International Journal of Molecular Sciences最新文献

Diacylglycerol Kinases and Its Role in Lipid Metabolism and Related Diseases. 二酰甘油激酶及其在脂质代谢和相关疾病中的作用。

IF 5.6 2区生物学

International Journal of Molecular Sciences Pub Date : 2024-12-09 DOI: 10.3390/ijms252313207

Yishi Liu, Zehui Yang, Xiaoman Zhou, Zijie Li, Nakanishi Hideki

引用次数: 0

Fabrication of Porous MXene/Cellulose Nanofibers Composite Membrane for Maximum Osmotic Energy Harvesting.

IF 5.6 2区生物学

International Journal of Molecular Sciences Pub Date : 2024-12-09 DOI: 10.3390/ijms252313226

Sha Wang, Zhe Sun, Mehraj Ahmad, Mengyu Miao

{"title":"Fabrication of Porous MXene/Cellulose Nanofibers Composite Membrane for Maximum Osmotic Energy Harvesting.","authors":"Sha Wang, Zhe Sun, Mehraj Ahmad, Mengyu Miao","doi":"10.3390/ijms252313226","DOIUrl":"https://doi.org/10.3390/ijms252313226","url":null,"abstract":"Two-dimensional (2D) nanofluidic channels are emerging as potential candidates for harnessing osmotic energy from salinity gradients. However, conventional 2D nanofluidic membranes suffer from high transport resistance and low ion selectivity, leading to inefficient transport dynamics and limiting energy conversion performance. In this study, we present a novel composite membrane consisting of porous MXene (PMXene) nanosheets featuring etched nanopores, in conjunction with cellulose nanofibers (CNF), yielding enhancement in ion flux and ion selectivity. A mild H2O2 oxidant is employed to etch and perforate the MXene sheets to create a robust network of cation transportation nanochannels that effectively reduces the energy barrier for cation transport. Additionally, CNF with a unique nanosize and high charge density further enhances the charge density and mechanical stability of the nanofluidic system. Under neutral pH and room temperature, the PMXene/CNF membrane demonstrates a maximum output power density of 0.95 W·m-2 at a 50-fold KCl gradient. Notably, this represents a 43% improvement over the performance of the pristine MXene/CNF membrane. Moreover, 36 nanofluidic devices connected in series are demonstrated to achieve a stable voltage output of 5.27 V and power a calculator successfully. This work holds great promise for achieving sustainable energy harvesting with efficient osmotic energy conversion utilization.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Role of Annexin 7 (ANXA7) as a Tumor Suppressor and a Regulator of Drug Resistance in Thyroid Cancer.

IF 5.6 2区生物学

International Journal of Molecular Sciences Pub Date : 2024-12-09 DOI: 10.3390/ijms252313217

Alakesh Bera, Surya Radhakrishnan, Narayanan Puthillathu, Madhan Subramanian, Nahbuma Gana, Eric Russ, Harvey B Pollard, Meera Srivastava

{"title":"Role of Annexin 7 (ANXA7) as a Tumor Suppressor and a Regulator of Drug Resistance in Thyroid Cancer.","authors":"Alakesh Bera, Surya Radhakrishnan, Narayanan Puthillathu, Madhan Subramanian, Nahbuma Gana, Eric Russ, Harvey B Pollard, Meera Srivastava","doi":"10.3390/ijms252313217","DOIUrl":"https://doi.org/10.3390/ijms252313217","url":null,"abstract":"Thyroid cancer is the most common endocrine malignancy in the United States, with an overall favorable prognosis. However, some patients experience poor outcomes due to the development of resistance to conventional therapies. Genetic alterations, including mutations in BRAF, Met, and p53, play critical roles in thyroid cancer progression, with the BRAF V600E mutation detected in over 60% of cases. This study investigates the tumor-suppressive role of Annexin A7 (ANXA7) in thyroid cancer, focusing on its potential impact on tumor behavior and therapeutic response. Our analysis, which included RNA sequencing and protein profiling, revealed reduced ANXA7 expression in thyroid cancer cells, particularly in those harboring the BRAF V600E mutation. Upon treatment with inhibitors targeting BRAF and MEK, ANXA7 expression increased, leading to reduced phosphorylation of ERK and activation of apoptotic pathways. Additionally, we identified the cyclin-dependent kinase inhibitor p21 as a key player in modulating resistance to BRAF inhibitors. Combination therapies aimed at concurrently increasing p21 and ANXA7 levels resulted in a marked enhancement of apoptosis. These findings suggest a previously uncharacterized regulatory network involving the ANXA7/p21/BRAF/MAPK/p53 axis, which may contribute to drug resistance in thyroid cancer. This study provides new insights into overcoming resistance to BRAF and MAPK inhibitors, with implications for treating thyroid cancer and potentially other BRAF-mutant tumors. Future efforts will focus on high-throughput screening approaches to explore ANXA7-targeted therapeutic strategies for thyroid cancer.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Probiotics Lacticaseibacillus paracasei, Lacticaseibacillus rhamnosus, and Limosilactobacillus fermentum Enhance Spermatozoa Motility Through Mitochondrial Function-Related Factors.

IF 5.6 2区生物学

International Journal of Molecular Sciences Pub Date : 2024-12-09 DOI: 10.3390/ijms252313220

Eun Hye Lee, Yu Jin Kim, Il Seon Jung, Dae Keun Kim, Jae Ho Lee

{"title":"The Probiotics Lacticaseibacillus paracasei, Lacticaseibacillus rhamnosus, and Limosilactobacillus fermentum Enhance Spermatozoa Motility Through Mitochondrial Function-Related Factors.","authors":"Eun Hye Lee, Yu Jin Kim, Il Seon Jung, Dae Keun Kim, Jae Ho Lee","doi":"10.3390/ijms252313220","DOIUrl":"https://doi.org/10.3390/ijms252313220","url":null,"abstract":"Idiopathic male infertility is characterized by increased mortality or reduced motility and vitality of sperm. There are several reports on probiotics in the male reproductive tract, but the effects of these probiotics on sperm motility remain to be elucidated. In this study, we investigated the impact and mechanism of probiotics on the vitality and motility of mouse sperm. We collected mature sperm from the caudal vas deferens of mice and prepared three probiotics donated by HEM Pharma Inc.: Lacticaseibacillus rhamnosus, Limosilactobacillus fermentum, and Lacticaseibacillus paracasei. We analyzed the vitality and motility of sperm according to the concentration and duration of probiotic treatment. The probiotics increased the motility and vitality of sperm. Specifically, they enhanced sperm motility by 30-40% compared with untreated sperms. The probiotics enhanced mitochondrial activity in sperm through specific factors like AMPK and SIRT1. All three probiotics enhanced the activities of mitochondrial function-related proteins in sperm. In conclusion, we found that the probiotics improved the vitality and motility of mouse sperm and increased mitochondrial function in mature sperm. These findings suggest that probiotics can be utilized to enhance sperm motility and treat male infertility.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effect of Organic Anion Transporting Polypeptide 1B1 on Plasma Concentration Dynamics of Clozapine in Patients with Treatment-Resistant Schizophrenia.

IF 5.6 2区生物学

International Journal of Molecular Sciences Pub Date : 2024-12-09 DOI: 10.3390/ijms252313228

Toshihiro Sato, Takeshi Kawabata, Masaki Kumondai, Nagomi Hayashi, Hiroshi Komatsu, Yuki Kikuchi, Go Onoguchi, Yu Sato, Kei Nanatani, Masahiro Hiratsuka, Masamitsu Maekawa, Hiroaki Yamaguchi, Takaaki Abe, Hiroaki Tomita, Nariyasu Mano

{"title":"Effect of Organic Anion Transporting Polypeptide 1B1 on Plasma Concentration Dynamics of Clozapine in Patients with Treatment-Resistant Schizophrenia.","authors":"Toshihiro Sato, Takeshi Kawabata, Masaki Kumondai, Nagomi Hayashi, Hiroshi Komatsu, Yuki Kikuchi, Go Onoguchi, Yu Sato, Kei Nanatani, Masahiro Hiratsuka, Masamitsu Maekawa, Hiroaki Yamaguchi, Takaaki Abe, Hiroaki Tomita, Nariyasu Mano","doi":"10.3390/ijms252313228","DOIUrl":"https://doi.org/10.3390/ijms252313228","url":null,"abstract":"The involvement of drug-metabolizing enzymes and transporters in plasma clozapine (CLZ) dynamics has not been well examined in Japanese patients with treatment-resistant schizophrenia (TRS). Therefore, this clinical study investigated the relationship between single nucleotide polymorphisms (SNPs) of various pharmacokinetic factors (drug-metabolizing enzymes and transporters) and dynamic changes in CLZ. Additionally, we aimed to determine whether CLZ acts as a substrate for pharmacokinetic factors using in vitro assays and molecular docking calculations. We found that 6 out of 10 patients with TRS and with multiple organic anion transporting polypeptide (OATP) variants (OATP1B1: *1b, *15; OATP1B3: 334T>G, 699G>A; and OATP2B1: *3, 935G>A, 601G>A, 76_84del) seemed to be highly exposed to CLZ and/or N-desmethyl CLZ. A CLZ uptake study using OATP-expressing HEK293 cells showed that CLZ was a substrate of OATP1B1 with Km and Vmax values of 38.9 µM and 2752 pmol/mg protein/10 min, respectively. The results of molecular docking calculations supported the differences in CLZ uptake among OATP molecules and the weak inhibitory effect of cyclosporine A, which is a strong inhibitor of OATPs, on CLZ uptake via OATP1B1. This is the first study to show that CLZ is an OATP1B1 substrate and that the presence of SNPs in OATPs potentially alters CLZ pharmacokinetic parameters.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibitory Effects of Gliadin Hydrolysates on BACE1 Expression and APP Processing to Prevent Aβ Aggregation. 麸质蛋白水解物对 BACE1 表达和 APP 处理的抑制作用可防止 Aβ 聚合。

IF 5.6 2区生物学

International Journal of Molecular Sciences Pub Date : 2024-12-09 DOI: 10.3390/ijms252313212

Chin-Yu Lin, Cheng-Hong Hsieh, Pei-Yu Lai, Ching-Wei Huang, Yung-Hui Chung, Shang-Ming Huang, Kuo-Chiang Hsu

{"title":"Inhibitory Effects of Gliadin Hydrolysates on BACE1 Expression and APP Processing to Prevent Aβ Aggregation.","authors":"Chin-Yu Lin, Cheng-Hong Hsieh, Pei-Yu Lai, Ching-Wei Huang, Yung-Hui Chung, Shang-Ming Huang, Kuo-Chiang Hsu","doi":"10.3390/ijms252313212","DOIUrl":"https://doi.org/10.3390/ijms252313212","url":null,"abstract":"Alzheimer's disease (AD), a leading neurodegenerative disorder, is closely associated with the accumulation of amyloid-beta (Aβ) peptides in the brain. The enzyme β-secretase (BACE1), pivotal in Aβ production, represents a promising therapeutic target for AD. While bioactive peptides derived from food protein hydrolysates have neuroprotective properties, their inhibitory effects on BACE1 remain largely unexplored. In this study, we evaluated the inhibitory potential of protein hydrolysates from gliadin, whey, and casein proteins prepared using bromelain, papain, and thermolysin. Through in vitro and cellular assays, bromelain-hydrolyzed gliadin (G-Bro) emerged as the most potent BACE1 inhibitor, with an IC50 of 0.408 mg/mL. G-Bro significantly reduced BACE1 expression and amyloid precursor protein (APP) processing in N2a/PS/APP cell cultures, suggesting its potential to attenuate Aβ aggregation. The unique peptide profile of G-Bro likely contributes to its inhibitory effect, with proline residues disrupting β-sheets, lysine residues introducing positive charges that hinder aggregation, hydrophobic residues stabilizing binding interactions, and glutamine residues enhancing solubility and stability. These findings highlight gliadin hydrolysates, particularly G-Bro, as potential natural BACE1 inhibitors with applications in dietary interventions for AD prevention. However, further studies are warranted to elucidate specific peptide interactions and their bioactivity in neural pathways to better understand their therapeutic potential.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142835299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Microbiome-Based Therapeutics for Insomnia.

IF 5.6 2区生物学

International Journal of Molecular Sciences Pub Date : 2024-12-09 DOI: 10.3390/ijms252313208

Chenyu Li, Sizhe Chen, Yun Wang, Qi Su

引用次数: 0

Modulating Amyloid-β Toxicity: In Vitro Analysis of Aβ42(G37V) Variant Impact on Aβ42 Aggregation and Cytotoxicity.

IF 5.6 2区生物学

International Journal of Molecular Sciences Pub Date : 2024-12-09 DOI: 10.3390/ijms252313219

Shu-Hsiang Huang, Shang-Ting Fang, Chin-Hao Yang, Je-Wen Liou, Yi-Cheng Chen

{"title":"Modulating Amyloid-β Toxicity: In Vitro Analysis of Aβ42(G37V) Variant Impact on Aβ42 Aggregation and Cytotoxicity.","authors":"Shu-Hsiang Huang, Shang-Ting Fang, Chin-Hao Yang, Je-Wen Liou, Yi-Cheng Chen","doi":"10.3390/ijms252313219","DOIUrl":"https://doi.org/10.3390/ijms252313219","url":null,"abstract":"Alzheimer's disease (AD) is primarily driven by the formation of toxic amyloid-β (Aβ) aggregates, with Aβ42 being a pivotal contributor to disease pathology. This study investigates a novel agent to mitigate Aβ42-induced toxicity by co-assembling Aβ42 with its G37V variant (Aβ42(G37V)), where Gly at position 37 is substituted with valine. Using a combination of Thioflavin-T (Th-T) fluorescence assays, Western blot analysis, atomic force microscopy (AFM)/transmission electron microscopy (TEM), and biochemical assays, we demonstrated that adding Aβ42(G37V) significantly accelerates Aβ42 aggregation rate and mass while altering the morphology of the resulting aggregates. Consequently, adding Aβ42(G37V) reduces the Aβ42 aggregates-induced cytotoxicity, as evidenced by improved cell viability assays. The possible mechanism for this effect is that adding Aβ42(G37V) reduces the production of reactive oxygen species (ROS) and lipid peroxidation, typically elevated in response to Aβ42, indicating its protective effects against oxidative stress. These findings suggest that Aβ42(G37V) could be a promising candidate for modulating Aβ42 aggregation dynamics and reducing its neurotoxic effects, providing a new avenue for potential therapeutic interventions in AD.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Emerging Role of p21 in Diabetes and Related Metabolic Disorders.

IF 5.6 2区生物学

International Journal of Molecular Sciences Pub Date : 2024-12-09 DOI: 10.3390/ijms252313209

Omar Elmitwalli, Radwan Darwish, Lana Al-Jabery, Ahmed Algahiny, Sornali Roy, Alexandra E Butler, Ammar S Hasan

{"title":"The Emerging Role of p21 in Diabetes and Related Metabolic Disorders.","authors":"Omar Elmitwalli, Radwan Darwish, Lana Al-Jabery, Ahmed Algahiny, Sornali Roy, Alexandra E Butler, Ammar S Hasan","doi":"10.3390/ijms252313209","DOIUrl":"https://doi.org/10.3390/ijms252313209","url":null,"abstract":"In the context of cell cycle inhibition, anti-proliferation, and the dysregulation observed in certain cancer pathologies, the protein p21 assumes a pivotal role. p21 links DNA damage responses to cellular processes such as apoptosis, senescence, and cell cycle arrest, primarily functioning as a regulator of the cell cycle. However, accumulating empirical evidence suggests that p21 is both directly and indirectly linked to a number of different metabolic processes. Intriguingly, recent investigations indicate that p21 significantly contributes to the pathogenesis of diabetes. In this review, we present a comprehensive evaluation of the scientific literature regarding the involvement of p21 in metabolic processes, diabetes etiology, pancreatic function, glucose homeostasis, and insulin resistance. Furthermore, we provide an encapsulated overview of therapies that target p21 to alleviate metabolic disorders. A deeper understanding of the complex interrelationship between p21 and diabetes holds promise for informing current and future therapeutic strategies to address this rapidly escalating health crisis.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Possible Impact of Peripheral Inflammatory Factors and Interleukin-1β (IL-1β) on Cognitive Functioning in Progressive Supranuclear Palsy-Richardson Syndrome (PSP-RS) and Progressive Supranuclear Palsy-Predominant Parkinsonism (PSP-P). 外周炎症因子和白细胞介素-1β（IL-1β）对进行性核上麻痹-理查森综合征（PSP-RS）和进行性核上麻痹为主的帕金森病（PSP-P）患者认知功能的可能影响。

IF 5.6 2区生物学

International Journal of Molecular Sciences Pub Date : 2024-12-09 DOI: 10.3390/ijms252313211

Patryk Chunowski, Dagmara Otto-Ślusarczyk, Karolina Duszyńska-Wąs, Agnieszka Drzewińska, Andrzej Załęski, Natalia Madetko-Alster, Alicja Wiercińska-Drapało, Marta Struga, Piotr Alster

{"title":"Possible Impact of Peripheral Inflammatory Factors and Interleukin-1β (IL-1β) on Cognitive Functioning in Progressive Supranuclear Palsy-Richardson Syndrome (PSP-RS) and Progressive Supranuclear Palsy-Predominant Parkinsonism (PSP-P).","authors":"Patryk Chunowski, Dagmara Otto-Ślusarczyk, Karolina Duszyńska-Wąs, Agnieszka Drzewińska, Andrzej Załęski, Natalia Madetko-Alster, Alicja Wiercińska-Drapało, Marta Struga, Piotr Alster","doi":"10.3390/ijms252313211","DOIUrl":"https://doi.org/10.3390/ijms252313211","url":null,"abstract":"Progressive supranuclear palsy (PSP) is a tauopathic atypical parkinsonian syndrome. Recent studies suggest that inflammation may play a role in PSP pathogenesis, highlighting markers like the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and cytokines such as IL-1β and IL-6. This study aimed to assess the relationship between peripheral inflammatory markers and psychological abnormalities in PSP-RS and PSP-P patients. The study included 24 participants: 12 with PSP-RS, 12 with PSP-P, and 12 controls. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA); however, the executive functions were evaluated using the Frontal Assessment Battery (FAB), while inflammatory markers such as IL-1β, IL6, NLR, and PLR were measured. The parameter correlation was executed using Spearman's correlation (rs). The analysis revealed significant negative correlations between NLR and MoCA (rs = -0.48), as well as between PLR and MoCA (rs = -0.60). The negative correlation between IL-1β and MoCA was statistically significant but relatively weak. This study highlights the relevance of inflammatory markers such as NLR and PLR in reflecting cognitive decline in PSP patients, with IL-1β potentially playing a protective role in cognitive function.","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"25 23","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142836145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0