n=258; mean age 57±11 years) were recruited to have static and dynamic retinal vascular assessment. Retinal arteriolar dilatation in response to flicker light (FI-RAD) was measured using the Digital Vessel Analyser and expressed as percentage increase over baseline diameter. Static retinal photographs were acquired utilising a digital fundus camera for measurement of central retinal artery and vein equivalent (CRAE and CRVE), arteriovenous nicking (AVN) and focal arteriolar narrowing (FAN). RESULTS: Intra-class correlation coefficient was 0.82 for flicker-light induced retinal arteriolar dilatation. There were modest associations in retinal vascular measurements between eyes. For each 10 µm decrease in retinal arteriolar diameter, the absolute increase in FI-RAD was 0.28% (95% CI 0.11, 0.45; p=0.002) independent of age, gender and atherosclerosis risk factors. AVN and FAN were associated with attenuated FI-RAD (ß=-0.67%; 95% CI -1.20, -0.15; p=0.012) and (ß=-0.83%; 95% CI -1.44, -0.23; p=0.007) respectively after adjustment for age and gender. CONCLUSION: Assessment of retinal microvascular endothelial function is reproducible and correlated with retinal microvascular structure and signs, independent of atherosclerosis risk factors. Assessment of retinal vascular structure and function may provide insights into atherosclerotic disease.

Comprehensive proteome analysis of lettuce latex using multidimensional protein-identification technology.

Commercially, lettuce (Lactuca sativa) is one of the most important leafy vegetables. Lettuce produces a milky latex of variable chemical compositions within its laticifers. As a step toward understanding the main physiological roles of this latex in higher plants, we embarked on its proteomic analysis. We investigated 587 latex proteins that were identified from the lettuce latex using multidimensional protein-identification technology. A bioinformatics analysis showed that the most frequently encountered proteins in the latex were organellar proteins from plastids and mitochondria, followed by nucleic and cytoplasmic proteins. Functional classification of the identified proteins showed that proteins related to metabolism, cell rescue, defense, and virulence were the most abundant in lettuce latex. Furthermore, numerous resistance proteins of lettuce and viral proteins were present in the latex suggesting for the first time a possible function of the lettuce latex in defense or pathogenesis. To the knowledge of the authors, this is the first large-scale proteome analysis of lettuce latex.