Current Issues in Molecular Biology

15 pages, 1756 KiB

Open AccessArticle

Peroxiredoxins and Hypoxia-Inducible Factor-1α in Duodenal Tissue: Emerging Factors in the Pathophysiology of Pediatric Celiac Disease Patients

by Fadime Aydın Köse, Aysun Pabuccuoglu, Miray Karakoyun and Sema Aydogdu

Curr. Issues Mol. Biol. 2023, 45(2), 1779-1793; https://doi.org/10.3390/cimb45020114 - 20 Feb 2023

Cited by 1 | Viewed by 2130

Abstract

Celiac disease (CD) is an autoimmune enteropathy. Peroxiredoxins (PRDXs) are powerful antioxidant enzymes having an important role in significant cellular pathways including cell survival, apoptosis, and inflammation. This study aimed at investigating the expression levels of all PRDX isoforms (1–6) and their possible [...] Read more.

Celiac disease (CD) is an autoimmune enteropathy. Peroxiredoxins (PRDXs) are powerful antioxidant enzymes having an important role in significant cellular pathways including cell survival, apoptosis, and inflammation. This study aimed at investigating the expression levels of all PRDX isoforms (1–6) and their possible relationships with a transcription factor, HIF-1α, in the small intestinal tissue samples of pediatric CD patients. The study groups consisted of first-diagnosed CD patients (n = 7) and non-CD patients with functional gastrointestinal tract disorders as the controls (n = 7). The PRDXs and HIF-1α expression levels were determined by using real-time PCR and Western blotting in duodenal biopsy samples. It was observed that the mRNA and protein expression levels of PRDX 5 were significantly higher in the CD patients, whereas the PRDX 1, -2, and -4 expressions were decreased in each case compared to the control group. No significant differences were detected in the PRDX 3 and PRDX 6 expressions. The expression of HIF-1α was also significantly elevated in CD patients. These findings indicate, for the first time, that PRDXs, particularly PRDX 5, may play a significant role in the pathogenesis of CD. Furthermore, our results suggest that HIF-1α may upregulate PRDX-5 transcription in the duodenal tissue of CD. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Regulation in Allergy and Immune Diseases, Immunodeficiencies)

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17 pages, 808 KiB

Open AccessReview

Neurobiology and Applications of Inositol in Psychiatry: A Narrative Review

by Carmen Concerto, Cecilia Chiarenza, Antonio Di Francesco, Antimo Natale, Ivan Privitera, Alessandro Rodolico, Antonio Trovato, Andrea Aguglia, Francesco Fisicaro, Manuela Pennisi, Rita Bella, Antonino Petralia, Maria Salvina Signorelli and Giuseppe Lanza

Curr. Issues Mol. Biol. 2023, 45(2), 1762-1778; https://doi.org/10.3390/cimb45020113 - 20 Feb 2023

Cited by 11 | Viewed by 13621

Abstract

Inositol is a natural sugar-like compound, commonly present in many plants and foods. It is involved in several biochemical pathways, most of them controlling vital cellular mechanisms, such as cell development, signaling and nuclear processes, metabolic and endocrine modulation, cell growth, signal transduction, [...] Read more.

Inositol is a natural sugar-like compound, commonly present in many plants and foods. It is involved in several biochemical pathways, most of them controlling vital cellular mechanisms, such as cell development, signaling and nuclear processes, metabolic and endocrine modulation, cell growth, signal transduction, etc. In this narrative review, we focused on the role of inositol in human brain physiology and pathology, with the aim of providing an update on both potential applications and current limits in its use in psychiatric disorders. Overall, imaging and biomolecular studies have shown the role of inositol levels in the pathogenesis of mood disorders. However, when administered as monotherapy or in addition to conventional drugs, inositol did not seem to influence clinical outcomes in both mood and psychotic disorders. Conversely, more encouraging results have emerged for the treatment of panic disorders. We concluded that, despite its multifaceted neurobiological activities and some positive findings, to date, data on the efficacy of inositol in the treatment of psychiatric disorders are still controversial, partly due to the heterogeneity of supporting studies. Therefore, systematic use of inositol in routine clinical practice cannot be recommended yet, although further basic and translational research should be encouraged. Full article

(This article belongs to the Special Issue Food-Derived Bioactive Compounds in Health and Disease)

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21 pages, 11399 KiB

Open AccessArticle

Vaccine- and Breakthrough Infection-Elicited Pre-Omicron Immunity More Effectively Neutralizes Omicron BA.1, BA.2, BA.4 and BA.5 Than Pre-Omicron Infection Alone

by Eveline Santos da Silva, Jean-Yves Servais, Michel Kohnen, Victor Arendt, Georges Gilson, Therese Staub, Carole Seguin-Devaux and Danielle Perez-Bercoff

Curr. Issues Mol. Biol. 2023, 45(2), 1741-1761; https://doi.org/10.3390/cimb45020112 - 19 Feb 2023

Cited by 3 | Viewed by 2062

Abstract

Since the emergence of SARS-CoV-2 Omicron BA.1 and BA.2, several Omicron sublineages have emerged, supplanting their predecessors. Here we compared the neutralization of Omicron sublineages BA.1, BA.2, BA.4 and BA.5 by human sera collected from individuals who were infected with the ancestral B.1 [...] Read more.

Since the emergence of SARS-CoV-2 Omicron BA.1 and BA.2, several Omicron sublineages have emerged, supplanting their predecessors. Here we compared the neutralization of Omicron sublineages BA.1, BA.2, BA.4 and BA.5 by human sera collected from individuals who were infected with the ancestral B.1 (D614G) strain, who were vaccinated (3 doses) or with breakthrough infection with pre-Omicron strains (Gamma or Delta). All Omicron sublineages exhibited extensive escape from all sera when compared to the ancestral B.1 strain and to Delta, albeit to different levels depending on the origin of the sera. Convalescent sera were unable to neutralize BA.1, and partly neutralized BA.2, BA.4 and BA.5. Vaccinee sera partly neutralized BA.2, but BA.1, BA.4 and BA.5 evaded neutralizing antibodies (NAb). Some breakthrough infections (BTI) sera were non-neutralizing. Neutralizing BTI sera had similar neutralizing ability against all Omicron sublineages. Despite similar levels of anti-Spike and anti-Receptor Binding Domain (RBD) antibodies in all groups, BTI sera had the highest cross-neutralizing ability against all Omicron sublineages and convalescent sera were the least neutralizing. Antibody avidity inferred from the NT50:antibody titer ratio was highest in sera from BTI patients, underscoring qualitative differences in antibodies elicited by infection or vaccination. Together, these findings highlight the importance of vaccination to trigger highly cross-reactive antibodies that neutralize phylogenetically and antigenically distant strains, and suggest that immune imprinting by first generation vaccines may restrict, but not abolish, cross-neutralization. Full article

(This article belongs to the Special Issue Molecular and Real-World Evidence Research of Respiratory Diseases and Infections)

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21 pages, 4517 KiB

Open AccessArticle

Quantification of the Diversity in Gene Structures Using the Principles of Polarization Mapping

by Dmitry Zimnyakov, Marina Alonova, Anatoly Skripal, Sergey Dobdin and Valentina Feodorova

Curr. Issues Mol. Biol. 2023, 45(2), 1720-1740; https://doi.org/10.3390/cimb45020111 - 18 Feb 2023

Cited by 4 | Viewed by 1680

Abstract

Results of computational analysis and visualization of differences in gene structures using polarization coding are presented. A two-dimensional phase screen, where each element of which corresponds to a specific basic nucleotide (adenine, cytosine, guanine, or thymine), displays the analyzed nucleotide sequence. Readout of [...] Read more.

Results of computational analysis and visualization of differences in gene structures using polarization coding are presented. A two-dimensional phase screen, where each element of which corresponds to a specific basic nucleotide (adenine, cytosine, guanine, or thymine), displays the analyzed nucleotide sequence. Readout of the screen with a coherent beam characterized by a given polarization state forms a diffracted light field with a local polarization structure that is unique for the analyzed nucleotide sequence. This unique structure is described by spatial distributions of local values of the Stokes vector components. Analysis of these distributions allows the comparison of nucleotide sequences for different strains of pathogenic microorganisms and frequency analysis of the sequences. The possibilities of this polarization-based technique are illustrated by the model data obtained from a comparative analysis of the spike protein gene sequences for three different model variants (Wuhan, Delta, and Omicron) of the SARS-CoV-2 virus. Various modifications of polarization encoding and analysis of gene structures and a possibility for instrumental implementation of the proposed method are discussed. Full article

(This article belongs to the Section Bioinformatics and Systems Biology)

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8 pages, 3834 KiB

Open AccessCase Report

Recurrent PIK3CA H1047R-Mutated Congenital Infiltrative Facial Lipomatosis: A Case Report and Review of Literature

by Kei Shing Oh, Hisham F. Bahmad, Kalin Veselinov Stoyanov, Ibrahim H. Amjad and Carole Brathwaite

Curr. Issues Mol. Biol. 2023, 45(2), 1712-1719; https://doi.org/10.3390/cimb45020110 - 17 Feb 2023

Cited by 4 | Viewed by 1949

Abstract

Congenital infiltrating lipomatosis of the face (CILF) is a rare, congenital, nonhereditary facial overgrowth due to post-zygomatic activating mutations in PIK3CA gene. It is unilateral and involves hypertrophy of both the soft and hard tissue structures on the affected side of the face. [...] Read more.

Congenital infiltrating lipomatosis of the face (CILF) is a rare, congenital, nonhereditary facial overgrowth due to post-zygomatic activating mutations in PIK3CA gene. It is unilateral and involves hypertrophy of both the soft and hard tissue structures on the affected side of the face. This commonly results in early eruption of the teeth, hypertrophy of the facial bones, macroglossia, and proliferation of the parotid gland. Less than 80 cases of CILF have been reported in the literature so far. Treatment modalities include liposuction and surgical excision. However, since the hallmark of CILF is mutation in the PIK3CA gene, PI3K inhibitors may play a therapeutic role in CILF. We report a case of an 8-year-old boy with recurrent CILF of the scalp and nose, with PIK3CA H1047R mutation. We discuss the differential diagnoses, clinical outcomes, and management of this rare entity. Full article

(This article belongs to the Special Issue Linking Genomic Changes with Cancer in the NGS Era)

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19 pages, 4294 KiB

Open AccessArticle

Genome-Wide Identification and Expression Analysis of Calmodulin-Like Gene Family in Paspalums vaginatium Revealed Their Role in Response to Salt and Cold Stress

by Meizhen Yang, Jingjin Chen, Tingting Liu, Leilei Xiang and Biao-Feng Zhou

Curr. Issues Mol. Biol. 2023, 45(2), 1693-1711; https://doi.org/10.3390/cimb45020109 - 16 Feb 2023

Cited by 5 | Viewed by 1909

Abstract

The calmodulin-like (CML) family is an important calcium (Ca²⁺) sensor in plants and plays a pivotal role in the response to abiotic and biotic stresses. As one of the most salt-tolerant grass species, Paspalums vaginatum is resistant to multiple abiotic stresses, [...] Read more.

The calmodulin-like (CML) family is an important calcium (Ca²⁺) sensor in plants and plays a pivotal role in the response to abiotic and biotic stresses. As one of the most salt-tolerant grass species, Paspalums vaginatum is resistant to multiple abiotic stresses, such as salt, cold, and drought. However, investigations of PvCML proteins in P. vaginatum have been limited. Based on the recently published P. vaginatum genome, we identified forty-nine PvCMLs and performed a comprehensive bioinformatics analysis of PvCMLs. The main results showed that the PvCMLs were unevenly distributed on all chromosomes and that the expansion of PvCMLs was shaped by tandem and segmental duplications. In addition, cis-acting element analysis, expression profiles, and qRT–PCR analysis revealed that PvCMLs were involved in the response to salt and cold stress. Most interestingly, we found evidence of a tandem gene cluster that independently evolved in P. vaginatum and may participate in cold resistance. In summary, our work provides important insight into how grass species are resistant to abiotic stresses such as salt and cold and could be the basis of further gene function research on CMLs in P. vaginatum. Full article

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

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12 pages, 2250 KiB

Open AccessArticle

Effect of C-Type Natriuretic Peptide (CNP) on Spermatozoa Maturation in Adult Rat Epididymis

by Hu Zhao, Yuejin Yu, Chunlei Mei, Tianyu Zhang, Yafei Kang, Na Li and Donghui Huang

Curr. Issues Mol. Biol. 2023, 45(2), 1681-1692; https://doi.org/10.3390/cimb45020108 - 16 Feb 2023

Cited by 3 | Viewed by 2206

Abstract

C-type natriuretic peptide (CNP) is highly expressed in male reproductive tissues, such as the epididymis. The aim of this study is to explore the role of CNP in the maturation of rat epididymal spermatozoa. First, the expression levels of CNP and its specific [...] Read more.

C-type natriuretic peptide (CNP) is highly expressed in male reproductive tissues, such as the epididymis. The aim of this study is to explore the role of CNP in the maturation of rat epididymal spermatozoa. First, the expression levels of CNP and its specific natriuretic peptide receptor-B (NPR-B) were detected in various tissues of rats and epididymis at different stages after birth. Then a castrated rat model was established to analyze the relationship between testosterone and CNP/NPR-B expression in the epididymis. Finally, CNP and different inhibitors (NPR-B inhibitors, cGMP inhibitors) were used to incubate epididymal sperm in vitro to examine sperm mobility and expression of sperm maturation-related factors. The results showed CNP/NPR-B mRNAs were expressed in all tissues of rats, but were extremely highly expressed in male genital ducts (seminal vesicle, prostate and epididymis). The expression of CNP/NPR-B in epididymis was the highest at birth and the fifth week after birth. In the epididymis, CNP/NPR-B were highly expressed in the caput and located in the epididymal epithelial cells. After castration, the expression of CNP/NPR-B decreased sharply and was restored quickly after testosterone supplementation. In vitro, CNP could significantly promote the acquisition of epididymal sperm motility through the NPR-B/cGMP pathway and induce the expression of sperm maturation-related factors (such as Bin1b, Catsper 1, Dnah17, Fertilin). This study shows that CNP plays a role in epididymal sperm maturation. The mechanism of CNP is to promote the acquisition of epididymal sperm fluidity through the NPR-B/cGMP signaling pathway and also to regulate sperm maturation-related genes. Moreover, the expression of CNP/NPR-B was regulated by testosterone. Full article

(This article belongs to the Special Issue Molecular Research in Reproductive Biology)

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26 pages, 5532 KiB

Open AccessArticle

Molecular Aspects of Hypoxic Stress Effects in Chronic Ethanol Exposure of Neuronal Cells

by Simona Isabelle Stoica, Gelu Onose, Ioana Madalina Pitica, Ana Iulia Neagu, Gabriela Ion, Lilia Matei, Laura Denisa Dragu, Lacramioara-Elena Radu, Mihaela Chivu-Economescu, Laura Georgiana Necula, Aurelian Anghelescu, Carmen Cristina Diaconu, Constantin Munteanu and Coralia Bleotu

Curr. Issues Mol. Biol. 2023, 45(2), 1655-1680; https://doi.org/10.3390/cimb45020107 - 16 Feb 2023

Cited by 5 | Viewed by 2720

Abstract

Experimental models of a clinical, pathophysiological context are used to understand molecular mechanisms and develop novel therapies. Previous studies revealed better outcomes for spinal cord injury chronic ethanol-consuming patients. This study evaluated cellular and molecular changes in a model mimicking spinal cord injury [...] Read more.

Experimental models of a clinical, pathophysiological context are used to understand molecular mechanisms and develop novel therapies. Previous studies revealed better outcomes for spinal cord injury chronic ethanol-consuming patients. This study evaluated cellular and molecular changes in a model mimicking spinal cord injury (hypoxic stress induced by treatment with deferoxamine or cobalt chloride) in chronic ethanol-consuming patients (ethanol-exposed neural cultures (SK-N-SH)) in order to explain the clinical paradigm of better outcomes for spinal cord injury chronic ethanol-consuming patients. The results show that long-term ethanol exposure has a cytotoxic effect, inducing apoptosis. At 24 h after the induction of hypoxic stress (by deferoxamine or cobalt chloride treatments), reduced ROS in long-term ethanol-exposed SK-N-SH cells was observed, which might be due to an adaptation to stressful conditions. In addition, the HIF-1α protein level was increased after hypoxic treatment of long-term ethanol-exposed cells, inducing fluctuations in its target metabolic enzymes proportionally with treatment intensity. The wound healing assay demonstrated that the cells recovered after stress conditions, showing that the ethanol-exposed cells that passed the acute step had the same proliferation profile as the cells unexposed to ethanol. Deferoxamine-treated cells displayed higher proliferative activity than the control cells in the proliferation–migration assay, emphasizing the neuroprotective effect. Cells have overcome the critical point of the alcohol-induced traumatic impact and adapted to ethanol (a chronic phenomenon), sustaining the regeneration process. However, further experiments are needed to ensure recovery efficiency is more effective in chronic ethanol exposure. Full article

(This article belongs to the Special Issue Molecular Research on Oxidative Stress and Health)

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11 pages, 1796 KiB

Open AccessCommunication

Stability of Dengue 2 Nonstructural Glycoprotein 1 (NS1) Is Affected by the Nature of Basic Residue at Position NS1-324

by Eva Ogire, Chaker El-Kalamouni, Philippe Desprès and Marjolaine Roche

Curr. Issues Mol. Biol. 2023, 45(2), 1644-1654; https://doi.org/10.3390/cimb45020106 - 14 Feb 2023

Cited by 1 | Viewed by 1884

Abstract

Dengue is the most prevalent mosquito-borne viral disease. It is caused by the infection of any of the four dengue virus (DENV) serotypes DENV-1 to DENV-4. The DENV non-structural glycoprotein 1 (NS1) plays an important role in virus replication and the immunopathogenesis of [...] Read more.

Dengue is the most prevalent mosquito-borne viral disease. It is caused by the infection of any of the four dengue virus (DENV) serotypes DENV-1 to DENV-4. The DENV non-structural glycoprotein 1 (NS1) plays an important role in virus replication and the immunopathogenesis of virus infection. The NS1 protein has been identified as both a cell-associated homodimer and a soluble secreted lipoprotein nanoparticle. The nature of the residues at positions NS1-272 and NS1-324 in the β-ladder domain may have an effect on the biological behaviors of DENV-2 NS1 protein in human hepatoma Huh7 cells. The stability of the NS1 protein from the Reunion 2018 DENV-2 strain was affected by the presence of lysine residues at positions 272 and 324. In the present study, we evaluated the impact of mutations into lysine at positions 272 and 324 on recombinant NS1 protein from the DES-14 DENV-2 strain bearing arginine residue on these two positions. The DES-14 NS1 protein mutant bearing a lysine at position 324 was deficient in protein stability and secretion compared to wild-type protein. The defect in the DES-14 NS1 protein mutant was associated to oxidative stress and pro-inflammatory cytokine activation in Huh7 cells. The ubiquitin-proteasome proteolytic pathway might play a key role in the stability of DENV-2 protein bearing a lysine residue at position 324. Full article

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

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17 pages, 40206 KiB

Open AccessArticle

Possible Mechanisms of the Neuroprotective Actions of Date Palm Fruits Aqueous Extracts against Valproic Acid-Induced Autism in Rats

by Abdelaziz M. Hussein, Seham Ahmed Mahmoud, Khalid Mohammed Elazab, Ahmed F. Abouelnaga, Marwa Abass, Ahmed A. H. Mosa, Mennatullah A. M. Hussein and Mohamed E. G. Elsayed

Curr. Issues Mol. Biol. 2023, 45(2), 1627-1643; https://doi.org/10.3390/cimb45020105 - 14 Feb 2023

Cited by 6 | Viewed by 2548

Abstract

The current study aimed to determine how palm date aqueous fruit extracts (AFE) affected the autistic-like behaviors brought on by valproic acid (VPA) injection, as well as any potential contributions from Sirt-1, oxidative stress, apoptosis, and autophagy. The pregnant Sprague Dawley females were [...] Read more.

The current study aimed to determine how palm date aqueous fruit extracts (AFE) affected the autistic-like behaviors brought on by valproic acid (VPA) injection, as well as any potential contributions from Sirt-1, oxidative stress, apoptosis, and autophagy. The pregnant Sprague Dawley females were treated with VPA at 12.5th gestation day and pregnant females and their offspring were treated with AFE orally at doses of 4 mg/Kg by gastric gavage for 45 days after birth. The elevated plus-T maze, water maze, and rotarod tests were used to examine autism-like behaviors. At the end of the study, the expression of Nrf2, heme oxygenase (HO-1), Sirt-1, caspase-3 (a marker of apoptosis), LC3 (a marker of autophagy), and NFκB (inflammatory cytokines) were evaluated along with the oxidative stress in brain tissues and the histological changes in the cerebellum and hippocampus. The neurobehavioral assessments significantly declined due to VPA, which also significantly increased oxidative stress in the brain tissues and significantly decreased Nrf2 and HO-1 expression. Additionally, VPA administration caused significant increase in the expression of caspase-3 in the cerebellar cortex, not in the hippocampus; LC3 and NFκB in the hippocampus, not in the cerebellar cortex; and significant reduction in the expression of Sirt-1 in the hippocampus, not in the cerebellum. On the other hand, AFE treatment significantly improved the neurobehavioral changes as well as it improved significantly the oxidative stress and the expression of LC3, NFκB, NrF2, HO-1, and Sirt-1 in the cerebellum and hippocampus. Conclusions: AFE administration might improve the autistic-like symptoms induced by VPA in rats via attenuation of the oxidative stress, upregulation of Nrf2 and HO-1, Sirt-1 and LC3 expression with downregulation of caspase-3, and NFκB expression in the cerebellum and hippocampus. Full article

(This article belongs to the Topic Autism: Molecular Bases, Diagnosis and Therapies)

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14 pages, 2747 KiB

Open AccessArticle

Neuroprotective Effects of Geopung-Chunghyuldan Based on Its Salvianolic Acid B Content Using an In Vivo Stroke Model

by Han-Gyul Lee, Seungwon Kwon, Sang-Kwan Moon, Seung-Yeon Cho, Seong-Uk Park, Woo-Sang Jung, Jung-Mi Park, Chang-Nam Ko and Ki-Ho Cho

Curr. Issues Mol. Biol. 2023, 45(2), 1613-1626; https://doi.org/10.3390/cimb45020104 - 13 Feb 2023

Cited by 5 | Viewed by 2175

Abstract

Background: Geopung-Chunghyuldan (GCD) has neuroprotective properties. Salviae miltiorrhizae Radix plays an essential role in GCD’s effect. The Salviae miltiorrhizae Radix marker compound is salvianolic acid B; however, its content is not uniform among samples. This study aimed to evaluate the neuroprotective effects of [...] Read more.

Background: Geopung-Chunghyuldan (GCD) has neuroprotective properties. Salviae miltiorrhizae Radix plays an essential role in GCD’s effect. The Salviae miltiorrhizae Radix marker compound is salvianolic acid B; however, its content is not uniform among samples. This study aimed to evaluate the neuroprotective effects of GCD based on salvianolic acid B content. Methods: The neuroprotective effects of GCD based on the salvianolic acid B content were evaluated by measuring infarct volume 24 h after permanent middle cerebral artery occlusion in an in vivo stroke model. For the experimental group, each GCD was administered immediately before surgery. The control groups were administered distilled water and aspirin (30 mg/kg) in the same way. The salvianolic acid B content in five types of Salviae Miltiorrhizae Radix (two Chinese and three Korean regions) based on different cultivation regions was analyzed by high-performance liquid chromatography. Results: Three samples met the Korean and Chinese Pharmacopeia standards for salvianolic acid B. However, two samples did not. GCDs with high salvianolic acid B showed marked neuroprotective effects compared to the control groups, whereas GCDs with low salvianolic acid B did not. Conclusions: The salvianolic acid B content of Salviae miltiorrhizae Radix affects the neuroprotection effect of GCD. Stable, raw Salviae miltiorrhizae Radix is essential for GCD homogenization. Full article

(This article belongs to the Special Issue Pathophysiology and Molecular Mechanisms of Acute Stroke)

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12 pages, 3071 KiB

Open AccessArticle

Isodorsmanin A Prevents Inflammatory Response in LPS-Stimulated Macrophages by Inhibiting the JNK and NF-κB Signaling Pathways

by You Chul Chung, Ami Lee, Jin Ah Ryuk and Youn-Hwan Hwang

Curr. Issues Mol. Biol. 2023, 45(2), 1601-1612; https://doi.org/10.3390/cimb45020103 - 13 Feb 2023

Cited by 3 | Viewed by 1757

Abstract

Natural and synthetic chalcones exhibit anti-inflammatory, antitumoral, antibacterial, antifungal, antimalarial, and antitubercular activities. Isodorsmanin A (IDA), a chalcone, is a well-known constituent of the dried seeds of Psoralea corylifolia L. (PC). Although other constituents of PC have been widely investigated, there are no [...] Read more.

Natural and synthetic chalcones exhibit anti-inflammatory, antitumoral, antibacterial, antifungal, antimalarial, and antitubercular activities. Isodorsmanin A (IDA), a chalcone, is a well-known constituent of the dried seeds of Psoralea corylifolia L. (PC). Although other constituents of PC have been widely investigated, there are no studies on the biological properties of IDA. In this study, we focused on the anti-inflammatory effects of IDA and evaluated its effects on lipopolysaccharide (LPS)-stimulated macrophages. The results showed that IDA suppressed the production of inflammatory mediators (nitric oxide [NO] and prostaglandin E₂ [PGE₂]) and proinflammatory cytokines (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6], and interleukin-1β [IL-1β]) without cytotoxicity. In addition, it downregulated the mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) within the treatment concentrations. In our mechanistic studies, IDA inhibited the phosphorylation of the c-Jun N-terminal kinase (JNK), mitogen-activated protein kinase (MAPK), and protected the nuclear factor of the kappa light polypeptide gene enhancer in the B-cells’ inhibitor, alpha (IκB-α), from degradation, thus preventing the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells’ (NF-κB) transcription factor. Our results suggest that IDA is a promising compound for attenuating excessive inflammatory responses. Full article

(This article belongs to the Topic Nitrite and Nitric Oxide in Life)

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14 pages, 3978 KiB

Open AccessArticle

Hesperetin Induces Autophagy and Delayed Apoptosis by Modulating the AMPK/Akt/mTOR Pathway in Human Leukemia Cells In Vitro

by Ching-Yeh Lin, Ya-Hui Chen and Ying-Chih Huang

Curr. Issues Mol. Biol. 2023, 45(2), 1587-1600; https://doi.org/10.3390/cimb45020102 - 13 Feb 2023

Cited by 8 | Viewed by 2572

Abstract

Background: Hesperetin has been reported to have anticancer properties. However, the molecular mechanisms underlying its action on leukemia cells remain unclear. This in vitro study evaluated the possible mechanisms of hesperetin in leukemia cells (HL-60 and U937). Methods: Cell viability was evaluated using [...] Read more.

Background: Hesperetin has been reported to have anticancer properties. However, the molecular mechanisms underlying its action on leukemia cells remain unclear. This in vitro study evaluated the possible mechanisms of hesperetin in leukemia cells (HL-60 and U937). Methods: Cell viability was evaluated using a cell counting kit-8 (CCK-8) assay. Apoptosis and autophagy assays were conducted through annexin V/PI staining and acidic vesicular organelle (AVO) staining. Cell cycle analysis was conducted through propidium iodide (PI) and flow cytometry. The expression of proteins related to apoptosis and autophagy, including cleaved-PARP-1, Bcl-2, Bax, LC3-I/II, Beclin-1, Atg5, p62, phospho-AMPK, AMPK, phospho-mTOR, mTOR, phospho-Akt, and Akt, in human leukemia cells were evaluated using Western blotting. Results: Hesperetin dose-dependently inhibited leukemia cell viability. However, we found a low degree of apoptosis and cell cycle arrest induced by hesperetin in U937 cells. These findings imply the presence of additional mechanisms modulating hesperetin-induced cell death. Next, we evaluated autophagy, the possible mechanism modulating cell death or survival, to clarify the underlying mechanism of hesperetin-induced cell death. Hesperetin also dose-dependently increased the ratio of LC3II/I, Atg5, and Beclin 1 and decreased p62. Moreover, 3-methyladenine (3-MA) and bafilomycin A1 (Baf-A1) inhibited hesperetin-induced autophagy. We suggest that hesperetin can protect cancer cells during the transient period and may extend survival. Furthermore, a decrease in p-mTOR and p-Akt expression and an increase in p-AMPK expression were observed. Collectively, these findings suggest that hesperetin induces autophagy by modulating the AMPK/Akt/mTOR pathway. Conclusion: Hesperetin promoted cell death in the human leukemic cell line U937 by inducing a low degree of slight apoptosis, cell cycle arrest, and autophagy. It is therefore a potential adjuvant to antileukemia therapy and may be combined with other chemotherapeutic drugs to reduce chemoresistance and side effects. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Leukemia)

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17 pages, 4382 KiB

Open AccessArticle

Analysis of the Properties of 44 ABC Transporter Genes from Biocontrol Agent Trichoderma asperellum ACCC30536 and Their Responses to Pathogenic Alternaria alternata Toxin Stress

by Hua-Ying Du, Yu-Zhou Zhang, Kuo Liu, Pei-Wen Gu, Shuang Cao, Xiang Gao, Zhi-Ying Wang, Zhi-Hua Liu and Ze-Yang Yu

Curr. Issues Mol. Biol. 2023, 45(2), 1570-1586; https://doi.org/10.3390/cimb45020101 - 12 Feb 2023

Cited by 5 | Viewed by 1801

Abstract

ATP-binding cassette (ABC) transporters are involved in transporting multiple substrates, such as toxins, and may be important for the survival of Trichoderma when encountering biotic toxins. In this study, genome searching revealed that there are 44 ABC transporters encoded in the genome of [...] Read more.

ATP-binding cassette (ABC) transporters are involved in transporting multiple substrates, such as toxins, and may be important for the survival of Trichoderma when encountering biotic toxins. In this study, genome searching revealed that there are 44 ABC transporters encoded in the genome of Trichoderma asperellum. These ABC transporters were divided into six types based on three-dimensional (3D) structure prediction, of which four, represented by 39 ABCs, are involved in transport and the remaining two, represented by 5 ABCs, are involved in regulating translation. The characteristics of nucleotide-binding domain (NBD) are important in the identification of ABC proteins. Even though the 3D structures of the 79 NBDs in the 44 ABCs are similar, multiple sequence alignment showed they can be divided into three classes. In total, 794 motifs were found in the promoter regions of the 44 ABC genes, of which 541 were cis-regulators related to stress responses. To characterize how their ABCs respond when T. asperellum interact with fungi or plants, T. asperellum was cultivated in either minimal media (MM) control, C-hungry, N-hungry, or poplar medium (PdPap) to simulate normal conditions, competition with pathogens, interaction with pathogens, and interaction with plants, respectively. The results show that 17 of 39 transport ABCs are highly expressed in at least one condition, whereas four of the five translation-regulating ABCs are highly expressed in at least one condition. Of these 21 highly expressed ABCs, 6 were chosen for RT-qPCR expression under the toxin stress of phytopathogen Alternaria alternata, and the results show ABC01, ABC04, ABC05, and ABC31 were highly expressed and may be involved in pathogen interaction and detoxifying toxins from A. alternata. Full article

(This article belongs to the Special Issue Microbial Engineering: Gene Expression Regulation and Its Application)

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2 pages, 174 KiB

Open AccessEditorial

Editorial for Special Issue: “Effects of Nanoparticles on Living Organisms”

by Yoshitaka Miyamoto

Curr. Issues Mol. Biol. 2023, 45(2), 1568-1569; https://doi.org/10.3390/cimb45020100 - 10 Feb 2023

Viewed by 1144

Abstract

This Special Issue provides an overview of the “Effects of Nanoparticles on Living Organisms” [...] Full article

(This article belongs to the Special Issue Effects of Nanoparticles on Living Organisms)

32 pages, 1679 KiB

Open AccessReview

Advances in Molecular Regulation of Prostate Cancer Cells by Top Natural Products of Malaysia

by Jose M. Prieto and Mohd Mukrish Mohd Hanafi

Curr. Issues Mol. Biol. 2023, 45(2), 1536-1567; https://doi.org/10.3390/cimb45020099 - 9 Feb 2023

Cited by 4 | Viewed by 4017

Abstract

Prostate cancer (PCa) remains both a global health burden and a scientific challenge. We present a review of the molecular targets driving current drug discovery to fight this disease. Moreover, the preventable nature of most PCa cases represents an opportunity for phytochemicals as [...] Read more.

Prostate cancer (PCa) remains both a global health burden and a scientific challenge. We present a review of the molecular targets driving current drug discovery to fight this disease. Moreover, the preventable nature of most PCa cases represents an opportunity for phytochemicals as chemopreventive when adequately integrated into nutritional interventions. With a renovated interest in natural remedies as a commodity and their essential role in cancer drug discovery, Malaysia is looking towards capitalizing on its mega biodiversity, which includes the oldest rainforest in the world and an estimated 1200 medicinal plants. We here explore whether the list of top Malay plants prioritized by the Malaysian government may fulfill the potential of becoming newer, sustainable sources of prostate cancer chemotherapy. These include Andrographis paniculate, Centella asiatica, Clinacanthus nutans, Eurycoma longifolia, Ficus deltoidea, Hibiscus sabdariffa, Marantodes pumilum (syn. Labisia pumila), Morinda citrifolia, Orthosiphon aristatus, and Phyllanthus niruri. Our review highlights the importance of resistance factors such as Smac/DIABLO in cancer progression, the role of the CXCL12/CXCR4 axis in cancer metastasis, and the regulation of PCa cells by some promising terpenes (andrographolide, Asiatic acid, rosmarinic acid), flavonoids (isovitexin, gossypin, sinensetin), and alkylresorcinols (labisiaquinones) among others. Full article

(This article belongs to the Special Issue Advances in Molecular Pathogenesis Regulation in Cancer)

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17 pages, 726 KiB

Open AccessReview

The Quest for Neurodegenerative Disease Treatment—Focusing on Alzheimer’s Disease Personalised Diets

by Matei Palimariciuc, Ioana-Miruna Balmus, Bogdan Gireadă, Alin Ciobica, Roxana Chiriță, Alin-Constantin Iordache, Mihai Apostu and Romeo Petru Dobrin

Curr. Issues Mol. Biol. 2023, 45(2), 1519-1535; https://doi.org/10.3390/cimb45020098 - 9 Feb 2023

Cited by 5 | Viewed by 2722

Abstract

Dementia represents a clinical syndrome characterised by progressive decline in memory, language, visuospatial and executive function, personality, and behaviour, causing loss of abilities to perform instrumental or essential activities of daily living. The most common cause of dementia is Alzheimer’s disease (AD), which [...] Read more.

Dementia represents a clinical syndrome characterised by progressive decline in memory, language, visuospatial and executive function, personality, and behaviour, causing loss of abilities to perform instrumental or essential activities of daily living. The most common cause of dementia is Alzheimer’s disease (AD), which accounts for up to 80% of all dementia cases. Despite that extensive studies regarding the etiology and risk factors have been performed in recent decades, and how the current knowledge about AD pathophysiology significantly improved with the recent advances in science and technology, little is still known about its treatment options. In this controverted context, a nutritional approach could be a promising way to formulate improved AD management strategies and to further analyse possible treatment strategy options based on personalised diets, as Nutritional Psychiatry is currently gaining relevance in neuropsychiatric disease treatment. Based on the current knowledge of AD pathophysiology, as well as based on the repeatedly documented anti-inflammatory and antioxidant potential of different functional foods, we aimed to find, describe, and correlate several dietary compounds that could be useful in formulating a nutritional approach in AD management. We performed a screening for relevant studies on the main scientific databases using keywords such as “Alzheimer’s disease”, “dementia”, “treatment”, “medication”, “treatment alternatives”, “vitamin E”, “nutrition”, “selenium”, “Ginkgo biloba”, “antioxidants”, “medicinal plants”, and “traditional medicine” in combinations. Results: nutrients could be a key component in the physiologic and anatomic development of the brain. Several nutrients have been studied in the pursuit of the mechanism triggered by the pathology of AD: vitamin D, fatty acids, selenium, as well as neuroprotective plant extracts (i.e., Ginkgo biloba, Panax ginseng, Curcuma longa), suggesting that the nutritional patterns could modulate the cognitive status and provide neuroprotection. The multifactorial origin of AD development and progression could suggest that nutrition could greatly contribute to the complex pathological picture. The identification of adequate nutritional interventions and the not yet fully understood nutrient activity in AD could be the next steps in finding several innovative treatment options for neurodegenerative disorders. Full article

(This article belongs to the Special Issue Aging, Age-Related Changes in the Brain and the Progression of Alzheimer’s Disease)

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19 pages, 1918 KiB

Open AccessArticle

Changes in the Expression Profile of Pyroptosis-Related Genes in Senescent Retinal Pigment Epithelial Cells after Lutein Treatment

by Barbara Strzalka-Mrozik, Marcel Madej, Natalia Kurowska, Celina Kruszniewska-Rajs, Magdalena Kimsa-Dudek, Jolanta Adamska and Joanna Magdalena Gola

Curr. Issues Mol. Biol. 2023, 45(2), 1500-1518; https://doi.org/10.3390/cimb45020097 - 9 Feb 2023

Cited by 6 | Viewed by 2397

Abstract

Retinal pigment epithelium (RPE) is a specialized structure essential for proper vision, which is constantly exposed to oxidative damage. With aging, this damage accumulates within the RPE cells, causing various diseases, including age-related macular degeneration (AMD). Numerous antioxidant substances are used to prevent [...] Read more.

Retinal pigment epithelium (RPE) is a specialized structure essential for proper vision, which is constantly exposed to oxidative damage. With aging, this damage accumulates within the RPE cells, causing various diseases, including age-related macular degeneration (AMD). Numerous antioxidant substances are used to prevent this process in humans, including lutein. This study aims to determine the differences in the expression patterns of pyroptosis genes in senescent human retinal pigment epithelial cell line ARPE-19 exposed to lutein. Changes in the expression of pyroptosis-related genes were assessed by oligonucleotide microarrays, and the results were validated by real-time RT-qPCR. The microarray analysis showed seven transcripts were differentially expressed both in the H₂O₂-treated cells versus the controls and in the lutein/H₂O₂-treated cells compared to the H₂O₂-treated cells (FC > 2.0). Depending on the used lutein, H₂O₂, or co-treatment of ARPE-19 cells, statistically significant differences in the expression of TXNIP, CXCL8, BAX, and CASP1 genes were confirmed by the RT-qPCR (p < 0.05). A STRING database analysis showed that the proteins encoded by the analyzed genes form a strong interaction network (p < 0.001). These data indicate that lutein modulates the expression level of pyroptosis-related genes, which may be useful for the development of new methods preventing pyroptosis pathway activation in the future. Full article

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

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17 pages, 4930 KiB

Open AccessArticle

Therapeutic Effects of Aloe saponaria against Ulcerative Colitis Induced by Dextran Sulfate Sodium

by Do Yeong Kweon, Hee Jin Song, Ji Eun Kim, You Jeong Jin, Yu Jeong Roh, Ayun Seol, Ju Min Park, Eun Suk Lee, Won Sik Choi and Dae Youn Hwang

Curr. Issues Mol. Biol. 2023, 45(2), 1483-1499; https://doi.org/10.3390/cimb45020096 - 9 Feb 2023

Cited by 4 | Viewed by 2451

Abstract

Aloe vera (A. vera) has been studied as a treatment option for ulcerative colitis (UC), but there is a lack of scientific evidence showing whether treatment with Aloe saponaria (A. saponaria) can also be beneficial. To investigate the therapeutic [...] Read more.

Aloe vera (A. vera) has been studied as a treatment option for ulcerative colitis (UC), but there is a lack of scientific evidence showing whether treatment with Aloe saponaria (A. saponaria) can also be beneficial. To investigate the therapeutic potential of A. saponaria as a treatment for UC, clinical symptoms, histopathological characteristics of the colon, inflammatory response, and toxicity were analyzed in dextran sulfate sodium (DSS)-induced UC mice after administration of aqueous extracts of A. saponaria (AAS) for 7 days. The total polyphenol and tannin content of AAS was 272 µg/g and 163 µg/g, respectively. AAS exhibited significant antioxidant activity. Several clinical symptoms, including body weight, colon length, and hematochezia, remarkably improved in the DSS+AAS treated group compared to the DSS+Vehicle-treated group. In addition, similar improvements were detected in the histopathological characteristics and mucin-secreting ability in the colon of DSS-induced UC mice after the administration of AAS. The levels of infiltrated inflammatory cells and cytokine expression were significantly decreased in a dose-dependent manner in the colon of the DSS+AAS-treated group. These alterations in inflammatory response were accompanied by a significant recovery of the protein kinase C/extracellular signal-regulated kinase (PKC/ERK) and phosphatidylinositol-3-kinase/serine-threonine protein kinase (PI3K/Akt) signaling pathways. However, the levels of key markers for hepatotoxicity and nephrotoxicity consistently remained between those of the DSS+AAS-treated and the No groups. Therefore, the results of the present study provide novel evidence that AAS may improve the clinical symptoms and attenuate the inflammatory response in DSS-induced UC mice and does not have any significant hepatotoxicity or nephrotoxicity. Full article

(This article belongs to the Special Issue Bioactives and Inflammation)

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12 pages, 2139 KiB

Open AccessCommunication

Proof-of-Concept Analysis of B Cell Receptor Repertoire in COVID-19 Patients Undergoing ECMO by Single-Cell V(D)J and Gene Expression Sequencing

by Alessia Gallo, Nicola Cuscino, Claudia Carcione, Rosalia Busà, Pier Giulio Conaldi and Matteo Bulati

Curr. Issues Mol. Biol. 2023, 45(2), 1471-1482; https://doi.org/10.3390/cimb45020095 - 9 Feb 2023

Viewed by 2313

Abstract

SARS-CoV-2, which causes COVID-19, has altered human activities all over the world and has become a global hazard to public health. Despite considerable advancements in pandemic containment techniques, in which vaccination played a key role, COVID-19 remains a global threat, particularly for frail [...] Read more.

SARS-CoV-2, which causes COVID-19, has altered human activities all over the world and has become a global hazard to public health. Despite considerable advancements in pandemic containment techniques, in which vaccination played a key role, COVID-19 remains a global threat, particularly for frail patients and unvaccinated individuals, who may be more susceptible to developing ARDS. Several studies reported that patients with COVID-19-related ARDS who were treated with ECMO had a similar survival rate to those with COVID-19-unrelated ARDS. In order to shed light on the potential mechanisms underlying the COVID-19 infection, we conducted this proof-of-concept study using single-cell V(D)J and gene expression sequencing of B cells to examine the dynamic changes in the transcriptomic BCR repertoire present in patients with COVID-19 at various stages. We compared a recovered and a deceased COVID-19 patient supported by ECMO with one COVID-19-recovered patient who did not receive ECMO treatment and one healthy subject who had never been infected previously. Our analysis revealed a downregulation of FXYD, HLA-DRB1, and RPS20 in memory B cells; MTATP8 and HLA-DQA1 in naïve cells; RPS4Y1 in activated B cells; and IGHV3-73 in plasma cells in COVID-19 patients. We further described an increased ratio of IgA + IgG to IgD + IgM, suggestive of an intensive memory antibody response, in the COVID ECMO D patient. Finally, we assessed a V(D)J rearrangement of heavy chain IgHV3, IGHJ4, and IGHD3/IGHD2 families in COVID-19 patients regardless of the severity of the disease. Full article

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

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28 pages, 1156 KiB

Open AccessReview

Multiple Sclerosis: Inflammatory and Neuroglial Aspects

by Giulio Papiri, Giordano D’Andreamatteo, Gabriella Cacchiò, Sonila Alia, Mauro Silvestrini, Cristina Paci, Simona Luzzi and Arianna Vignini

Curr. Issues Mol. Biol. 2023, 45(2), 1443-1470; https://doi.org/10.3390/cimb45020094 - 8 Feb 2023

Cited by 27 | Viewed by 4212

Abstract

Multiple sclerosis (MS) represents the most common acquired demyelinating disorder of the central nervous system (CNS). Its pathogenesis, in parallel with the well-established role of mechanisms pertaining to autoimmunity, involves several key functions of immune, glial and nerve cells. The disease’s natural history [...] Read more.

Multiple sclerosis (MS) represents the most common acquired demyelinating disorder of the central nervous system (CNS). Its pathogenesis, in parallel with the well-established role of mechanisms pertaining to autoimmunity, involves several key functions of immune, glial and nerve cells. The disease’s natural history is complex, heterogeneous and may evolve over a relapsing-remitting (RRMS) or progressive (PPMS/SPMS) course. Acute inflammation, driven by infiltration of peripheral cells in the CNS, is thought to be the most relevant process during the earliest phases and in RRMS, while disruption in glial and neural cells of pathways pertaining to energy metabolism, survival cascades, synaptic and ionic homeostasis are thought to be mostly relevant in long-standing disease, such as in progressive forms. In this complex scenario, many mechanisms originally thought to be distinctive of neurodegenerative disorders are being increasingly recognized as crucial from the beginning of the disease. The present review aims at highlighting mechanisms in common between MS, autoimmune diseases and biology of neurodegenerative disorders. In fact, there is an unmet need to explore new targets that might be involved as master regulators of autoimmunity, inflammation and survival of nerve cells. Full article

(This article belongs to the Special Issue Molecular Mechanisms in Demyelinating Disorders of the Central Nervous System)

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21 pages, 6442 KiB

Open AccessArticle

Synthesis, Molecular Docking, and Dynamic Simulation Targeting Main Protease (Mpro) of New, Thiazole Clubbed Pyridine Scaffolds as Potential COVID-19 Inhibitors

by Adel Alghamdi, Amr S. Abouzied, Abdulwahab Alamri, Sirajudheen Anwar, Mukhtar Ansari, Ibrahim Khadra, Yasser H. Zaki and Sobhi M. Gomha

Curr. Issues Mol. Biol. 2023, 45(2), 1422-1442; https://doi.org/10.3390/cimb45020093 - 7 Feb 2023

Cited by 35 | Viewed by 3005

Abstract

Many biological activities of pyridine and thiazole derivatives have been reported, including antiviral activity and, more recently, as COVID-19 inhibitors. Thus, in this paper, we designed, synthesized, and characterized a novel series of N-aminothiazole-hydrazineethyl-pyridines, beginning with a N′-(1-(pyridine-3-yl)ethylidene)hydrazinecarbothiohydrazide derivative and various [...] Read more.

Many biological activities of pyridine and thiazole derivatives have been reported, including antiviral activity and, more recently, as COVID-19 inhibitors. Thus, in this paper, we designed, synthesized, and characterized a novel series of N-aminothiazole-hydrazineethyl-pyridines, beginning with a N′-(1-(pyridine-3-yl)ethylidene)hydrazinecarbothiohydrazide derivative and various hydrazonoyl chlorides and phenacyl bromides. Their Schiff bases were prepared from the condensation of N-aminothiazole derivatives with 4-methoxybenzaldehyde. FTIR, MS, NMR, and elemental studies were used to identify new products. The binding energy for non-bonding interactions between the ligand (studied compounds) and receptor was determined using molecular docking against the SARS-CoV-2 main protease (PDB code: 6LU7). Finally, the best docked pose with highest binding energy (8a = −8.6 kcal/mol) was selected for further molecular dynamics (MD) simulation studies to verify the outcomes and comprehend the thermodynamic properties of the binding. Through additional in vitro and in vivo research on the newly synthesized chemicals, it is envisaged that the achieved results will represent a significant advancement in the fight against COVID-19. Full article

(This article belongs to the Special Issue Drug Development and Repositioning Methodology on COVID-19)

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15 pages, 18625 KiB

Open AccessArticle

Urinary Proteome Differences in Patients with Type 2 Diabetes Pre and Post Liraglutide Treatment

by Mohamed Rafiullah, Hicham Benabdelkamel, Afshan Masood, Aishah A. Ekhzaimy, Mohthash Musambil, Salini Scaria Joy and Assim A. Alfadda

Curr. Issues Mol. Biol. 2023, 45(2), 1407-1421; https://doi.org/10.3390/cimb45020092 - 6 Feb 2023

Cited by 8 | Viewed by 2226

Abstract

Diabetes mellitus is a chronic multisystem disease with a high global prevalence. The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide is known to lower glucose levels and reduce weight. However, the mechanisms underlying the benefits of liraglutide treatment in patients with type 2 diabetes [...] Read more.

Diabetes mellitus is a chronic multisystem disease with a high global prevalence. The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide is known to lower glucose levels and reduce weight. However, the mechanisms underlying the benefits of liraglutide treatment in patients with type 2 diabetes mellitus (T2DM) remain unclear. Twelve male patients with T2DM (pre and post liraglutide treatment) and HbA1c between 8% and 11% were recruited. In the present study, a two-dimensional difference gel electrophoresis (2D-DIGE) matrix-assisted laser desorption/ionization-time of flight (MALDI TOF) mass spectrometric approach combined with bioinformatics and network pathway analysis was used to explore the urine proteomic profile. The mean age of the patients was 52.4 ± 7.5 years. After treatment with liraglutide, a statistically significant change (p < 0.006) was observed in HbA1c with no significant changes in body weight or markers of dyslipidemia. Two-dimensional difference gel electrophoresis identified significant changes (≥1.5-fold change, ANOVA, p ≤ 0.05) in 32 proteins (4 down- and 28 upregulated) in liraglutide post treatment compared to the pre-treatment state. Albumin, serotransferrin, metallothionein-2 (MT-2), and keratins K1 and K10 were found to be upregulated after liraglutide treatment. The patients showed significant improvement in glycemic control after the 12-week treatment with liraglutide. The renoprotective effect of liraglutide may be linked to the increased urinary abundance of MT-2 and the decreased abundance of zinc alpha 2-glycoprotein (ZAG) and Alpha-1 antitrypsin (α1-AT). More studies are needed to elucidate the molecular mechanisms behind the renoprotective effects of liraglutide. Full article

(This article belongs to the Special Issue Natural Products as Potential Sources of Antidiabetic Compounds)

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11 pages, 5176 KiB

Open AccessArticle

Chloride Intracellular Channel Protein 1 Expression and Angiogenic Profile of Liver Metastasis of Digestive Origin

by Amalia Raluca Ceausu, Alexandru Ciolofan, Alexandru Blidisel, Andrei Alexandru Cosma, Pusa Nela Gaje and Octavian Cretu

Curr. Issues Mol. Biol. 2023, 45(2), 1396-1406; https://doi.org/10.3390/cimb45020091 - 6 Feb 2023

Viewed by 1660

Abstract

Chloride intracellular channel 1 (CLIC1) is involved in cell migration and metastasis. The histological growth patterns of liver metastasis are as follows: desmoplastic (d-HGP), replacement (r-HGP), pushing (p-HGP), and mixed. The aim of this study was to evaluate the relation between HGP, angiogenesis, [...] Read more.

Chloride intracellular channel 1 (CLIC1) is involved in cell migration and metastasis. The histological growth patterns of liver metastasis are as follows: desmoplastic (d-HGP), replacement (r-HGP), pushing (p-HGP), and mixed. The aim of this study was to evaluate the relation between HGP, angiogenesis, and CLIC1 expression. Materials and Methods: A total of 40 cases of primary tumors and their LM: d-HGP (12 cases), r-HGP (13 cases), and p-HGP (15 cases), were evaluated through simple and double immunostaining. CLIC1 assessment was conducted as follows: scores of 0 (less than 10% of positive cells), 1 (10–30%), 2 (30–50%), or 3 (more than 50%) were assigned. Heterogeneous CLIC1 expression was found. CLIC1 in primary tumors correlated with grade G for all cases of LM with a p-HGP (p = 0.004). The CLIC1 score for LMs with an r-HGP correlated with grade G of the corresponding primary tumor (p = 0.027). CLIC1 and CD34+/Ki67+ vessels (p = 0.006) correlated in primary tumors. CLIC1 in primary tumors correlated with CD34+/Ki67+ vessels of LMs with a d HGP (p = 0.024). Conclusions: The CLIC1 score may have prognostic value, mainly for LMs with a p-HGP and r-HGP, and therapeutic value for LMs with a d-HGP. Full article

(This article belongs to the Special Issue Molecular-Based Approaches in Therapy for Gastrointestinal Cancers)

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9 pages, 606 KiB

Open AccessArticle

In Silico Integrated Analysis of Genomic, Transcriptomic, and Proteomic Data Reveals QTL-Specific Genes for Bacterial Canker Resistance in Tomato (Solanum lycopersicum L.)

by Ibrahim Celik

Curr. Issues Mol. Biol. 2023, 45(2), 1387-1395; https://doi.org/10.3390/cimb45020090 - 6 Feb 2023

Cited by 2 | Viewed by 1815

Abstract

Bacterial canker of tomato, caused by Clavibacter michiganensis subsp. michiganensis (Cmm), is a devasting disease that leads to significant yield losses. Although QTLs originating from three wild species (Solanum arcanum, S. habrochaites, and S. pimpinellifolium) were identified, [...] Read more.

Bacterial canker of tomato, caused by Clavibacter michiganensis subsp. michiganensis (Cmm), is a devasting disease that leads to significant yield losses. Although QTLs originating from three wild species (Solanum arcanum, S. habrochaites, and S. pimpinellifolium) were identified, none of the QTLs was annotated for candidate gene identification. In the present study, a QTL-based physical map was constructed to reveal the meta-QTLs for Cmm resistance. As a result, seven major QTLs were mapped. Functional annotation of QTLs revealed 48 candidate genes. Additionally, experimentally validated Cmm resistance-related genes based on transcriptomic and proteomic studies were mapped in the genome and 25 genes were found to be located in the QTL regions. The present study is the first report to construct a physical map for Cmm resistance QTLs and identify QTL-specific candidate genes. The candidate genes identified in the present study are valuable targets for fine mapping and developing markers for marker-assisted selection in tomatoes for Cmm resistance breeding. Full article

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

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14 pages, 1549 KiB

Open AccessReview

Carbonic Anhydrase II Activators in Osteopetrosis Treatment: A Review

by Zikra Alkhayal, Zakia Shinwari, Ameera Gaafar and Ayodele Alaiya

Curr. Issues Mol. Biol. 2023, 45(2), 1373-1386; https://doi.org/10.3390/cimb45020089 - 6 Feb 2023

Cited by 6 | Viewed by 2915

Abstract

Osteopetrosis is a rare hereditary illness generated by failure in osteoclasts resulting in elevated bone densities. Patients with osteopetrosis possess several complications, like dental caries, earlier teeth loss, delayed eruption, malformed crowns and roots, and lamina dura thickening. Since deficiency of carbonic anhydrase [...] Read more.

Osteopetrosis is a rare hereditary illness generated by failure in osteoclasts resulting in elevated bone densities. Patients with osteopetrosis possess several complications, like dental caries, earlier teeth loss, delayed eruption, malformed crowns and roots, and lamina dura thickening. Since deficiency of carbonic anhydrase II is a major cause behind osteopetrosis, carbonic anhydrase II activators have a large number of applications in osteopetrosis treatment. There is a lack of a comprehensive review on osteopetrosis, pathogenesis of dental abnormalities, and the role of carbonic anhydrase II activators in osteopetrosis treatment. To address this research gap, the authros perfomed a comprehensive review on osteopetrosis and its types, pathogenesis of dental abnormalities, and the role of carbonic anhydrase II activators in osteopetrosis treatment. A brief introduction to the pathogenesis of dental abnormalities and regeneration is provided in this survey. A discussion of types of osteopetrosis depending on genetic inheritance, such as autosomal dominant, autosomal recessive, and X-linked inheritance osteopetrosis, is presented in this survey. The paper also focuses on the importance of carbonic anhydrase II activators as a potential drug therapy for dental osteopetrosis. In addition, a brief note on the role of azole and fluconazole in treating osteopetrosis is given. Finally, future directions involving gene therapy for dental osteopetrosis are described. Full article

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

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24 pages, 6647 KiB

Open AccessArticle

Development and Optimization of Label-Free Quantitative Proteomics under Different Crossing Periods of Bottle Gourd

by Anurag Malik, Virender Singh Mor, Himani Punia, D. S. Duhan, Jayanti Tokas, Axay Bhuker, Mohammed Nasser Alyemeni and Awais Shakoor

Curr. Issues Mol. Biol. 2023, 45(2), 1349-1372; https://doi.org/10.3390/cimb45020088 - 6 Feb 2023

Cited by 3 | Viewed by 2304

Abstract

Bottle gourd, a common vegetable in the human diet, has been valued for its medicinal and energetic properties. In this experiment, the time-resolved analysis of the changes in the proteins’ electrophoretic patterning of the seed development at different crossing periods was studied in [...] Read more.

Bottle gourd, a common vegetable in the human diet, has been valued for its medicinal and energetic properties. In this experiment, the time-resolved analysis of the changes in the proteins’ electrophoretic patterning of the seed development at different crossing periods was studied in bottle gourd using label-free quantitative proteomics. Hybrid HBGH-35 had the highest observed protein levels at the 4th week of the crossing period (F₄) compared to the parental lines, viz. G-2 (M) and Pusa Naveen (F). The crossing period is significantly correlated with grain filling and reserve accumulation. The observed protein expression profile after storage was related to seed maturation and grain filling in bottle gourds. A total of 2517 proteins were identified in differentially treated bottle gourd fruits, and 372 proteins were differentially expressed between different crossing periods. Proteins related to carbohydrate and energy metabolism, anthocyanin biosynthesis, cell stress response, and fruit firmness were characterized and quantified. Some proteins were involved in the development, while others were engaged in desiccation and the early grain-filling stage. F4 was distinguished by an increase in the accumulation of low molecular weight proteins and enzymes such as amylase, a serine protease, and trypsin inhibitors. The seed vigor also followed similar patterns of differential expression of seed storage proteins. Our findings defined a new window during seed production, which showed that at F₄, maximum photosynthetic assimilates accumulated, resulting in an enhanced source–sink relationship and improved seed production. Our study attempts to observe the protein expression profiling pattern under different crossing periods using label-free quantitative proteomics in bottle gourd. It will facilitate future detailed investigation of the protein associated with quality traits and the agronomic importance of bottle gourd through selective breeding programs. Full article

(This article belongs to the Special Issue Genetic Sight: Plant Traits during Postharvest)

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16 pages, 2238 KiB

Open AccessArticle

Ozoile Reduces the LPS-Induced Inflammatory Response in Colonic Epithelial Cells and THP-1 Monocytes

by Maria Paola Bertuccio, Valentina Rizzo, Salvatore Arena, Alessandra Trainito, Angela Simona Montalto, Daniela Caccamo, Monica Currò, Carmelo Romeo and Pietro Impellizzeri

Curr. Issues Mol. Biol. 2023, 45(2), 1333-1348; https://doi.org/10.3390/cimb45020087 - 5 Feb 2023

Cited by 9 | Viewed by 2697

Abstract

Inappropriate activation of immune functions in intestinal epithelial cells can lead to inflammation that is characterized also by infiltration into intestinal tissue of monocytes/macrophages. Current therapies for intestinal inflammation include anti-inflammatory, immunosuppressive and biological drugs. Ozoile (stable ozonides) has been reported to exert [...] Read more.

Inappropriate activation of immune functions in intestinal epithelial cells can lead to inflammation that is characterized also by infiltration into intestinal tissue of monocytes/macrophages. Current therapies for intestinal inflammation include anti-inflammatory, immunosuppressive and biological drugs. Ozoile (stable ozonides) has been reported to exert anti-inflammatory effects. However, ozonated oil has been used mainly for topical applications and no data are available about its effects on intestinal cells or immune cells. In this study, we evaluated Ozoile effects on human HT-29 colonic cells and THP-1 monocytic cells stimulated with LPS to induce inflammation. HT-29 and THP-1 cells were treated with LPS in the presence/absence of Ozoile for 4 h. Biomarkers of inflammation, some members of tight junctions and the adhesion molecule ICAM were assessed by qRT-PCR. Protein expression was analyzed by Western blotting. The release of TNF-α and IL-1β was measured by ELISA. In HT-29, Ozoile inhibited LPS-induced expression of TNF-α, IL-1β, ZO-1, CLDN1, NOS2 and MMP-2 and increased the expression of Nrf2 and SOD2 antioxidant proteins. In THP-1 cells, the LPS induction of TNF-α, IL-1β and ICAM was counteracted by Ozoile treatment. Our in vitro results demonstrate the effectiveness of Ozoile in reducing the inflammatory response in intestinal and monocytic cells. Further in vivo studies are necessary to confirm its possible use for intestinal inflammatory conditions. Full article

(This article belongs to the Special Issue Bioactives and Inflammation)

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19 pages, 6027 KiB

Open AccessArticle

Network Pharmacological Analysis of a New Herbal Combination Targeting Hyperlipidemia and Efficacy Validation In Vitro

by Tae-Hyoung Kim, Ga-Ram Yu, Hyuck Kim, Jai-Eun Kim, Dong-Woo Lim and Won-Hwan Park

Curr. Issues Mol. Biol. 2023, 45(2), 1314-1332; https://doi.org/10.3390/cimb45020086 - 4 Feb 2023

Cited by 7 | Viewed by 3062

Abstract

The network pharmacology (NP) approach is a valuable novel methodology for understanding the complex pharmacological mechanisms of medicinal herbs. In addition, various in silico analysis techniques combined with the NP can improve the understanding of various issues used in natural product research. This [...] Read more.

The network pharmacology (NP) approach is a valuable novel methodology for understanding the complex pharmacological mechanisms of medicinal herbs. In addition, various in silico analysis techniques combined with the NP can improve the understanding of various issues used in natural product research. This study assessed the therapeutic effects of Arum ternata (AT), Poria cocos (PC), and Zingiber officinale (ZO) on hyperlipidemia after network pharmacologic analysis. A protein–protein interaction (PPI) network of forty-one key targets was analyzed to discover core functional clusters of the herbal compounds. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene ontology (GO) term enrichment analysis identified significant categories of hypolipidemic mechanisms. The STITCH database indicated a high connection with several statin drugs, deduced by the similarity in targets. AT, PC, and ZO regulated the genes related to the energy metabolism and lipogenesis in HepG2 cells loaded with free fatty acids (FFAs). Furthermore, the mixture of three herbs had a combinational effect. The herbal combination exerted superior efficacy compared to a single herb, particularly in regulating acetyl-CoA carboxylase (ACC) and carnitine palmitoyltransferase 1 (CPT-1). In conclusion, the network pharmacologic approach was used to assess potential targets of the herbal combination for treatment. Experimental data from FFA-induced HepG2 cells suggested that the combination of AT, PC, and ZO might attenuate hyperlipidemia and its associated hepatic steatosis. 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, 2599 KiB

Open AccessArticle

Prophylaxis of Antifungal Drugs against Systemic Fungemia induced by Oral Candidiasis in Mice

by Kazunori Ninomiya, Hiroki Katagiri, Hajime Hara, Kayoko Fukui, Maiko Haga-Tsujimura, Ken Nakahara and Kenjirou Nakamura

Curr. Issues Mol. Biol. 2023, 45(2), 1306-1313; https://doi.org/10.3390/cimb45020085 - 4 Feb 2023

Cited by 1 | Viewed by 1550

Abstract

Oral mucositis is highly prevalent among the elderly, for whom oral care is often difficult. Oral mucositis, such as candidiasis, can induce systemic fungemia. Antifungal prophylaxis may be useful in such cases to prevent systemic fungemia; however, studies on this are limited. The [...] Read more.

Oral mucositis is highly prevalent among the elderly, for whom oral care is often difficult. Oral mucositis, such as candidiasis, can induce systemic fungemia. Antifungal prophylaxis may be useful in such cases to prevent systemic fungemia; however, studies on this are limited. The objective of this study was to demonstrate the effectiveness of antifungal prophylaxis to prevent systemic Candida dissemination compared to oral care using a mice model. Oral candidiasis was induced using chemotherapy and inoculation with C. albicans in 8-week-old male mice. Group A was given oral care, Group B was orally administered an antifungal drug, Group C was intravenously administered an antifungal drug, and Group D was used as the negative control group. Macroscopic features of the tongue surface, colony forming units (CFU) on the tongue, and blood culture for C. albicans were evaluated. CFU was significantly higher in Group A than in Groups B and C. The oral care group, but not the groups administered antifungal agents, showed significantly higher positive numbers of animals with C. albicans in the blood as compared to the control group, indicating the effectiveness of antifungal prophylaxis over oral care. Antifungal prophylaxis may be an option for the prevention of systemic fungemia in individuals with difficulty in oral care. Full article

(This article belongs to the Special Issue Advances in Research on Molecular Oral Microorganisms)

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Curr. Issues Mol. Biol., Volume 45, Issue 2 (February 2023) – 63 articles

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