Article
Engineering, Environmental
Shen Chen, Liping Chen, Lizhu Ye, Yue Jiang, Qiong Li, Haiyan Zhang, Rui Zhang, Huiyao Li, Dianke Yu, Rong Zhang, Yujie Niu, Qun Zhao, Jianhui Liu, Gangfeng Ouyang, Michael Aschner, Yuxin Zheng, Lihua Zhang, Wen Chen, Daochuan Li
Summary: The study showed that the PP2A-mTOR-p70S6K/4E-BP1 signaling pathway plays a critical role in mediating macrophage M1 polarization, contributing to PM-induced pulmonary injury.
JOURNAL OF HAZARDOUS MATERIALS
(2022)
Article
Immunology
Ning Wang, Ke Zhou, Zhi Liang, Ruiqi Sun, Hong Tang, Zhentao Yang, Wentao Zhao, Yiyang Peng, Penghong Song, Shusen Zheng, Haiyang Xie
Summary: A third-generation mTOR inhibitor, RapaLink-1, demonstrates effectiveness in inhibiting T-cell proliferation and prolonging graft survival time in organ transplantation. It achieves this by reducing p-4EBP1 levels in T cells, increasing Treg cell population, and decreasing Th1 and Th17 cell populations, resulting in improved rejection outcomes.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Cell Biology
Rong Li, Dan Huang, Mei Ju, Hong-ying Chen, Chao Luan, Jia-an Zhang, Kun Chen
Summary: The long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) is highly expressed in various cancers and plays an oncogenic role. In this study, we found that PVT1 was upregulated in cutaneous squamous cell carcinoma (cSCC) tissues and cell lines. Knockdown of PVT1 inhibited cell proliferation, induced cell cycle arrest and apoptosis, and suppressed cell migration and invasion in cSCC. Further analysis revealed that 4E-binding protein 1 (4EBP1) is a potential downstream target effector of PVT1, and PVT1 interacts with 4EBP1 in the cytoplasm of cSCC cells. PVT1 combined with 4EBP1 may serve as a potential new therapeutic target for cSCC.
CELL DEATH DISCOVERY
(2023)
Article
Biochemistry & Molecular Biology
Burak Kucuk, Beyza Kibar, Ercan Cacan
Summary: This study analyzed RGS10 expression levels in ovarian cancer samples through public microarray datasets, confirming changes in RGS10 expression with cancer progression and chemotherapy exposure, and investigated its relationship with chemoresistance. Results indicated that certain chemotherapeutic agents may be beneficial in reducing chemoresistance in ovarian cancer.
CELL BIOCHEMISTRY AND FUNCTION
(2021)
Article
Oncology
Yonghong Chen, Catherine R. Dufour, Lingwei Han, Ting Li, Hui Xia, Vincent Giguere
Summary: Dysregulation of mTOR signaling is critical in promoting prostate cancer growth. This study reveals that mTOR interacts with and phosphorylates HOXB13, leading to the regulation of a specific gene program with oncogenic implications in prostate cancer. These findings uncover a previously unknown molecular cascade and provide a potential therapeutic avenue for advanced prostate cancer management.
MOLECULAR CANCER RESEARCH
(2023)
Article
Neurosciences
Lena H. Nguyen, Manas Sharma, Angelique Bordey
Summary: This study investigated the effects of reducing cap-dependent translation by expressing a constitutively active form of the translational repressor 4E-BP1 downstream of mTORC1 on cortical malformations and seizures. The results showed that 4E-BP1CA expression reduced neuronal hypertrophy and cortical mislamination induced by mTORC1, but ectopic neurons still persisted in deep layers and white matter. Moreover, 4E-BP1CA expression in radial glia exacerbated the severity of behavioral seizures associated with mTORC1 hyperactivation, while conditional expression in migratory neurons mitigated the severity of behavioral seizures without changing seizure frequency.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Cell Biology
Yanan Wang, Jiapeng Lei, Song Zhang, Xiaomei Wang, Jiangbo Jin, Yufeng Liu, Mingxi Gan, Yi Yuan, Longhua Sun, Xiaolei Li, Tianyu Han, Jian-Bin Wang
Summary: This study discovered a novel mechanism of 4EBP1 as a cellular glucose sensor in regulating cancer cell death under glucose deprivation conditions. It found that 4EBP1 levels increased in the central region of tumors under nutrient deprivation, and it interacted with STAT3 to induce cell apoptosis.
CELL DEATH & DISEASE
(2022)
Review
Cell Biology
Richard Odle, Oliver Florey, Nicholas T. Ktistakis, Simon J. Cook
Summary: Autophagy and cap-dependent mRNA translation are tightly regulated during mitosis, with a switch from mTORC1 to CDK1-mediated regulation being a significant factor. Recent studies have shown repression of autophagy initiation and maintenance of cap-dependent mRNA translation even when mTORC1 activity is repressed. This highlights the complexity of regulation during mitosis and the need for further research in this area.
TRENDS IN CELL BIOLOGY
(2021)
Article
Cell Biology
Kai Voeltzke, Katerina Scharov, Cornelius Maximilian Funk, Alisa Kahler, Daniel Picard, Laura Hauffe, Martin F. Orth, Marc Remke, Irene Esposito, Thomas Kirchner, Alexander Schramm, Barak Rotblat, Thomas G. P. Grunewald, Guido Reifenberger, Gabriel Leprivier
Summary: In neuroblastoma patients, high expression of EIF4EBP1 is correlated with MYCN amplification, advanced stage, high-risk classification, and poor prognosis. EIF4EBP1 may serve as a potential prognostic marker and aid in risk stratification of neuroblastoma patients.
CELL DEATH DISCOVERY
(2022)
Article
Biochemistry & Molecular Biology
Ha-yeon Jee, Yoon-Gyeong Lee, Sol Lee, Rosalie Elvira, Hye-eun Seo, Ji-Yeon Lee, Jaeseok Han, Kyungho Lee
Summary: The study revealed that AZD8055 inhibits protein synthesis and activates ERK and p38 pathways, leading to decreased phosphorylation of 4E-BP1. Combination treatment with MEK1/2 or p38 inhibitors can significantly reduce protein synthesis. These results suggest that MAPK activation may interfere with mTORC1/2 inhibition of protein synthesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Lily Keane, Ignazio Antignano, Sean-Patrick Riechers, Raphael Zollinger, Anaelle A. Dumas, Nina Offermann, Maria E. Bernis, Jenny Russ, Frederike Graelmann, Patrick Neil McCormick, Julia Esser, Dario Tejera, Ai Nagano, Jun Wang, Claude Chelala, Yvonne Biederbick, Annett Halle, Paolo Salomoni, Michael T. Heneka, Melania Capasso
Summary: Microglia in aged individuals show increased mTOR signaling and upregulation of inflammatory mediators, resulting in stronger responses to inflammatory stimuli. Genetic ablation of mTOR signaling can reduce microglia activation and inflammation response, alleviating sickness behavior in aged mice.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Biochemistry & Molecular Biology
Raphael Boehm, Stefan Imseng, Roman P. Jakob, Michael N. Hall, Timm Maier, Sebastian Hiller
Summary: The study reveals that mTORC1 achieves hierarchical phosphorylation of 4E-BP1 through specific interactions, facilitating efficient activation of translation. Furthermore, mTORC1 is capable of recognizing both free and eIF4E-bound 4E-BP1, enabling rapid phosphorylation of the entire 4E-BP1 pool.
Article
Multidisciplinary Sciences
Muttarin Lothong, Watchara Sakares, Pornchai Rojsitthisak, Chizu Tanikawa, Koichi Matsuda, Varalee Yodsurang
Summary: COL17 has been found to suppress breast cancer by affecting cell proliferation and growth, as well as the AKT/mTOR signaling pathway. High expression of COL17 is associated with low-proliferation tumors, extended tumor-free period, and overall survival in breast cancer patients.
Article
Biology
Mark L. McGlynn, Alejandro M. Rosales, Christopher W. Collins, Dustin R. Slivka
Summary: Post-exercise cooling has inhibitory effects on skeletal muscle growth markers. The isolated effect of local cold application and its combination with exercise on skeletal muscle gene expression remains unclear. This study aimed to determine the effects of a 4-hour local cold application on the myogenic and proteolytic response in the vastus lateralis.
Article
Multidisciplinary Sciences
Lin Hu, Fuxian Chen, Chao Wu, Jun Wang, Si-si Chen, Xiang-rong Li, Jing Wang, Linpeng Wu, Jian-ping Ding, Jian-chuan Wang, Chao Huang, Hui Zheng, Yu Rao, Yu Sun, Zhijie Chang, Wei Deng, Cheng Luo, Y. Eugene Chin
Summary: The FKBP12-mTOR association is tightly regulated by an acetylation-deacetylation cycle. Acetylated FKBP12 associates with Rheb, while SIRT2-deacetylated FKBP12 switches its association to mTOR. Strengthening of FKBP12-mTOR association by rapamycin can disrupt mTOR's antiviral activity by recruiting SIRT2.
Article
Biochemistry & Molecular Biology
Hafsa Mamsa, Rachelle L. Stark, Kara M. Shin, Aaron M. Beedle, Rachelle H. Crosbie
Summary: In Duchenne muscular dystrophy (DMD), overexpression of sarcospan enhances the laminin-binding capacity of dystroglycan by increasing matriglycan glycosylation of alpha-dystroglycan, improving disease pathology. Sarcospan also alters the adhesion and signaling by decreasing the association between integrin beta 1D and dystroglycan complexes, increasing the resilience of the myofiber membrane.
HUMAN MOLECULAR GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Mandeep Kumar Arora, Anish Ratra, Syed Mohammed Basheeruddin Asdaq, Ali A. Alshamrani, Abdulkhaliq J. Alsalman, Mehnaz Kamal, Ritu Tomar, Jagannath Sahoo, Jangra Ashok, Mohd Imran
Summary: This study demonstrated that plumbagin, a hydroxy-1,4-naphthoquinone, alleviates behavioral and memory deficits induced by QA through its antioxidant and anti-inflammatory properties. It also restores cholinergic function and mitochondrial impairment. These findings suggest that plumbagin could be a potential pharmacological approach for mitigating neurobehavioral changes associated with neurodegeneration.
Article
Pharmacology & Pharmacy
Hafsa Hafsa, Ammara Zamir, Muhammad Fawad Rasool, Imran Imran, Hamid Saeed, Tanveer Ahmad, Sary Alsanea, Ali A. Alshamrani, Abdullah H. Alruwaili, Faleh Alqahtani
Summary: This study evaluated the pharmacokinetic differences after intravenous and oral administration of labetalol in healthy and diseased populations. A physiologically based pharmacokinetic (PBPK) model was developed to predict the drug disposition in patients with renal and hepatic diseases. The model was evaluated based on error calculations and box-whisker plots.
Article
Biochemistry & Molecular Biology
Adel Alghamdi, Mansour Almuqbil, Mohammad A. Alrofaidi, Abdulhadi S. Burzangi, Ali A. Alshamrani, Abdullah R. Alzahrani, Mehnaz Kamal, Mohd. Imran, Sultan Alshehri, Basheerahmed Abdulaziz Mannasaheb, Nasser Fawzan Alomar, Syed Mohammed Basheeruddin Asdaq
Summary: This study found that apigenin has antidepressant properties in an experimental mouse model of chronic mild stress (CMS). Apigenin can alleviate stress-induced behavioral deficits and increase preference for sucrose. Additionally, apigenin can increase antioxidant levels and decrease plasma corticosterone and nitrite levels induced by chronic stress.
Article
Biology
Wael A. Alanazi, Hussain N. Alhamami, Ali A. Alshamrani, Faleh Alqahtani, Abdulrahman Alshammari, Khalid Alhazzani, Mohammed Alswayyed
Summary: This study aimed to determine the protective roles of valsartan (VAL), an angiotensin-II type-1 receptor (AT1R) inhibitor, in preventing lung inflammation, oxidative stress, and metabolites alteration induced by gefitinib (GEF). Results showed that the combination of VAL and GEF reduced inflammation and oxidative stress caused by GEF monotherapy, and normalized plasma metabolites.
SAUDI JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Article
Immunology
Ahmed Nadeem, Samiyah Alshehri, Naif O. Al-Harbi, Sheikh F. Ahmad, Norah A. Albekairi, Saleh A. Alqarni, Khaild E. Ibrahim, Ali S. Alfardan, Ali A. Alshamrani, Sami B. Bin Salman, Sabry M. Attia
Summary: Asthmatic inflammation can be categorized into different types. Severe asthma is characterized by mixed granulocytic inflammation, which is unresponsive to corticosteroids. The dysregulation of neutrophilic oxidative stress and histone deacetylase 2 (HDAC2) in the lungs is thought to be the cause of corticosteroid insensitivity. In this study, the inhibition of Bruton's tyrosine kinase (BTK) was used to restore corticosteroid responsiveness in mixed granulocytic asthma. The combination of BTK inhibitor (ibrutinib) and corticosteroid (dexamethasone) effectively reduced both neutrophilic and eosinophilic inflammation in mice.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Immunology
Sheikh F. Ahmad, Ahmed Nadeem, Mushtaq A. Ansari, Saleh A. Bakheet, Hatun A. Alomar, Haneen A. Al-Mazroua, Khalid E. Ibrahim, Ali A. Alshamrani, Mohammed A. Al-Hamamah, Ali S. Alfardan, Sabry M. Attia
Summary: In this study, the CXCR3-specific antagonist NBI-74330 was used to inhibit T-cell-mediated signaling in a mouse model of rheumatoid arthritis (RA). The results showed that NBI-74330 treatment significantly reduced arthritis symptoms and histopathological changes. Additionally, NBI-74330 treatment downregulated the percentages and gene expression levels of Th1, Th17, and Th22 cells. These findings suggest that NBI-74330 has potential as a treatment for RA.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Ali A. Alshamrani, Ahmed M. Assiri, Omar A. Almohammed
Summary: This study evaluated the effectiveness of different therapies for hospitalized COVID-19 patients in Saudi Arabia. The use of TCT, favipiravir, dexamethasone, or CCP was associated with longer hospitalization and ICU stay, while remdesivir was associated with lower in-hospital mortality. The worsened outcomes with dexamethasone or favipiravir were due to the severity stage rather than the medication use.
SAUDI PHARMACEUTICAL JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Ali A. Alshamrani, Samiyah Alshehri, Sana S. Alqarni, Sheikh F. Ahmad, Hanan Alghibiwi, Naif O. Al-Harbi, Saleh A. Alqarni, Laila Y. Al-Ayadhi, Sabry M. Attia, Ali S. Alfardan, Saleh A. Bakheet, Ahmed Nadeem
Summary: Autism spectrum disorder (ASD) is a complex disorder involving environmental, immune, and genetic factors. This study investigated the role of DNA methylation and the expression of DNMT1 in neutrophils of children with ASD. The study found that ASD subjects had reduced DNMT1 expression, DNA hypomethylation, and increased inflammatory mediators. The environmental pollutant DEHP further downregulated DNMT1 expression, highlighting its impact on epigenetic machinery in neutrophils of ASD subjects.
Article
Biotechnology & Applied Microbiology
S. M. Attia, S. F. Ahmad, A. Nadeem, M. S. M. Attia, M. A. Ansari, N. B. Alsaleh, A. F. Alasmari, M. A. Al-Hamamah, A. Alanazi, A. A. Alshamrani, S. A. Bakheet, G. I. Harisa
Summary: Multiple sclerosis (MS) is a demyelinating disorder that causes damage to the myelin sheath, leading to various neurological complications. The pathogenesis of MS is unclear, and there are currently no effective therapies available. DNA damage and repair failure have been suggested as genetic risk factors for MS, but inconsistent evidence has been found. Further investigations are needed to determine whether DNA damage/repair is altered in this disorder. Therapies that prevent DNA damage or enhance DNA repair could be promising strategies for MS treatment.
MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
(2023)
Article
Pharmacology & Pharmacy
Naif O. Al-Harbi, Faisal Imam, Mohammad Matar Al-Harbi, Wajhul Qamar, Khaldoon Aljerian, Md. Khalid Anwer, Mohammed Alharbi, Sultan Almudimeegh, Abdullah S. Alhamed, Ali A. Alshamrani
Summary: Phosphodiesterase-4 inhibitor apremilast (AP) can alleviate lung injury induced by lipopolysaccharides (LPS), and protect lung tissue by regulating immune and inflammatory responses. AP pretreatment can reduce the changes of immunomodulatory factors induced by LPS, and decrease the abnormal expression of intracellular proteins. The results indicate that AP has a therapeutic effect on LPS-induced pulmonary toxicity.
SAUDI PHARMACEUTICAL JOURNAL
(2023)
Article
Medicine, General & Internal
Abdulrahman M. Alwhaibi, Ali A. Alshamrani, Miteb A. Alenazi, Shroog F. Altwalah, Nouf N. Alameel, Noura N. Aljabali, Sara B. Alghamdi, Abdulwahab I. Bineid, Monira Alwhaibi, Mohamed N. Al Arifi
Summary: This retrospective study analyzed first-time users of vincristine between 2016 and 2022 and found that approximately 34.6% of patients were diagnosed with neuropathy after vincristine administration. Autonomic neuropathy was common in both adult and pediatric patients, while cranial neuropathy was more frequent in pediatric patients. Dose rounding of vincristine was significantly associated with increased neuropathy occurrence.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Ali A. Alshamrani, Mohammed A. Al-Hamamah, Norah A. Albekairi, Mohamed S. M. Attia, Sheikh F. Ahmad, Mohammed A. Assiri, Mushtaq A. Ansari, Ahmed Nadeem, Saleh A. Bakheet, Wael A. Alanazi, Sabry M. Attia
Summary: This study investigated the effects of saxagliptin and dapagliflozin treatments on the gonads in a male mouse model of diabetes. The results showed that dapagliflozin restored testicular abnormalities induced by diabetes, while saxagliptin exacerbated the reduction in sperm count and motility. Both drugs restored the gonadal redox imbalances in diabetic mice.
Article
Environmental Sciences
Ali A. Alshamrani, Mohammad Y. Alwetaid, Mohammed A. Al-Hamamah, Mohamed S. M. Attia, Sheikh F. Ahmad, Majed A. Algonaiah, Ahmed Nadeem, Mushtaq A. Ansari, Saleh A. Bakheet, Sabry M. Attia
Summary: The pathophysiology of autism is influenced by a combination of environmental and genetic factors. In addition, individuals with autism have a higher risk of developing cancer, possibly due to Aflatoxin B1 (AFB1) exposure. This study investigated the effects of AFB1 on genomic instability and apoptosis in a mouse model of autism. The findings showed that AFB1 exposure increased micronuclei generation, oxidative DNA strand breaks, and apoptosis in the mice, indicating a disturbed redox balance and dysregulation in the DNA damage/repair pathway. These results suggest that AFB1-related genomic instability may accelerate cancer development and that mitigating redox imbalance and DNA damage/repair dysregulation could be potential therapeutic approaches.
Article
Environmental Sciences
Nasser B. Alsaleh, Mohammed A. Assiri, Anas M. Aljarbou, Mohammed M. Almutairi, Homood M. As Sobeai, Ali A. Alshamrani, Sultan Almudimeegh
Summary: The use of engineered nanomaterials (ENMs) in various applications has increased, leading to increased human exposure. Previous research mainly focused on studying the toxicity of ENMs in high-exposure settings, potentially overlooking adverse effects at low and subtoxic exposure levels. This study investigated the cellular outcomes of exposure to subtoxic concentrations of zinc oxide (ZnONPs) and nickel oxide (NiONPs) nanoparticles. The findings suggest that exposure to ENMs at subtoxic levels may have adverse health outcomes, emphasizing the importance of establishing sensitive endpoints of exposure and toxicity beyond conventional toxicological testing.
Review
Oncology
Xinru Zhou, Yin Jia, Chuanbin Mao, Shanrong Liu
Summary: Small extracellular vesicles (sEVs), such as exosomes, have emerged as crucial targets for liquid biopsy and promising drug delivery vehicles in tumor progression. They can serve as biomarkers for tumor diagnosis and as drug carriers for cancer treatment.
Article
Oncology
Ruochan Chen, Ju Zhu, Xiao Zhong, Jie Li, Rui Kang, Daolin Tang
Summary: The interplay between autophagy and apoptosis plays a crucial role in tumorigenesis and cancer therapy, with HMGB1 serving as a key regulator in these processes.
Article
Oncology
Zongfu Pan, Xixuan Lu, Tong Xu, Jinming Chen, Lisha Bao, Ying Li, Yingying Gong, Yulu Che, Xiaozhou Zou, Zhuo Tan, Ping Huang, Minghua Ge
Summary: This study uncovered the emerging role of HN1 in promoting dedifferentiation of anaplastic thyroid cancer (ATC) cells. HN1 negatively regulated the thyroid differentiation markers and had an inhibitory effect on the transcriptional activation of CTCF, thereby influencing the chromatin accessibility of thyroid differentiation genes.
Article
Oncology
Yi Qin, Shengjun Xiong, Jun Ren, Gautam Sethi
Summary: Autophagy plays an important regulatory role in glioblastoma, and its dysregulation can lead to drug resistance and radioresistance. It also affects stem cell characteristics, overall growth, and metastasis. Therefore, autophagy is a promising target for glioblastoma therapy.
Article
Oncology
Katsuya Nagaoka, Xuewei Bai, Dan Liu, Kevin Cao, Joud Mulla, Chengcheng Ji, Hongze Chen, Muhammad Azhar Nisar, Amalia Bay, William Mueller, Grace Hildebrand, Jin-Song Gao, Shaolei Lu, Hiroko Setoyama, Yasuhito Tanaka, Jack R. Wands, Chiung-Kuei Huang
Summary: This study found that serum 2-OG levels in cholangiocarcinoma patients are associated with the effectiveness of chemotherapy. Patients with progressive disease showed significantly higher levels of serum 2-OG compared to stable disease and partial response patients. The study also revealed that overexpression of ASPH mimics the effects of 2-OG, and knockdown of ASPH improves chemotherapy. Targeting ASPH enhances the effects of chemotherapy by modulating ATM and ATR, two key regulators of DDRs.