Vol 27, No 5 (2024)

Chemistry

Combinatorial Study of Chemical Graphs

Liu J.
Combinatorial Chemistry & High Throughput Screening. 2024;27(5):649-649
pages 649-649 views

A Feature Selection Method Based on Graph Theory for Cancer Classification

Zhou K., Yin Z., Gu J., Zeng Z.

Abstract

Objective:Gene expression profile data is a good data source for people to study tumors, but gene expression data has the characteristics of high dimension and redundancy. Therefore, gene selection is a very important step in microarray data classification.

Method:In this paper, a feature selection method based on the maximum mutual information coefficient and graph theory is proposed. Each feature of gene expression data is treated as a vertex of the graph, and the maximum mutual information coefficient between genes is used to measure the relationship between the vertices to construct an undirected graph, and then the core and coritivity theory is used to determine the feature subset of gene data.

Results:In this work, we used three different classification models and three different evaluation metrics such as accuracy, F1-Score, and AUC to evaluate the classification performance to avoid reliance on any one classifier or evaluation metric. The experimental results on six different types of genetic data show that our proposed algorithm has high accuracy and robustness compared to other advanced feature selection methods.

Conclusion:In this method, the importance and correlation of features are considered at the same time, and the problem of gene selection in microarray data classification is solved.

Combinatorial Chemistry & High Throughput Screening. 2024;27(5):650-660
pages 650-660 views

Further Results for Some Eccentric Based Indices

Kirgiz H., Maden A.

Abstract

Background:Topological indices have a significant role in determining a molecule’s topology in the light of theoretical chemistry.

Objectives:This study aimed to find new bounds for some eccentric-based topological indices.

Methods:We used comparison theorem for integrals.

Results:We found new bounds for the eccentric-based harmonic index and atom-bond connectivity index. Our results are better than previous results in the literature.

Conclusion:This study has contributed to the chemical graph theory literature by giving a new method to find eccentric-based topological indices with lower and upper bounds.

Combinatorial Chemistry & High Throughput Screening. 2024;27(5):661-665
pages 661-665 views

Study for Some Eccentricity-based Topological Indices of Second Type of Dominating David-derived Network

Liu J., Ali H., Ali D., Umer A., Ali P., Kirmani S.A.

Abstract

Background:Dominating David-derived networks are widely studied due to their fractal nature, with applications in topology, chemistry, and computer sciences. The use of molecular structure descriptors is a standard procedure that is used to correlate the biological activity of molecules with their chemical structures, which can be useful in the field of pharmacology.

Objective:This article's goal is to develop analytically closed computing formulas for eccentricitybased descriptors of the second type of dominating David-derived network. Thermodynamic characteristics, physicochemical properties, and chemical and biological activities of chemical graphs are just a few of the many properties that may be determined using these computation formulas.

Methods:Vertex sets were initially divided according to their degrees, eccentricities, and cardinalities of occurrence. The eccentricity-based indices are then computed using some combinatorics and these partitions.

Results:Total eccentricity, average eccentricity, and the Zagreb index are distance-based topological indices utilized in this study for the second type of dominating David-derived network, denoted as D2(m).

Conclusion:These calculations will assist the readers in estimating the fractal and difficult-tohandle thermodynamic and physicochemical aspects of chemical structure. Apart from configuration and impact resistance, the D2(m) design has been used for fundamental reasons in a variety of technical and scientific advancements.

Combinatorial Chemistry & High Throughput Screening. 2024;27(5):666-673
pages 666-673 views

The Potential Effect of Dapsone on the Inflammatory Reactions in COVID-19: Staggering View

Al-Kuraishy H., Al-Gareeb A., Elekhnawy E., Alexiou A., Batiha G.E.

Abstract

Severe SARS-CoV-2 infection is linked with an overstated immune response with the succeeding release of pro-inflammatory cytokines and progression of the cytokine storm. In addition, severe SARS-CoV-2 infection is associated with the development of oxidative stress and coagulopathy. Dapsone (DPS) is a bacteriostatic antibiotic that has a potent anti-inflammatory effect. Thus, this mini-review aimed to elucidate the potential role of DPS in mitigating inflammatory disorders in COVID-19 patients. DPS inhibits neutrophil myeloperoxidase, inflammation, and neutrophil chemotaxis. Therefore, DPS could be effective against neutrophilia-induced complications in COVID-19. In addition, DPS could be effective in mitigating inflammatory and oxidative stress disorders by suppressing the expression of inflammatory signaling pathways and the generation of reactive oxygen species (ROS) correspondingly. In conclusion, DPS might be effective in the management of COVID-19 through the attenuation of inflammatory disorders. Therefore, preclinical and clinical studies are reasonable in this regard.

Combinatorial Chemistry & High Throughput Screening. 2024;27(5):674-678
pages 674-678 views

Vicatia thibetica de Boiss: Botany, Traditional Uses, Phytochemistry, Quantitative Analysis, and Pharmacology

Wang Q., He N., Qiu Y., Jiang W., Zhong G., Sang Z., Ma Q., Wei R.

Abstract

Background:Vicatia thibetica de Boiss is a common Tibetan medicine used for both medicine and food, belonging to the family Apiaceae. This plant has the functions of dispelling wind, removing dampness, dispersing cold, and relieving pain. It has great development potential and application prospects in food development and medicinal value.

Methods:The related references on botany, traditional uses, phytochemistry, quantitative analysis, and pharmacology of V. thibetica de Boiss had been retrieved from both online and offline databases, including PubMed, ScienceDirect, Web of Science, Elsevier, Willy, SpringLink, SciFinder, Google Scholar, Baidu Scholar, ACS publications, SciHub, Scopus, and CNKI.

Results:V. thibetica de Boiss exerts nourishing, appetizing, and digestive effects according to the theory of Tibetan medicine. Phytochemical reports have revealed that V. thibetica de Boiss contains flavonoids, coumarins, sterols, and organic acids. Meanwhile, the quantitative analysis of the chemical constituents of V. thibetica de Boiss has been done by means of UPLC-Q-TOF-MS. It has also been found that V. thibetica de Boiss possesses multiple pharmacological activities, including anti-fatigue, anti-oxidant, anti-aging, and non-toxic activities.

Conclusion:This paper has comprehensively summarized botany, traditional uses, phytochemistry, quantitative analysis, and pharmacology of V. thibetica de Boiss. It will not only provide an important clue for further studying V. thibetica de Boiss, but also offer an important theoretical basis and valuable reference for in-depth research and exploitation of this plant in the future.

Combinatorial Chemistry & High Throughput Screening. 2024;27(5):679-687
pages 679-687 views

Recent Advances in Biologically Active Ingredients from Natural Drugs for Sepsis Treatment

Zheng Z., Song X., Shi Y., Long X., Li J., Zhang M.

Abstract

Sepsis refers to the dysregulated host response to infection; its incidence and mortality rates are high. It is a worldwide medical problem but there is no specific drug for it. In recent years, clinical and experimental studies have found that many monomer components of traditional Chinese medicine have certain effects on the treatment of sepsis. This paper reviews the advances in research on the active ingredients of traditional Chinese medicine involved in the treatment of sepsis in recent years according to their chemical structure; it could provide ideas and references for further research and development in Chinese materia medica for the treatment of sepsis.

Combinatorial Chemistry & High Throughput Screening. 2024;27(5):688-700
pages 688-700 views

Natural Products as Monoamine Oxidase Inhibitors: Potential Agents for Neurological Disorders

Agrawal N., Bhardwaj A., Singh S., Goyal A., Gaurav A.

Abstract

The role of medicinal plants has been advantageous due to their manifestation through various cellular and molecular mechanisms. Inhibition of the monoamine oxidase enzyme is suspected to be a highly effective treatment for various neurological illnesses like Alzheimer's disease, Parkinson’s disease, depression, social phobia, and panic disorders. The study of phytochemicals and plant extracts used as a traditional source of medication revealed that they possess the vast potential for monoamine oxidase inhibition. Thus, the article focuses on the potential use of plant extracts and phytochemicals as sources of novel MAO inhibitors for treating neurological disorders. Exhaustive literature search revealed that a variety of phytochemicals from the categories such as flavonoids, alkaloids, glycosides, alkyl phenyl ketones, coumarin derivatives and essential oils have displayed potential MAO inhibition. This review highlights the progress made in the discovery and development of plant-based MAO inhibitors and aims to provide medicinal chemists with an overview of this information to aid in the development of clinically viable drugs.

Combinatorial Chemistry & High Throughput Screening. 2024;27(5):701-714
pages 701-714 views

Expression and Prognostic Role of PANK1 in Glioma

Zhao Z., Xu X., Ma S., Li L.

Abstract

Background:Malignant gliomas are the most common type of primary malignant brain tumors. Pantothenate kinase 1 (PANK1) mRNA is highly expressed in several metabolic processes, implying that PANK1 plays a potential role in metabolic programming in cancers. However, the role of PANK1 in glioma has not been fully explored.

Methods:Public datasets (The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Gravendeel and Rembrandt) and validation cohort were used to explore the expression of PANK1 in glioma tissues. Kaplan–Meier and Cox regression analyses were used to explore the relationship between PANK1 and prognosis in glioma. Cell proliferation and invasion were determined using Cell Counting Kit-8 (CCK8) and transwell invasion in vitro assays.

Results:Analysis using the four public datasets and the validation cohort showed that PANK1 expression was significantly downregulated in glioma tissues compared with non-tumor tissues (P(<0.01). PANK1 expression was negatively correlated with World Health Organization (WHO) grade, 1p/19q non-codeletion and isocitric dehydrogenase 1/2 (IDH1/2) wildtype. Furthermore, high expression of PANK1 was correlated with significantly better prognosis of glioma patients compared to patients with low expression of PANK1 (all P(<0.01 in the four datasets). Besides, both lower-grade glioma (LGG) and glioblastoma multiform (GBM) patients with high expression of PANK1 had a significantly better prognosis than those with low expression of PANK1 in TCGA, Gravendeel and Rembrandt datasets (all P (<0.01). Multivariate Cox regression analysis revealed that low PANK1 expression was an independent risk factor associated with a worse prognosis of glioma patients. Moreover, overexpression of PANK1 significantly inhibited the proliferation and invasion of U87 and U251 cells.

Conclusion:PANK1 expression is downregulated in glioma tissues and is a novel prognostic biomarker in glioma patients

Combinatorial Chemistry & High Throughput Screening. 2024;27(5):715-724
pages 715-724 views

LncRNA SNHG25 Predicts Poor Prognosis and Promotes Progression in Osteosarcoma via the miR-497-5p/SOX4 Axis

Wan N., Liu Q., Shi J., Wang S.

Abstract

Background:Osteosarcoma is a disease that primarily affects adolescents with skeletal immaturity. LncRNAs are abnormally expressed and correlated with osteosarcoma patients' prognosis. We identified aberrant expression of LncRNA SNHG25 (small nucleolar RNA host gene 25) in osteosarcoma and analyzed the molecular mechanisms by which it regulates osteosarcoma progression.

Methods:The expression levels of SNHG25 in tumour specimens and cells were measured by RTqPCR. Loss-of-function assays were conducted to investigate the functional role of SNHG25 in vitro and in vivo. Bioinformatic predictions, dual-luciferase reporter assays, and western blotting were performed to explore the possible underlying mechanisms.

Results:SNHG25 was highly expressed in osteosarcoma cells and tissues. The Kaplan–Meier curve showed that the survival rate of patients with high SNHG25 expression was significantly lower than those with low SNHG25 expression. Functional studies have indicated that inhibition of SNHG25 suppresses cell proliferation, migration, and invasion, while promoting apoptosis. SNHG25 knockdown suppresses osteosarcoma tumour growth in vivo. SNHG25 functions as a sponge for miR-497-5p in osteosarcoma cells. The level of SNHG25 was negatively correlated with that of miR-497-5p. The proliferation, invasion, and migration of osteosarcoma cells were restored by transfection of the miR-497-5p inhibitor in the SNHG25 knockdown group

Conclusion:SNHG25 was determined to function as an oncogene by promoting osteosarcoma cell proliferation, invasion, and migration through the miR-497-5p/SOX4 axis. Upregulation of SNHG25 expression indicated poor prognosis in patients with osteosarcoma, which showed that SNHG25 may serve as a potential therapeutic target and prognostic biomarker in osteosarcoma.

Combinatorial Chemistry & High Throughput Screening. 2024;27(5):725-744
pages 725-744 views

HTNpedia: A Knowledge Base for Hypertension Research

Loganathan L., Jeyaraman J., Muthusamy K.

Abstract

Background:Hypertension is notably a serious public health concern due to its high prevalence and strong association with cardiovascular disease and renal failure. It is reported to be the fourth leading disease that leads to death worldwide.

Objective:Currently, there is no active operational knowledge base or database for hypertension or cardiovascular illness.

Methods:The primary data source was retrieved from the research outputs obtained from our laboratory team working on hypertension research. We have presented a preliminary dataset and external links to the public repository for detailed analysis to readers.

Results:As a result, HTNpedia was created to provide information regarding hypertension-related proteins and genes.

Conclusion:The complete webpage is accessible via www.mkarthikeyan.bioinfoau.org/HTNpedia.

Combinatorial Chemistry & High Throughput Screening. 2024;27(5):745-753
pages 745-753 views

Integrated Network Pharmacology and Metabolomics to Dissect the Mechanisms of Naringin for Treating Cervical Cancer

Yin Z., Hua X., Lu M.

Abstract

Introduction:Cervical cancer is one of the malignant cancers with high mortality among women worldwide. Although vaccines and early detection have reduced cervical cancer mortality, it remains a malignancy with a high mortality rate in women.

Objective:We aimed to develop a novel integrated strategy that combines metabolomics with network pharmacology to explore the therapeutic mechanisms of naringin in cervical cancer. The mechanism of naringin intervention in cervical cancer was initially clarified by metabolomics and network pharmacology.

Methods:The method of LC-MS and network pharmacology for the detection and identification of potential biomarkers and the mechanisms of action of naringin was used. The metabolites were detected and identified based on ultra-high-performance liquid chromatography coupled with Quadrupole- Exactive Orbitrap MS (UHPLC-Q-Exactive Orbitrap MS) and followed by the network pharmacology analysis.

Results:In network pharmacology, naringin played a synergetic role through regulatory shared pathways, such as steroid hormone biosynthesis, sphingolipid signaling pathway and arachidonic acid metabolism, etc. Besides, the metabolomics analysis showed that 20 differential metabolites and 10 metabolic pathways were mainly involved in the therapeutic effect of naringin on cervical cancer. The result showed that naringin treatment for cervical cancer mainly occurs through the following metabolic pathways: amino acid metabolism and arachidonic acid metabolism.

Conclusion:This work provided valuable information and a scientific basis for further studies of naringin in the treatment of cervical cancer.

Combinatorial Chemistry & High Throughput Screening. 2024;27(5):754-764
pages 754-764 views

Evaluation of the Antioxidant and Anti-inflammatory Activity of the Anacyclus Valentinus L. Essential Oil and its Oxygenated Fraction

Ainseba N., Soulimane A., Mami I., Dib M.E., Muselli A.

Abstract

Aim and Objective:Synthetic antioxidants and anti-inflammatories are widely used by the food and pharmaceutical industries. Like any synthetic product, these are toxic and represent a significant health risk. The objective of this study was to determine the chemical composition of Anacyclus valentinus essential oil and its oxygenated fraction, as well as their in-vitro antioxidant and anti-inflammatory properties.

Methods:The essential oil was hydrodistilled using a Clevenger-type device and the oxygenated fraction was obtained by column chromatography using diethyl ether. The essential oil and its oxygenated fraction were analysed by GC and GC/MS. The antioxidant activities were performed using three different methods Radical scavenging activity (DPPH), β-carotene bleaching test, and the Ferric-Reducing Antioxidant Power (FRAP), using BHT as a positive control. The activity of antiinflammatory of essential oil and its oxygenated fraction was assessed by the protein denaturation method using the diclofenac sodium as a positive control.

Results:The essential oil of Anacyclus valentinus was represented mainly by oxygenated sesquiterpene compounds (37.7%), hydrocarbon sesquiterpenes (14.7%), oxygenated monoterpenes (18.4%) and non-terpenic compounds (15.6%). The oxygenated fraction was composed mainly of oxygenated sesquiterpenes (40.6%), oxygenated monoterpenes (38.5%), and non-terpene compounds (19.4%). Essential oil and oxygenated fraction showed antioxidant activity. The most potent activity was observed by the oxygenated fraction in the DPPH (IC50 = 8.2 mL/L) and β- carotene bleaching (IC50 = 5.6 mL/L) tests. While the essential oil of A. valentinus showed very good anti-inflammatory activity with an IC50 of 0.3 g/L higher than that of diclofenac (IC50= 0.53 g/L).

Conclusion:The results showed that the essential oil and the oxygenated fraction of A. valentinus are rich in sesquiterpene compounds and possess interesting antioxidant and anti-inflammatory properties. However, other studies are necessary to be able to offer these extracts to the pharmaceutical and food industries.

Combinatorial Chemistry & High Throughput Screening. 2024;27(5):765-772
pages 765-772 views

Therapeutic Effect and Mechanism Prediction of Fuzi-Gancao Herb Couple on Non-alcoholic Fatty Liver Disease (NAFLD) based on Network Pharmacology and Molecular Docking

Liu K., Yang X., Zhang G., Xiang Z.

Abstract

Background:Fuzi-Gancao herb couple is one of the most common herb couples involved in the TCM formula, which was used for the treatment of chronic diseases. The herb couple has a hepatoprotective effect. However, its main components and therapeutic mechanism are not yet clear. This study aims to elucidate the therapeutic effect and mechanism of the Fuzi-Gancao herb couple on NAFLD from animal experiments, network pharmacology, and molecular docking.

Methods:60 Male C57BL/6 mice (20 g ± 2 g) were randomly divided into six groups including the blank group (n=10) and NALFD group (n=50). The mice of the NALFD group were fed with a high-fat diet for 20 weeks to establish the NAFLD model and the NALFD mice were randomly divided into five groups including positive group (berberine), model group and F-G groups with three dosages (0.257, 0.514, 0.771 g/kg) (n=10). After 10 weeks of administration, the serum was collected for the analysis of ALT, AST, LDL-c, HDL-c, and TC, and liver tissues were collected for pathological analysis. The TCMAS database was used to collect the main components and targets of the Fuzi-Gancao herb couple. The GeneCards database was used to collect NAFLD-related targets, and the key targets were obtained by intersecting with herbal targets. The diseasecomponent- target relationship diagram was constructed by Cytoscape 3.9.1. The obtained key targets were imported into the String database to obtain the PPI network, and imported into the DAVID database for KEGG pathway analysis and GO analysis. Finally, the key targets and key gene proteins were imported into Discovery Studio 2019 for molecular docking verification.

Results:In this study, H-E staining indicated the pathological changes of liver tissue in Fuzi- Gancao groups were significantly improved, and the levels of AST, ALT, TC, HDL-c, and LDL-c in serum of Fuzi-Gancao groups decreased in a dose-dependent manner, compared with the model group. 103 active components and 299 targets in the Fuzi-Gancao herb couple were confirmed in the TCMSP database and 2062 disease targets in NAFLD were obtained. 142 key targets and 167 signal pathways were screened, such as the AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, IL-17 signaling pathway, TNF signaling pathway, and so on. The main bioactive ingredients of Fuzi-Gancao herb couple in the treatment of NAFLD are quercetin, kaempferol, naringenin, inermine, (R)-norcoclaurine, isorhamnetin, ignavine, 2,7-Dideacetyl-2,7- dibenzoyl-taxayunnanine F, glycyrol mainly involving IL6, AKT1, TNF, TP53, IL1B, VEGFA and other core targets. Molecular docking analysis indicated that there is a good affinity between the key components and the key targets.

Conclusion:This study preliminarily explained the main components and mechanism of the Fuzi- Gancao herb couple in the treatment of NAFLD and provided an idea for subsequent research.

Combinatorial Chemistry & High Throughput Screening. 2024;27(5):773-785
pages 773-785 views

Ziyin Bushen Fang improves Diabetic Osteoporosis by Inhibiting Autophagy and Oxidative Stress In vitro and In vivo

Jiang B., Mou Y., Zhang X., Lu K., Xie P., Rao Y., Cong Z., Sun Q.g.

Abstract

Objective::Diabetic osteoporosis (DOP) belongs to the group of diabetes-induced secondary osteoporosis and is the main cause of bone fragility and fractures in many patients with diabetes. The aim of this study was to determine whether Ziyin Bushen Fang (ZYBSF) can improve DOP by inhibiting autophagy and oxidative stress.

background:The aim of this experiment is to study whether Ziyin Bushen Fang (ZYBSF) can treat DOP through autophagy and oxidative stress.

Methods::Type 1 diabetes mellitus (T1DM) was induced in rats using a high-fat high-sugar diet combined with streptozotocin. Micro-CT scanning was used to quantitatively observe changes in the bone microstructure in each group. Changes in the serum metabolites of DOP rats were analyzed using UHPLC-QTOF-MS. The DOP mouse embryonic osteoblast precursor cell model (MC3T3-E1) was induced using high glucose levels.

Results::After ZYBSF treatment, bone microstructure significantly improved. The bone mineral density, trabecular number, and trabecular thickness in the ZYBSF-M and ZYBSF-H groups significantly increased. After ZYBSF treatment, the femur structure of the rats was relatively intact, collagen fibers were significantly increased, and osteoporosis was significantly improved. A total of 1239 metabolites were upregulated and 1527 were downregulated in the serum of T1DM and ZYBSF-treated rats. A total of 20 metabolic pathways were identified. In cellular experiments, ZYBSF reduced ROS levels and inhibited the protein expression of LC3II / I, Beclin-1, and p- ERK.

Conclusion::ZYBSF may improve DOP by inhibiting the ROS/ERK-induced autophagy signaling pathway.

Combinatorial Chemistry & High Throughput Screening. 2024;27(5):786-796
pages 786-796 views