Life | October 2024 - Browse Articles

11 pages, 7781 KiB

Open AccessArticle

Anticancer Effects of Weizmannia coagulans MZY531 Postbiotics in CT26 Colorectal Tumor-Bearing Mice by Regulating Apoptosis and Autophagy

by Bao Zhong, Yujuan Zhao, Lei Gao, Ge Yang, Yansong Gao, Fenglin Li and Shengyu Li

Life 2024, 14(10), 1334; https://doi.org/10.3390/life14101334 (registering DOI) - 19 Oct 2024

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Abstract

Weizmannia coagulans has been shown to have anticancer properties. However, there is limited research on the effects of postbiotic W. coagulans on colorectal cancer cell proliferation. Additionally, the exact mechanisms through which it influences apoptosis- and autophagy-related signaling pathways are yet to be [...] Read more.

Weizmannia coagulans has been shown to have anticancer properties. However, there is limited research on the effects of postbiotic W. coagulans on colorectal cancer cell proliferation. Additionally, the exact mechanisms through which it influences apoptosis- and autophagy-related signaling pathways are yet to be thoroughly elucidated. This study explored the role of W. coagulans MZY531 as a postbiotic in inhibiting tumor growth by modulating apoptosis and autophagy in tumor cells. During the experimental period in the model group, tumors proliferated, tumor markers increased significantly, and immunofluorescence results showed that caspase-3 and terminal deoxynucleotidyl transferase dUTP nick-end labeling were significantly decreased. Conversely, supplementation with W. coagulans MZY531 postbiotics significantly reduced the levels of tumor markers carcinoembryonic antigen, colon cancer antigen, and extracellular protein kinase A and promoted cell apoptosis by increasing the caspase-3-positive count and terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells in tumor tissue. Mechanistically, W. coagulans MZY531 postbiotics inhibit tumor growth through the modulation of the Bax/Bcl-2/caspase-3 and JAK2/STAT3 apoptosis pathways and PI3K/AKT/mTOR and TGF-β/SMAD4 cell autophagy pathways. W. coagulans MZY531 postbiotics had a more significant effect than that of W. coagulans MZY531 alone. Probiotics are expected to become effective natural functional foods for the treatment of colorectal cancer. Full article

(This article belongs to the Special Issue Microbiota in Health and Disease)

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21 pages, 12597 KiB

Open AccessArticle

Impact of Plant Growth-Promoting Microorganism (PGPM) Consortium on Biochemical Properties and Yields of Tomato Under Drought Stress

by Ram Krishna, Waquar Akhter Ansari, Mohammad Altaf, Durgesh Kumar Jaiswal, Sudhakar Pandey, Achuit Kumar Singh, Sudhir Kumar and Jay Prakash Verma

Life 2024, 14(10), 1333; https://doi.org/10.3390/life14101333 (registering DOI) - 18 Oct 2024

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Abstract

Drought is the most important abiotic stress that restricts the genetically predetermined yield potential of the crops. In the present study, four tomato varieties: Kashi Vishesh, Kashi Aman, Kashi Abhiman, and Kashi Amrit, were used to study the effect of PGPMs (plant growth-promoting [...] Read more.

Drought is the most important abiotic stress that restricts the genetically predetermined yield potential of the crops. In the present study, four tomato varieties: Kashi Vishesh, Kashi Aman, Kashi Abhiman, and Kashi Amrit, were used to study the effect of PGPMs (plant growth-promoting microorganisms). PGPM strains, Bacillus megaterium BHUPSB14, Pseudomonas fluorescens BHUPSB06, Pseudomonas aeruginosa BHUPSB01, Pseudomonas putida BHUPSB0, Paenibacillus polymixa BHUPSB17, and Trichoderma horzianum, were used as the consortium. The control group was irrigated up to 80% of field capacity, while 7-, 14-, and 21-day water-deficit-exposed (DWD) plants’ pot soil moisture was maintained to 40, 25, and 15% of the field capacity, both with and without the PGPM inoculation condition. The physiological parameters, such as electrolyte leakage, relative water content, photosynthetic efficiency, and chlorophyll color index, were significantly improved by PGPM application under progressive drought stress, compared to the control. PGPM application enhanced the proline accumulation and reduced the formation of hydrogen peroxide and lipid peroxidation under drought stress. The plant growth attributes were significantly increased by PGPM application. The Kashi Amrit variety showed the highest fruit yield among the four varieties under all the treatments. The PGPM consortium application also improved the soil physico-biological properties and nutrient availability in the soil. The PGPM consortium used in this study can potentially mitigate drought stress on tomato in drought-prone regions and act as a biofertilizer. The present study will open a new avenue of drought stress management in tomato. Full article

(This article belongs to the Special Issue Plant Biotic and Abiotic Stresses 2024)

9 pages, 673 KiB

Open AccessBrief Report

Inverse Shifting-PCR Modified by Capillary Electrophoresis for Detecting F8 int22h and int1h Inversions in Severe Hemophilia A Patients and Probable Carriers

by Rosa Michel Martínez-Contreras, Silvia Sofía García-López, Hilda Luna-Záizar and Ana Rebeca Jaloma-Cruz

Life 2024, 14(10), 1332; https://doi.org/10.3390/life14101332 (registering DOI) - 18 Oct 2024

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Abstract

Globally, intron 22 inversions (Inv22s) of the factor VIII gene (F8) are the most frequent pathogenic variants and account for 45–50% of severe hemophilia A (SHA) cases, while intron 1 inversion (Inv1) explains 1–5% of SHA cases. The detection of both inversions by [...] Read more.

Globally, intron 22 inversions (Inv22s) of the factor VIII gene (F8) are the most frequent pathogenic variants and account for 45–50% of severe hemophilia A (SHA) cases, while intron 1 inversion (Inv1) explains 1–5% of SHA cases. The detection of both inversions by an inverse shifting-polymerase chain reaction (IS-PCR) is the first choice worldwide for the diagnosis of patients and carriers of SHA. To improve its sensitivity and reproducibility in the visualization of PCR products, we approached the IS-PCR with fluorescent capillary electrophoresis instead of agarose electrophoresis. Based on the original protocol, we modified two primers by 5’-end labeling with FAM™ fluorescent dye for the detection of the PCR products by capillary electrophoresis. Additionally, the “fast enzymes” BclI and T4-Ligase were incorporated for work saving in the genomic digestion and ligation reactions, respectively. Once we accomplished the standardization and verified the reproducibility of the modified IS-PCR method, we applied it for the diagnosis of a cohort of SHA patients and carriers. The modified IS-PCR by fluorescent capillary electrophoresis for PCR product detection is more sensitive than agarose electrophoresis. The method was also improved by using the new rapid enzymes to save time in the whole process. Full article

(This article belongs to the Special Issue Hemophilia)

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12 pages, 2107 KiB

Open AccessCase Report

Hydatid Cysts of the Psoas Muscle: Insights from the Past Five Years

by Octavian Catalin Ciobotaru, Oana-Monica Duca, Oana Roxana Ciobotaru, Elena Stamate, Alin Ionut Piraianu, Adrian George Dumitrascu, Georgiana Bianca Constantin, Madalina Nicoleta Matei, Doina Carina Voinescu and Stefan-Alexandru Luchian

Life 2024, 14(10), 1331; https://doi.org/10.3390/life14101331 - 18 Oct 2024

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Abstract

Echinococcosis represents a major public health issue and continues to be endemic in various regions around the world. Hydatid cysts are commonly located in the liver (primary site), followed by the lungs (secondary site). However, they are also found in less typical organs [...] Read more.

Echinococcosis represents a major public health issue and continues to be endemic in various regions around the world. Hydatid cysts are commonly located in the liver (primary site), followed by the lungs (secondary site). However, they are also found in less typical organs such as the spleen, kidneys, peritoneum, retroperitoneum, pancreas, gallbladder, and various other organs, as well as in striate muscles. Hydatid cysts involving the psoas muscle are rare, and in the past five years, only a few articles have addressed this condition due to its low incidence. Symptoms can be quite vague, and serological testing might return negative, making imaging studies crucial for an accurate diagnosis. Treatment options involve surgery alongside antiparasitic agents. Despite having a low mortality rate, the recurrence of hydatid disease remains high. This paper aims to provide new clinical data through our case presentation, while also offering a review of the cases of hydatid cysts involving the psoas muscle that have been published over the past five years. Full article

(This article belongs to the Section Medical Research)

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10 pages, 2952 KiB

Open AccessBrief Report

The HOMO-LUMO Gap as Discriminator of Biotic from Abiotic Chemistries

by Roman Abrosimov and Bernd Moosmann

Life 2024, 14(10), 1330; https://doi.org/10.3390/life14101330 - 18 Oct 2024

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Abstract

Low-molecular-mass organic chemicals are widely discussed as potential indicators of life in extraterrestrial habitats. However, demarcation lines between biotic chemicals and abiotic chemicals have been difficult to define. Here, we have analyzed the potential utility of the quantum chemical property, HOMO-LUMO gap (HLG), [...] Read more.

Low-molecular-mass organic chemicals are widely discussed as potential indicators of life in extraterrestrial habitats. However, demarcation lines between biotic chemicals and abiotic chemicals have been difficult to define. Here, we have analyzed the potential utility of the quantum chemical property, HOMO-LUMO gap (HLG), as a novel proxy variable of life, since a significant trend towards incrementally smaller HLGs has been described in the genetically encoded amino acids. The HLG is a zeroth-order predictor of chemical reactivity. Comparing a set of 134 abiotic organic molecules recovered from meteorites, with 570 microbial and plant secondary metabolites thought to be exclusively biotic, we found that the average HLG of biotic molecules was significantly narrower (−10.4 ± 0.9 eV versus −12.4 ± 1.6 eV), with an effect size of g = 1.87. Limitation to hydrophilic molecules (XlogP < 2) improved the separation of biotic from abiotic compounds (g = 2.52). The “hydrophilic reactivity” quadrant defined by |HLG| < 11.25 eV and XlogP < 2 was populated exclusively by 183 biotic compounds and 6 abiotic compounds, 5 of which were nucleobases. We conclude that hydrophilic molecules with small HLGs represent valuable indicators of biotic activity, and we discuss the evolutionary plausibility of this inference. Full article

(This article belongs to the Special Issue Feature Papers in Origins of Life 2024)

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20 pages, 1023 KiB

Open AccessReview

Pathophysiology of Congenital High Production of IgE and Its Consequences: A Narrative Review Uncovering a Neglected Setting of Disorders

by Francesca Galletta, Antonella Gambadauro, Simone Foti Randazzese, Stefano Passanisi, Vito Sinatra, Lucia Caminiti, Giuseppina Zirilli and Sara Manti

Life 2024, 14(10), 1329; https://doi.org/10.3390/life14101329 - 18 Oct 2024

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Abstract

Elevated serum IgE levels serve as a critical marker for uncovering hidden immunological disorders, particularly inborn errors of immunity (IEIs), which are often misdiagnosed as common allergic conditions. IgE, while typically associated with allergic diseases, plays a significant role in immune defense, especially [...] Read more.

Elevated serum IgE levels serve as a critical marker for uncovering hidden immunological disorders, particularly inborn errors of immunity (IEIs), which are often misdiagnosed as common allergic conditions. IgE, while typically associated with allergic diseases, plays a significant role in immune defense, especially against parasitic infections. However, extremely high levels of IgE can indicate more severe conditions, such as Hyper-IgE syndromes (HIES) and disorders with similar features, including Omenn syndrome, Wiskott-Aldrich syndrome, and IPEX syndrome. Novel insights into the genetic mutations responsible for these conditions highlight their impact on immune regulation and the resulting clinical features, including recurrent infections, eczema, and elevated IgE. This narrative review uniquely integrates recent advances in the genetic understanding of IEIs and discusses how these findings impact both diagnosis and treatment. Additionally, emerging therapeutic strategies, such as hematopoietic stem cell transplantation (HSCT) and gene therapies, are explored, underscoring the potential for personalized treatment approaches. Emphasizing the need for precise diagnosis and tailored interventions aims to enhance patient outcomes and improve the quality of care for those with elevated IgE levels and associated immunological disorders. Full article

(This article belongs to the Special Issue Pathophysiology, Diagnosis and Treatment of Immune Disease)

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34 pages, 5277 KiB

Open AccessArticle

Determining the Identity of Nucleotides and the Energy of Binding of tRNAs to Their Aminoacyl-tRNA Synthetases Using a Simple Logistic Model

by Piotr H. Pawłowski and Piotr Zielenkiewicz

Life 2024, 14(10), 1328; https://doi.org/10.3390/life14101328 - 18 Oct 2024

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Abstract

This study showed that the predictor in logistic regression can be applied to estimating the Gibbs free energy of tRNAs’ recognition of and binding to their aminoacyl-tRNA synthetases. Then, 24 linear logistic regression models predicting different classes of tRNAs loaded with a corresponding [...] Read more.

This study showed that the predictor in logistic regression can be applied to estimating the Gibbs free energy of tRNAs’ recognition of and binding to their aminoacyl-tRNA synthetases. Then, 24 linear logistic regression models predicting different classes of tRNAs loaded with a corresponding amino acid were trained in a machine learning classification method, reducing the misclassification error to zero. The models were based on minimal subsets of Boolean explanatory variables describing the favorite presence of nucleotides or nucleosides localized in the different parts of the tRNA. In 90% of cases, they agree with the components of the consensus strand in a class of tRNAs loaded by a given amino acid. According to the proposed theoretical model, the values of the free energy for the entry of the recognition state in the process of tRNA charging were obtained, and the inputs from identity nucleotides and the tRNA strand backbone were distinguished. Almost all the resulting models indicated leading anticodon tandems defining the first and second positions of the anticodon (positions 35 and 36 of the tRNA strand) and the small sets (up to six positions) of the other nucleotides as the natural identity nucleotides most influential in the free energy balance. The magnitude of their input to this energy depends on the position in the strand, favoring positions −1, 35, and 36. The role of position 34 is relatively smaller. These identity attributes may not always be fully arranged in a real single adaptor molecule but were comprehensively present in a given tRNA class. A detailed analysis of the resulting models showed that the absolute value of the energy of binding the tandem 35–36 decreases with the number of identity positions, as well as with the decreasing number of possible hydrogen bonds. On the other hand, in these conditions, the absolute value of the energy of binding of other identity nucleotides increases. All the models indicate that the nucleotide-independent energy of the repulsion tRNA backbone decreases with the number of identity nucleotides. It was also shown that the total free energy change in entering the recognition state increases with the amino acid mass, making this process less spontaneous, which may have an evolutionary reference. Full article

(This article belongs to the Special Issue What Is Life?)

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20 pages, 1202 KiB

Open AccessArticle

Allelic, Genotypic, and Haplotypic Analysis of Cytokine IL17A, IL17F, and Toll-like Receptor TLR4 Gene Polymorphisms in Metabolic-Dysfunction-Associated Steatotic Liver Disease: Insights from an Exploratory Study

by Sorina-Cezara Coste, Olga Hilda Orășan, Angela Cozma, Vasile Negrean, Teodora Gabriela Alexescu, Mirela Georgiana Perne, George Ciulei, Adriana Corina Hangan, Roxana Liana Lucaciu, Mihaela Iancu and Lucia-Maria Procopciuc

Life 2024, 14(10), 1327; https://doi.org/10.3390/life14101327 - 18 Oct 2024

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Abstract

(1) Background: Interleukin 17 (IL17) and toll-like receptor 4 (TLR4) elevate the risk of metabolic and liver diseases. (2) Methods: This study’s objective was to explore the association of IL17 and TLR4 gene polymorphisms with MASLD susceptibility and test their effect on serum [...] Read more.

(1) Background: Interleukin 17 (IL17) and toll-like receptor 4 (TLR4) elevate the risk of metabolic and liver diseases. (2) Methods: This study’s objective was to explore the association of IL17 and TLR4 gene polymorphisms with MASLD susceptibility and test their effect on serum IL17 and TLR4 levels. A total of 43 patients with MASLD (MASH/MAFL) and 38 healthy individuals were genotyped for IL17F-A7488G, IL17A-G197A, TLR4-Asp299Gly, and TLR4-Thr399Ile polymorphisms using PCR-RFLP. ELISA methods determined IL17F, IL17A, and TLR4 serum levels. (3) Conclusions: Patients carrying the variant genotypes (A/G + G/G) of IL17-A7448G (OR = 5.25), (G/A + A/A) of IL17-G197A (OR = 10.57), (Asp/Gly + Gly/Gly) of TLR4-Asp299Gly (OR = 3.52), or (Thr/Ile + Ile/Ile) of TLR4-Thr399Ile (OR = 9.87) had significantly increased odds of MASH. Genotype (G/A + A/A) of IL17-G197A was significantly associated with the odds of MAFL (p = 0.0166). Allele A of the IL17-G197A polymorphism was significantly related to increased odds of MAFL (OR = 4.13, p = 0.0133). In contrast, allele A of IL17-G197A (OR = 5.41, p = 0.008), allele Gly of TLR4-Asp299Gly (OR = 3.19, p = 0.046), and allele Ile of TLR4-Thr399Ile (OR = 6.94, p = 0.008) polymorphisms were significantly related to an increased risk of MASH. Allele A of IL17A-G197A, allele Gly of TLR4-Asp299Gly, and allele Ile of TLR4-Thr399Ile gene polymorphisms were significantly associated with the increased odds of MASLD. In patients with MASLD, we found significant influence from the IL17A-G197A gene polymorphism on IL17F levels (p = 0.0343). Full article

(This article belongs to the Special Issue Metabolic Health: The Interplay between NAFLD, MAFLD, MASLD and Cardiovascular Disease)

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10 pages, 1189 KiB

Open AccessArticle

Fractional Flow Reserve Implications for Clinical Decision Making in Coronary Artery Disease

by Andrei Grib, Marcel Abras, Artiom Surev and Livi Grib

Life 2024, 14(10), 1326; https://doi.org/10.3390/life14101326 - 18 Oct 2024

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Abstract

Fractional flow reserve (FFR) is regarded as the gold standard for assessing the functional significance of coronary artery lesions. However, its utilization in clinical practice remains limited. This study aims to determine whether FFR results can influence treatment decisions for coronary artery disease [...] Read more.

Fractional flow reserve (FFR) is regarded as the gold standard for assessing the functional significance of coronary artery lesions. However, its utilization in clinical practice remains limited. This study aims to determine whether FFR results can influence treatment decisions for coronary artery disease compared to visual assessments of angiographic images. We conducted a retrospective study involving 63 patients diagnosed with either chronic coronary syndrome (n = 39, 61.9%) or acute coronary syndrome (n = 24, 38.1%) who underwent an FFR assessment. Three experienced interventional cardiologists (>300 PCI procedures/year) reevaluated 105 ambiguous coronary lesions in these patients, blinded to the FFR results. The objective was to assess lesion significance and determine the treatment strategy based on a visual angiographic evaluation. The three operators reached concordant agreement (≥two operators) to perform PCI in 60 (57.1%) of the evaluated lesions based on the angiographic assessment. Of these, nine lesions (15%) were deemed functionally non-significant by FFR (FFR > 0.80). Conversely, they agreed to defer PCI in 45 (42.9%) lesions, but 4 lesions (8.9%) were found to be functionally significant (FFR ≤ 0.80) and required a re-evaluation for PCI. Visual-guided decision making by interventional cardiologists shows variability and does not always align with the functional significance of coronary lesions as determined by FFR. Incorporating FFR into routine decision making could enhance treatment accuracy and patient outcomes. Full article

(This article belongs to the Special Issue Management of Ischemia and Heart Failure—2nd Edition)

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13 pages, 290 KiB

Open AccessArticle

30 Years of Change: Declining Motor Fitness and Anthropometric Shifts in Polish University Students (1994–2024)

by Robert Podstawski and Krzysztof Borysławski

Life 2024, 14(10), 1325; https://doi.org/10.3390/life14101325 - 18 Oct 2024

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Abstract

Background: To assess changes in the anthropometric and motor characteristics of male and female Polish university students between 1994 and 2024. Methods: The first study was conducted in 1994 on 712 female and 495 male university students aged 19–25 years (19.94 ± 1.09), [...] Read more.

Background: To assess changes in the anthropometric and motor characteristics of male and female Polish university students between 1994 and 2024. Methods: The first study was conducted in 1994 on 712 female and 495 male university students aged 19–25 years (19.94 ± 1.09), and the second study was conducted in 2024 on 323 female and 339 male university students aged 19–25 years (19.92 ± 1.08). The participants’ body mass and height were measured, and the students participated in a modified version of Pilicz’s test consisting of four motor ability tests. The changes in the students’ performance over time were also analyzed in the context of their socioeconomic status (SES), including the place of permanent residence and the parents’ education. Results: The students’ BMI values (as well as body mass and body height in female students) were significantly higher (p < 0.001) in 2024 than in 1994. The male students examined in 1994 demonstrated significantly higher strength abilities in the medicine ball forward throw test. In turn, the females studied in 1994 received significantly better scores in motor ability tests, including the zig-zag run, 1-Minute Burpee Test, and the medicine ball forward throw (29.4 s, 22 cycles, 591.3 cm, respectively) than those examined in 2024 (30.1 s, 19.3 cycles, and 463.3 cm, respectively). The variations in the results were similar when the participants’ SES was considered in the analysis, which suggests that these factors had no significant effect on the analyzed characteristics over time. Conclusions: This study revealed a greater decline in the anthropometric and motor characteristics of female than male university students over a period of 30 years. The observed changes were not influenced by SES factors such as the place of permanent residence or the parents’ education. Full article

(This article belongs to the Section Physiology and Pathology)

3 pages, 146 KiB

Open AccessEditorial

Various Viewpoints to Investigate the Origins of Life Are Needed

by Tony Z. Jia and Kuhan Chandru

Life 2024, 14(10), 1324; https://doi.org/10.3390/life14101324 - 18 Oct 2024

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Abstract

How life first arose on Earth is a mystery that humankind has sought to understand for millennia, and includes scientific, philosophical, societal, and religious aspects, amongst others [...] Full article

(This article belongs to the Special Issue Feature Papers in Origins of Life)

7 pages, 1203 KiB

Open AccessReview

Proposal of a Theoretically Feasible Method to Perform Perilymph Sampling in Clinical Settings

by Federico Maria Gioacchini, Massimo Re, Alfonso Scarpa, Giuseppe Chiarella, Pasquale Viola, Davide Pisani, Giannicola Iannella, Massimo Ralli and Arianna Di Stadio

Life 2024, 14(10), 1323; https://doi.org/10.3390/life14101323 - 18 Oct 2024

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Abstract

The ability to analyze perilymph could allow inner ear pathologies to be studied. However, today, perilymph sampling is only performed for research purposes because of the risk of negative outcomes such as hearing loss or balance disorders. This paper aims to analyze the [...] Read more.

The ability to analyze perilymph could allow inner ear pathologies to be studied. However, today, perilymph sampling is only performed for research purposes because of the risk of negative outcomes such as hearing loss or balance disorders. This paper aims to analyze the current literature on perilymph sampling and propose a method to collect perilymph in clinical settings. The published literature on perilymph sampling and its analyses was screened, and the results were analyzed and discussed in this mini review. Also, articles that discussed microneedle technology were reviewed and included in the analysis of the data. Based on the results of this review, we would like to propose a feasible technique to perform perilymph sampling in clinical settings. A total of eight studies analyzing perilymph were identified; data on proteomic, metabolomic and miRNA features present within human perilymph were collected and described. Two articles describing the use and auditory outcomes post microneedle drug injection into the inner ear were identified. Based on the methods for perilymph sampling described in humans and the recent innovations introduced by the use of microneedles, we suggested a feasible method to collect perilymph in the outpatient setting. The analysis of perilymph undoubtedly represents a valid instrument to fully understand inner ear diseases. A combination of traditional and innovative techniques, such as gaining access to the round window through the transcanalar approach using micro-endoscopes and microneedles to perform sampling, might simplify the sampling procedure and make it practicable in a clinical setting. Full article

(This article belongs to the Section Medical Research)

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20 pages, 11630 KiB

Open AccessArticle

Pangenome Data Analysis Reveals Characteristics of Resistance Gene Analogs Associated with Sclerotinia sclerotiorum Resistance in Sunflower

by Yan Lu, Jiaying Huang, Dongqi Liu, Xiangjiu Kong, Yang Song and Lan Jing

Life 2024, 14(10), 1322; https://doi.org/10.3390/life14101322 - 17 Oct 2024

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Abstract

The sunflower, an important oilseed crop and food source across the world, is susceptible to several pathogens, which cause severe losses in sunflower production. The utilization of genetic resistance is the most economical, effective measure to prevent infectious diseases. Based on the sunflower [...] Read more.

The sunflower, an important oilseed crop and food source across the world, is susceptible to several pathogens, which cause severe losses in sunflower production. The utilization of genetic resistance is the most economical, effective measure to prevent infectious diseases. Based on the sunflower pangenome, in this study, we explored the variability of resistance gene analogs (RGAs) within the species. According to a comparative analysis of RGA candidates in the sunflower pangenome using the RGAugury pipeline, a total of 1344 RGAs were identified, comprising 1107 conserved, 199 varied, and 38 rare RGAs. We also identified RGAs associated with resistance against Sclerotinia sclerotiorum (S. sclerotiorum) in sunflower at the quantitative trait locus (QTL). A total of 61 RGAs were found to be located at four quantitative trait loci (QTLs). Through a detailed expression analysis of RGAs in one susceptible and two tolerant sunflower inbred lines (ILs) across various time points post inoculation, we discovered that 348 RGAs exhibited differential expression in response to Sclerotinia head rot (SHR), with 17 of these differentially expressed RGAs being situated within the QTL regions. In addition, 15 RGA candidates had gene introgression. Our data provide a better understanding of RGAs, which facilitate genomics-based improvements in disease resistance in sunflower. Full article

(This article belongs to the Section Plant Science)

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14 pages, 4869 KiB

Open AccessArticle

The Outcomes of Adult Acquired Buried Penis Surgical Reconstruction

by Marco Falcone, Natalia Plamadeala, Lorenzo Cirigliano, Mirko Preto, Federica Peretti, Ilaria Ferro, Martina Scavone, Emanuele Zupo and Paolo Gontero

Life 2024, 14(10), 1321; https://doi.org/10.3390/life14101321 - 17 Oct 2024

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Abstract

Adult Acquired Buried Penis (AABP) is a morbid condition that often requires surgical intervention. This retrospective study of 46 patients who underwent AABP surgery from November 2017 to July 2023 evaluates surgical outcomes, functional outcomes, and patient-reported outcomes. The median follow-up (FU) was [...] Read more.

Adult Acquired Buried Penis (AABP) is a morbid condition that often requires surgical intervention. This retrospective study of 46 patients who underwent AABP surgery from November 2017 to July 2023 evaluates surgical outcomes, functional outcomes, and patient-reported outcomes. The median follow-up (FU) was 46 months. Patients were categorized by surgical complexity using the Pariser classification, with 76.1% undergoing high-complexity procedures (Pariser ≥ III). Common comorbidities included obesity (58.7%), prior circumcision (52.2%), and hypertension (52.2%). The low-complexity group had a shorter hospital stay (p = 0.02). No other significant differences were noted between groups in terms of Body Mass Index, operative time, or FU. Sexual dysfunction (45.7%) and urinary issues (38.1%) were the main reasons for surgical consultation. Skin grafting was required in 63.0% of patients; partial graft loss was more common in full thicknes skin graft group (p = 0.04). Postoperative complications occurred in 32.6% of patients, 13.3% of which were classified severe (Clavien ≥ III). The median increase in stretched penile length was 2 cm. The recurrence rate was 21.7%. The 12-month recurrence-free survival rate was 89.1%. All groups saw significant improvements in urinary and sexual function post-surgery (p < 0.05), and high patient satisfaction was reported (90.3%). Despite the complication rate, AABP surgery significantly improves quality of life, with ongoing advancements in technique anticipated to enhance outcomes further. Full article

(This article belongs to the Section Medical Research)

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21 pages, 1553 KiB

Open AccessArticle

Selection and Effect of Plant Growth-Promoting Bacteria on Pine Seedlings (Pinus montezumae and Pinus patula)

by Francisco David Moreno-Valencia, Miguel Ángel Plascencia-Espinosa, Yolanda Elizabeth Morales-García and Jesús Muñoz-Rojas

Life 2024, 14(10), 1320; https://doi.org/10.3390/life14101320 - 17 Oct 2024

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Abstract

Forest cover is deteriorating rapidly due to anthropogenic causes, making its restoration urgent. Plant growth-promoting bacteria (PGPB) could offer a viable solution to ensure successful reforestation efforts. This study aimed to select bacterial strains with mechanisms that promote plant growth and enhance seedling [...] Read more.

Forest cover is deteriorating rapidly due to anthropogenic causes, making its restoration urgent. Plant growth-promoting bacteria (PGPB) could offer a viable solution to ensure successful reforestation efforts. This study aimed to select bacterial strains with mechanisms that promote plant growth and enhance seedling development. The bacterial strains used in this study were isolated from the rhizosphere and endophyte regions of Pinus montezumae Lamb. and Pinus patula Schl. et Cham., two Mexican conifer species commonly used for reforestation purposes. Sixteen bacterial strains were selected for their ability to produce auxins, chitinase, and siderophores, perform nitrogen fixation, and solubilize inorganic phosphates; they also harbored genes encoding antimicrobial production and ACC deaminase. The adhesion to seeds, germination rate, and seedling response of P. montezumae and P. patula were performed following inoculation with 10 bacterial strains exhibiting high plant growth-promoting potential. Some strains demonstrated the capacity to enhance seedling growth. The selected strains were taxonomically characterized and belonged to the genus Serratia, Buttiauxella, and Bacillus. These strains exhibited at least two mechanisms of action, including the production of indole-3-acetic acid, biological nitrogen fixation, and phosphate solubilization, and could serve as potential alternatives for the reforestation of affected areas. Full article

(This article belongs to the Collection Feature Papers in Microbiology)

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8 pages, 619 KiB

Open AccessArticle

Perioperative and Long-Term Outcomes After Combined Liver and Kidney Transplantation: A Single-Center Experience

by Kosta Cerović, Benjamin Hadžialjević, Simon Hawlina and Blaž Trotovšek

Life 2024, 14(10), 1319; https://doi.org/10.3390/life14101319 - 17 Oct 2024

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Abstract

Combined liver–kidney transplantation (CLKT) has evolved as a therapeutic option for patients with concurrent end-stage liver and renal diseases. This study evaluates the perioperative and long-term outcomes of CLKT at a single center in Slovenia, highlighting the challenges and successes of simultaneous organ [...] Read more.

Combined liver–kidney transplantation (CLKT) has evolved as a therapeutic option for patients with concurrent end-stage liver and renal diseases. This study evaluates the perioperative and long-term outcomes of CLKT at a single center in Slovenia, highlighting the challenges and successes of simultaneous organ transplantation. We retrospectively analyzed all patients undergoing simultaneous CLKT at the University Medical Centre Ljubljana from April 2014 to June 2023. Data on demographics, cause of liver and kidney disease, operative details, postoperative complications, patient and graft survival, and follow-up were collected and analyzed. Five patients aged 27 to 60 years underwent CLKT within the study period. All transplants involved deceased donors with whole-liver grafts. Indications for CLKT were polycystic liver disease (n = 3), Caroli’s disease (n = 1), and alcoholic cirrhosis (n = 1). The mean follow-up duration was 45.2 months, with a 100% survival rate. The incidence of surgical and postoperative complications was low. This pioneering series of simultaneous CLKTs in Slovenia demonstrates the feasibility and effectiveness of the procedure in smaller transplant centers. Despite challenges, including T cell-mediated kidney rejection and surgical complications, the study emphasizes the importance of comprehensive postoperative care and management in optimizing outcomes for CLKT recipients. Full article

(This article belongs to the Section Medical Research)

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16 pages, 3185 KiB

Open AccessArticle

The Effect of Szigetvár Medicinal Water on HaCaT Cells Exposed to Dithranol

by István Szabó, Ágnes Szenczi, Afshin Zand, Tímea Varjas and Csaba Varga

Life 2024, 14(10), 1318; https://doi.org/10.3390/life14101318 - 17 Oct 2024

Viewed by 308

Abstract

(1) Introduction: Topical dithranol is still commonly used today as an effective treatment for psoriasis. Dithranol treatment is often supplemented with balneotherapy, which has been shown to increase effectiveness and reduce side effects. The inorganic salts (sulfhide, selenium, zinc) are usually thought to [...] Read more.

(1) Introduction: Topical dithranol is still commonly used today as an effective treatment for psoriasis. Dithranol treatment is often supplemented with balneotherapy, which has been shown to increase effectiveness and reduce side effects. The inorganic salts (sulfhide, selenium, zinc) are usually thought to be responsible for the effect. The antioxidant effect of the waters is thought to be behind the therapeutic effect, for which inorganic substances (sulfides, selenium, zinc) are thought to be responsible. The organic matter content of medicinal waters is also particularly important, as humic acids, which are often found in medicinal waters, have antioxidant effects. (2) Methods: In this short-term experiment, we aimed to test the possible protective effect of Szigetvár medicinal water and its organic matter isolate on HaCaT cells exposed to dithranol. Malondialdehyde levels were measured, and RT-qPCR was used to investigate the gene expression of selected cytokines relevant in the oxidative stress response (IL-6, IL-8, TNF-α, GM-CSF) and the expression of microRNA-21. (3) Results: Szigetvár medicinal water and the organic isolate prevented the increase in malondialdehyde levels caused by dithranol treatment. The cytokine gene expressions elevated by dithranol exposure were reduced by the treatment. (4) Conclusions: Szigetvár medicinal water and organic substances alone may have a protective effect on patients’ healthy skin surfaces against dithranol damage. We also demonstrated that the organic compounds are also responsible for the protective effect. Full article

(This article belongs to the Special Issue Current Research on Dermatology: Pathology, Clinical Manifestation, Investigation and Therapy: 2nd Edition)

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12 pages, 4072 KiB

Open AccessArticle

Erosive Tarsal Conjunctival Lesions Following Immunogenic Events in Early Development of Ocular Graft-vs-Host Disease

by Marcus G. Kohnstam, Pier Luigi Surico and Zhonghui K. Luo

Life 2024, 14(10), 1317; https://doi.org/10.3390/life14101317 - 17 Oct 2024

Viewed by 230

Abstract

Purpose: Ocular graft-versus-host disease (oGVHD) affects more than half of the patients following allogeneic hematopoietic stem cell transplantation (HSCT). The disease onset and the pathogenesis of oGVHD are not well understood. We hope to identify the triggers and explore the clinical signs and [...] Read more.

Purpose: Ocular graft-versus-host disease (oGVHD) affects more than half of the patients following allogeneic hematopoietic stem cell transplantation (HSCT). The disease onset and the pathogenesis of oGVHD are not well understood. We hope to identify the triggers and explore the clinical signs and symptoms of oGVHD development at the early stages. Methods: The records of post-HSCT patients seen consecutively in a 1-year span in a single provider’s clinic were reviewed. The history, symptoms, and clinical findings of the patients with erosive tarsal conjunctival lesions (ETCLs) were analyzed. Results: Out of the 228 patients screened, 19 had clinically witnessed ETCL in at least one eye during the period. Twelve (63%) patients had a never-before-described nodular erosion on the subtarsal conjunctiva; seven (37%) had previously described pseudomembranous erosions. The ocular symptom onset was within 1 month after immunosuppression (IS) taper, vaccination, or donor lymphocyte infusion (DLI) in 16 of the 19 patients. While 16 (84%) patients reported painless mucous discharge, only 9 (47%) reported dryness as the initial symptom. Within 6 months, only 4 (21%) had discharge but 15 (82%) patients endorsed dryness. Subepithelial conjunctival fibrosis followed ETCL immediately in situ. Corneal punctate staining increased with time, while aqueous tear production decreased. Conclusions: The ETCL described is likely one of the earliest detectable findings of oGVHD and triggered by certain immunogenic events. The ocular symptoms of wet mucous discharge should be considered a warning sign for oGVHD onset, particularly when it occurs shortly after prominently immunogenic events. Full article

(This article belongs to the Special Issue Eye Diseases: Diagnosis and Treatment, 2nd Edition)

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17 pages, 5472 KiB

Open AccessArticle

The Nephroprotective Effect of Punica granatum Peel Extract on LPS-Induced Acute Kidney Injury

by Sena Sahin Aktura, Kazim Sahin, Levent Tumkaya, Tolga Mercantepe, Atilla Topcu, Esra Pinarbas and Zihni Acar Yazici

Life 2024, 14(10), 1316; https://doi.org/10.3390/life14101316 - 16 Oct 2024

Viewed by 410

Abstract

Sepsis is an exaggerated immune response resulting from systemic inflammation, which can damage tissues and organs. Acute kidney injury has been detected in at least one-third of patients with sepsis. Sepsis-associated acute kidney injury increases the risk of a secondary infection. Rapid diagnosis [...] Read more.

Sepsis is an exaggerated immune response resulting from systemic inflammation, which can damage tissues and organs. Acute kidney injury has been detected in at least one-third of patients with sepsis. Sepsis-associated acute kidney injury increases the risk of a secondary infection. Rapid diagnosis and appropriate initiation of antibiotics can significantly reduce mortality and morbidity. However, microorganisms are known to develop resistance to antibiotics. Estimations indicate that the annual casualties caused by microbial resistance will surpass cancer fatalities by 2050. The prevalence of bacterial infections and their growing antibiotic resistance has brought immediate attention to the search for novel treatments. Plant-derived supplements contain numerous bioactive components with therapeutic potential against a variety of conditions, including infections. Punica granatum peel is rich in phenolic compounds. The purpose of this study was to determine the anti-inflammatory and anti-bacterial properties of P. granatum peel extract (PGPE) on lipopolysaccharide (LPS)-induced acute kidney injury. Experimental groups were Control, LPS (10 mg/kg LPS, intraperitoneally), PGPE100, and PGPE300 (100 and 300 mg/mL PGPE via oral gavage, respectively, for 7 days). According to biochemical results, serum blood urea nitrogen (BUN), creatinine (Cr) and C-reactive protein (CRP), kidney tissue thiobarbituric acid reactive substances (TBARS), and reduced glutathione (GSH) levels significantly decreased in the PGPE groups compared to the LPS group. Histopathological and immunohistochemical findings revealed that toll-like receptor 4 (TLR4) level and nuclear factor kappa B (NF-κB) expression increased in the LPS group compared to the Control group. In addition, the anti-Gram-negative activity showed a dose-dependent effect on Acinetobacter baumannii, Escherichia coli, and Pseudomonas aeruginosa with the agar well diffusion method and the minimal inhibitory concentration (MIC). The MIC value was remarkable, especially on A. baumannii. We conclude that PGPE has the potential to generate desirable anti-bacterial and anti-inflammatory effects on LPS-induced acute kidney injury in rats. Full article

(This article belongs to the Special Issue Bioactive Natural Compounds: Therapeutic Insights and Applications)

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12 pages, 1620 KiB

Open AccessReview

Omega-3 and Sports: Focus on Inflammation

by Roberto Cannataro, Diana Marisol Abrego-Guandique, Natascia Straface and Erika Cione

Life 2024, 14(10), 1315; https://doi.org/10.3390/life14101315 - 16 Oct 2024

Viewed by 389

Abstract

Inflammation is expected in sports, especially when practiced at a high level. The human body is pushed toward its limit, and this is perceived as a “stressogenic agent”. Athletes, especially elite ones, desire it because their bodies can react with super-compensation, i.e., improve [...] Read more.

Inflammation is expected in sports, especially when practiced at a high level. The human body is pushed toward its limit, and this is perceived as a “stressogenic agent”. Athletes, especially elite ones, desire it because their bodies can react with super-compensation, i.e., improve muscle mass, strength, speed, resistance, and, therefore, athletic performance. Thus, the inflammatory stimuli should be there during training but also counteracted to have the body placed in the optimal conditions for reacting with super-compensation. In this sense, omega-3 fatty acids have been shown to have anti-inflammatory biochemical activity. In this review, we will present the biochemical mechanisms of action of omega-3 fatty acids through their mediators, specialized pro-resolving mediators, which have anti-inflammatory activity. A focus will be on studies on omega-3 fatty acid supplementation in sports, and we will provide indications for possible practical applications and future studies, which are undoubtedly necessary to clarify the omega-3 fatty acids used in sports practice. Full article

(This article belongs to the Special Issue Nutritional Supplementation, Body Composition and Performance in Athletes)

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15 pages, 4465 KiB

Open AccessArticle

An Adapted Physical Activity Program for Adolescents with an Intellectual Disability: An International Classification of Functioning, Disability, and Health Perspective

by Xin Shen, Peiying Huang, Bing Nie, Maolin Su, Dan Liu, Yin Guo and Lan Zheng

Life 2024, 14(10), 1314; https://doi.org/10.3390/life14101314 - 16 Oct 2024

Viewed by 295

Abstract

The International Classification of Functioning, Disability, and Health (ICF) offers a comprehensive bio-psycho-social model for evaluating the multifaceted needs of individuals with disabilities. While its adoption in healthcare settings is widespread, its utilization within the domain of physical activity interventions, particularly for adolescents [...] Read more.

The International Classification of Functioning, Disability, and Health (ICF) offers a comprehensive bio-psycho-social model for evaluating the multifaceted needs of individuals with disabilities. While its adoption in healthcare settings is widespread, its utilization within the domain of physical activity interventions, particularly for adolescents with intellectual disabilities (IDs), remains insufficiently explored. This study rigorously examines the efficacy of a 6-month ICF-based Adaptive Physical Activity (APA) intervention on the development of fundamental motor skills (FMSs), improvements in physical fitness (PF), and enhancements in quality of life (QoL) among adolescents with ID. A total of thirty-eight adolescents were randomly allocated into either an intervention group (IG), which participated in the tailored APA program, or a control group (CG), which received standard physical education. The findings demonstrated statistically significant improvements in the IG’s test of gross motor development (TGMD) total, locomotor, object control, and QOL scores relative to the CG (p < 0.001, η² = 0.330, 0.249, 0.224, and 0.439, respectively). Furthermore, substantial gains were observed in PF measures, including upper and lower limb strength as well as cardiorespiratory fitness (p < 0.001, η² = 0.254, 0.351, 0.176). Strong positive correlations were noted between FMS, PF, and QoL (r = 0.34–0.71, p < 0.05). This study underscores the importance of tailoring physical activity programs for adolescents with ID, offering insights into the relationships between FMS, PF, and QoL, and guidance for future interventions aimed at improving health outcomes in this population. Full article

(This article belongs to the Special Issue Physical Activity in People with Cognitive Impairment)

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22 pages, 4866 KiB

Open AccessArticle

TCEDN: A Lightweight Time-Context Enhanced Depression Detection Network

by Keshan Yan, Shengfa Miao, Xin Jin, Yongkang Mu, Hongfeng Zheng, Yuling Tian, Puming Wang, Qian Yu and Da Hu

Life 2024, 14(10), 1313; https://doi.org/10.3390/life14101313 - 16 Oct 2024

Viewed by 266

Abstract

The automatic video recognition of depression is becoming increasingly important in clinical applications. However, traditional depression recognition models still face challenges in practical applications, such as high computational costs, the poor application effectiveness of facial movement features, and spatial feature degradation due to [...] Read more.

The automatic video recognition of depression is becoming increasingly important in clinical applications. However, traditional depression recognition models still face challenges in practical applications, such as high computational costs, the poor application effectiveness of facial movement features, and spatial feature degradation due to model stitching. To overcome these challenges, this work proposes a lightweight Time-Context Enhanced Depression Detection Network (TCEDN). We first use attention-weighted blocks to aggregate and enhance video frame-level features, easing the model’s computational workload. Next, by integrating the temporal and spatial changes of video raw features and facial movement features in a self-learning weight manner, we enhance the precision of depression detection. Finally, a fusion network of 3-Dimensional Convolutional Neural Network (3D-CNN) and Convolutional Long Short-Term Memory Network (ConvLSTM) is constructed to minimize spatial feature loss by avoiding feature flattening and to achieve depression score prediction. Tests on the AVEC2013 and AVEC2014 datasets reveal that our approach yields results on par with state-of-the-art techniques for detecting depression using video analysis. Additionally, our method has significantly lower computational complexity than mainstream methods. Full article

(This article belongs to the Special Issue Modeling and Theoretical Analysis of Artificial Neural Networks for Life Sciences)

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19 pages, 1172 KiB

Open AccessReview

Unlocking the Potential of Circulating miRNAs as Biomarkers in Glioblastoma

by Sanika Suvarnapathaki, Antolin Serrano-Farias, Jonathan C. Dudley, Chetan Bettegowda and Jordina Rincon-Torroella

Life 2024, 14(10), 1312; https://doi.org/10.3390/life14101312 - 16 Oct 2024

Viewed by 449

Abstract

Using microRNAs (miRNAs) as potential circulating biomarkers in diagnosing and treating glioblastoma (GBM) has garnered a lot of scientific and clinical impetus in the past decade. As an aggressive primary brain tumor, GBM poses challenges in early detection and effective treatment with significant [...] Read more.

Using microRNAs (miRNAs) as potential circulating biomarkers in diagnosing and treating glioblastoma (GBM) has garnered a lot of scientific and clinical impetus in the past decade. As an aggressive primary brain tumor, GBM poses challenges in early detection and effective treatment with significant current diagnostic constraints and limited therapeutic strategies. MiRNA dysregulation is present in GBM. The intricate involvement of miRNAs in altering cell proliferation, invasion, and immune escape makes them prospective candidates for identifying and monitoring GBM diagnosis and response to treatment. These miRNAs could play a dual role, acting as both potential diagnostic markers and targets for therapy. By modulating the activity of various oncogenic and tumor-suppressive proteins, miRNAs create opportunities for precision medicine and targeted therapies in GBM. This review centers on the critical role and function of circulating miRNA biomarkers in GBM diagnosis and treatment. It highlights their significance in providing insights into disease progression, aiding in early diagnosis, and potential use as targets for novel therapeutic interventions. Ultimately, the study of miRNA would contribute to improving patient outcomes in the challenging landscape of GBM management. Full article

(This article belongs to the Special Issue Novel Approaches to Early Cancer Detection)

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13 pages, 2693 KiB

Open AccessArticle

Cohesin RAD21 Gene Promoter Methylation in Patients with Acute Myeloid Leukemia

by Kalliopi N. Manola, Sophia Zachaki, Katerina Kakosaiou, Agapi Ioannidou, Marina Kalomoiraki and Theodoros Rampias

Life 2024, 14(10), 1311; https://doi.org/10.3390/life14101311 - 16 Oct 2024

Viewed by 245

Abstract

Background: Aberrant gene promoter methylation is one of the hallmarks of Acute Myeloid Leukemia (AML). RAD21 is an important gene, implicated in sister chromatids cohesion, DNA repair, the regulation of gene transcription, apoptosis and hematopoiesis. Methods: In this study, we investigate the possible [...] Read more.

Background: Aberrant gene promoter methylation is one of the hallmarks of Acute Myeloid Leukemia (AML). RAD21 is an important gene, implicated in sister chromatids cohesion, DNA repair, the regulation of gene transcription, apoptosis and hematopoiesis. Methods: In this study, we investigate the possible implication of RAD21 promoter methylation in AML pathogenesis using a cohort of AML patients and a cohort of healthy individuals. Results: RAD21 promoter methylation was found in 24% of patients and in none of the controls (p = 0.023), indicating a possible contribution to AML development. Interestingly, a statistically higher frequency of RAD21 methylation was observed in patients with trisomy 8 (9/21, 42.9%, p = 0.021), while none of the patients with aberrations of chromosome 11 had RAD21 gene promoter methylation (0%, 0/11, p = 0.048). Patients with monosomal and complex karyotypes showed low frequencies of RAD21 methylation (7.7% and 15.4%, respectively) without reaching statistical significance. Moreover, ASXL1 mutations were not found to be associated with RAD21 methylation. Conclusions: This is the first study which provides evidence for a possible pathogenetic role of RAD21 promoter methylation in AML development and especially in AML with trisomy 8. Further studies of RAD21 promoter methylation in large series of different AML genetic subgroups may contribute to the elucidation of AML pathogenesis and to the identification of new epigenetic biomarkers with diagnostic and prognostic value. Full article

(This article belongs to the Section Physiology and Pathology)

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11 pages, 2481 KiB

Open AccessArticle

Inflammatory and Lipid Biomarkers in Early Atherosclerosis: A Comprehensive Analysis

by Alim Namitokov, Karina Karabakhtsieva and Olga Malyarevskaya

Life 2024, 14(10), 1310; https://doi.org/10.3390/life14101310 - 16 Oct 2024

Viewed by 272

Abstract

Introduction: Atherosclerosis is a leading cause of cardiovascular disease, characterized by lipid accumulation and chronic inflammation within arterial walls. Early detection in young adults is crucial for preventing adverse cardiovascular events. This study investigates the associations between inflammatory indices, lipid biomarkers, and the [...] Read more.

Introduction: Atherosclerosis is a leading cause of cardiovascular disease, characterized by lipid accumulation and chronic inflammation within arterial walls. Early detection in young adults is crucial for preventing adverse cardiovascular events. This study investigates the associations between inflammatory indices, lipid biomarkers, and the presence of atherosclerosis in patients aged 18 to 55 years. Methods: A cross-sectional study was conducted involving 89 participants divided into two groups: 62 patients with documented atherosclerosis (main group) and 27 healthy controls without significant atherosclerosis. Comprehensive data—including demographic information, medication use, imaging results, laboratory parameters, and calculated inflammatory indices (SIRI, SII, AISI, NLR, PLR, MLR)—were collected. Statistical analyses included correlation assessments, group comparisons using the Mann–Whitney U test, logistic regression modeling, feature importance analysis with Random Forest and Gradient Boosting classifiers, receiver operating characteristic (ROC) curves, and K-means clustering. Results: Significant differences were observed between the main and control groups. Patients with atherosclerosis exhibited elevated inflammatory indices (SIRI, NLR, MLR, SII) and lipid profile abnormalities (higher TC and LDL-C, lower HDL-C). Lp(a) and ANGPTL3 levels were significantly higher in the main group (p < 0.001 and p < 0.01, respectively). Logistic regression identified SIRI and ANGPTL3 as significant predictors of atherosclerosis, with the model demonstrating high accuracy (77%) and sensitivity (93%). Feature importance analysis confirmed the significance of SIRI and ANGPTL3, alongside traditional lipid biomarkers, in predicting disease presence. ROC analysis showed excellent model performance (AUC > 0.80). Clustering analysis revealed two distinct patient subgroups characterized by predominant inflammatory profiles or lipid metabolism disturbances. Conclusions: Systemic inflammation and lipid abnormalities play significant roles in early atherosclerosis among young adults. Elevated SIRI and ANGPTL3 levels are potent predictors of disease presence. The integration of inflammatory indices and lipid biomarkers into predictive models enhances risk stratification and supports personalized medicine approaches. Full article

(This article belongs to the Special Issue Emerging Biomarkers: Recent Findings and Application in Pathological Condition Detection—2nd Edition)

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9 pages, 213 KiB

Open AccessArticle

One-Year Effect of Elexacaftor/Tezacaftor/Ivacaftor Therapy on HbA1c Levels and Insulin Requirement in Patients with Insulin-Dependent Cystic Fibrosis-Related Diabetes: A Retrospective Observational Study

by Marta Bassi, Marina Francesca Strati, Gaia Spiandorello, Marta Scalas, Federico Cresta, Maria Grazia Calevo, Giuseppe d’Annunzio, Carlo Castellani, Nicola Minuto, Mohamad Maghnie and Rosaria Casciaro

Life 2024, 14(10), 1309; https://doi.org/10.3390/life14101309 - 16 Oct 2024

Viewed by 312

Abstract

Introduction: The impact of ETI therapy on pulmonary function and nutritional status has been widely studied; the literature on the possible outcomes on glycemic control and insulin requirement in patients affected by CFRD is controversial. Aim: The main objective of our study was [...] Read more.

Introduction: The impact of ETI therapy on pulmonary function and nutritional status has been widely studied; the literature on the possible outcomes on glycemic control and insulin requirement in patients affected by CFRD is controversial. Aim: The main objective of our study was to evaluate HbA1c levels in patients with cystic fibrosis-related diabetes (CFRD) after one year of therapy with elexacaftor/tezacaftor/ivacaftor (ETI). The secondary objective was to study the changes in the total daily insulin dose (TDD), pulmonary function and metabolism in this population. Materials and methods: A retrospective single-center observational study was conducted at the Regional Cystic Fibrosis Centre and Diabetology Centre of IRCCS Istituto Giannina Gaslini. The observation period was divided into four different time points: initiation (T0), 3 months (T_3mo), 6 months (T_6mo) and 12 months (T_12mo) of ETI therapy. Demographic and clinical data were collected. The results were then stratified by genotype (homozygous or heterozygous F508del). Results: Twenty-eight patients with CFRD undergoing insulin therapy were included. TDD (IU) significantly decreased at T_3mo and T_6mo, but not at T_12mo, whereas HbA1c decreased significantly at all three times. The number of hospitalizations and pulmonary exacerbations decreased significantly. Conclusion: We demonstrated both improvement in glycemic control (by means of HbA1c) and insulin requirement in insulin-dependent CFRD patients after one year of ETI treatment. Full article

(This article belongs to the Special Issue Cystic Fibrosis: A Disease with a New Face)

12 pages, 1767 KiB

Open AccessArticle

Proteome Expression Signatures: Differences between Orbital and Subcutaneous Abdominal Adipose Tissues

by Noam Castel, Edward Vitkin, Sharon Shabo, Ariel Berl, Julia Wise, Amir Duenyas, Eliyahu Michael Aharon Cohen, Alexander Golberg and Avshalom Shalom

Life 2024, 14(10), 1308; https://doi.org/10.3390/life14101308 - 15 Oct 2024

Viewed by 326

Abstract

Differences between orbital and subcutaneous abdominal fat in the same patient have been noted but not formally investigated, previously. The objective of this research was to compare the differential expression of protein profiles in subcutaneous abdominal and orbital adipose tissues. In this cross-sectional, [...] Read more.

Differences between orbital and subcutaneous abdominal fat in the same patient have been noted but not formally investigated, previously. The objective of this research was to compare the differential expression of protein profiles in subcutaneous abdominal and orbital adipose tissues. In this cross-sectional, observational study, orbital fat tissue was sampled from 10 patients who underwent blepharoplasty and agreed to provide a small sample of subcutaneous abdominal fat. Shotgun mass spectrometry was performed on the extracted proteome. Data were analyzed using protein appearance patterns, differential expression and statistical enrichment. Protein analysis revealed significant differences in proteomics and differential expression between the orbital and subcutaneous abdominal adipose tissues, which presented five proteins that were uniquely expressed in the orbital fat and 18 in the subcutaneous abdominal fat. Gene Ontology analysis identified significantly different cellular processes and components related to the extracellular matrix or basement membrane components. This analysis shows the differences between orbital and subcutaneous abdominal fat found in proteomics differential expression, uniquely expressed proteins, and cellular processes. Further research is needed to correlate specific proteins and cellular processes to the mechanism of fat accumulation and obesity. Full article

(This article belongs to the Section Physiology and Pathology)

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31 pages, 5219 KiB

Open AccessReview

On the Roles of Protein Intrinsic Disorder in the Origin of Life and Evolution

by Vladimir N. Uversky

Life 2024, 14(10), 1307; https://doi.org/10.3390/life14101307 - 15 Oct 2024

Viewed by 382

Abstract

Obviously, the discussion of different factors that could have contributed to the origin of life and evolution is clear speculation, since there is no way of checking the validity of most of the related hypotheses in practice, as the corresponding events not only [...] Read more.

Obviously, the discussion of different factors that could have contributed to the origin of life and evolution is clear speculation, since there is no way of checking the validity of most of the related hypotheses in practice, as the corresponding events not only already happened, but took place in a very distant past. However, there are a few undisputable facts that are present at the moment, such as the existence of a wide variety of living forms and the abundant presence of intrinsically disordered proteins (IDPs) or hybrid proteins containing ordered domains and intrinsically disordered regions (IDRs) in all living forms. Since it seems that the currently existing living forms originated from a common ancestor, their variety is a result of evolution. Therefore, one could ask a logical question of what role(s) the structureless and highly dynamic but vastly abundant and multifunctional IDPs/IDRs might have in evolution. This study represents an attempt to consider various ideas pertaining to the potential roles of protein intrinsic disorder in the origin of life and evolution. Full article

(This article belongs to the Special Issue What Is Life?)

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18 pages, 1356 KiB

Open AccessReview

Moderate Sedation or Deep Sedation for ERCP: What Are the Preferences in the Literature?

by Giuseppinella Melita, Vincenzo Francesco Tripodi, Socrate Pallio, Endrit Shahini, Alessandro Vitello, Emanuele Sinagra, Antonio Facciorusso, Anna Teresa Mazzeo, Arup Choudhury, Jahnvi Dhar, Jayanta Samanta and Marcello Fabio Maida

Life 2024, 14(10), 1306; https://doi.org/10.3390/life14101306 - 15 Oct 2024

Viewed by 352

Abstract

One of the most essential procedures for individuals with biliopancreatic disorders is endoscopic retrograde cholangiopancreatography (ERCP). It is based on the combination of endoscopy and radiology to study the biliopancreatic ducts and apply therapeutic solutions. ERCP is currently used to treat choledocholithiasis with [...] Read more.

One of the most essential procedures for individuals with biliopancreatic disorders is endoscopic retrograde cholangiopancreatography (ERCP). It is based on the combination of endoscopy and radiology to study the biliopancreatic ducts and apply therapeutic solutions. ERCP is currently used to treat choledocholithiasis with or without cholangitis, as well as pancreatic duct stones, benign bile, and pancreatic leaks. On the other hand, ERCP is an unpleasant procedure that must be conducted under anesthetic (moderate sedation, deep sedation, or general anesthesia). With procedures becoming more challenging, the role of anesthesia in ERCP has become even more relevant, and the use of general anesthesia has become better defined. In the last decades, many drugs have been used and some new drugs, like dexmedetomidine, have been recently introduced for sedation or anesthesia during ERCP. Moreover, the scientific community is still divided on the level of sedation to be applied, as well as on appropriate airway management. We therefore performed a narrative review of the literature to assess currently available anesthetic medications for elective ERCP and evidence supporting their effectiveness. Full article

(This article belongs to the Special Issue Novel Diagnosis and Treatment of Gastrointestinal Disease)

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16 pages, 2630 KiB

Open AccessArticle

Blood Growth Factor Levels in Patients with Systemic Lupus Erythematosus: High Neuregulin-1 Is Associated with Comorbid Cardiovascular Pathology

by Evgeny A. Ermakov, Mark M. Melamud, Anastasiia S. Boiko, Svetlana A. Ivanova, Alexey E. Sizikov, Georgy A. Nevinsky and Valentina N. Buneva

Life 2024, 14(10), 1305; https://doi.org/10.3390/life14101305 - 14 Oct 2024

Viewed by 340

Abstract

Patients with systemic lupus erythematosus (SLE) are known to frequently suffer from comorbid cardiovascular diseases (CVDs). There are abundant data on cytokine levels and their role in the pathogenesis of SLE, while growth factors have received much less attention. The aim of this [...] Read more.

Patients with systemic lupus erythematosus (SLE) are known to frequently suffer from comorbid cardiovascular diseases (CVDs). There are abundant data on cytokine levels and their role in the pathogenesis of SLE, while growth factors have received much less attention. The aim of this study was to analyze growth factor levels in SLE patients and their association with the presence of comorbid CVDs. The serum concentrations for the granulocyte-macrophage colony-stimulating factor (GM-CSF), nerve growth factor β (NGFβ), glial cell line-derived neurotrophic factor (GDNF), and neuregulin-1 β (NRG-1β) were determined in the SLE patients (n = 35) and healthy individuals (n = 38) by a Luminex multiplex assay. The NGFβ and NRG-1β concentrations were shown to be significantly higher in the total group of SLE patients (median [Q1–Q3]: 3.6 [1.3–4.5] and 52.5 [8.5–148], respectively) compared with the healthy individuals (2.9 [1.3–3.4] and 13.7 [4.4–42] ng/mL, respectively). The GM-CSF and GDNF levels did not differ. Interestingly, elevated NRG-1β levels were associated with the presence of CVDs, as SLE patients with CVDs had significantly higher NRG-1β levels (99 [22–242]) compared with the controls (13.7 [4.4–42]) and patients without CVDs (19 [9–80] ng/mL). The model for the binary classification of SLE patients with and without CVDs based on the NRG-1β level had an average predictive ability (AUC = 0.67). Thus, altered levels of growth factors may be associated with comorbid CVDs in SLE patients. Full article

(This article belongs to the Special Issue Common and Novel Markers of Inflammation and Tissue Damage in Various Pathological Conditions)

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