Current Issues in Molecular Biology

14 pages, 4872 KiB

Open AccessArticle

Lycopus lucidus Turcz Water Extract Ameliorates the Metabolic Disorder by Up-Regulated Major Urinary Protein Expression in High-Fat Diet-Induced Obesity

by Youngji Han, Ji-Young Choi and Eun-Young Kwon

Curr. Issues Mol. Biol. 2022, 44(5), 2417-2430; https://doi.org/10.3390/cimb44050165 - 23 May 2022

Cited by 2 | Viewed by 2450

Abstract

Despite a century of research on obesity, metabolic disorders and their complications, including dyslipidemia, insulin resistance, and fatty liver disease remain a serious global health problem. Lycopus lucidus Turcz (LT) is a traditional medicine used for its anti-inflammatory properties that has not been [...] Read more.

Despite a century of research on obesity, metabolic disorders and their complications, including dyslipidemia, insulin resistance, and fatty liver disease remain a serious global health problem. Lycopus lucidus Turcz (LT) is a traditional medicine used for its anti-inflammatory properties that has not been evaluated for its efficacy in improving obesity. In this study, mice were fed a normal diet (n = 10) or obesity was induced with a high-fat diet (HFD, n = 20, 60% kcal from fat) for 4 weeks. The HFD mice were then divided into two groups, one of which received LT supplementation with water extract for 13 weeks [HFD (n = 10) or HFD with LT water extract (n = 10, 1.5%)]. LT reduced body and adipose tissue weight by elevating energy expenditure by increasing fatty oxidation in epididymal white adipose tissue (eWAT) and muscle. LT ameliorated dyslipidemia and hepatic steatosis by restricting lipogenesis. Additionally, LT normalized the impaired glucose homeostasis by diet-induced obesity to improve pancreatic islet dysfunction with increasing hepatic major urinary protein expression. Moreover, LT attenuated the inflammation and collagen accumulation in the liver and eWAT. In conclusion, these results suggest that LT can treat obesity-related metabolic disorders such as adiposity, dyslipidemia, hepatic steatosis, insulin resistance, and inflammation. Full article

(This article belongs to the Section Bioorganic Chemistry and Medicinal Chemistry)

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16 pages, 2260 KiB

Open AccessArticle

Release of Endocannabinoids into the Cerebrospinal Fluid during the Induction of the Trigemino-Hypoglossal Reflex in Rats

by Marek Zubrzycki, Maria Zubrzycka, Grzegorz Wysiadecki, Janusz Szemraj, Hanna Jerczynska and Mariusz Stasiolek

Curr. Issues Mol. Biol. 2022, 44(5), 2401-2416; https://doi.org/10.3390/cimb44050164 - 23 May 2022

Viewed by 2458

Abstract

The endocannabinoid system (ECS) plays an important role in pain processing and modulation. Since the specific effects of endocannabinoids within the orofacial area are largely unknown, we aimed to determine whether an increase in the endocannabinoid concentration in the cerebrospinal fluid (CSF) caused [...] Read more.

The endocannabinoid system (ECS) plays an important role in pain processing and modulation. Since the specific effects of endocannabinoids within the orofacial area are largely unknown, we aimed to determine whether an increase in the endocannabinoid concentration in the cerebrospinal fluid (CSF) caused by the peripheral administration of the FAAH inhibitor URB597 and tooth pulp stimulation would affect the transmission of impulses between the sensory and motor centers localized in the vicinity of the third and fourth cerebral ventricles. The study objectives were evaluated on rats using a method that allowed the recording of the amplitude of evoked tongue jerks (ETJ) in response to noxious tooth pulp stimulation and URB597 treatment. The amplitude of ETJ was a measure of the effect of endocannabinoids on the neural structures. The concentrations of the endocannabinoids tested (AEA and 2-AG) were determined in the CSF, along with the expression of the cannabinoid receptors (CB1 and CB2) in the tissues of the mesencephalon, thalamus, and hypothalamus. We demonstrated that anandamide (AEA), but not 2-arachidonoylglycerol (2-AG), was significantly increased in the CSF after treatment with a FAAH inhibitor, while tooth pulp stimulation had no effect on the AEA and 2-AG concentrations in the CSF. We also found positive correlations between the CSF AEA concentration and cannabinoid receptor type 1 (CB1R) expression in the brain, and between 2-AG and cannabinoid receptor type 2 (CB2R), and negative correlations between the CSF concentration of AEA and brain CB2R expression, and between 2-AG and CB1R. Our study shows that endogenous AEA, which diffuses through the cerebroventricular ependyma into CSF and exerts a modulatory effect mediated by CB1Rs, alters the properties of neurons in the trigeminal sensory nuclei, interneurons, and motoneurons of the hypoglossal nerve. In addition, our findings may be consistent with the emerging concept that AEA and 2-AG have different regulatory mechanisms because they are involved differently in orofacial pain. We also suggest that FAAH inhibition may offer a therapeutic approach to the treatment of orofacial pain. Full article

(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)

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14 pages, 2796 KiB

Open AccessArticle

Antioxidant Activity of Vitamin C against LPS-Induced Septic Cardiomyopathy by Down-Regulation of Oxidative Stress and Inflammation

by Ayed A. Shati, Mohamed Samir A. Zaki, Youssef A. Alqahtani, Saleh M. Al-Qahtani, Mohamed A. Haidara, Amal F. Dawood, Asmaa M. AlMohanna, Mahmoud H. El-Bidawy, Muhammad Alaa Eldeen and Refaat A. Eid

Curr. Issues Mol. Biol. 2022, 44(5), 2387-2400; https://doi.org/10.3390/cimb44050163 - 23 May 2022

Cited by 9 | Viewed by 2800

Abstract

In severe cases of sepsis, endotoxin-induced cardiomyopathy can cause major damage to the heart. This study was designed to see if Vitamin C (Vit C) could prevent lipopolysaccharide-induced heart damage. Eighteen Sprague Dawley male rats (n = 6) were divided into three [...] Read more.

In severe cases of sepsis, endotoxin-induced cardiomyopathy can cause major damage to the heart. This study was designed to see if Vitamin C (Vit C) could prevent lipopolysaccharide-induced heart damage. Eighteen Sprague Dawley male rats (n = 6) were divided into three groups. Rats received 0.5 mL saline by oral gavage in addition to a standard diet (Control group), rats received one dose of endotoxin on day 15 (lipopolysaccharide) (LPS) (6 mg/kg), which produced endotoxemia (Endotoxin group), and rats that received 500 mg/Kg BW of Vit C by oral gavage for 15 days before LPS administration (Endotoxin plus Vit C group). In all groups, blood and tissue samples were collected on day 15, six hours after LPS administration, for histopathological and biochemical analysis. The LPS injection lowered superoxide dismutase (SOD) levels and increased malondialdehyde in tissues compared with a control group. Furthermore, the endotoxin group showed elevated inflammatory biomarkers, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Both light and electron microscopy showed that the endotoxic-treated group’s cardiomyocytes, intercalated disks, mitochondria, and endothelial cells were damaged. In endotoxemic rats, Vit C pretreatment significantly reduced MDA levels and restored SOD activity, minimized biomarkers of inflammation, and mitigated cardiomyocyte damage. In conclusion: Vit C protects against endotoxin-induced cardiomyopathy by inhibiting oxidative stress cytokines. Full article

(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)

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13 pages, 1685 KiB

Open AccessArticle

Methods for Collection of Extracellular Vesicles and Their Content RNA as Liquid Biopsy for Lung Cancer Detection: Application of Differential Centrifugation and Annexin A5 Coated Beads

by Mei-Chia Wang, Guan-Yu Gong, Chih-Liang Wang, How-Wen Ko, Rong-Xuan Weng, Pi-Yueh Chang and Chiuan-Chian Chiou

Curr. Issues Mol. Biol. 2022, 44(5), 2374-2386; https://doi.org/10.3390/cimb44050162 - 23 May 2022

Cited by 6 | Viewed by 2650

Abstract

Extracellular vesicles (EVs) contain abundant extracellular RNA (exRNA), which can be a valuable source of liquid biopsy. However, as various RNA species exist in different types of EVs, lack of detailed characterization of these RNA species and efficient collection methods limits the clinical [...] Read more.

Extracellular vesicles (EVs) contain abundant extracellular RNA (exRNA), which can be a valuable source of liquid biopsy. However, as various RNA species exist in different types of EVs, lack of detailed characterization of these RNA species and efficient collection methods limits the clinical application of exRNA. In the present study, we measured two mRNAs, CK19 and PCTK1; one lncRNA, MALAT1; and two miRNAs, miR21 and miR155, in different EV fractions separated by differential centrifugation or captured by magnetic beads coated with annexin A5 (ANX beads). The results showed that in a cultured medium, the majority of mRNA and lncRNA exist in larger EVs, whereas miRNA exist in both large and small EVs from the differential centrifugation fractions. All these RNA species exist in ANX beads captured EVs. We then used ANX beads to capture EVs in plasma samples from non-small-cell lung cancer patients and age-matched healthy volunteers. We found that the ANX bead capturing could efficiently improve RNA detection from human plasma, compared with direct extraction of RNA from plasma. Using ANX-bead capturing and reverse transcription and quantitative PCR, we detected significantly higher levels of CK19 mRNA, MALAT1 lncRNA, and miR155 miRNA in the plasma of lung cancer patients. These facts suggested the collection methods strongly affect the results of exRNA measurement from EVs, and that ANX beads can be a useful tool for detecting exRNA from plasma samples in clinical application. Full article

(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)

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12 pages, 1184 KiB

Open AccessReview

The Protective Role of 4-Acetylarylquinolinol B in Different Pathological Processes

by Huijie Zhao, Huiyang Liu, Yihan Yang and Honggang Wang

Curr. Issues Mol. Biol. 2022, 44(5), 2362-2373; https://doi.org/10.3390/cimb44050161 - 23 May 2022

Viewed by 2412

Abstract

Antrodia cinnamomea is a traditional plant and a unique fungus native to Taiwan that has been reported to have many biological functions, including anti-inflammatory and anticancer activities. The compound 4-acetylarylquinolinol B (4-AAQB) is one of the main bioactive compounds in the stamens of [...] Read more.

Antrodia cinnamomea is a traditional plant and a unique fungus native to Taiwan that has been reported to have many biological functions, including anti-inflammatory and anticancer activities. The compound 4-acetylarylquinolinol B (4-AAQB) is one of the main bioactive compounds in the stamens of Antrodia cinnamomea, and has many biological functions, such as anti-inflammatory, antiproliferative, blood sugar reduction, antimetastasis, and vascular tone relaxation. In recent years, the increasing evidences have shown that 4-AAQB is involved in many diseases; however, the relevant mechanisms have not been fully clarified. This review aimed to clarify the improvement by 4-AAQB in different pathological processes, as well as the compound’s molecular mechanisms, in order to provide a theoretical reference for future related research Full article

(This article belongs to the Collection Application of Natural and Pseudo Natural Products in Drug Discovery and Development)

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12 pages, 906 KiB

Open AccessReview

Rice Lesion Mimic Gene Cloning and Association Analysis for Disease Resistance

by Anpeng Zhang, Hongzhen Jiang, Huangwei Chu, Liming Cao and Jingguang Chen

Curr. Issues Mol. Biol. 2022, 44(5), 2350-2361; https://doi.org/10.3390/cimb44050160 - 22 May 2022

Cited by 10 | Viewed by 3864

Abstract

Lesion mimic mutants refer to a class of mutants that naturally form necrotic lesions similar to allergic reactions on leaves in the absence of significant stress or damage and without being harmed by pathogens. Mutations in most lesion mimic genes, such as OsACL-A2 [...] Read more.

Lesion mimic mutants refer to a class of mutants that naturally form necrotic lesions similar to allergic reactions on leaves in the absence of significant stress or damage and without being harmed by pathogens. Mutations in most lesion mimic genes, such as OsACL-A2 and OsSCYL2, can enhance mutants’ resistance to pathogens. Lesion mimic mutants are ideal materials for studying programmed cell death (PCD) and plant defense mechanisms. Studying the genes responsible for the rice disease-like phenotype is of great significance for understanding the disease resistance mechanism of rice. In this paper, the nomenclature, occurrence mechanism, genetic characteristics, regulatory pathways, and the research progress on the cloning and disease resistance of rice lesion mimic mutant genes were reviewed, in order to further analyze the various lesion mimic mutants of rice. The mechanism lays a theoretical foundation and provides a reference for rice breeding. Full article

(This article belongs to the Special Issue Functional Genomics and Comparative Genomics Analysis in Plants)

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15 pages, 1633 KiB

Open AccessArticle

Neuropharmacological and Antidiarrheal Potentials of Duabanga grandiflora (DC.) Walp. Stem Bark and Prospective Ligand–Receptor Interactions of Its Bioactive Lead Molecules

by Israt Jahan, Mohammad Forhad Khan, Mohammed Abu Sayeed, Laiba Arshad, Md. Amjad Hossen, Md. Jakaria, Duygu Ağagündüz, Md. Areeful Haque and Raffaele Capasso

Curr. Issues Mol. Biol. 2022, 44(5), 2335-2349; https://doi.org/10.3390/cimb44050159 - 20 May 2022

Cited by 19 | Viewed by 3378

Abstract

Duabanga grandiflora (DC.) Walp. is an ethnomedicinally significant plant used to treat various illnesses, but there is little scientific evidence to support its use. This study explored the pharmacological activities of methanol extract of D. grandiflora stem barks (MEDG) through in vivo approaches [...] Read more.

Duabanga grandiflora (DC.) Walp. is an ethnomedicinally significant plant used to treat various illnesses, but there is little scientific evidence to support its use. This study explored the pharmacological activities of methanol extract of D. grandiflora stem barks (MEDG) through in vivo approaches in Swiss albino mice and a computer-aided molecular approach. The forced swimming test (FST), tail suspension test (TST), elevated plus maze (EPM), and hole board test (HBT) were used to determine anti-depressant and anxiolytic activity in experimental mice. In addition, anti-diarrheal studies were performed using castor oil-induced diarrhea, castor oil-induced enter pooling, and the charcoal-induced gastrointestinal motility test. MEDG showed substantial depletions in the immobility times in both FST and TST after treatment with the MEDG extract, whereas moderate anxiolytic activity was manifested at a higher dose (400 mg/kg) compared with the control. Correspondingly, MEDG extract revealed a significant reduction in wet feces and decreased the small intestinal transit of charcoal meal in castor oil-induced diarrhea and charcoal-induced gastrointestinal motility test. In the computer-aided molecular approaches, vanillin displayed a promising binding score for both anxiolytic and anti-diarrheal activities, while duabanganal C showed a promising score for the anti-depressant activity. The present experimental findings along with a computer-aided model conclude that MEDG could be a possible Phyto therapeutic agent with potential anti-depressant, anxiolytic and anti-diarrheal activity. Full article

(This article belongs to the Special Issue Involvement of Medicinal Plants and Food in the Molecular Mechanisms of Disease Prevention)

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14 pages, 1822 KiB

Open AccessArticle

In Vitro Assessment of Bio-Functional Properties from Lactiplantibacillus plantarum Strains

by Francesco Letizia, Gianluca Albanese, Bruno Testa, Franca Vergalito, Diletta Bagnoli, Catello Di Martino, Petronia Carillo, Lucia Verrillo, Mariantonietta Succi, Elena Sorrentino, Raffaele Coppola, Patrizio Tremonte, Silvia Jane Lombardi, Roberto Di Marco and Massimo Iorizzo

Curr. Issues Mol. Biol. 2022, 44(5), 2321-2334; https://doi.org/10.3390/cimb44050158 - 19 May 2022

Cited by 17 | Viewed by 3699

Abstract

In recent years, alongside the conventional screening procedures for the evaluation of probiotics for human usage, the pharmaceutical and food industries have encouraged scientific research towards the selection of new probiotic bacterial strains with particular functional features. Therefore, this study intended to explore [...] Read more.

In recent years, alongside the conventional screening procedures for the evaluation of probiotics for human usage, the pharmaceutical and food industries have encouraged scientific research towards the selection of new probiotic bacterial strains with particular functional features. Therefore, this study intended to explore novel functional properties of five Lactiplantibacillus plantarum strains isolated from bee bread. Specifically, antioxidant, antimicrobial and β-glucosidase activities, exopolysaccharides (EPS) production and the ability to synthesize γ-aminobutyric acid (GABA) were evaluated. The results demonstrated that the investigated L. plantarum strains were effective in inhibiting the growth of some human opportunistic pathogens in vitro (Pseudomonas aeruginosa, Escherichia coli, Proteus mirabilis, Enterococcus faecalis and Staphylococcus aureus). Moreover, the evaluation of antioxidant and β-glucosidase activity and of EPS and GABA production, revealed a different behavior among the strains, testifying how these properties are strongly strain-dependent. This suggests that a careful selection within a given species is important in order to identify appropriate strains for specific biotechnological applications. The results highlighted that the five strains of L. plantarum are promising candidates for application as dietary supplements in the human diet and as microbial cultures in specific food productions. Full article

(This article belongs to the Collection Feature Papers in Current Issues in Molecular Biology)

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12 pages, 1646 KiB

Open AccessReview

Ovarian Stem Cells (OSCs) from the Cryopreserved Ovarian Cortex: A Potential for Neo-Oogenesis in Women with Cancer-Treatment Related Infertility: A Case Report and a Review of Literature

by Erica Silvestris, Carla Minoia, Attilio Guarini, Giuseppina Opinto, Antonio Negri, Miriam Dellino, Raffaele Tinelli, Gennaro Cormio, Angelo Virgilio Paradiso and Giuseppe De Palma

Curr. Issues Mol. Biol. 2022, 44(5), 2309-2320; https://doi.org/10.3390/cimb44050157 - 19 May 2022

Cited by 7 | Viewed by 3418

Abstract

Cancer treatment related infertility (CTRI) affects more than one third of young women undergoing anti-cancer protocols, inducing a premature exhaustion of the ovarian reserve. In addition to ovarian suppression by GnRHa, oocyte and cortex cryopreservation has gained interest in patients with estrogen-sensitive tumors [...] Read more.

Cancer treatment related infertility (CTRI) affects more than one third of young women undergoing anti-cancer protocols, inducing a premature exhaustion of the ovarian reserve. In addition to ovarian suppression by GnRHa, oocyte and cortex cryopreservation has gained interest in patients with estrogen-sensitive tumors for whom the hormonal burst to prompt the multiple follicular growth could provide a further pro-life tumor pulsing. On the other hand, cortex reimplantation implies a few drawbacks due to the unknown consistency of the follicles to be reimplanted or the risk of reintroducing malignant cells. The capability of ovarian stem cells (OCSs) from fresh ovarian cortex fragments to differentiate in vitro to mature oocytes provides a tool to overcome these drawbacks. In fact, since ovarian cortex sampling and cryopreservation is practicable before gonadotoxic treatments, the recruitment of OSCs from defrosted fragments could provide a novel opportunity to verify their suitability to be expanded in vitro as oocyte like cells (OLCs). Here, we describe in very preliminary experiments the consistency of an OSC population from a single cryopreserved ovarian cortex after thawing as well as both their viability and their suitability to be further explored in their property to differentiate in OLCs, thus reinforcing interest in stemness studies in the treatment of female CTRI. Full article

(This article belongs to the Special Issue Recent Advances in Ovarian Stem Cells)

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9 pages, 1743 KiB

Open AccessArticle

Odontogenic Differentiation-Induced Tooth Regeneration by Psoralea corylifolia L.

by Hye-Ock Jang, Tea-Young Ahn, Ji-Min Ju, Soo-Kyung Bae, Hyung-Ryong Kim and Da-Sol Kim

Curr. Issues Mol. Biol. 2022, 44(5), 2300-2308; https://doi.org/10.3390/cimb44050156 - 19 May 2022

Cited by 4 | Viewed by 3236

Abstract

Psoralea corylifolia L. (P. corylifolia) has been used as an oriental phytomedicine to treat coldness of hands and feet in bone marrow injury. Hydroxyapatite is usually used for tooth regeneration. In this study, the role of P. corylifolia and bakuchiol, a [...] Read more.

Psoralea corylifolia L. (P. corylifolia) has been used as an oriental phytomedicine to treat coldness of hands and feet in bone marrow injury. Hydroxyapatite is usually used for tooth regeneration. In this study, the role of P. corylifolia and bakuchiol, a compound originated from P. corylifolia as differentiation-inducing substances for tooth regeneration, was determined by monitoring odontogenic differentiation in human dental pulp stem cells (hDPSCs). We confirmed that P. corylifolia extracts and bakuchiol increased the odontogenic differentiation of hDPSCs. In addition, the expression of the odontogenic differentiation marker genes alkaline phosphatase (APL), Runt-related transcription factor 2 (RUNX-2), osteocalcin (OC), and dentin matrix acidic phosphoprotein-1 (DMP-1) was proved by real-time polymerase chain reaction, and protein expression of dentin matrix acidic phosphoprotein-1 (DMP-1) and dentin sialophosphoprotein (DSPP) was proved by western blotting. Further, by confirming the increase in small mothers against decapentaplegia (SMAD) 1/5/8 phosphorylation, the SMAD signaling pathway was found to increase the differentiation of odontoblasts. This study confirmed that P. corylifolia L. extracts and bakuchiol alone promote odontogenic differentiation in hDPSCs. These results suggest that bakuchiol from P. corylifolia is responsible for odontogenic differentiation, and they encourage future in vivo studies on dentin regeneration. Full article

(This article belongs to the Special Issue Advances of Molecular Sciences in Dental Diseases Detection and Treatment)

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13 pages, 841 KiB

Open AccessArticle

DeepMHADTA: Prediction of Drug-Target Binding Affinity Using Multi-Head Self-Attention and Convolutional Neural Network

by Lei Deng, Yunyun Zeng, Hui Liu, Zixuan Liu and Xuejun Liu

Curr. Issues Mol. Biol. 2022, 44(5), 2287-2299; https://doi.org/10.3390/cimb44050155 - 19 May 2022

Cited by 14 | Viewed by 4112

Abstract

Drug-target interactions provide insight into the drug-side effects and drug repositioning. However, wet-lab biochemical experiments are time-consuming and labor-intensive, and are insufficient to meet the pressing demand for drug research and development. With the rapid advancement of deep learning, computational methods are increasingly [...] Read more.

Drug-target interactions provide insight into the drug-side effects and drug repositioning. However, wet-lab biochemical experiments are time-consuming and labor-intensive, and are insufficient to meet the pressing demand for drug research and development. With the rapid advancement of deep learning, computational methods are increasingly applied to screen drug-target interactions. Many methods consider this problem as a binary classification task (binding or not), but ignore the quantitative binding affinity. In this paper, we propose a new end-to-end deep learning method called DeepMHADTA, which uses the multi-head self-attention mechanism in a deep residual network to predict drug-target binding affinity. On two benchmark datasets, our method outperformed several current state-of-the-art methods in terms of multiple performance measures, including mean square error (MSE), consistency index (CI),

r_{m}^{2}

, and PR curve area (AUPR). The results demonstrated that our method achieved better performance in predicting the drug–target binding affinity. Full article

(This article belongs to the Special Issue New Sight: Enzymes as Targets for Drug Development)

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12 pages, 549 KiB

Open AccessArticle

The Search for Cancer Biomarkers: Assessing the Distribution of INDEL Markers in Different Genetic Ancestries

by Roberta B. Andrade, Giovanna C. Cavalcante, Marcos A. T. Amador, Fabiano Cordeiro Moreira, André S. Khayat, Paulo P. Assumpção, Ândrea Ribeiro-dos-Santos, Ney P. C. Santos and Sidney Santos

Curr. Issues Mol. Biol. 2022, 44(5), 2275-2286; https://doi.org/10.3390/cimb44050154 - 19 May 2022

Cited by 3 | Viewed by 2430

Abstract

Cancer is a multifactorial group of diseases, being highly incident and one of the leading causes of death worldwide. In Brazil, there is a great variation in cancer incidence and impact among the different geographic regions, partly due to the genetic heterogeneity of [...] Read more.

Cancer is a multifactorial group of diseases, being highly incident and one of the leading causes of death worldwide. In Brazil, there is a great variation in cancer incidence and impact among the different geographic regions, partly due to the genetic heterogeneity of the population in this country, composed mainly by European (EUR), Native American (NAM), African (AFR), and Asian (ASN) ancestries. Among different populations, genetic markers commonly present diverse allelic frequencies, but in admixed populations, such as the Brazilian population, data is still limited, which is an issue that might influence cancer incidence. Therefore, we analyzed the allelic and genotypic distribution of 12 INDEL polymorphisms of interest in populations from the five Brazilian geographic regions and in populations representing EUR, NAM, AFR, and ASN, as well as tissue expression in silico. Genotypes were obtained by multiplex PCR and the statistical analyses were done using R, while data of tissue expression for each marker was extracted from GTEx portal. We highlight that all analyzed markers presented statistical differences in at least one of the population comparisons, and that we found 39 tissues to be differentially expressed depending on the genotype. Here, we point out the differences in genotype distribution and gene expression of potential biomarkers for risk of cancer development and we reinforce the importance of this type of study in populations with different genetic backgrounds. Full article

(This article belongs to the Special Issue Molecules at Play in Cancer)

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18 pages, 7066 KiB

Open AccessHypothesis

New Insight into Drugs to Alleviate Atopic March via Network Pharmacology-Based Analysis

by Ki-Kwang Oh, Md. Adnan and Dong-Ha Cho

Curr. Issues Mol. Biol. 2022, 44(5), 2257-2274; https://doi.org/10.3390/cimb44050153 - 18 May 2022

Cited by 2 | Viewed by 3019

Abstract

In the present study, a subject of atopic dermatitis (AD) is exposed progressively to allergic rhinitis (AR) and asthma (AS), which is defined as atopic march (AM). However, both the targets and compounds against AM are still largely unknown. Hence, we investigated the [...] Read more.

In the present study, a subject of atopic dermatitis (AD) is exposed progressively to allergic rhinitis (AR) and asthma (AS), which is defined as atopic march (AM). However, both the targets and compounds against AM are still largely unknown. Hence, we investigated the overlapping targets related directly to the occurrence and development of AD, AR, and AS through public databases (DisGeNET, and OMIM). The final overlapping targets were considered as key targets of AM, which were visualized by a Venn diagram. The protein–protein interaction (PPI) network was constructed using R package software. We retrieved the association between targets and ligands via scientific journals, and the ligands were filtered by physicochemical properties. Lastly, we performed a molecular docking test (MDT) to identify the significant ligand on each target. A total of 229 overlapping targets were considered as AM causal elements, and 210 out of them were interconnected with each other. We adopted 65 targets representing the top 30% highest in degree centrality among 210 targets. Then, we obtained 20 targets representing the top 30% greatest in betweenness centrality among 65 targets. The network analysis unveiled key targets against AM, and the MDT confirmed the affinity between significant compounds and targets. In this study, we described the significance of the eight uppermost targets (CCL2, CTLA4, CXCL8, ICAM1, IL10, IL17A, IL1B, and IL2) and eight ligands (Bindarit, CTLA-4 inhibitor, Danirixin, A-205804, AX-24 HCl, Y-320, T-5224, and Apilimod) against AM, providing a scientific basis for further experiments. Full article

(This article belongs to the Collection Application of Natural and Pseudo Natural Products in Drug Discovery and Development)

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14 pages, 3628 KiB

Open AccessArticle

Using Next-Generation Sequencing and Bioinformatic Methods to Predict New Genes That May Be Regulated by CD47 in Oral Squamous Cell Carcinoma

by Chung-Chih Tseng, Chen-Han Tsou, Shi-Ying Huang, Chia-Wei Wu and Tsung-Hua Hsieh

Curr. Issues Mol. Biol. 2022, 44(5), 2243-2256; https://doi.org/10.3390/cimb44050152 - 17 May 2022

Cited by 1 | Viewed by 2807

Abstract

Oral squamous cell carcinoma (OSCC) is one of the most common cancers in the world, and the incidence and death rate of OSCC in men is twice that of women. CD47 is a ubiquitous cell surface transmembrane protein, also known as integrin-related protein [...] Read more.

Oral squamous cell carcinoma (OSCC) is one of the most common cancers in the world, and the incidence and death rate of OSCC in men is twice that of women. CD47 is a ubiquitous cell surface transmembrane protein, also known as integrin-related protein (IAP). Previous studies have pointed out that CD47 can inhibit the growth of OSCC, but the detailed mechanism is not clear. This study aimed to explore the effect of CD47 gene expression profiles in OSCC. The OSCC cell lines, OECM-1 and OC-2, overexpressed CD47, and the expression profiles of mRNAs were analyzed through next-generation sequencing (NGS) with a bioinformatic approach. A total of 14 differentially expressed genes (DEGs) were listed. In addition, ingenuity pathway analysis (IPA) was used to analyze the molecular function (MF), biological process (BP), and cellular component (CC) network signaling. The human protein atlas (HPA) database was used to analyze gene expression and the survivability of human cancer. The results found that HSPA5, HYOU1, and PDIA4 were involved in the IPA network and when highly expressed, mediated the survivability of cancer. In addition, HSPA5 was positively and significantly correlated with CD47 expression (p < 0.0001) and induced by CD47-overexpression in the OECM-1 and OC-2 OSCC cancer cell lines. These findings provide important insights into possible new diagnostic strategies, including unfolded protein for OSCC-targeting CD47. Full article

(This article belongs to the Special Issue Targeting Tumor Microenvironment for Cancer Therapy)

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13 pages, 1327 KiB

Open AccessArticle

Antigenotoxic Effect of Ascorbic Acid and Resveratrol in Erythrocytes of Ambystoma mexicanum, Oreochromis niloticus and Human Lymphocytes Exposed to Glyphosate

by Carlos Alvarez-Moya, Alexis Gerardo Sámano-León, Mónica Reynoso-Silva, Rafael Ramírez-Velasco, Mario Alberto Ruiz-López and Alma Rosa Villalobos-Arámbula

Curr. Issues Mol. Biol. 2022, 44(5), 2230-2242; https://doi.org/10.3390/cimb44050151 - 17 May 2022

Cited by 5 | Viewed by 2865

Abstract

Glyphosate is a controversial herbicide. Its genotoxicity and presence in various ecosystems have been reported. The use of ascorbic acid and resveratrol could protect different organisms from glyphosate-induced genetic damage. In the present study, specific genetic damage induced by glyphosate was evaluated in [...] Read more.

Glyphosate is a controversial herbicide. Its genotoxicity and presence in various ecosystems have been reported. The use of ascorbic acid and resveratrol could protect different organisms from glyphosate-induced genetic damage. In the present study, specific genetic damage induced by glyphosate was evaluated in erythrocytes of Oreochromis niloticus, Ambystoma mexicanum and human lymphocytes. Simultaneously, the antigenotoxic capacity of various concentrations of ascorbic acid and resveratrol was evaluated by means of pretreatment and simultaneous treatment protocols. The 0.03, 0.05 and 0.07 mM concentrations of glyphosate induced significant genotoxic activity (p < 0.05) in human lymphocytes and in erythrocytes of the species studied, and could cause genomic instability in these populations. The reduction in genetic damage observed in human lymphocytes exposed to high concentrations of glyphosate is only apparent: excessive genetic damage was associated with undetectable excessive tail migration length. A significant (p < 0.05) antigenotoxic effect of ascorbic acid and resveratrol was observed in all concentrations, organisms and protocols used. Both ascorbic acid and resveratrol play an important role in maintaining the integrity of DNA. Ascorbic acid in Oreochromis niloticus, Ambystoma mexicanum reduced glyphosate-induced genetic damage to a basal level. Therefore, our data indicate that these antioxidants could help preserve the integrity of the DNA of organisms exposed to glyphosate. The consumption of antioxidants is a useful tool against the genotoxicity of glyphosate. Full article

(This article belongs to the Collection Application of Natural and Pseudo Natural Products in Drug Discovery and Development)

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13 pages, 965 KiB

Open AccessReview

Calcium–Permeable Channels and Endothelial Dysfunction in Acute Lung Injury

by Ying Hao, Zhuang Wang, Francis Frimpong and Xingjuan Chen

Curr. Issues Mol. Biol. 2022, 44(5), 2217-2229; https://doi.org/10.3390/cimb44050150 - 16 May 2022

Cited by 14 | Viewed by 3426

Abstract

The increased permeability of the lung microvascular endothelium is one critical initiation of acute lung injury (ALI). The disruption of vascular-endothelium integrity results in leakiness of the endothelial barrier and accumulation of protein-rich fluid in the alveoli. During ALI, increased endothelial-cell (EC) permeability [...] Read more.

The increased permeability of the lung microvascular endothelium is one critical initiation of acute lung injury (ALI). The disruption of vascular-endothelium integrity results in leakiness of the endothelial barrier and accumulation of protein-rich fluid in the alveoli. During ALI, increased endothelial-cell (EC) permeability is always companied by high frequency and amplitude of cytosolic Ca²⁺ oscillations. Mechanistically, cytosolic calcium oscillations include calcium release from internal stores and calcium entry via channels located in the cell membrane. Recently, numerous publications have shown substantial evidence that calcium-permeable channels play an important role in maintaining the integrity of the endothelium barrier function of the vessel wall in ALI. These novel endothelial signaling pathways are future targets for the treatment of lung injury. This short review focuses on the up-to-date research and provide insight into the contribution of calcium influx via ion channels to the disruption of lung microvascular endothelial-barrier function during ALI. Full article

(This article belongs to the Topic Blood Physiology: Molecular Mechanisms of Vascular Wall Functioning)

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23 pages, 1938 KiB

Open AccessReview

A Glance at the Molecules That Regulate Oligodendrocyte Myelination

by Shunqi Wang, Yingxing Wang and Suqi Zou

Curr. Issues Mol. Biol. 2022, 44(5), 2194-2216; https://doi.org/10.3390/cimb44050149 - 15 May 2022

Cited by 12 | Viewed by 7985

Abstract

Oligodendrocyte (OL) myelination is a critical process for the neuronal axon function in the central nervous system. After demyelination occurs because of pathophysiology, remyelination makes repairs similar to myelination. Proliferation and differentiation are the two main stages in OL myelination, and most factors [...] Read more.

Oligodendrocyte (OL) myelination is a critical process for the neuronal axon function in the central nervous system. After demyelination occurs because of pathophysiology, remyelination makes repairs similar to myelination. Proliferation and differentiation are the two main stages in OL myelination, and most factors commonly play converse roles in these two stages, except for a few factors and signaling pathways, such as OLIG2 (Oligodendrocyte transcription factor 2). Moreover, some OL maturation gene mutations induce hypomyelination or hypermyelination without an obvious function in proliferation and differentiation. Herein, three types of factors regulating myelination are reviewed in sequence. Full article

(This article belongs to the Special Issue Multipotent and Multisystem Biomolecules—Associated Interlinking Networks and Crossing Organ Differentiation)

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8 pages, 1733 KiB

Open AccessCommunication

Whole-Transcriptome Profiling on Small FFPE Samples: Which Sequencing Kit Should Be Used?

by Marc Hilmi, Lucile Armenoult, Mira Ayadi and Rémy Nicolle

Curr. Issues Mol. Biol. 2022, 44(5), 2186-2193; https://doi.org/10.3390/cimb44050148 - 13 May 2022

Cited by 3 | Viewed by 4427

Abstract

RNA sequencing (RNA-Seq) appears as a great tool with huge clinical potential, particularly in oncology. However, sufficient sample size is often a limiting factor and the vast majority of samples from patients with cancer are formalin-fixed paraffin-embedded (FFPE). To date, several sequencing kits [...] Read more.

RNA sequencing (RNA-Seq) appears as a great tool with huge clinical potential, particularly in oncology. However, sufficient sample size is often a limiting factor and the vast majority of samples from patients with cancer are formalin-fixed paraffin-embedded (FFPE). To date, several sequencing kits are proposed for FFPE samples yet no comparison on low quantities were performed. To select the most reliable, cost-effective, and relevant RNA-Seq approach, we applied five FFPE-compatible kits (based on 3′ capture, exome-capture and ribodepletion approaches) using 8 ng to 400 ng of FFPE-derived RNA and compared them to Nanostring on FFPE samples and to a reference PolyA (Truseq) approach on flash-frozen samples of the same tumors. We compared gene expression correlations and reproducibility. The Smarter Pico V3 ribodepletion approach appeared systematically the most comparable to Nanostring and Truseq (p < 0.001) and was a highly reproducible technique. In comparison with exome-capture and 3′ kits, the Smarter appeared more comparable to Truseq (p < 0.001). Overall, our results suggest that the Smarter is the most robust RNA-Seq technique to study small FFPE samples and 3′ Lexogen presents an interesting quality–price ratio for samples with less limiting quantities. Full article

(This article belongs to the Special Issue Next-Generation Sequencing (NGS) Technique and Personalized Medicine)

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11 pages, 1307 KiB

Open AccessArticle

3,3′,4,5′-Tetramethoxy-trans-stilbene Improves Insulin Resistance by Activating the IRS/PI3K/Akt Pathway and Inhibiting Oxidative Stress

by Yi Tan, Lingchao Miao, Jianbo Xiao and Wai San Cheang

Curr. Issues Mol. Biol. 2022, 44(5), 2175-2185; https://doi.org/10.3390/cimb44050147 - 12 May 2022

Cited by 13 | Viewed by 5261

Abstract

The potential anti-diabetic effect of resveratrol derivative, 3,3′,4,5′-tetramethoxy-trans-stilbene (3,3′,4,5′-TMS) and its underlying mechanism in high glucose (HG) and dexamethasone (DXMS)-stimulated insulin-resistant HepG2 cells (IR-HepG2) were investigated. 3,3′,4,5′-TMS did not reduce the cell viability of IR-HepG2 cells at the concentrations of 0.5–10 µM. 3,3′,4,5′-TMS [...] Read more.

The potential anti-diabetic effect of resveratrol derivative, 3,3′,4,5′-tetramethoxy-trans-stilbene (3,3′,4,5′-TMS) and its underlying mechanism in high glucose (HG) and dexamethasone (DXMS)-stimulated insulin-resistant HepG2 cells (IR-HepG2) were investigated. 3,3′,4,5′-TMS did not reduce the cell viability of IR-HepG2 cells at the concentrations of 0.5–10 µM. 3,3′,4,5′-TMS increased the potential of glucose consumption and glycogen synthesis in a concentration-dependent manner in IR-HepG2 cells. 3,3′,4,5′-TMS ameliorated insulin resistance by enhancing the phosphorylation of glycogen synthase kinase 3 beta (GSK3β), inhibiting phosphorylation of insulin receptor substrate-1 (IRS-1), and activating phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway in IR-HepG2 cells. Furthermore, 3,3′,4,5′-TMS significantly suppressed levels of reactive oxygen species (ROS) with up-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) expression. To conclude, the beneficial effect of 3,3′,4,5′-TMS against insulin resistance to increase glucose consumption and glycogen synthesis was mediated through activation of IRS/PI3K/Akt signaling pathways in the IR-HepG2 cells, accomplished with anti-oxidative activity through up-regulation of Nrf2. Full article

(This article belongs to the Special Issue Bioactive Compounds of Natural Products on Metabolic Disorders and Complications)

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8 pages, 2225 KiB

Open AccessArticle

Sostdc1 Secreted from Cutaneous Lymphatic Vessels Acts as a Paracrine Factor for Hair Follicle Growth

by Sun-Young Yoon and Michael Detmar

Curr. Issues Mol. Biol. 2022, 44(5), 2167-2174; https://doi.org/10.3390/cimb44050146 - 12 May 2022

Cited by 9 | Viewed by 3902

Abstract

In our previous study, we found that lymphatic vessels stimulate hair follicle growth through paracrine effects on dermal papilla cells. However, the paracrine factors secreted from cutaneous lymphatic vessels that can activate dermal papilla cells are still unknown. In this study, we investigated [...] Read more.

In our previous study, we found that lymphatic vessels stimulate hair follicle growth through paracrine effects on dermal papilla cells. However, the paracrine factors secreted from cutaneous lymphatic vessels that can activate dermal papilla cells are still unknown. In this study, we investigated whether lymphatic endothelial cells might secrete paracrine factors that activate dermal papilla cells in vitro. We found that Sostdc1 was more expressed in lymphatic endothelial cells compared with blood vascular endothelial cells. In addition, Sostdc1 expression levels were significantly increased during the anagen phase in the back skin of C57BL/6J mice, as compared to the telogen phase. We also observed that incubation of dermal papilla cells with 200 ng/mL Sostdc1 for 72 h induced the expression levels of Lef-1, a downstream target of Wnt signaling. Taken together, our results reveal that Sostdc1, a BMP antagonist, secreted from cutaneous lymphatic vessels, may act as a paracrine factor for hair follicle growth. Full article

(This article belongs to the Topic Blood Physiology: Molecular Mechanisms of Vascular Wall Functioning)

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14 pages, 3601 KiB

Open AccessArticle

Punicalagin Targets Atherosclerosis: Gene Expression Profiling of THP-1 Macrophages Treated with Punicalagin and Molecular Docking

by Etimad Huwait, Sanaa Almowallad, Rehab Al-Massabi, Salma Saddeek, Kalamegam Gauthaman and Alexandre Prola

Curr. Issues Mol. Biol. 2022, 44(5), 2153-2166; https://doi.org/10.3390/cimb44050145 - 12 May 2022

Cited by 8 | Viewed by 2907

Abstract

Atherosclerosis is an important cause of cardiovascular disorders worldwide. Natural botanical drugs have attracted attention due to their antioxidant, anti-inflammatory, and antiatherogenic properties in the treatment of atherosclerosis. Punicalagin is the major bioactive component of pomegranate peel, and has been shown to have [...] Read more.

Atherosclerosis is an important cause of cardiovascular disorders worldwide. Natural botanical drugs have attracted attention due to their antioxidant, anti-inflammatory, and antiatherogenic properties in the treatment of atherosclerosis. Punicalagin is the major bioactive component of pomegranate peel, and has been shown to have antioxidant, anti-inflammatory, antiviral, anti proliferation, and anticancer properties. To explore its antiatherogenic properties at a molecular level, we investigated the genome-wide expression changes that occur in differentiated THP1 cells following treatment with a non-toxic dose of punicalagin. We also conducted a molecular docking simulation study to identify the molecular targets of punicalagin. Full article

(This article belongs to the Collection Application of Natural and Pseudo Natural Products in Drug Discovery and Development)

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14 pages, 2762 KiB

Open AccessArticle

Inhibition of eNOS Partially Blunts the Beneficial Effects of Nebivolol on Angiotensin II-Induced Signaling in H9c2 Cardiomyoblasts

by Rukhsana Gul, Nouf Alsalman and Assim A. Alfadda

Curr. Issues Mol. Biol. 2022, 44(5), 2139-2152; https://doi.org/10.3390/cimb44050144 - 10 May 2022

Cited by 3 | Viewed by 2729

Abstract

We have recently illustrated that nebivolol can inhibit angiotensin II (Ang II)-mediated signaling in cardiomyoblasts; however, to date, the detailed mechanism for the beneficial effects of nebivolol has not been studied. Here, we investigated whether the inhibition of NO bioavailability by blocking eNOS [...] Read more.

We have recently illustrated that nebivolol can inhibit angiotensin II (Ang II)-mediated signaling in cardiomyoblasts; however, to date, the detailed mechanism for the beneficial effects of nebivolol has not been studied. Here, we investigated whether the inhibition of NO bioavailability by blocking eNOS (endothelial nitric oxide synthase) using L-NG-nitroarginine methyl ester (L-NAME) would attenuate nebivolol-mediated favorable effects on Ang II-evoked signaling in H9c2 cardiomyoblasts. Our data reveal that the nebivolol-mediated antagonistic effects on Ang II-induced oxidative stress were retreated by concurrent pretreatment with L-NAME and nebivolol. Similarly, the expressions of pro-inflammatory markers TNF-α and iNOS stimulated by Ang II were not decreased with the combination of nebivolol plus L-NAME. In contrast, the nebivolol-induced reduction in the Ang II-triggered mTORC1 pathway and the mRNA levels of hypertrophic markers ANP, BNP, and β-MHC were not reversed with the addition of L-NAME to nebivolol. In compliance with these data, the inhibition of eNOS by L-N⁵-(1-Iminoethyl) ornithine (LNIO) and its upstream regulator AMP-activated kinase (AMPK) with compound C in the presence of nebivolol showed effects similar to those of the L-NAME plus nebivolol combination on Ang II-mediated signaling. Pretreatment with either compound C plus nebivolol or LNIO plus nebivolol showed similar effects to those of the L-NAME plus nebivolol combination on Ang II-mediated signaling. In conclusion, our data indicate that the rise in NO bioavailability caused by nebivolol via the stimulation of AMPK/eNOS signaling is key for its anti-inflammatory and antioxidant properties but not for its antihypertrophic response upon Ang II stimulation. Full article

(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)

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17 pages, 2418 KiB

Open AccessArticle

Investigating the Link between Alpha-1 Antitrypsin and Human Neutrophil Elastase in Bronchoalveolar Lavage Fluid of COVID-19 Patients

by Maura D’Amato, Valentina Vertui, Laura Pandolfi, Sara Bozzini, Tommaso Fossali, Riccardo Colombo, Anna Aliberti, Marco Fumagalli, Paolo Iadarola, Camilla Didò, Simona Viglio and Federica Meloni

Curr. Issues Mol. Biol. 2022, 44(5), 2122-2138; https://doi.org/10.3390/cimb44050143 - 10 May 2022

Cited by 6 | Viewed by 4196

Abstract

Neutrophils play a pathogenic role in COVID-19 by releasing Neutrophils Extracellular Traps (NETs) or human neutrophil elastase (HNE). Given that HNE is inhibited by α1-antitrypsin (AAT), we aimed to assess the content of HNE, α1-antitrypsin (AAT) and HNE–AAT complexes (the AAT/HNE balance) in [...] Read more.

Neutrophils play a pathogenic role in COVID-19 by releasing Neutrophils Extracellular Traps (NETs) or human neutrophil elastase (HNE). Given that HNE is inhibited by α1-antitrypsin (AAT), we aimed to assess the content of HNE, α1-antitrypsin (AAT) and HNE–AAT complexes (the AAT/HNE balance) in 33 bronchoalveolar lavage fluid (BALf) samples from COVID-19 patients. These samples were submitted for Gel-Electrophoresis, Western Blot and ELISA, and proteins (bound to AAT or HNE) were identified by Liquid Chromatography-Mass Spectrometry. NETs’ release was analyzed by confocal microscopy. Both HNE and AAT were clearly detectable in BALf at high levels. Contrary to what was previously observed in other settings, the formation of HNE–AAT complex was not detected in COVID-19. Rather, HNE was found to be bound to acute phase proteins, histones and C3. Due to the relevant role of NETs, we assessed the ability of free AAT to bind to histones. While confirming this binding, AAT was not able to inhibit NET formation. In conclusion, despite the finding of a high burden of free and bound HNE, the lack of the HNE–AAT inhibitory complex in COVID-19 BALf demonstrates that AAT is not able to block HNE activity. Furthermore, while binding to histones, AAT does not prevent NET formation nor their noxious activity. Full article

(This article belongs to the Special Issue Omics in Infectious Pulmonary Diseases)

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15 pages, 21035 KiB

Open AccessArticle

Effects of Luteolin on Human Breast Cancer Using Gene Expression Array: Inferring Novel Genes

by Shih-Ho Wang, Chin-Hu Wu, Chin-Chuan Tsai, Tai-Yu Chen, Kuen-Jang Tsai, Chao-Ming Hung, Chia-Yi Hsu, Chia-Wei Wu and Tsung-Hua Hsieh

Curr. Issues Mol. Biol. 2022, 44(5), 2107-2121; https://doi.org/10.3390/cimb44050142 - 9 May 2022

Cited by 10 | Viewed by 3668

Abstract

Taraxacum officinale (dandelion) is often used in traditional Chinese medicine for the treatment of cancer; however, the downstream regulatory genes and signaling pathways mediating its effects on breast cancer remain unclear. The present study aimed to explore the effects of luteolin, the main [...] Read more.

Taraxacum officinale (dandelion) is often used in traditional Chinese medicine for the treatment of cancer; however, the downstream regulatory genes and signaling pathways mediating its effects on breast cancer remain unclear. The present study aimed to explore the effects of luteolin, the main biologically active compound of T. officinale, on gene expression profiles in MDA-MB-231 and MCF-7 breast cancer cells. The results revealed that luteolin effectively inhibited the proliferation and motility of the MDA-MB-231 and MCF-7 cells. The mRNA expression profiles were determined using gene expression array analysis and analyzed using a bioinformatics approach. A total of 41 differentially expressed genes (DEGs) were found in the luteolin-treated MDA-MB-231 and MCF-7 cells. A Gene Ontology analysis revealed that the DEGs, including AP2B1, APP, GPNMB and DLST, mainly functioned as oncogenes. The human protein atlas database also found that AP2B1, APP, GPNMB and DLST were highly expressed in breast cancer and that AP2B1 (cut-off value, 75%) was significantly associated with survival rate (p = 0.044). In addition, a Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the DEGs were involved in T-cell leukemia virus 1 infection and differentiation. On the whole, the findings of the present study provide a scientific basis that may be used to evaluate the potential benefits of luteolin in human breast cancer. Further studies are required, however, to fully elucidate the role of the related molecular pathways. Full article

(This article belongs to the Special Issue Targeting Tumor Microenvironment for Cancer Therapy)

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18 pages, 1991 KiB

Open AccessArticle

Subtilisin of Leishmania amazonensis as Potential Druggable Target: Subcellular Localization, In Vitro Leishmanicidal Activity and Molecular Docking of PF-429242, a Subtilisin Inhibitor

by Pollyanna Stephanie Gomes, Monique Pacheco Duarte Carneiro, Patrícia de Almeida Machado, Valter Viana de Andrade-Neto, Alessandra Marcia da Fonseca-Martins, Amy Goundry, João Vitor Marques Pereira da Silva, Daniel Claudio Oliveira Gomes, Ana Paula Cabral de Araujo Lima, Vítor Ennes-Vidal, Ana Carolina Rennó Sodero, Salvatore Giovanni De-Simone and Herbert L. de Matos Guedes

Curr. Issues Mol. Biol. 2022, 44(5), 2089-2106; https://doi.org/10.3390/cimb44050141 - 9 May 2022

Cited by 5 | Viewed by 3359

Abstract

Subtilisin proteases, found in all organisms, are enzymes important in the post-translational steps of protein processing. In Leishmania major and L. donovani, this enzyme has been described as essential to their survival; however, few compounds that target subtilisin have been investigated for [...] Read more.

Subtilisin proteases, found in all organisms, are enzymes important in the post-translational steps of protein processing. In Leishmania major and L. donovani, this enzyme has been described as essential to their survival; however, few compounds that target subtilisin have been investigated for their potential as an antileishmanial drug. In this study, we first show, by electron microscopy and flow cytometry, that subtilisin has broad localization throughout the cytoplasm and membrane of the parasite in the promastigote form with foci in the flagellar pocket. Through in silico analysis, the similarity between subtilisin of different Leishmania species and that of humans were determined, and based on molecular docking, we evaluated the interaction capacity of a serine protease inhibitor against both life cycle forms of Leishmania. The selected inhibitor, known as PF-429242, has already been used against the dengue virus, arenaviruses, and the hepatitis C virus. Moreover, it proved to have antilipogenic activity in a mouse model and caused hypolipidemia in human cells in vitro. Here, PF-429242 significantly inhibited the growth of L. amazonensis promastigotes of four different strains (IC₅₀ values = 3.07 ± 0.20; 0.83 ± 0.12; 2.02 ± 0.27 and 5.83 ± 1.2 µM against LTB0016, PH8, Josefa and LV78 strains) whilst having low toxicity in the host macrophages (CC₅₀ = 170.30 µM). We detected by flow cytometry that there is a greater expression of subtilisin in the amastigote form; however, PF-429242 had a low effect against this intracellular form with an IC50 of >100 µM for intracellular amastigotes, as well as against axenic amastigotes (94.12 ± 2.8 µM for the LV78 strain). In conclusion, even though PF-429242 does not affect the intracellular forms, this drug will serve as a tool to explore pharmacological and potentially leishmanicidal targets. Full article

(This article belongs to the Collection Application of Natural and Pseudo Natural Products in Drug Discovery and Development)

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20 pages, 1803 KiB

Open AccessArticle

Protocol for Increasing the Sensitivity of MS-Based Protein Detection in Human Chorionic Villi

by Timur Shkrigunov, Pavel Pogodin, Victor Zgoda, Olesya Larina, Yulia Kisrieva, Maria Klimenko, Oleg Latyshkevich, Peter Klimenko, Andrey Lisitsa and Natalia Petushkova

Curr. Issues Mol. Biol. 2022, 44(5), 2069-2088; https://doi.org/10.3390/cimb44050140 - 9 May 2022

Cited by 5 | Viewed by 3653

Abstract

An important step in the proteomic analysis of missing proteins is the use of a wide range of tissues, optimal extraction, and the processing of protein material in order to ensure the highest sensitivity in downstream protein detection. This work describes a purification [...] Read more.

An important step in the proteomic analysis of missing proteins is the use of a wide range of tissues, optimal extraction, and the processing of protein material in order to ensure the highest sensitivity in downstream protein detection. This work describes a purification protocol for identifying low-abundance proteins in human chorionic villi using the proposed “1DE-gel concentration” method. This involves the removal of SDS in a short electrophoresis run in a stacking gel without protein separation. Following the in-gel digestion of the obtained holistic single protein band, we used the peptide mixture for further LC–MS/MS analysis. Statistically significant results were derived from six datasets, containing three treatments, each from two tissue sources (elective or missed abortions). The 1DE-gel concentration increased the coverage of the chorionic villus proteome. Our approach allowed the identification of 15 low-abundance proteins, of which some had not been previously detected via the mass spectrometry of trophoblasts. In the post hoc data analysis, we found a dubious or uncertain protein (PSG7) encoded on human chromosome 19 according to neXtProt. A proteomic sample preparation workflow with the 1DE-gel concentration can be used as a prospective tool for uncovering the low-abundance part of the human proteome. Full article

(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)

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15 pages, 2608 KiB

Open AccessArticle

Indole-3-Carbinol, a Phytochemical Aryl Hydrocarbon Receptor-Ligand, Induces the mRNA Overexpression of UBE2L3 and Cell Proliferation Arrest

by Claudia Vanessa Arellano-Gutiérrez, Laura Itzel Quintas-Granados, Hernán Cortés, Manuel González del Carmen, Gerardo Leyva-Gómez, Lilia Patricia Bustamante-Montes, Miguel Rodríguez-Morales, Israel López-Reyes, Juan Ramón Padilla-Mendoza, Lorena Rodríguez-Páez, Gabriela Figueroa-González and Octavio Daniel Reyes-Hernández

Curr. Issues Mol. Biol. 2022, 44(5), 2054-2068; https://doi.org/10.3390/cimb44050139 - 8 May 2022

Cited by 12 | Viewed by 3636

Abstract

Cervical cancer (CC) is one of the most common cancers in women, and is linked to human papillomavirus (HPV) infection. The virus oncoprotein E6 binds to p53, resulting in its degradation and allowing uncontrolled cell proliferation. Meanwhile, the HPV E7 protein maintains host [...] Read more.

Cervical cancer (CC) is one of the most common cancers in women, and is linked to human papillomavirus (HPV) infection. The virus oncoprotein E6 binds to p53, resulting in its degradation and allowing uncontrolled cell proliferation. Meanwhile, the HPV E7 protein maintains host cell differentiation by targeting retinoblastoma tumor suppressor. The host cell can ubiquitinate E6 and E7 through UBE2L3, whose expression depends on the interaction between the aryl hydrocarbon receptor (AhR) with Xenobiotic Responsive Elements (XREs) located in the UBE2L3 gene promoter. In this study, we used cell culture to determine the effect of indole-3-carbinol (I3C) over cellular viability, apoptosis, cell proliferation, and mRNA levels of UBE2L3 and CYP1A1. In addition, patients’ samples were used to determine the mRNA levels of UBE2L3 and CYP1A1 genes. We found that I3C promotes the activation of AhR and decreases cell proliferation, possibly through UBE2L3 mRNA induction, which would result in the ubiquitination of HPV E7. Since there is a strong requirement for selective and cost-effective cancer treatments, natural AhR ligands such as I3C could represent a novel strategy for cancer treatment. Full article

(This article belongs to the Special Issue New Sights: Phytochemicals and Cancer)

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16 pages, 7300 KiB

Open AccessArticle

Time-Series Clustering of lncRNA-mRNA Expression during the Adipogenic Transdifferentiation of Porcine Skeletal Muscle Satellite Cells

by Xiaoyu Qiu, Guangliang Gao, Lei Du, Jing Wang, Qi Wang, Feiyun Yang, Xiaorong Zhou, Dingbiao Long, Jinxiu Huang, Zuohua Liu and Renli Qi

Curr. Issues Mol. Biol. 2022, 44(5), 2038-2053; https://doi.org/10.3390/cimb44050138 - 6 May 2022

Cited by 7 | Viewed by 3199

Abstract

Skeletal muscle satellite cells (SMSCs), which are multifunctional muscle-derived stem cells, can differentiate into adipocytes. Long-chain non-coding RNA (lncRNA) has diverse biological functions, including the regulation of gene expression, chromosome silencing, and nuclear transport. However, the regulatory roles and mechanism of lncRNA during [...] Read more.

Skeletal muscle satellite cells (SMSCs), which are multifunctional muscle-derived stem cells, can differentiate into adipocytes. Long-chain non-coding RNA (lncRNA) has diverse biological functions, including the regulation of gene expression, chromosome silencing, and nuclear transport. However, the regulatory roles and mechanism of lncRNA during adipogenic transdifferentiation in muscle cells have not been thoroughly investigated. Here, porcine SMSCs were isolated, cultured, and induced for adipogenic differentiation. The expressions of lncRNA and mRNA at different time points during transdifferentiation were analysed using RNA-seq analysis. In total, 1005 lncRNAs and 7671 mRNAs showed significant changes in expression at differential differentiation stages. Time-series expression analysis showed that the differentially expressed (DE) lncRNAs and mRNAs were clustered into 5 and 11 different profiles with different changes, respectively. GO, KEGG, and REACTOME enrichment analyses revealed that DE mRNAs with increased expressions during the trans-differentiation were mainly enriched in the pathways for lipid metabolism and fat cell differentiation. The genes with decreased expressions were mainly enriched in the regulation of cell cycle and genetic information processing. In addition, 1883 DE mRNAs were regulated by 193 DE lncRNAs, and these genes were related to the controlling in cell cycle mainly. Notably, three genes in the fatty acid binding protein (FABP) family significantly and continuously increased during trans-differentiation, and 15, 13, and 11 lncRNAs may target FABP3, FABP4, and FABP5 genes by cis- or trans-regulation, respectively. In conclusion, these studies identify a set of new potential regulator for adipogenesis and cell fate and help us in better understanding the molecular mechanisms of trans-differentiation. Full article

(This article belongs to the Special Issue Multipotent and Multisystem Biomolecules—Associated Interlinking Networks and Crossing Organ Differentiation)

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9 pages, 1843 KiB

Open AccessArticle

Effect of Porcine Placental Extract Mixture on Alcohol-Induced Hepatotoxicity in Rats

by Se-Mi Kim, Wen-Jing Diao, Wen An, Hyun-Jin Kim, Ha-Jong Lim, Keun-Nam Kim, Gun-Won Bae and Ju-Seop Kang

Curr. Issues Mol. Biol. 2022, 44(5), 2029-2037; https://doi.org/10.3390/cimb44050137 - 1 May 2022

Cited by 4 | Viewed by 2917

Abstract

This study was conducted to examine the effect of porcine placenta extract mixture (pPEM, enzymatic/acidic extract = 1/3) on alcoholic hepatotoxicity after pPEM dosing with alcohol in rats. The experimental groups were normal, control, silymarin, three pPEM (590, 1771, and 2511 mg/kg/day, po), [...] Read more.

This study was conducted to examine the effect of porcine placenta extract mixture (pPEM, enzymatic/acidic extract = 1/3) on alcoholic hepatotoxicity after pPEM dosing with alcohol in rats. The experimental groups were normal, control, silymarin, three pPEM (590, 1771, and 2511 mg/kg/day, po), and silymarin (100 mg/kg/day, po) groups (n = 10). Alcoholic hepatotoxicity was caused by a liquid ethanol diet for 4 weeks. The effect of pPEM and silymarin on alcoholic hepatotoxicity was evaluated by serology, hepatic ADH and ALDH activities, and histopathological findings. After oral dosing with alcohol for 4 weeks, ALT and AST were significantly increased to 33.7 → 115.6 and 81.37 → 235.0 in the alcohol group, respectively. These levels were decreased significantly to 83.9 and 126.7 in the silymarin group and dose-dependently to 73.6–56.9 and 139.2–122.8 in all pPEM groups. Hepatic ADH and ALDH might have been increased in the control and not in the silymarin and pPEM groups for hepatic ADH. All pPEM groups exhibited no effects on hepatic ALDH except for the high pPEM group. Mild inflammation and fatty lesions were observed in the alcohol group and were attenuated in the silymarin and pPEM groups. As a results, the pPEM showed protective activities against alcoholic hepatotoxicity on the serological markers, hepatic ADH and ALDH, and pathological findings. Full article

(This article belongs to the Topic Clinical, Translational and Basic Research on Liver Diseases)

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14 pages, 1028 KiB

Open AccessArticle

The Role of the Microbiome in Gastroentero-Pancreatic Neuroendocrine Neoplasms (GEP-NENs)

by Amr Mohamed, Sylvia L. Asa, Thomas McCormick, Hilmi Al-Shakhshir, Arvind Dasari, Retuerto Mauricio, Iman Salem, Lee M. Ocuin, David Bajor, Richard T. Lee, J. Eva Selfridge, Arash Kardan, Zhenghong Lee, Norbert Avril, Shelby Kopp, Jordan M. Winter, Jeffrey M. Hardacre, John B. Ammori and Mahmoud A. Ghannoum

Curr. Issues Mol. Biol. 2022, 44(5), 2015-2028; https://doi.org/10.3390/cimb44050136 - 30 Apr 2022

Cited by 12 | Viewed by 3860

Abstract

Gut microbiome balance plays a key role in human health and maintains gut barrier integrity. Dysbiosis, referring to impaired gut microbiome, is linked to a variety of diseases, including cancers, through modulation of the inflammatory process. Most studies concentrated on adenocarcinoma of different [...] Read more.

Gut microbiome balance plays a key role in human health and maintains gut barrier integrity. Dysbiosis, referring to impaired gut microbiome, is linked to a variety of diseases, including cancers, through modulation of the inflammatory process. Most studies concentrated on adenocarcinoma of different sites with very limited information on gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). In this study, we have analyzed the gut microbiome (both fungal and bacterial communities) in patients with metastatic GEP-NENs. Fecal samples were collected and compared with matched healthy control samples using logistic regression distances utilizing R package MatchIt (version 4.2.0, Daniel E. Ho, Stanford, CA, USA). We examined differences in microbiome profiles between GEP-NENs and control samples using small subunit (SSU) rRNA (16S), ITS1, ITS4 genomic regions for their ability to accurately characterize bacterial and fungal communities. We correlated the results with different behavioral and dietary habits, and tumor features including differentiation, grade, primary site, and therapeutic response. All tests are two-sided and p-values ≤ 0.05 were considered statistically significant. Gut samples of 34 patients (12 males, 22 females, median age 64 years) with metastatic GEP-NENs (22 small bowel, 10 pancreatic, 1 gall bladder, and 1 unknown primary) were analyzed. Twenty-nine patients had well differentiated GEP-neuroendocrine tumors (GEP-NETs), (G1 = 14, G2 = 12, G3 = 3) and five patients had poorly differentiated GEP-neuroendocrine carcinomas (GEP-NECs). Patients with GEP-NENs had significantly decreased bacterial species and increased fungi (notably Candida species, Ascomycota, and species belonging to saccharomycetes) compared to controls. Patients with GEP-NECs had significantly enriched populations of specific bacteria and fungi (such as Enterobacter hormaechei, Bacteroides fragilis and Trichosporon asahii) compared to those with GEP-NETs (p = 0.048, 0.0022 and 0.034, respectively). In addition, higher grade GEP-NETs were associated with significantly higher Bacteroides fragilis (p = 0.022), and Eggerthella lenta (p = 0.00018) species compared to lower grade tumors. There were substantial differences associated with dietary habits and therapeutic responses. This is the first study to analyze the role of the microbiome environment in patients with GEP-NENs. There were significant differences between GEP-NETs and GEP-NECs, supporting the role of the gut microbiome in the pathogenesis of these two distinct entities. Full article

(This article belongs to the Topic Cancer Biology and Therapy)

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