Current Issues in Molecular Biology

18 pages, 6927 KiB

Open AccessArticle

Pereskia sacharosa Griseb. (Cactaceae) Prevents Lipopolysaccharide-Induced Neuroinflammation in Rodents via Down-Regulating TLR4/CD14 Pathway and GABAA γ2 Activity

by María Fernanda Prado-Fernández, Víctor Manuel Magdaleno-Madrigal, Emmanuel Cabañas-García, Samuel Mucio-Ramírez, Salvador Almazán-Alvarado, Eugenio Pérez-Molphe-Balch, Yenny Adriana Gómez-Aguirre and Edith Sánchez-Jaramillo

Curr. Issues Mol. Biol. 2024, 46(7), 6885-6902; https://doi.org/10.3390/cimb46070411 (registering DOI) - 3 Jul 2024

Abstract

Pereskia sacharosa Griseb. is a plant used in traditional herbal medicine to treat inflammation. We analyzed the phenolic content of P. sacharosa leaves (EEPs) by liquid chromatography–tandem mass spectrometry (LC-MS/MS) and investigated the anti-inflammatory properties of EEPs and its flavonoid fraction (F10) in [...] Read more.

Pereskia sacharosa Griseb. is a plant used in traditional herbal medicine to treat inflammation. We analyzed the phenolic content of P. sacharosa leaves (EEPs) by liquid chromatography–tandem mass spectrometry (LC-MS/MS) and investigated the anti-inflammatory properties of EEPs and its flavonoid fraction (F10) in animal models subjected to acute neuroinflammation induced by bacterial lipopolysaccharide (LPS). Coronal brain sections of C57BL/6JN male mice or Wistar male rats administered with EEPs or F10 before LPS were subjected to in situ hybridization to determine c-fos and CD14 mRNA levels in the hypothalamus or GABA_A γ2 mRNA levels in the hippocampus. Theta oscillations were recorded every 6 h in the hippocampus of Wistar rats. In total, five flavonoids and eight phenolic acids were identified and quantified in P. sacharosa leaves. Either EEPs or F10 crossed the blood–brain barrier (BBB) into the brain and reduced the mRNA expression of c-fos, CD14, and GABA_A γ2. A decrease in theta oscillation was observed in the hippocampus of the LPS group, while the F10 + LPS group overrode the LPS effect on theta activity. We conclude that the bioactive compounds of P. sacharosa reduce the central response to inflammation, allowing the early return of ambulatory activity and well-being of the animal. Full article

(This article belongs to the Special Issue Bioactive Molecules: Structure-Activity Relationship)

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17 pages, 558 KiB

Open AccessReview

Interplay among Oxidative Stress, Autophagy, and the Endocannabinoid System in Neurodegenerative Diseases: Role of the Nrf2- p62/SQSTM1 Pathway and Nutraceutical Activation

by Federica Armeli, Beatrice Mengoni, Debra L. Laskin and Rita Businaro

Curr. Issues Mol. Biol. 2024, 46(7), 6868-6884; https://doi.org/10.3390/cimb46070410 (registering DOI) - 2 Jul 2024

Abstract

The onset of neurodegenerative diseases involves a complex interplay of pathological mechanisms, including protein aggregation, oxidative stress, and impaired autophagy. This review focuses on the intricate connection between oxidative stress and autophagy in neurodegenerative disorders, highlighting autophagy as pivotal in disease pathogenesis. Reactive [...] Read more.

The onset of neurodegenerative diseases involves a complex interplay of pathological mechanisms, including protein aggregation, oxidative stress, and impaired autophagy. This review focuses on the intricate connection between oxidative stress and autophagy in neurodegenerative disorders, highlighting autophagy as pivotal in disease pathogenesis. Reactive oxygen species (ROS) play dual roles in cellular homeostasis and autophagy regulation, with disruptions of redox signaling contributing to neurodegeneration. The activation of the Nrf2 pathway represents a critical antioxidant mechanism, while autophagy maintains cellular homeostasis by degrading altered cell components. The interaction among p62/SQSTM1, Nrf2, and Keap1 forms a regulatory pathway essential for cellular stress response, whose dysregulation leads to impaired autophagy and aggregate accumulation. Targeting the Nrf2-p62/SQSTM1 pathway holds promise for therapeutic intervention, mitigating oxidative stress and preserving cellular functions. Additionally, this review explores the potential synergy between the endocannabinoid system and Nrf2 signaling for neuroprotection. Further research is needed to elucidate the involved molecular mechanisms and develop effective therapeutic strategies against neurodegeneration. Full article

(This article belongs to the Special Issue Molecular Genetics and Genomics in Brain Disorders)

15 pages, 599 KiB

Open AccessArticle

Telomere Length in a South African Population Co-Infected with HIV and Helminths

by Engelinah D. Macamo, Zilungile L. Mkhize-Kwitshana, Zamathombeni Duma, Julian Mthombeni and Pragalathan Naidoo

Curr. Issues Mol. Biol. 2024, 46(7), 6853-6867; https://doi.org/10.3390/cimb46070409 (registering DOI) - 2 Jul 2024

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Abstract

Biological ageing refers to the gradual decrease in physiological functions, resulting in immune senescence, cellular damage and apoptosis. Telomere length is a biomarker of biological ageing. Limited studies have associated shorter telomere length with HIV and parasite single infections, with no studies reporting [...] Read more.

Biological ageing refers to the gradual decrease in physiological functions, resulting in immune senescence, cellular damage and apoptosis. Telomere length is a biomarker of biological ageing. Limited studies have associated shorter telomere length with HIV and parasite single infections, with no studies reporting the association of HIV and parasite co-infection with telomere length. The study aimed to investigate whether telomere length shortening is accelerated in a South African population co-infected with HIV and helminths compared to participants singly infected with either HIV or helminths. Additionally, telomere length data were compared with participants’ biochemical and full blood count parameters. A total of 200 participants were in groups of uninfected control, HIV single infection, helminth single infection and HIV and helminth co-infection groups. Relative telomere length (RTL) was determined using Real-Time PCR and associated with biochemical and full blood count parameters using multivariate regression analysis models that were adjusted for confounders. The uninfected control group was used as a reference group. The uninfected control group had the highest mean RTL (1.21 ± 0.53) while the HIV-infected (0.96 ± 0.42) and co-infected (0.93 ± 0.41) groups had similar RTLs, and lastly, the helminth-infected group (0.83 ± 0.33) had the lowest RTL (p = 0.0002). When compared to the uninfected control group, a significant association between RTL and biochemical parameters, including blood iron (β = −0.48), ferritin (β = −0.48), transferrin saturation (β = −0.57), transferrin (β = −0.57), phosphate (β = −0.47), vitamin A (β = −0.49) and C-reactive protein (β = −0.52) were noted in the co-infected group (p < 0.05). In addition, a significant association between RTL and full blood count, including (β = −0.47), haematocrit (β = −0.46), mean corpuscular volume (β = −0.47), lymphocytes (β = −0.45), mean corpuscular haemoglobin concentration (β = −0.45), red cell distribution width (β = −0.47), monocytes (β = −0.45), eosinophils (β = −0.45), basophils (β = −0.44) and transferrin saturation (β = −0.57) were also noted in the co-infected group (p < 0.05). Accelerated biological ageing, as indicated by telomere length shortening, is associated with HIV and helminth co-infections. Full article

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

17 pages, 3652 KiB

Open AccessArticle

Reciprocal Interactions of Human Monocytes and Cancer Cells in Co-Cultures In Vitro

by Roman Paduch, Maria Klatka, Paulina Pieniądz, Iwona Wertel, Anna Pawłowska and Janusz Klatka

Curr. Issues Mol. Biol. 2024, 46(7), 6836-6852; https://doi.org/10.3390/cimb46070408 (registering DOI) - 2 Jul 2024

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Abstract

The tumor microenvironment (TME) includes immune and stromal cells and noncellular extracellular matrix (ECM) components. Tumor-associated macrophages (TAMs) are the most important immune cells in TME and are crucial for carcinomas’ progression. The purpose was to analyze direct and indirect interactions in co-culture [...] Read more.

The tumor microenvironment (TME) includes immune and stromal cells and noncellular extracellular matrix (ECM) components. Tumor-associated macrophages (TAMs) are the most important immune cells in TME and are crucial for carcinomas’ progression. The purpose was to analyze direct and indirect interactions in co-culture of tumor cells with monocytes/macrophages and, additionally, to indicate which interactions are more important for cancer development. Cytokines, reactive oxygen species, nitric oxide level, tumor cell cycle and changes in tumor cell morphology after human tumor cells (Hep-2 and RK33 cell lines) with human monocyte/macrophage (THP-1 cell line) interactions were tested. Morphology and cytoskeleton organization of tumor cells did not change after co-culture with macrophages. In co-culture of tumor cells with human monocyte, changes in the percentage of tumor cells in cell cycle phases was observed. No significant changes in reactive oxygen species (ROS) were found in the co-culture as compared to the tumor cell mono-culture. Monocytes produced about three times higher ROS than tumor cells. In co-cultures, a lower nitric oxide (NO_x) level was found as compared to the sum of the production by both mono-cultures. Co-culture conditions limited the production of cytokines (IL-4, IL-10 and IL-13) as compared to the sum of their level in mono-cultures. In conclusion, macrophages influence tumor cell growth and functions. Mutual (direct and paracrine) interactions between tumor cells and macrophages changed cytokine production and tumor cell cycle profile. The data obtained may allow us to initially indicate which kind of interactions may have a greater impact on cancer development processes. Full article

(This article belongs to the Special Issue Tumor Immunology: From Molecular Mechanisms to Treatment)

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16 pages, 672 KiB

Open AccessReview

Muscarinic Receptors and Alzheimer’s Disease: New Perspectives and Mechanisms

by Martina Monaco, Hanna Trebesova and Massimo Grilli

Curr. Issues Mol. Biol. 2024, 46(7), 6820-6835; https://doi.org/10.3390/cimb46070407 (registering DOI) - 2 Jul 2024

Viewed by 129

Abstract

Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative diseases on a global scale. Historically, this pathology has been linked to cholinergic transmission, and despite the scarcity of effective therapies, numerous alternative processes and targets have been proposed as potential avenues for [...] Read more.

Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative diseases on a global scale. Historically, this pathology has been linked to cholinergic transmission, and despite the scarcity of effective therapies, numerous alternative processes and targets have been proposed as potential avenues for comprehending this complex illness. Nevertheless, the fundamental pathophysiological mechanisms underpinning AD remain largely enigmatic, with a growing body of evidence advocating for the significance of muscarinic receptors in modulating the brain’s capacity to adapt and generate new memories. This review summarizes the current state of the art in the field of muscarinic receptors’ involvement in AD. A specific key factor was the relationship between comorbidity and the emergence of new mechanisms. Full article

(This article belongs to the Special Issue Metabolism and Molecular Pathology Related Features in Neurological Diseases)

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15 pages, 1425 KiB

Open AccessArticle

The Promising Effect of Ascorbic Acid and Paracetamol as Anti-Biofilm and Anti-Virulence Agents against Resistant Escherichia coli

by Sara M. Eltabey, Ali H. Ibrahim, Mahmoud M. Zaky, Adel Ehab Ibrahim, Yahya Bin Abdullah Alrashdi, Sami El Deeb and Moustafa M. Saleh

Curr. Issues Mol. Biol. 2024, 46(7), 6805-6819; https://doi.org/10.3390/cimb46070406 (registering DOI) - 2 Jul 2024

Viewed by 164

Abstract

Escherichia coli is a major cause of serious infections, with antibiotic resistance rendering many treatments ineffective. Hence, novel strategies to combat this pathogen are needed. Anti-virulence therapy is a promising new approach for the subsequent era. Recent research has examined the impact of [...] Read more.

Escherichia coli is a major cause of serious infections, with antibiotic resistance rendering many treatments ineffective. Hence, novel strategies to combat this pathogen are needed. Anti-virulence therapy is a promising new approach for the subsequent era. Recent research has examined the impact of sub-inhibitory doses of ascorbic acid and paracetamol on Escherichia coli virulence factors. This study evaluated biofilm formation, protease production, motility behavior, serum resistance, expression of virulence-regulating genes (using RT-PCR), and survival rates in a mouse model. Ascorbic acid significantly reduced biofilm formation, protease production, motility, and serum resistance from 100% in untreated isolates to 22–89%, 10–89%, 2–57%, and 31–35% in treated isolates, respectively. Paracetamol also reduced these factors from 100% in untreated isolates to 16–76%, 1–43%, 16–38%, and 31–35%, respectively. Both drugs significantly down-regulated virulence-regulating genes papC, fimH, ompT_m, stcE, fliC, and kpsMTII. Mice treated with these drugs had a 100% survival rate compared with 60% in the positive control group control inoculated with untreated bacteria. This study highlights the potential of ascorbic acid and paracetamol as anti-virulence agents, suggesting their use as adjunct therapies alongside conventional antimicrobials or as alternative treatments for resistant Escherichia coli infections. Full article

(This article belongs to the Special Issue Molecular Biology in Drug Design and Precision Therapy)

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22 pages, 2141 KiB

Open AccessReview

A Comprehensive View on the Impact of Chlorogenic Acids on Colorectal Cancer

by Andreea-Adriana Neamțu, Teodor Andrei Maghiar, Violeta Turcuș, Paula Bianca Maghiar, Anca-Maria Căpraru, Bianca-Andreea Lazar, Cristina-Adriana Dehelean, Ovidiu Laurean Pop, Carmen Neamțu, Bogdan Dan Totolici and Endre Mathe

Curr. Issues Mol. Biol. 2024, 46(7), 6783-6804; https://doi.org/10.3390/cimb46070405 (registering DOI) - 2 Jul 2024

Viewed by 157

Abstract

Chlorogenic acids are plant secondary metabolites, chemically—polyphenols with similar biological activity, formed through the esterification of quinic acid and hydrocinnamic acid moieties. They are best known for their high concentration in coffee and other dietary sources and the antioxidant properties that they exhibit. [...] Read more.

Chlorogenic acids are plant secondary metabolites, chemically—polyphenols with similar biological activity, formed through the esterification of quinic acid and hydrocinnamic acid moieties. They are best known for their high concentration in coffee and other dietary sources and the antioxidant properties that they exhibit. Both chlorogenic acids and plant extracts containing significant amounts of the compounds show promising in vitro activity against colorectal cancer. With coffee being the most popular drink in the world, and colorectal cancer at an unfortunate peak in incidence and mortality, the mechanisms through which the anti-tumorigenic effect of chlorogenic acids could be functionalized for CRC prevention seem appealing to study. Therefore, this review aims to enable a better understanding of the modes of action of chlorogenic acids in combating carcinogenesis, with a focus on cell cycle arrest, the induction of apoptosis, and the modulation of Wnt, Pi3K/Akt, and MAPK signal transduction pathways, alongside the reduction in the number of inflammatory cytokines and chemokines and the counterintuitive beneficial elevation of oxidative stress. Full article

(This article belongs to the Special Issue Molecular Research in Bioactivity of Natural Products)

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14 pages, 825 KiB

Open AccessArticle

Secondary Metabolites with Antioxidant and Antimicrobial Activities from Camellia fascicularis

by Jiandong Tang, Ruonan Li, Boxiao Wu, Junrong Tang, Huan Kan, ** Zhao, Yingjun Zhang, Weihua Wang and Yun Liu

Curr. Issues Mol. Biol. 2024, 46(7), 6769-6782; https://doi.org/10.3390/cimb46070404 (registering DOI) - 2 Jul 2024

Viewed by 198

Abstract

Camellia fascicularis has important ornamental, medicinal, and food value. It also has tremendous potential for exploiting bioactivities. However, the bioactivities of secondary metabolites in C. fascicularis have not been reported. The structures of compounds were determined by spectral analysis and nuclear magnetic resonance [...] Read more.

Camellia fascicularis has important ornamental, medicinal, and food value. It also has tremendous potential for exploiting bioactivities. However, the bioactivities of secondary metabolites in C. fascicularis have not been reported. The structures of compounds were determined by spectral analysis and nuclear magnetic resonance (NMR) combined with the available literature on secondary metabolites of C. fascicularis leaves. In this study, 15 compounds were identified, including 5 flavonoids (1–5), a galactosylglycerol derivative (6), a terpenoid (7), 4 lignans (8–11), and 4 phenolic acids (12–15). Compounds 6–7 and 9–12 were isolated from the genus Camellia for the first time. The remaining compounds were also isolated from C. fascicularis for the first time. Evaluation of antioxidant and antimicrobial activities revealed that compounds 5 and 8–11 exhibited stronger antioxidant activity than the positive drug ascorbic acid, while compounds 7, 13, and 15 showed similar activity to ascorbic acid. The minimum inhibitory concentration (MIC) of antibacterial activity for compounds 5, 7, 9, 11, and 13 against Pseudomonas aeruginosa was comparable to that of the positive control drug tetracycline at a concentration of 62.50 µg/mL; other secondary metabolites inhibited Escherichia coli and Staphylococcus aureus at concentrations ranging from 125–250 µg/mL. Full article

(This article belongs to the Special Issue Molecular Insights into Food-Derived Natural Products and Their Biological Activities)

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12 pages, 1099 KiB

Open AccessReview

VEGF as a Key Actor in Recurrent Respiratory Papillomatosis: A Narrative Review

by Sandra Gazzini, Raffaele Cerullo and Davide Soloperto

Curr. Issues Mol. Biol. 2024, 46(7), 6757-6768; https://doi.org/10.3390/cimb46070403 (registering DOI) - 1 Jul 2024

Viewed by 162

Abstract

Recurrent respiratory papillomatosis (RRP) is a benign disease of the upper aerodigestive tract caused by human papillomavirus (HPV) types 6 and 11. The clinical course is unpredictable and some patients, especially younger children, experience a high rate of recurrence with a significant impact [...] Read more.

Recurrent respiratory papillomatosis (RRP) is a benign disease of the upper aerodigestive tract caused by human papillomavirus (HPV) types 6 and 11. The clinical course is unpredictable and some patients, especially younger children, experience a high rate of recurrence with a significant impact on their quality of life. The molecular mechanisms of HPV infection in keratinocytes have been extensively studied throughout the years, with particular regard to its role in causing malignant tumors, like cervical cancer and head and neck carcinomas. A minor but not negligible amount of the literature has investigated the molecular landscape of RRP patients, and some papers have studied the role of angiogenesis (the growth of blood vessels from pre-existing vasculature) in this disease. A central role in this process is played by vascular endothelial growth factor (VEGF), which activates different signaling cascades on multiple levels. The increased knowledge has led to the introduction of the VEGF inhibitor bevacizumab in recent years as an adjuvant treatment in some patients, with good results. This review summarizes the current evidence about the role of VEGF in the pathophysiology of RRP, the molecular pathways activated by binding with its receptors, and the current and future roles of anti-angiogenic treatment. Full article

(This article belongs to the Special Issue Molecular Mechanism of HPV’s Involvement in Cancers)

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11 pages, 1272 KiB

Open AccessArticle

The Potential MicroRNA Diagnostic Biomarkers in Oral Squamous Cell Carcinoma of the Tongue

by Young-Nam Park, Jae-Ki Ryu and Yeongdon Ju

Curr. Issues Mol. Biol. 2024, 46(7), 6746-6756; https://doi.org/10.3390/cimb46070402 (registering DOI) - 1 Jul 2024

Viewed by 172

Abstract

Oral squamous cell carcinoma (OSCC) of the tongue is a common type of head and neck malignancy with a poor prognosis, underscoring the urgency for early detection. MicroRNAs (miRNAs) have remarkable stability and are easily measurable. Thus, miRNAs may be a promising biomarker [...] Read more.

Oral squamous cell carcinoma (OSCC) of the tongue is a common type of head and neck malignancy with a poor prognosis, underscoring the urgency for early detection. MicroRNAs (miRNAs) have remarkable stability and are easily measurable. Thus, miRNAs may be a promising biomarker candidate among biomarkers in cancer diagnosis. Biomarkers have the potential to facilitate personalized medicine approaches by guiding treatment decisions and optimizing therapy regimens for individual patients. Utilizing data from The Cancer Genome Atlas, we identified 13 differentially expressed upregulated miRNAs in OSCC of the tongue. Differentially expressed miRNAs were analyzed by enrichment analysis to reveal underlying biological processes, pathways, or functions. Furthermore, we identified miRNAs associated with the progression of OSCC of the tongue, utilizing receiver operating characteristic analysis to evaluate their potential as diagnostic biomarkers. A total of 13 upregulated miRNAs were identified as differentially expressed in OSCC of the tongue. Five of these miRNAs had high diagnostic power. In particular, miR-196b has the potential to serve as one of the most effective diagnostic biomarkers. Then, functional enrichment analysis for the target gene of miR-196b was performed, and a protein–protein interaction network was constructed. This study assessed an effective approach for identifying miRNAs as early diagnostic markers for OSCC of the tongue. Full article

(This article belongs to the Special Issue Oral Cancer: Prophylaxis, Etiopathogenesis and Treatment)

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21 pages, 1192 KiB

Open AccessReview

Examining the Potential Applicability of Orexigenic and Anorexigenic Peptides in Veterinary Medicine for the Management of Obesity in Companion Animals

by Cezary Osiak-Wicha, Katarzyna Kras, Ewa Tomaszewska, Siemowit Muszyński and Marcin B. Arciszewski

Curr. Issues Mol. Biol. 2024, 46(7), 6725-6745; https://doi.org/10.3390/cimb46070401 (registering DOI) - 1 Jul 2024

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Abstract

This review article comprehensively explores the role of orexigenic and anorexigenic peptides in the management of obesity in companion animals, with a focus on clinical applications. Obesity in domestic animals, particularly dogs and cats, is prevalent, with significant implications for their health and [...] Read more.

This review article comprehensively explores the role of orexigenic and anorexigenic peptides in the management of obesity in companion animals, with a focus on clinical applications. Obesity in domestic animals, particularly dogs and cats, is prevalent, with significant implications for their health and well-being. Factors contributing to obesity include overfeeding, poor-quality diet, lack of physical activity, and genetic predispositions. Despite the seriousness of this condition, it is often underestimated, with societal perceptions sometimes reinforcing unhealthy behaviors. Understanding the regulation of food intake and identifying factors affecting the function of food intake-related proteins are crucial in combating obesity. Dysregulations in these proteins, whether due to genetic mutations, enzymatic dysfunctions, or receptor abnormalities, can have profound health consequences. Molecular biology techniques play a pivotal role in elucidating these mechanisms, offering insights into potential therapeutic interventions. The review categorizes food intake-related proteins into anorexigenic peptides (inhibitors of food intake) and orexigenic peptides (enhancers of food intake). It thoroughly examines current research on regulating energy balance in companion animals, emphasizing the clinical application of various peptides, including ghrelin, phoenixin (PNX), asprosin, glucagon-like peptide 1 (GLP-1), leptin, and nesfatin-1, in veterinary obesity management. This comprehensive review aims to provide valuable insights into the complex interplay between peptides, energy balance regulation, and obesity in companion animals. It underscores the importance of targeted interventions and highlights the potential of peptide-based therapies in improving the health outcomes of obese pets. Full article

(This article belongs to the Special Issue Protein and Bioactive Peptides: Bioactivity, Applications and Health Benefits)

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15 pages, 2049 KiB

Open AccessArticle

Feasibility Trial Exploring Immune-Related Biomarkers Pertaining to Rapid Immune Surveillance and Cytokine Changes after Consuming a Nutraceutical Supplement Containing Colostrum- and Egg-Based Low-Molecular-Weight Peptides

by Liu Yu, Ifeanyi Iloba, Dina Cruickshank and Gitte S. Jensen

Curr. Issues Mol. Biol. 2024, 46(7), 6710-6724; https://doi.org/10.3390/cimb46070400 (registering DOI) - 30 Jun 2024

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Abstract

Immune protection associated with consuming colostrum-based peptides is effective against bacterial and viral insults. The goal for this study was to document acute changes to immune surveillance and cytokine levels after consuming a single dose of a nutraceutical blend in the absence of [...] Read more.

Immune protection associated with consuming colostrum-based peptides is effective against bacterial and viral insults. The goal for this study was to document acute changes to immune surveillance and cytokine levels after consuming a single dose of a nutraceutical blend in the absence of an immune challenge. A double-blind, randomized, placebo-controlled, cross-over pilot study involved healthy participants attending two clinic visits. Blood draws were performed pre-consumption and at 1, 2, and 24 h after consuming a blend of bovine colostrum- and hen’s egg-based low-molecular-weight peptides (CELMPs) versus a placebo. Immunophenoty** was performed by flow cytometry, and serum cytokines were measured by multiplex cytokine arrays. Consumption of CELMPs triggered increased immune surveillance after 1 h, involving monocytes (p < 0.1), natural killer (NK) cells (p < 0.1), and natural killer T (NKT) cells (p < 0.05). The number of NKT cells expressing the CD25 immunoregulatory marker increased at 1 and 2 h (p < 0.1). Increased serum levels of monocyte chemoattractant protein-1 (MCP-1) was observed at 2 and 24 h (24 h: p < 0.05). Selective reduction in pro-inflammatory cytokines was seen at 1, 2, and 24 h, where the 2-h reduction was highly significant for IL-6, IFN-γ, and IL-13. The rapid, transient increase in immune surveillance, in conjunction with the reduced levels of inflammatory markers, suggests that the CELMP blend of natural peptides provides immune benefits of use in preventive medicine. Further studies are warranted in chronic inflammatory conditions. Full article

(This article belongs to the Special Issue The Protection and Toxic Reactions of Dietary Supplements: Focusing on Molecular Mechanisms and Treatment)

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20 pages, 1100 KiB

Open AccessReview

Common Denominator of MASLD and Some Non-Communicable Diseases

by Katarzyna Ferenc, Sara Jarmakiewicz-Czaja, Aneta Sokal-Dembowska, Katarzyna Stasik and Rafał Filip

Curr. Issues Mol. Biol. 2024, 46(7), 6690-6709; https://doi.org/10.3390/cimb46070399 (registering DOI) - 29 Jun 2024

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Abstract

Currently, steatohepatitis has been designated as metabolic dysfunction-associated steatohepatitis (MASLD). MASLD risk factors mainly include metabolic disorders but can also include genetic, epigenetic, and environmental factors. Disease entities such as obesity, diabetes, cardiovascular disease, and MASLD share similar pathomechanisms and risk factors. Moreover, [...] Read more.

Currently, steatohepatitis has been designated as metabolic dysfunction-associated steatohepatitis (MASLD). MASLD risk factors mainly include metabolic disorders but can also include genetic, epigenetic, and environmental factors. Disease entities such as obesity, diabetes, cardiovascular disease, and MASLD share similar pathomechanisms and risk factors. Moreover, a bidirectional relationship is observed between the occurrence of certain chronic diseases and MASLD. These conditions represent a global public health problem that is responsible for poor quality of life and high mortality. It seems that paying holistic attention to these problems will not only help increase the chances of reducing the incidence of these diseases but also assist in the prevention, treatment, and support of patients. Full article

(This article belongs to the Special Issue Cellular and Molecular Mechanisms of Nonalcoholic Fatty Liver Disease)

15 pages, 603 KiB

Open AccessReview

Potential New Inflammatory Markers in Bronchiectasis: A Literature Review

by Francesco Rocco Bertuccio, Nicola Baio, Simone Montini, Valentina Ferroni, Vittorio Chino, Lucrezia Pisanu, Marianna Russo, Ilaria Giana, Alessandro Cascina, Valentina Conio, Amelia Grosso, Erica Gini, Federica Albicini, Angelo Guido Corsico and Giulia Maria Stella

Curr. Issues Mol. Biol. 2024, 46(7), 6675-6689; https://doi.org/10.3390/cimb46070398 (registering DOI) - 29 Jun 2024

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Abstract

Specific molecular and inflammatory endotypes have been identified for chronic respiratory disorders, including asthma and COPD (chronic obstructive pulmonary disease). These endotypes correspond with clinical aspects of disease, enabling targeted medicines to address certain pathophysiologic pathways, often referred to as “precision medicine”. With [...] Read more.

Specific molecular and inflammatory endotypes have been identified for chronic respiratory disorders, including asthma and COPD (chronic obstructive pulmonary disease). These endotypes correspond with clinical aspects of disease, enabling targeted medicines to address certain pathophysiologic pathways, often referred to as “precision medicine”. With respect to bronchiectasis, many comorbidities and underlying causes have been identified. Inflammatory endotypes have also been widely studied and reported. Additionally, several genes have been shown to affect disease progression. However, the lack of a clear classification has also hampered our understanding of the disease’s natural course. The aim of this review is, thus, to summarize the current knowledge on biomarkers and actionable targets of this complex pathologic condition and to point out unmet needs, which are required in the design of effective diagnostic and therapeutic trials. Full article

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

10 pages, 559 KiB

Open AccessArticle

Genetic Markers of Helicobacter pylori Resistance to Clarithromycin and Levofloxacin in Moscow, Russia

by Natalia Bodunova, Larisa Tsapkova, Vera Polyakova, Irina Baratova, Konstantin Rumyantsev, Natalia Dekhnich, Karina Nikolskaya, Margarita Chebotareva, Irina Voynovan, Elena Parfenchikova, Galina Pronina, Ekaterina Chernikova and Dmitry Bordin

Curr. Issues Mol. Biol. 2024, 46(7), 6665-6674; https://doi.org/10.3390/cimb46070397 (registering DOI) - 29 Jun 2024

Viewed by 241

Abstract

The Maastricht VI/Florence consensus recommends, as one of the measures to enhance the efficacy of Helicobacter pylori infection eradication, a personalized treatment approach involving the selection of an antimicrobial agent based on the pre-determined resistance of H. pylori. To address the need to [...] Read more.

The Maastricht VI/Florence consensus recommends, as one of the measures to enhance the efficacy of Helicobacter pylori infection eradication, a personalized treatment approach involving the selection of an antimicrobial agent based on the pre-determined resistance of H. pylori. To address the need to develop test systems for personalized drug selection, this study was designed to analyze the molecular resistance of H. pylori using a newly developed Sanger sequencing test platform. The characteristics of the test system were determined on 25 pure culture samples of H. pylori with known resistance. Sensitivity and specificity for detecting resistance to clarithromycin was 100% and those to levofloxacin were 93% and 92%, respectively. The test system has been tested in real clinical practice on 112 H. pylori-positive patients who had not previously received proton pump inhibitors (PPIs) or antibacterial drugs. Mutations indicating resistance to clarithromycin were found in 27 (24%) samples and those indicating resistance to levofloxacin were found in 26 (23%) samples. Double resistance was observed in 16 (14%) samples. The most common mutations leading to clarithromycin resistance were 2143G and 2142G and to levofloxacin resistance—261A and 271A in the gyrA gene, which account for 69% of all identified genetic determinants in levofloxacin-resistant bacteria. Thus, a personalized approach to the selection of H. pylori eradication therapy based on the detection of bacterial resistance before prescribing first-line therapy could help to avoid the prescription of ineffective H. pylori eradication therapies and, overall, contribute to the control of antibiotic resistance of H. pylori. Full article

(This article belongs to the Special Issue Infectious Diseases and Molecular Epidemiology: Focus on Pathogenic Microorganisms)

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19 pages, 8483 KiB

Open AccessArticle

Genome-Wide Identification and Expression Analysis of BrBASS Genes in Brassica rapa Reveals Their Potential Roles in Abiotic Stress Tolerance

by Zhao**g Ji, Ruolan Wang, Meiqi Zhang, Luhan Chen, Yuexin Wang, Jiyun Hui, Shiya Hao, Bingcan Lv, Qiwei Jiang and Yunyun Cao

Curr. Issues Mol. Biol. 2024, 46(7), 6646-6664; https://doi.org/10.3390/cimb46070396 - 28 Jun 2024

Viewed by 458

Abstract

The bile acid sodium symporter (BASS) family plays an important role in transporting substances and coordinating plants’ salt tolerance. However, the function of BASS in Brassica rapa has not yet been elucidated. In this study, eight BrBASS genes distributed on five chromosomes were [...] Read more.

The bile acid sodium symporter (BASS) family plays an important role in transporting substances and coordinating plants’ salt tolerance. However, the function of BASS in Brassica rapa has not yet been elucidated. In this study, eight BrBASS genes distributed on five chromosomes were identified that belonged to four subfamilies. Expression profile analysis showed that BrBASS7 was highly expressed in roots, whereas BrBASS4 was highly expressed in flowers. The promoter element analysis also identified several typical homeopathic elements involved in abiotic stress tolerance and stress-related hormonal responses. Notably, under salt stress, the expression of BrBASS2 was significantly upregulated; under osmotic stress, that of BrBASS4 increased and then decreased; and under cold stress, that of BrBASS7 generally declined. The protein–protein interaction analysis revealed that the BrBASS2 homologous gene AtBASS2 interacted with Nhd1 (N-mediated heading date-1) to alleviate salt stress in plants, while the BrBASS4 homologous gene AtBASS3 interacted with BLOS1 (biogenesis of lysosome-related organelles complex 1 subunit 1) via co-regulation with SNX1 (sorting nexin 1) to mitigate an unfavorable growing environment for roots. Further, Bra-miR396 (Bra-microRNA396) targeting BrBASS4 and BrBASS7 played a role in the plant response to osmotic and cold stress conditions, respectively. This research demonstrates that BrBASS2, BrBASS4, and BrBASS7 harbor great potential for regulating abiotic stresses. The findings will help advance the study of the functions of the BrBASS gene family. Full article

(This article belongs to the Special Issue Functional Genomics and Comparative Genomics Analysis in Plants, 2nd Edition)

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13 pages, 772 KiB

Open AccessReview

Potential Protective Factors for Allergic Rhinitis Patients Infected with COVID-19

by Jiaoyue Dong, Dingyuan Su, Binbin Zhao, Jiayang Han, Mengjie Tu, Kaifeng Zhang, Fengling Wang and Yang An

Curr. Issues Mol. Biol. 2024, 46(7), 6633-6645; https://doi.org/10.3390/cimb46070395 - 28 Jun 2024

Viewed by 617

Abstract

At the beginning of the 2019 coronavirus disease (COVID-19) pandemic, airway allergic diseases such as asthma and allergic rhinitis (AR) were considered as risk factors for COVID-19, as they would aggravate symptoms. With further research, more and more literature has shown that airway [...] Read more.

At the beginning of the 2019 coronavirus disease (COVID-19) pandemic, airway allergic diseases such as asthma and allergic rhinitis (AR) were considered as risk factors for COVID-19, as they would aggravate symptoms. With further research, more and more literature has shown that airway allergic disease may not be a high-risk factor, but may be a protective factor for COVID-19 infection, which is closely related to its low-level expression of the ACE2 receptor and the complex cytokines network as underlying molecular regulatory mechanisms. In addition, steroid hormones and age factors could not be ignored. In this review, we have summarized some current evidence on the relationship between COVID-19 and allergic rhinitis to highlight the underlying mechanisms of COVID-19 infection and provide novel insights for its prevention and treatment. The key findings show that allergic rhinitis and its related molecular mechanisms may have a protective effect against COVID-19 infection. Full article

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

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13 pages, 580 KiB

Open AccessArticle

Validation of Selected MicroRNA Transcriptome Data in the Bovine Corpus Luteum during Early Pregnancy by RT-qPCR

by Rreze M. Gecaj, Behlul Behluli and Curtis R. Youngs

Curr. Issues Mol. Biol. 2024, 46(7), 6620-6632; https://doi.org/10.3390/cimb46070394 - 27 Jun 2024

Viewed by 227

Abstract

In cattle, the corpus luteum (CL) is pivotal in maintaining early pregnancy by secreting progesterone. To establish pregnancy, the conceptus produces interferon-τ, preventing luteolysis and initiating the transformation of the CL spurium into a CL verum. Although this transformation is tightly regulated, limited [...] Read more.

In cattle, the corpus luteum (CL) is pivotal in maintaining early pregnancy by secreting progesterone. To establish pregnancy, the conceptus produces interferon-τ, preventing luteolysis and initiating the transformation of the CL spurium into a CL verum. Although this transformation is tightly regulated, limited data are available on the expression of microRNAs (miRNAs) during and after this process. To address this gap, we re-analyzed previously published RNA-Seq data of CL from pregnant cows and regressed CL from non-pregnant cows. This analysis identified 44 differentially expressed miRNAs. From this pool, three miRNAs—bta-miR-222-3p, bta-miR-29c, and bta-miR-2411-3p—were randomly selected for relative quantification. Using bovine ovaries (n = 14) obtained from an abattoir, total RNA (including miRNAs) was extracted and converted to cDNA for RT-qPCR. The results revealed that bta-miR-222-3p was downregulated (p = 0.016) in pregnant females compared to non-pregnant cows with regressed CL. However, no differences in miRNA expression were observed between CL of pregnant and non-pregnant cows for bta-miR-29c (p > 0.32) or bta-miR-2411-3p (p > 0.60). In silico prediction approaches indicated that these miRNAs are involved in pathways regulating pregnancy maintenance, such as the VEGF- and FoxO-signaling pathways. Additionally, their biogenesis is regulated by GABPA and E2F4 transcription factors. The validation of selected miRNA expression in the CL during pregnancy by RT-qPCR provides novel insights that could potentially lead to the identification of biomarkers related to CL physiology and pregnancy outcome. Full article

(This article belongs to the Special Issue The Contribution and Application of Molecular Biology in the Applied Biosciences — Focusing on Medicine, Biomaterials and Tissue Engineering Fields)

20 pages, 1434 KiB

Open AccessReview

Chemopreventive Agents from Nature: A Review of Apigenin, Rosmarinic Acid, and Thymoquinone

by Reem Fawaz Abutayeh, Maram Altah, Amani Mehdawi, Israa Al-Ataby and Adel Ardakani

Curr. Issues Mol. Biol. 2024, 46(7), 6600-6619; https://doi.org/10.3390/cimb46070393 - 27 Jun 2024

Viewed by 238

Abstract

Cancer, a major challenge to global health and healthcare systems, requires the study of alternative and supportive treatments due to the limitations of conventional therapies. This review examines the chemopreventive potential of three natural compounds: rosmarinic acid, apigenin, and thymoquinone. Derived from various [...] Read more.

Cancer, a major challenge to global health and healthcare systems, requires the study of alternative and supportive treatments due to the limitations of conventional therapies. This review examines the chemopreventive potential of three natural compounds: rosmarinic acid, apigenin, and thymoquinone. Derived from various plants, these compounds have demonstrated promising chemopreventive properties in in vitro, in vivo, and in silico studies. Specifically, they have been shown to inhibit cancer cell growth, induce apoptosis, and modulate key signaling pathways involved in cancer progression. The aim of this review is to provide a comprehensive overview of the current research on these phytochemicals, elucidating their mechanisms of action, therapeutic efficacy, and potential as adjuncts to traditional cancer therapies. This information serves as a valuable resource for researchers and healthcare providers interested in expanding their knowledge within the field of alternative cancer therapies. Full article

(This article belongs to the Special Issue Phytochemicals in Cancer Chemoprevention and Treatment)

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20 pages, 1318 KiB

Open AccessArticle

The Autophagic and Apoptotic Death of Forebrain Neurons of Rats with Global Brain Ischemia Is Diminished by the Intranasal Administration of Insulin: Possible Mechanism of Its Action

by Irina O. Zakharova, Liubov V. Bayunova, Daria K. Avrova, Alina D. Tretyakova, Alexander O. Shpakov and Natalia F. Avrova

Curr. Issues Mol. Biol. 2024, 46(7), 6580-6599; https://doi.org/10.3390/cimb46070392 - 27 Jun 2024

Viewed by 150

Abstract

Insulin is a promising neuroprotector. To better understand the mechanism of insulin action, it was important to show its ability to diminish autophagic neuronal death in animals with brain ischemic and reperfusion injury. In forebrain ischemia and reperfusion, the number of live neurons [...] Read more.

Insulin is a promising neuroprotector. To better understand the mechanism of insulin action, it was important to show its ability to diminish autophagic neuronal death in animals with brain ischemic and reperfusion injury. In forebrain ischemia and reperfusion, the number of live neurons in the hippocampal CA1 region and frontal cortex of rats decreased to a large extent. Intracerebroventricular administration of the autophagy and apoptosis inhibitors to ischemic rats significantly increased the number of live neurons and showed that the main part of neurons died from autophagy and apoptosis. Intranasal administration of 0.5 IU of insulin per rat (before ischemia and daily during reperfusion) increased the number of live neurons in the hippocampal CA1 region and frontal brain cortex. In addition, insulin significantly diminished the level of autophagic marker LC3B-II in these forebrain regions, which markedly increased during ischemia and reperfusion. Our studies demonstrated for the first time the ability of insulin to decrease autophagic neuronal death, caused by brain ischemia and reperfusion. Insulin administered intranasally activated the Akt-kinase (activating the mTORC1 complex, which inhibits autophagy) and inhibited the AMP-activated protein kinase (which activates autophagy) in the hippocampus and frontal cortex of rats with brain ischemia and reperfusion. Full article

(This article belongs to the Special Issue Molecular Mechanisms and Treatment of Ischemia–Reperfusion Injury)

14 pages, 11623 KiB

Open AccessArticle

An In Vitro Investigation of the Antiproliferative and Antimetastatic Effects of Levosimendan: Potential Drug Repurposing for Cervical Cancer

by Zsuzsanna Schelz, Hiba F. Muddather, Fatemeh Sheihaki Jaski, Noémi Bózsity and István Zupkó

Curr. Issues Mol. Biol. 2024, 46(7), 6566-6579; https://doi.org/10.3390/cimb46070391 - 27 Jun 2024

Viewed by 212

Abstract

Cervical cancer presents a significant challenge to the global health of women. Despite substantial advances in human papillomavirus (HPV)-related cervical cancer vaccines, non-HPV-related cervical cancer is still waiting novel therapeutic options. Drug repurposing has provided a promising approach to improve cancer therapy in [...] Read more.

Cervical cancer presents a significant challenge to the global health of women. Despite substantial advances in human papillomavirus (HPV)-related cervical cancer vaccines, non-HPV-related cervical cancer is still waiting novel therapeutic options. Drug repurposing has provided a promising approach to improve cancer therapy in recent years. Our study aimed to explore the potential in vitro antineoplastic effects of levosimendan on cervical cancer cells. The antiproliferative effects of levosimendan were investigated on cervical cancer cells using a standard MTT assay. Fluorescent double staining was performed to identify its ability to induce apoptosis and necrosis. The possible mechanism of action of levosimendan was explored using cell-cycle analysis. Furthermore, antimetastatic effects were investigated using a wound-healing assay and a Boyden chamber assay. Our results revealed that levosimendan exhibited the highest growth-inhibitory effect in the HPV-negative C33A cell line. However, the effects were modest compared to the standard agent, cisplatin. Cell-cycle analysis detected that levosimendan can induce cell-cycle arrest in C33A cells by increasing the G1 and G2/M phases, decreasing the S phase, and enhancing the hypodiploid subG1 population. Levosimendan inhibited cell migration and invasion in a concentration-dependent manner. As levosimendan showed antimetastatic efficacy, it could be considered for repurposing to contribute to overcoming resistance to therapy in cervical cancer. Full article

(This article belongs to the Special Issue Advances in Pharmacotherapeutic Strategies to Prevent Tumor Development, Progression and Treatment Resistance)

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33 pages, 2088 KiB

Open AccessReview

Translation of Epigenetics in Cell-Free DNA Liquid Biopsy Technology and Precision Oncology

by Wan Ying Tan, Snigdha Nagabhyrava, Olivia Ang-Olson, Paromita Das, Luisa Ladel, Bethsebie Sailo, Linda He, Anup Sharma and Nita Ahuja

Curr. Issues Mol. Biol. 2024, 46(7), 6533-6565; https://doi.org/10.3390/cimb46070390 - 27 Jun 2024

Viewed by 354

Abstract

Technological advancements in cell-free DNA (cfDNA) liquid biopsy have triggered exponential growth in numerous clinical applications. While cfDNA-based liquid biopsy has made significant strides in personalizing cancer treatment, the exploration and translation of epigenetics in liquid biopsy to clinical practice is still nascent. [...] Read more.

Technological advancements in cell-free DNA (cfDNA) liquid biopsy have triggered exponential growth in numerous clinical applications. While cfDNA-based liquid biopsy has made significant strides in personalizing cancer treatment, the exploration and translation of epigenetics in liquid biopsy to clinical practice is still nascent. This comprehensive review seeks to provide a broad yet in-depth narrative of the present status of epigenetics in cfDNA liquid biopsy and its associated challenges. It highlights the potential of epigenetics in cfDNA liquid biopsy technologies with the hopes of enhancing its clinical translation. The momentum of cfDNA liquid biopsy technologies in recent years has propelled epigenetics to the forefront of molecular biology. We have only begun to reveal the true potential of epigenetics in both our understanding of disease and leveraging epigenetics in the diagnostic and therapeutic domains. Recent clinical applications of epigenetics-based cfDNA liquid biopsy revolve around DNA methylation in screening and early cancer detection, leading to the development of multi-cancer early detection tests and the capability to pinpoint tissues of origin. The clinical application of epigenetics in cfDNA liquid biopsy in minimal residual disease, monitoring, and surveillance are at their initial stages. A notable advancement in fragmentation patterns analysis has created a new avenue for epigenetic biomarkers. However, the widespread application of cfDNA liquid biopsy has many challenges, including biomarker sensitivity, specificity, logistics including infrastructure and personnel, data processing, handling, results interpretation, accessibility, and cost effectiveness. Exploring and translating epigenetics in cfDNA liquid biopsy technology can transform our understanding and perception of cancer prevention and management. cfDNA liquid biopsy has great potential in precision oncology to revolutionize conventional ways of early cancer detection, monitoring residual disease, treatment response, surveillance, and drug development. Adapting the implementation of liquid biopsy workflow to the local policy worldwide and develo** point-of-care testing holds great potential to overcome global cancer disparity and improve cancer outcomes. Full article

(This article belongs to the Special Issue Genomic Analysis of Common Disease)

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11 pages, 569 KiB

Open AccessArticle

Genetic Insights into Azoospermia and Severe Oligozoospermia: Discovering Seven SNPs through GWAS and In Silico Analysis

by Alexia Chatziparasidou, Maria-Anna Kyrgiafini, Theologia Sarafidou, Katerina A. Moutou and Zissis Mamuris

Curr. Issues Mol. Biol. 2024, 46(7), 6522-6532; https://doi.org/10.3390/cimb46070389 - 27 Jun 2024

Viewed by 417

Abstract

Azoospermia and severe oligozoospermia represent the most extreme forms of male infertility. Despite their prevalence, the genetic foundations of these conditions are not well understood, with only a limited number of genetic factors identified so far. This study aimed to identify single-nucleotide polymorphisms [...] Read more.

Azoospermia and severe oligozoospermia represent the most extreme forms of male infertility. Despite their prevalence, the genetic foundations of these conditions are not well understood, with only a limited number of genetic factors identified so far. This study aimed to identify single-nucleotide polymorphisms (SNPs) linked to both azoospermia and severe oligozoospermia. We conducted a genome-wide association study (GWAS) involving 280 Greek males with normal semen parameters and 85 Greek males diagnosed with either azoospermia or severe oligozoospermia. Following rigorous quality control measures, our analysis identified seven SNPs associated with azoospermia/severe oligozoospermia. An in silico functional annotation was subsequently used to further investigate their role. These SNPs, found in regions not previously associated with male reproductive disorders, suggest novel genetic pathways that may contribute to these forms of infertility and pave the way for future studies. Additionally, this study sheds light on the significant role of noncoding RNAs in the pathogenesis of male infertility, with three of the identified SNPs situated in long intergenic non-coding RNAs (lincRNAs). Our findings highlight the intricate genetic landscape of azoospermia and severe oligozoospermia, underlining the necessity for more detailed studies to fully grasp the underlying mechanisms and their potential for informing diagnostic and therapeutic strategies. Full article

(This article belongs to the Special Issue Molecular Research in Reproductive Biology, 2nd Edition)

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14 pages, 4487 KiB

Open AccessArticle

Map** and Candidate Gene Analysis of the Low-Temperature-Sensitive Albino Gene OsLTSA8 in Rice Seedlings

by Yu Wei, **aoqiong Li, Dongxiu Li, Xuejun Su, Yunchuan Huang, Qiuwen Li, Manling Liang and **nghai Yang

Curr. Issues Mol. Biol. 2024, 46(7), 6508-6521; https://doi.org/10.3390/cimb46070388 - 27 Jun 2024

Viewed by 148

Abstract

Chloroplasts are organelles responsible for photosynthesis in plants, providing energy for growth and development. However, the genetic regulatory mechanisms underlying early chloroplast development in rice remain incompletely understood. In this study, we identified a rice seedling thermosensitive chlorophyll-deficient mutant, osltsa8, and the [...] Read more.

Chloroplasts are organelles responsible for photosynthesis in plants, providing energy for growth and development. However, the genetic regulatory mechanisms underlying early chloroplast development in rice remain incompletely understood. In this study, we identified a rice seedling thermosensitive chlorophyll-deficient mutant, osltsa8, and the genetic analysis of two F₂ populations suggested that this trait may be controlled by more than one pair of alleles. Through reciprocal F₂ populations and QTL-seq technology, OsLTSA8 was mapped to the interval of 24,280,402–25,920,942 bp on rice chromosome 8, representing a novel albino gene in rice. Within the candidate gene region of OsLTSA8, there were 258 predicted genes, among which LOC_Os08g39050, LOC_Os08g39130, and LOC_Os08g40870 encode pentatricopeptide repeat (PPR) proteins. RNA-seq identified 18 DEGs (differentially expressed genes) within the candidate interval, with LOC_Os08g39420 showing homology to the pigment biosynthesis-related genes Zm00001d017656 and Sb01g000470; LOC_Os08g39430 and LOC_Os08g39850 were implicated in chlorophyll precursor synthesis. RT-qPCR was employed to assess the expression levels of LOC_Os08g39050, LOC_Os08g39130, LOC_Os08g40870, LOC_Os08g39420, LOC_Os08g39430, and LOC_Os08g39850 in the wild-type and mutant plants. Among them, the differences in the expression levels of LOC_Os08g39050 and LOC_Os08g39430 were the most significant. This study will contribute to further elucidating the molecular mechanisms of rice chloroplast development. Full article

(This article belongs to the Section Molecular Plant Sciences)

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19 pages, 4041 KiB

Open AccessArticle

In Silico Approach: Anti-Tuberculosis Activity of Caespitate in the H37Rv Strain

by Andrea Moreno-Ceballos, Norma A. Caballero, María Eugenia Castro, Jose Manuel Perez-Aguilar, Liliana Mammino and Francisco J. Melendez

Curr. Issues Mol. Biol. 2024, 46(7), 6489-6507; https://doi.org/10.3390/cimb46070387 - 27 Jun 2024

Viewed by 231

Abstract

Tuberculosis is a highly lethal bacterial disease worldwide caused by Mycobacterium tuberculosis (Mtb). Caespitate is a phytochemical isolated from Helichrysum caespititium, a plant used in African traditional medicine that shows anti-tubercular activity, but its mode of action remains unknown. It [...] Read more.

Tuberculosis is a highly lethal bacterial disease worldwide caused by Mycobacterium tuberculosis (Mtb). Caespitate is a phytochemical isolated from Helichrysum caespititium, a plant used in African traditional medicine that shows anti-tubercular activity, but its mode of action remains unknown. It is suggested that there are four potential targets in Mtb, specifically in the H37Rv strain: InhA, MabA, and UGM, enzymes involved in the formation of Mtb’s cell wall, and PanK, which plays a role in cell growth. Two caespitate conformational structures from DFT conformational analysis in the gas phase (GC) and in solution with DMSO (CS) were selected. Molecular docking calculations, MM/GBSA analysis, and ADME parameter evaluations were performed. The docking results suggest that CS is the preferred caespitate conformation when interacting with PanK and UGM. In both cases, the two intramolecular hydrogen bonds characteristic of caespitate’s molecular structure were maintained to achieve the most stable complexes. The MM/GBSA study confirmed that PanK/caespitate and UGM/caespitate were the most stable complexes. Caespitate showed favorable pharmacokinetic characteristics, suggesting rapid absorption, permeability, and high bioavailability. Additionally, it is proposed that caespitate may exhibit antibacterial and antimonial activity. This research lays the foundation for the design of anti-tuberculosis drugs from natural sources, especially by identifying potential drug targets in Mtb. Full article

(This article belongs to the Special Issue Natural Products in Biomedicine and Pharmacotherapy)

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17 pages, 1385 KiB

Open AccessArticle

Significance of CD10 for Mucosal Immunomodulation by β-Casomorphin-7 in Exacerbation of Ulcerative Colitis

by Yoshihiro Miyagawa, Rina Fujiwara-Tani, Ayaka Ikemoto, Rika Sasaki, Ruiko Ogata, Yukiko Nishiguchi, Kei Goto, Isao Kawahara, Takamitsu Sasaki and Hiroki Kuniyasu

Curr. Issues Mol. Biol. 2024, 46(7), 6472-6488; https://doi.org/10.3390/cimb46070386 - 26 Jun 2024

Viewed by 215

Abstract

β-Casomorphin-7 (BCM), a breakdown product of milk β-casein, exhibits opioid activity. Opioids are known to affect the immune system, but the effects of BCM on ulcerative colitis (UC) are not clear. We examined the effects of BCM on mucosal immunity using a mouse [...] Read more.

β-Casomorphin-7 (BCM), a breakdown product of milk β-casein, exhibits opioid activity. Opioids are known to affect the immune system, but the effects of BCM on ulcerative colitis (UC) are not clear. We examined the effects of BCM on mucosal immunity using a mouse dextran sulfate sodium-induced colitis model and an in vitro CD8+ T cell activation model. Human UC patients were examined to reveal the relationship between CD10 and mucosal immunity. Combined treatment of the colitis model with thiorphan (TOP) inhibited BCM degradation by suppressing CD10 in the intestinal mucosa, activating mouse mucosal CD8, and suppressing CD4 and Treg. In the CD8+ T cell in vitro activation assay using mouse splenocytes, BCM inhibited the oxidative phosphorylation (OXPHOS) of CD8+ T cells and induced the glycolytic pathway, promoting their activation. Conversely, in a culture system, BCM suppressed OXPHOS and decreased defensin α production in IEC6 mouse intestinal epithelial cells. In the mouse model, BCM reduced defensin α and butyrate levels in the colonic mucosa. During the active phase of human ulcerative colitis, the downward regulation of ileal CD10 expression by CpG methylation of the gene promoter was observed, resulting in increased CD8 activation and decreased defensin α and butyrate levels. BCM is a potential aggravating factor for UC and should be considered in the design of dietary therapy. In addition, decreased CD10 expression may serve as an indicator of UC activity and recurrence, but further clinical studies are needed. Full article

(This article belongs to the Section Molecular Medicine)

32 pages, 3176 KiB

Open AccessReview

Hereditary Gastrointestinal Tumor Syndromes: When Risk Comes with Your Genes

by María Jesús Fernández Aceñero and Cristina Díaz del Arco

Curr. Issues Mol. Biol. 2024, 46(7), 6440-6471; https://doi.org/10.3390/cimb46070385 - 26 Jun 2024

Viewed by 333

Abstract

Despite recent campaigns for screening and the latest advances in cancer therapy and molecular biology, gastrointestinal (GI) neoplasms remain among the most frequent and lethal human tumors. Most GI neoplasms are sporadic, but there are some well-known familial syndromes associated with a significant [...] Read more.

Despite recent campaigns for screening and the latest advances in cancer therapy and molecular biology, gastrointestinal (GI) neoplasms remain among the most frequent and lethal human tumors. Most GI neoplasms are sporadic, but there are some well-known familial syndromes associated with a significant risk of develo** both benign and malignant GI tumors. Although some of these entities were described more than a century ago based on clinical grounds, the increasing molecular information obtained with high-throughput techniques has shed light on the pathogenesis of several of them. The vast amount of information gained from next-generation sequencing has led to the identification of some high-risk genetic variants, although others remain to be discovered. The opportunity for genetic assessment and counseling in these families has dramatically changed the management of these syndromes, though it has also resulted in significant psychological distress for the affected patients, especially those with indeterminate variants. Herein, we aim to summarize the most relevant hereditary cancer syndromes involving the stomach and colon, with an emphasis on new molecular findings, novel entities, and recent changes in the management of these patients. Full article

(This article belongs to the Special Issue Next-Generation Sequencing Approaches for the Study of Hereditary Tumors)

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17 pages, 1328 KiB

Open AccessReview

Structural Variations of Prions and Prion-like Proteins Associated with Neurodegeneration

by Carter Sky Christensen, Sean Wang, Wenshu Li, Danyang Yu and Henry James Li

Curr. Issues Mol. Biol. 2024, 46(7), 6423-6439; https://doi.org/10.3390/cimb46070384 - 26 Jun 2024

Viewed by 438

Abstract

Neurodegeneration is becoming one of the leading causes of death worldwide as the population expands and grows older. There is a growing desire to understand the mechanisms behind prion proteins as well as the prion-like proteins that make up neurodegenerative diseases (NDs), including [...] Read more.

Neurodegeneration is becoming one of the leading causes of death worldwide as the population expands and grows older. There is a growing desire to understand the mechanisms behind prion proteins as well as the prion-like proteins that make up neurodegenerative diseases (NDs), including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Both amyloid-β (Aβ) and hyperphosphorylated tau (p-tau) proteins behave in ways similar to those of the infectious form of the prion protein, PrP^Sc, such as aggregating, seeding, and replicating under not yet fully understood mechanisms, thus the designation of prion-like. This review aims to highlight the shared mechanisms between prion-like proteins and prion proteins in the structural variations associated with aggregation and disease development. These mechanisms largely focus on the dysregulation of protein homeostasis, self-replication, and protein aggregation, and this knowledge could contribute to diagnoses and treatments for the given NDs. Full article

(This article belongs to the Special Issue Latest Multifactorial Developments on Neuropsychiatric Disorders and Manifestations)

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16 pages, 5611 KiB

Open AccessArticle

Implications of a De Novo Variant in the SOX12 Gene in a Patient with Generalized Epilepsy, Intellectual Disability, and Childhood Emotional Behavioral Disorders

by Simone Treccarichi, Francesco Calì, Mirella Vinci, Alda Ragalmuto, Antonino Musumeci, Concetta Federico, Carola Costanza, Maria Bottitta, Donatella Greco, Salvatore Saccone and Maurizio Elia

Curr. Issues Mol. Biol. 2024, 46(7), 6407-6422; https://doi.org/10.3390/cimb46070383 - 26 Jun 2024

Viewed by 293

Abstract

SRY-box transcription factor (SOX) genes, a recently discovered gene family, play crucial roles in the regulation of neuronal stem cell proliferation and glial differentiation during nervous system development and neurogenesis. Whole exome sequencing (WES) in patients presenting with generalized epilepsy, intellectual [...] Read more.

SRY-box transcription factor (SOX) genes, a recently discovered gene family, play crucial roles in the regulation of neuronal stem cell proliferation and glial differentiation during nervous system development and neurogenesis. Whole exome sequencing (WES) in patients presenting with generalized epilepsy, intellectual disability, and childhood emotional behavioral disorder, uncovered a de novo variation within SOX12 gene. Notably, this gene has never been associated with neurodevelopmental disorders. No variants in known genes linked with the patient’s symptoms have been detected by the WES Trio analysis. To date, any MIM phenotype number associated with intellectual developmental disorder has not been assigned for SOX12. In contrast, both SOX4 and SOX11 genes within the same C group (SoxC) of the Sox gene family have been associated with neurodevelopmental disorders. The variant identified in the patient here described was situated within the critical high-mobility group (HMG) functional site of the SOX12 protein. This domain, in the Sox protein family, is essential for DNA binding and bending, as well as being responsible for transcriptional activation or repression during the early stages of gene expression. Sequence alignment within SoxC (SOX12, SOX4 and SOX11) revealed a high conservation rate of the HMG region. The in silico predictive analysis described this novel variant as likely pathogenic. Furthermore, the mutated protein structure predictions unveiled notable changes with potential deleterious effects on the protein structure. The aim of this study is to establish a correlation between the SOX12 gene and the symptoms diagnosed in the patient. Full article

(This article belongs to the Special Issue Genetics and Epigenetics of Neurodegenerative Diseases)

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17 pages, 4590 KiB

Open AccessArticle

Safety of Exposure to 0.2 T and 4 Hz Rotating Magnetic Field: A Ten-Month Study on C57BL/6 Mice

by Hua Yang, Yu Han, Cai Zhou, Shenglan Nie, Mengqing Li, Qinyao Yu, Yunpeng Wei and **aomei Wang

Curr. Issues Mol. Biol. 2024, 46(7), 6390-6406; https://doi.org/10.3390/cimb46070382 - 26 Jun 2024

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Abstract

Amidst the burgeoning interest in rotating magnetic fields (RMF) within biological research, there remains a notable gap in the scientific evidence concerning the long-term safety of RMF. Thus, this study aimed to investigate the safety of protracted exposure to a 0.2 T, 4 [...] Read more.

Amidst the burgeoning interest in rotating magnetic fields (RMF) within biological research, there remains a notable gap in the scientific evidence concerning the long-term safety of RMF. Thus, this study aimed to investigate the safety of protracted exposure to a 0.2 T, 4 Hz RMF over 10 months in mice. Two-month-old female C57BL/6 mice were randomly allocated to either the RMF group (exposed to 0.2 T, 4 Hz real RMF) or the SHAM group (exposed to 0 T, 4 Hz sham RMF). Throughout the experiment, the murine weekly body weights were recorded, and their behavioral traits were assessed via open field tests. In the final month, a comprehensive evaluation of the murine overall health was conducted, encompassing analyses of blood parameters, histomorphological examination of major organs, and skeletal assessments using X-ray and micro-CT imaging. The murine immune system and lipid metabolism were evaluated through immunochip analysis and metabolomics. Notably, no discernible adverse effects with RMF exposure were observed. Murine body weight, locomotor behavior, organ histomorphology, and skeletal health remained unaffected by RMF. Blood analysis revealed subtle changes in hormone and lipid levels between the SHAM and RMF groups, yet these differences did not reach statistical significance. Moreover, RMF led to elevated serum interleukin-28 (IL-28) levels, albeit within the normal range, and modest alterations in serum lipid metabolites. Conclusively, mice exposed to the 0.2 T, 4 Hz RMF for 10 months displayed no significant signs of chronic toxicity, indicating its potential clinical application as a physical therapy. Full article

(This article belongs to the Special Issue Molecular Research in Osteoarthritis and Osteoarticular Diseases)

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