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23 pages, 2091 KiB  
Article
Exploring the Impact of Bioactive Compounds Found in Extra Virgin Olive Oil on NRF2 Modulation in Alzheimer’s Disease
by Marilena M. Bourdakou, Eleni M. Loizidou and George M. Spyrou
Antioxidants 2025, 14(8), 952; https://doi.org/10.3390/antiox14080952 (registering DOI) - 2 Aug 2025
Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by amyloid-β (Aβ) plaques, neurofibrillary tangles, blood–brain barrier dysfunction, oxidative stress (OS), and neuroinflammation. Current treatments provide symptomatic relief, but do not halt the disease’s progression. OS plays a crucial role in AD pathogenesis [...] Read more.
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by amyloid-β (Aβ) plaques, neurofibrillary tangles, blood–brain barrier dysfunction, oxidative stress (OS), and neuroinflammation. Current treatments provide symptomatic relief, but do not halt the disease’s progression. OS plays a crucial role in AD pathogenesis by promoting Aβ accumulation. Nuclear factor erythroid 2-related factor 2 (NRF2) is a key regulator of the antioxidant response, influencing genes involved in OS mitigation, mitochondrial function, and inflammation. Dysregulation of NRF2 is implicated in AD, making it a promising therapeutic target. Emerging evidence suggests that adherence to a Mediterranean diet (MD), which is particularly rich in polyphenols from extra virgin olive oil (EVOO), is associated with improved cognitive function and a reduced risk of mild cognitive impairment. Polyphenols can activate NRF2, enhancing endogenous antioxidant defenses. This study employs a computational approach to explore the potential of bioactive compounds in EVOO to modulate NRF2-related pathways in AD. We analyzed transcriptomic data from AD and EVOO-treated samples to identify NRF2-associated genes, and used chemical structure-based analysis to compare EVOO’s bioactive compounds with known NRF2 activators. Enrichment analysis was performed to identify common biological functions between NRF2-, EVOO-, and AD-related pathways. Our findings highlight important factors and biological functions that provide new insight into the molecular mechanisms through which EVOO consumption might influence cellular pathways associated with AD via modulation of the NRF2 pathway. The presented approach provides a different perspective in the discovery of compounds that may contribute to neuroprotective mechanisms in the context of AD. Full article
27 pages, 15012 KiB  
Article
New Insights in the Helicellini Ihering, 1909 with Description of Kherattolactea Gen. Nov. and the First Record of Orexana Chueca, Gómez-Moliner, Madeira & Pfenninger, 2018 from Algeria
by Issaad Kawther Ezzine, Houria Bouaziz-Yahiatene, Willy De Mattia and Eike Neubert
Diversity 2025, 17(8), 550; https://doi.org/10.3390/d17080550 (registering DOI) - 2 Aug 2025
Abstract
Recent sampling efforts in northern Algeria and the investigation of some collection material has revealed the presence of taxa with conchological and genital morphological similarities to the Candidula-like group. A detailed investigation of the anatomy of the genitalia combined with the analysis [...] Read more.
Recent sampling efforts in northern Algeria and the investigation of some collection material has revealed the presence of taxa with conchological and genital morphological similarities to the Candidula-like group. A detailed investigation of the anatomy of the genitalia combined with the analysis of two mitochondrial and two nuclear markers of representatives of the known genera as well as two Algerian taxa has been conducted. The result confirms the affiliation of the latter in the Candidula-like complex. Comparative anatomical analysis led to the description of a new genus, Kherattolactea gen. nov., endemic to northern Algeria with Xerophila keratae, Kobelt, 1892 as the type species. The anatomical distinction corroborates the result of the molecular analysis that reveals apomorphic nucleotide substitution. Moreover, the result of the combined analysis provides the first confirmed record of the genus Orexana Chueca, Gómez-Moliner, Madeira & Pfenninger, 2018, in north Africa, represented by the species Orexana lemoinei Kobelt, 1882 nov. comb. A new Xerogyra species, Xerogyra halgassi nov. sp., from the Apennine Mountain has been described based on the combination of morphoanatomical and molecular traits. For the first time, the morphoanatomical description of the known Xerogyra species has been presented. Full article
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10 pages, 1191 KiB  
Article
RNA Sequencing on Muscle Biopsies from Exertional Rhabdomyolysis Patients Revealed Down-Regulation of Mitochondrial Function and Enhancement of Extracellular Matrix Composition
by Mingqiang Ren, Luke P. Michaelson, Ognoon Mungunsukh, Peter Bedocs, Liam Friel, Kristen Cofer, Carolyn E. Dartt, Nyamkhishig Sambuughin and Francis G. O’Connor
Genes 2025, 16(8), 930; https://doi.org/10.3390/genes16080930 (registering DOI) - 2 Aug 2025
Abstract
Background/Objective: Exertional rhabdomyolysis (ER) is primarily driven by mechanical stress on muscles during strenuous or unaccustomed exercise, often exacerbated by environmental factors like heat and dehydration. While the general cellular pathway involving energy depletion and calcium overload is understood in horse ER models, [...] Read more.
Background/Objective: Exertional rhabdomyolysis (ER) is primarily driven by mechanical stress on muscles during strenuous or unaccustomed exercise, often exacerbated by environmental factors like heat and dehydration. While the general cellular pathway involving energy depletion and calcium overload is understood in horse ER models, the underlying mechanisms specific to the ER are not universally known within humans. This study aimed to evaluate whether patients with ER exhibited transcriptional signatures that were significantly different from those of healthy individuals. Methods: This study utilized RNA sequencing on skeletal muscle samples from 19 human patients with ER history, collected at a minimum of six months after the most recent ER event, and eight healthy controls to investigate the transcriptomic landscape of ER. To identify any alterations in biological processes between the case and control groups, functional pathway analyses were conducted. Results: Functional pathway enrichment analyses of differentially expressed genes revealed strong suppression of mitochondrial function. This suppression included the “aerobic electron transport chain” and “oxidative phosphorylation” pathways, indicating impaired energy production. Conversely, there was an upregulation of genes associated with adhesion and extracellular matrix-related pathways, indicating active restoration of muscle function in ER cases. Conclusions: The study demonstrated that muscle tissue exhibited signs of suppressed mitochondrial function and increased extracellular matrix development. Both of these facilitate muscle recovery within several months after an ER episode. Full article
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12 pages, 757 KiB  
Brief Report
DNA-Programmable Oligonucleotide Insecticide Eriola-11 Targets Mitochondrial 16S rRNA and Exhibits Strong Insecticidal Activity Against Woolly Apple Aphid (Eriosoma lanigerum) Hausmann
by Vol Oberemok, Kate Laikova, Oksana Andreeva, Anastasia Dmitrienko, Tatiana Rybareva, Jamin Ali and Nikita Gal’chinsky
Int. J. Mol. Sci. 2025, 26(15), 7486; https://doi.org/10.3390/ijms26157486 (registering DOI) - 2 Aug 2025
Abstract
The potent and selective ‘genetic zipper’ method for insect pest control consists of three essential components: an antisense DNA (the finder), its complementary mature rRNA or pre-rRNA of the pest (the target), and the host’s endogenous DNA-guided rRNase (the degrader). Although this approach [...] Read more.
The potent and selective ‘genetic zipper’ method for insect pest control consists of three essential components: an antisense DNA (the finder), its complementary mature rRNA or pre-rRNA of the pest (the target), and the host’s endogenous DNA-guided rRNase (the degrader). Although this approach has been validated, the spectrum of effective rRNA targets remains insufficiently explored. In this study, we report for the first time the insecticidal efficacy of a novel oligonucleotide insecticide, Eriola-11, which targets the mitochondrial 16S rRNA of the woolly apple aphid Eriosoma lanigerum Hausmann. We hypothesized that the antisense-mediated silencing of mitochondrial rRNA would impair aphid viability and lead to physiological disruptions associated with mitochondrial energy metabolism. Eriola-11 was applied either once or twice (with a 24 h interval) to aphid-infested plants, and aphid mortality was recorded over 14 days. Mitochondrial 16S rRNA expression levels were quantified using molecular assays, and the degradation kinetics of Eriola-11 were assessed in aphid tissue homogenates. Results showed significant insecticidal activity, with 67.55% mortality after a single treatment and 83.35% after two treatments. Treated aphids exhibited the loss of their characteristic white woolly wax covering, and mitochondrial 16S rRNA expression was reduced 0.66-fold relative to the control. Additionally, Eriola-11 was fully degraded by aphid DNases from tissue homogenates within 3 h, highlighting its rapid biodegradability. These findings establish mitochondrial 16S rRNA as a viable target for antisense insecticides and expand the catalogue of potential rRNA-based targets, offering a promising avenue for environmentally sustainable pest control strategies. Full article
(This article belongs to the Special Issue Antisense Oligonucleotides: Versatile Tools with Broad Applications)
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21 pages, 1705 KiB  
Article
Antioxidant Effects of Exogenous Mitochondria: The Role of Outer Membrane Integrity
by Sadab Sipar Ibban, Jannatul Naima, Ryo Kato, Taichi Kuroda and Yoshihiro Ohta
Antioxidants 2025, 14(8), 951; https://doi.org/10.3390/antiox14080951 (registering DOI) - 2 Aug 2025
Abstract
The administration of isolated mitochondria is a promising strategy for protecting cells from oxidative damage. This study aimed to identify mitochondrial characteristics that contribute to stronger protective effects. We compared two types of mitochondria isolated from C6 cells with similar ATP-producing capacity but [...] Read more.
The administration of isolated mitochondria is a promising strategy for protecting cells from oxidative damage. This study aimed to identify mitochondrial characteristics that contribute to stronger protective effects. We compared two types of mitochondria isolated from C6 cells with similar ATP-producing capacity but differing in outer membrane integrity. To evaluate their stability in extracellular conditions, we examined their behavior in serum. Both types underwent mitochondrial permeability transition to a similar extent; however, under intracellular-like conditions after serum incubation, mitochondria with intact membranes retained more polarized mitochondria. Notably, mitochondria with intact outer membranes were internalized more efficiently than those with damaged membranes. In H9c2 cells, both types of mitochondria similarly increased intracellular ATP levels 1 h after administration under all tested conditions. When co-administered with H2O2, both suppressed oxidative damage to a comparable degree, as indicated by similar H2O2-scavenging activity in solution, comparable intracellular ROS levels, and equivalent preservation of electron transport chain activity. However, at higher H2O2 concentrations, cells treated with mitochondria possessing intact outer membranes exhibited greater survival 24 h after co-administration. Furthermore, when mitochondria were added after H2O2-induced damage and their removal, intact mitochondria conferred superior cell survival compared to damaged ones. These findings suggest that while both mitochondrial types exert comparable antioxidant effects, outer membrane integrity prior to administration plays a critical role in enhancing cell survival under conditions of oxidative stress. Full article
(This article belongs to the Section ROS, RNS and RSS)
10 pages, 503 KiB  
Brief Report
RAGE Knockout Mitigates Diet-Induced Obesity and Metabolic Disruption
by Isabelle L. Palmer, Genevieve Parker, Alden T. Chiu, Colson G. Beus, Ethan P. Evans, Jack H. Radford, Cameron R. Braithwaite, Ryan D. van Slooten, Elijah T. Cooper-Leavitt, Zachary E. Moore, Derek M. Clarke, R. Ryley Parrish, Juan A. Arroyo, Paul R. Reynolds and Benjamin T. Bikman
Metabolites 2025, 15(8), 524; https://doi.org/10.3390/metabo15080524 (registering DOI) - 2 Aug 2025
Abstract
Background/Objectives: The receptor for advanced glycation end products (RAGEs) has been implicated in obesity and metabolic dysfunction. However, its precise role in diet-induced obesity remains unclear. Methods: In this study, we investigated the metabolic consequences of RAGE knockout (RAGE KO) in mice subjected [...] Read more.
Background/Objectives: The receptor for advanced glycation end products (RAGEs) has been implicated in obesity and metabolic dysfunction. However, its precise role in diet-induced obesity remains unclear. Methods: In this study, we investigated the metabolic consequences of RAGE knockout (RAGE KO) in mice subjected to a Western diet (WD). Results: Our findings demonstrate that RAGE KO mice remained significantly leaner than their wild-type (WT) counterparts when fed a WD, exhibiting reduced body weight gain and smaller adipocyte size. Indirect calorimetry revealed that RAGE KO mice had increased oxygen consumption and locomotor activity compared to WT mice, indicating enhanced energy expenditure. Mitochondrial respiration assays indicated significantly greater oxygen consumption in RAGE KO animals. Additionally, systemic inflammation markers, such as TNF-α, were significantly lower in RAGE KO mice when fed a WD, indicating a reduction in diet-induced inflammatory responses. Conclusions: These findings suggest that RAGE plays a key role in metabolic homeostasis, and its deletion confers resistance to obesity and metabolic disruption induced by a Western diet. Targeting RAGE may provide a novel therapeutic approach for combating obesity and related metabolic disorders. Full article
(This article belongs to the Special Issue Fat and Glucose Metabolism)
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16 pages, 3678 KiB  
Article
The Antitumor Role of Incomptine A in a Breast Cancer Murine Model: Impairment of Hexokinase II Expression and Apoptosis Induction
by Angel Giovanni Arietta-García, Fernando Calzada, Antonio Franco-Vadillo, Irais Monserrat Barrientos-Buendía, Francisco Javier Alarcón-Aguilar, Elihú Bautista, Paola Santana-Sánchez, Israel Ramírez-Sánchez and Rosa María Ordoñez-Razo
Cells 2025, 14(15), 1192; https://doi.org/10.3390/cells14151192 (registering DOI) - 2 Aug 2025
Abstract
Breast cancer (BC) is the most common type of cancer in women worldwide. Hexokinase II (HKII) overexpression is associated with the proliferation and survival of tumor cells, as it inhibits apoptosis. Incomptine A (IA) is cytotoxic to breast cancer cells, likely due to [...] Read more.
Breast cancer (BC) is the most common type of cancer in women worldwide. Hexokinase II (HKII) overexpression is associated with the proliferation and survival of tumor cells, as it inhibits apoptosis. Incomptine A (IA) is cytotoxic to breast cancer cells, likely due to a decrease in the expression of HKII. This study evaluated the antitumor activity of IA in an in vivo mouse model of BC. A model was generated from 4T1 cells and grouped tumor-bearing animals according to treatment: in IA or doxorubicin (DOXO), or untreated (UT). Comparing the body weight and tumor size between groups, tumors were analyzed using histopathological, Western blot, flow cytometry, and mitochondrial activity assays. Tumors IA-treated showed a reduction in size, weight, and number of tumor cells; the expression of HKII and Bcl-2 decreased, while that of Caspase-3 increased. IA treatment increased apoptosis and reduced mitochondrial activity in tumor cells. This data showed that IA has an impact on tumor cells by reducing tumor volume and size, increasing cell apoptosis, and decreasing mitochondrial activity, all of which could be attributed to reduced HKII expression. Therefore, IA may be a promising compound that requires further studies to elucidate its mechanism of action and analyze its possible future use in BC. Full article
(This article belongs to the Special Issue Targeting Hallmarks of Cancer)
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14 pages, 2230 KiB  
Article
Complete Mitochondrial (mtDNA) Genome Analysis of Economically Significant Fish Cirrhinus cirrhosus in Bangladesh
by Tajmirul Huda, Md. Alamgir Kabir and Md. Golam Rabbane
Int. J. Mol. Sci. 2025, 26(15), 7473; https://doi.org/10.3390/ijms26157473 (registering DOI) - 2 Aug 2025
Abstract
Complete mitochondrial DNA genome annotation of an ecologically and commercially important fish species Cirrhinus cirrhosus was executed with next-generation sequencing (NGS) for nucleotide and phylogenetic analyses. The findings of this study showed that the Cirrhinus cirrhosus mitochondrial genome contained 16,593 bp, including 13 [...] Read more.
Complete mitochondrial DNA genome annotation of an ecologically and commercially important fish species Cirrhinus cirrhosus was executed with next-generation sequencing (NGS) for nucleotide and phylogenetic analyses. The findings of this study showed that the Cirrhinus cirrhosus mitochondrial genome contained 16,593 bp, including 13 protein-coding genes, 2 ribosomal RNA genes, 22 tRNA genes, and a D-loop region. The overall base composition was 32% adenine, 25% thiamine, 16% guanine, and 27% cytosine. This mitochondrial DNA exhibits an AT biasness, with 56% AT content in its genome. Significant fluctuations were identified in the AT and GC skew values of the ND6 gene, indicating that the selection and mutation forces acting on this gene might be different from those acting on other genes. The Ka/Ks ratios of most protein-coding genes were less than 1, indicating very strong natural selection pressure. Phylogenetic analysis of Cirrhinus cirrhosus with Cirrhinus mrigala and Bangana tungting suggested a closer evolutionary relationship among these species, which might have shared a more recent common ancestor. It has been also found that the genera Labeo and Cirrhinus are not monophyletic. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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9 pages, 4266 KiB  
Protocol
Protocol for the Systematic Quantitative Ultrastructural Analysis of Mitochondria in Cardiac Tissue
by Rebecca Schönmehl, Lina Winter, Daniel H. Mendelsohn, Wing-Hoi Cheung, Ronald Man Yeung Wong, Steffen Pabel, Samuel Sossalla and Christoph Brochhausen
Methods Protoc. 2025, 8(4), 87; https://doi.org/10.3390/mps8040087 (registering DOI) - 2 Aug 2025
Abstract
Mitochondria play a crucial role in adapting to fluctuating energy demands, particularly in various heart diseases. In addition to functional analyses such as the measurement of ROS or ATP, analysis of mitochondrial ultrastructure can be used to draw further conclusions about their functions [...] Read more.
Mitochondria play a crucial role in adapting to fluctuating energy demands, particularly in various heart diseases. In addition to functional analyses such as the measurement of ROS or ATP, analysis of mitochondrial ultrastructure can be used to draw further conclusions about their functions and effects in tissue. In this protocol, we introduce a set of measurements to compare the ultrastructural and functional characteristics of human left ventricular mitochondria, using transmission electron microscopy (TEM). Measured parameters included mean size in µm2, elongation, count, percental mitochondrial area in the measuring frame, and a conglomeration score. We also introduce a novel method of defining hydropic mitochondria as a comparable evaluation standard. With this cluster of measurement parameters, we aim to contribute a protocol for studying human mitochondrial morphology, distribution, and functionality. Full article
(This article belongs to the Section Biomedical Sciences and Physiology)
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10 pages, 868 KiB  
Article
The Response of Cell Cultures to Nutrient- and Serum-Induced Changes in the Medium
by Marijana Leventić, Katarina Mišković Špoljarić, Karla Vojvodić, Nikolina Kovačević, Marko Obradović and Teuta Opačak-Bernardi
Sci 2025, 7(3), 105; https://doi.org/10.3390/sci7030105 (registering DOI) - 2 Aug 2025
Abstract
Cell culture models are of central importance for the investigation of cellular metabolism, proliferation and stress responses. In this study, the effects of different concentrations of glucose (1 g/L vs. 4.5 g/L) and fetal bovine serum (FBS; 5%, 10%, 15%) on viability, mitochondrial [...] Read more.
Cell culture models are of central importance for the investigation of cellular metabolism, proliferation and stress responses. In this study, the effects of different concentrations of glucose (1 g/L vs. 4.5 g/L) and fetal bovine serum (FBS; 5%, 10%, 15%) on viability, mitochondrial function and autophagy are investigated in four human cell lines: MRC-5, HeLa, Caco-2 and SW-620. Cells were cultured in defined media for 72 h, and viability was assessed by LDH release, mitochondrial membrane potential using Rhodamine 123, ATP content by luminescence and autophagy activity by dual fluorescence staining. The results showed that HeLa and SW-620 cancer cells exhibited increased proliferation and mitochondrial activity under high glucose conditions, while low glucose media resulted in decreased ATP content and increased membrane permeability in HeLa cells. MRC-5 fibroblasts and Caco-2 cells showed greater resilience to nutrient stress, with minimal changes in LDH release and consistent proliferation. Autophagy was activated under all conditions, with a significant increase only in selected cell-medium combinations. These results highlight the importance of medium composition in influencing cellular bioenergetics and stress responses, which has implications for cancer research, metabolic disease modelling and the development of serum-free culture systems for regenerative medicine. Full article
(This article belongs to the Section Biology Research and Life Sciences)
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32 pages, 1447 KiB  
Article
Haplotypes of Echinococcus granulosus sensu stricto in Chile and Their Comparison Through Sequences of the Mitochondrial cox1 Gene with Haplotypes from South America and Other Continents
by Nicole Urriola-Urriola, Gabriela Rossi-Vargas and Yenny Nilo-Bustios
Parasitologia 2025, 5(3), 40; https://doi.org/10.3390/parasitologia5030040 (registering DOI) - 1 Aug 2025
Abstract
Cystic echinococcosis is a zoonosis caused by the cestode Echinococcus granulosus sensu stricto. Population genetic studies and phylogeographic patterns are essential to understanding the transmission dynamics of this parasite under varying environmental conditions. In this study, the genetic diversity of E. granulosus [...] Read more.
Cystic echinococcosis is a zoonosis caused by the cestode Echinococcus granulosus sensu stricto. Population genetic studies and phylogeographic patterns are essential to understanding the transmission dynamics of this parasite under varying environmental conditions. In this study, the genetic diversity of E. granulosus s.s. was evaluated using 46 hydatid cyst samples obtained from sheep, goats, cattle, and humans across three regions of Chile: Coquimbo, La Araucanía, and Magallanes. Mitochondrial cox1 gene sequences were analyzed and compared with reference sequences reported from South America, Europe, Africa, Asia, and Oceania. In Chile, the EG01 haplotype was the predominant haplotype. A total of four haplotypes were identified, with low haplotype diversity (Hd = 0.461 ± 0.00637) and low nucleotide diversity (π = 0.00181 ± 0.00036). The haplotype network displayed a star-like configuration, with the EG01 genotype at the center, suggesting a potentially ancestral or widely distributed lineage. In Coquimbo (Tajima’s D = −0.93302, p = 0.061; Fu’s Fs = −0.003, p = 0.502) and Magallanes (Tajima’s D = −0.17406, p = 0.386; Fu’s Fs = −0.121, p = 0.414), both neutrality tests were non-significant, indicating no strong evidence for recent population expansion or selection. Star-like haplotype network patterns were also observed in populations from Europe, the Middle East, Asia, Africa, and Oceania, with the EG01 genotype occupying the central position. The population genetic structure of Echinococcus granulosus s.s. in Chile demonstrates considerable complexity, with EG01 as the predominant haplotype. Further comprehensive studies are required to assess the intraspecific genetic variability of E. granulosus s.s. throughout Chile and to determine whether this variability influences the key biological traits of the parasite. This structure may prove even more complex when longer fragments are analyzed, which could allow for the detection of finer-scale microdiversity among isolates from different hosts. We recommended that future cystic echinococcosis control programs take into account the genetic variability of E. granulosus s.s. strains circulating in each endemic region, to better understand their epidemiological, immunological, and possibly pathological differences. Full article
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16 pages, 12280 KiB  
Article
Description of a New Species of Hainania Koller (Teleostei, Cypriniformes, Xenocyprididae) from Guangdong Province, Southern China
by Haotian Lei, Ziyu Gong and Xuankun Li
Diversity 2025, 17(8), 549; https://doi.org/10.3390/d17080549 (registering DOI) - 1 Aug 2025
Abstract
Hainania Koller (Teleostei, Cypriniformes, Xenocyprididae) is known as a monotypic genus of sharpbelly fish that is endemic to Hainan Island, China. We describe Ha. minzhengi sp. nov., the second species of Hainania collected from Guangdong, based on morphology and molecular evidence. [...] Read more.
Hainania Koller (Teleostei, Cypriniformes, Xenocyprididae) is known as a monotypic genus of sharpbelly fish that is endemic to Hainan Island, China. We describe Ha. minzhengi sp. nov., the second species of Hainania collected from Guangdong, based on morphology and molecular evidence. Phylogenetic relationships were inferred based on the mitochondrial cytochrome b (Cyt b) gene and cytochrome oxidase subunit 1 (COI) gene, by maximum likelihood and Bayesian methods and different partitioning schemes. Our result supports the sister group relationship between Ha. serrata and Ha. minzhengi sp. nov., but the monophyly of Pseudohemiculter or Hemiculterella was not recovered. A diagnostic key to Chinese species of Hainania and Pseudohemiculter is provided. Full article
(This article belongs to the Special Issue Evolution, Systematic and Conservation of Freshwater Fishes)
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15 pages, 245 KiB  
Article
Exploring Single-Nucleotide Polymorphisms in Primary and Secondary Male Infertility
by Fatina W. Dahadhah, Mohanad Odeh, Heba A. Ali, Jihad A. M. Alzyoud and Manal Issam Abu Alarjah
Med. Sci. 2025, 13(3), 109; https://doi.org/10.3390/medsci13030109 (registering DOI) - 1 Aug 2025
Abstract
Background/Objectives: Infertility, defined as the failure to achieve pregnancy after one year of regular unprotected intercourse, represents a significant global health challenge, with male factors contributing to approximately 50% of cases. In this epidemiological context, both primary male infertility (the inability to conceive [...] Read more.
Background/Objectives: Infertility, defined as the failure to achieve pregnancy after one year of regular unprotected intercourse, represents a significant global health challenge, with male factors contributing to approximately 50% of cases. In this epidemiological context, both primary male infertility (the inability to conceive a first child) and secondary male infertility (which occurs when a man who has already fathered a child faces difficulty conceiving again) remain poorly understood at the genetic level. This study explored the role of single-nucleotide polymorphisms (SNPs) in mitochondrial genes (MT-ND3, MT-ND4L, and MT-ND4) in primary and secondary male infertility. Methods: This study analyzed the genotype distributions of SNPs in 68 infertile males (49 with primary infertility and 19 with secondary infertility) using Sanger sequencing. Results: Key findings revealed that studied SNPs were significantly associated with infertility type. Specifically, rs2857285 (T>C,G) in the ND4 gene showed a significant correlation (p = 0.023) with the TT genotype, which is prominent in primary infertility. Another SNP, rs28358279 (T>A,C) in the ND4L gene, also demonstrated a significant correlation (p = 0.046) with the TT genotype, being more common in primary infertility. In addition, rs869096886 (A>G) in the ND4 gene had a borderline correlation (p = 0.051), indicating a possible association between this SNP and reproductive duration. Conclusions: This study emphasizes the potential relevance of mitochondrial malfunction in male infertility, specifically the effects of studied SNPs on sperm survival and function over time. These findings suggest that certain mitochondrial SNPs might be potential biomarkers for infertility risk. Larger studies are needed to confirm these associations and examine the functional effects of these SNPs. Combining genetic analysis with environmental and lifestyle factors could enhance our understanding of male infertility and improve diagnostic and therapeutic strategies. Full article
20 pages, 1221 KiB  
Article
Circulating Lipid Profiles Indicate Incomplete Metabolic Recovery After Weight Loss, Suggesting the Need for Additional Interventions in Severe Obesity
by Alina-Iuliana Onoiu, Vicente Cambra-Cortés, Andrea Jiménez-Franco, Anna Hernández-Aguilera, David Parada, Francesc Riu, Antonio Zorzano, Jordi Camps and Jorge Joven
Biomolecules 2025, 15(8), 1112; https://doi.org/10.3390/biom15081112 (registering DOI) - 1 Aug 2025
Abstract
The effects of long-term adjustments in body weight on the lipid balance in patients with severe obesity are not well understood. This study aimed to evaluate a non-invasive lipidomic approach to identifying biomarkers that could help predict which patients may require additional therapies [...] Read more.
The effects of long-term adjustments in body weight on the lipid balance in patients with severe obesity are not well understood. This study aimed to evaluate a non-invasive lipidomic approach to identifying biomarkers that could help predict which patients may require additional therapies before and after weight loss. Using mass spectrometry, 275 lipid species were analysed in non-obese controls, patients with severe obesity, and patients one year after bariatric surgery. The results showed that severe obesity disrupts lipid pathways, contributing to lipotoxicity, inflammation, mitochondrial stress, and abnormal lipid metabolism. Although weight loss improved these disturbances, surgery did not fully normalise the lipid profiles of all patients. Outcomes varied depending on their baseline liver health and genetic differences. Persistent alterations in cholesterol handling, membrane composition, and mitochondrial function were observed in partial responders. Elevated levels of sterol lipids, glycerophospholipids, and sphingolipids emerged as markers of complete metabolic recovery, identifying candidates for targeted post-surgical interventions. These findings support the use of lipidomics to personalise obesity treatment and follow-up. Full article
(This article belongs to the Section Molecular Biomarkers)
26 pages, 1030 KiB  
Review
Natural Flavonoids for the Prevention of Sarcopenia: Therapeutic Potential and Mechanisms
by Ye Eun Yoon, Seong Hun Ju, Yebean Kim and Sung-Joon Lee
Int. J. Mol. Sci. 2025, 26(15), 7458; https://doi.org/10.3390/ijms26157458 (registering DOI) - 1 Aug 2025
Abstract
Sarcopenia, characterized by progressive skeletal muscle loss and functional decline, represents a major public heath challenge in aging populations. Despite increasing awareness, current management strategies—primarily resistance exercise and nutritional support—remain limited by accessibility, adherence, and inconsistent outcomes. This underscores the urgent need for [...] Read more.
Sarcopenia, characterized by progressive skeletal muscle loss and functional decline, represents a major public heath challenge in aging populations. Despite increasing awareness, current management strategies—primarily resistance exercise and nutritional support—remain limited by accessibility, adherence, and inconsistent outcomes. This underscores the urgent need for novel, effective, and scalable therapeutics. Flavonoids, a diverse class of plant-derived polyphenolic compounds, have attracted attention for their muti-targeted biological activities, including anti-inflammatory, antioxidant, metabolic, and myogenic effects. This review aims to evaluate the anti-sarcopenic potential of selected flavonoids—quercetin, rutin, kaempferol glycosides, baicalin, genkwanin, isoschaftoside, naringin, eriocitrin, and puerarin—based on recent preclinical findings and mechanistic insights. These compounds modulate key pathways involved in muscle homeostasis, such as NF-κB and Nrf2 signaling, AMPK and PI3K/Akt activation, mitochondrial biogenesis, proteosomal degradation, and satellite cell function. Importantly, since muscle wasting also features prominently in cancer cachexia—a distinct but overlapping syndrome—understanding flavonoid action may offer broader therapeutic relevance. By targeting shared molecular axes, flavonoids may provide a promising, biologically grounded approach to mitigating sarcopenia and the related muscle-wasting conditions. Further translational studies and clinical trials are warranted to assess their efficacy and safety in human populations. Full article
(This article belongs to the Special Issue Role of Natural Products in Human Health and Disease)
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