Decoding NAD+ Metabolism in COVID-19: Implications for Immune Modulation and Therapy DOI Creative Commons
Shixu Song,

Jianhong Gan,

Qiuyue Long

и другие.

Vaccines, Год журнала: 2024, Номер 13(1), С. 1 - 1

Опубликована: Дек. 24, 2024

The persistent threat of COVID-19, particularly with the emergence new variants, underscores urgency for innovative therapeutic strategies beyond conventional antiviral treatments. Current immunotherapies, including IL-6/IL-6R monoclonal antibodies and JAK inhibitors, exhibit suboptimal efficacy, necessitating alternative approaches. Our review delves into significance NAD+ metabolism in COVID-19 pathology, marked by decreased levels upregulated NAD+-consuming enzymes such as CD38 poly (ADP-ribose) polymerases (PARPs). Recognizing NAD+'s pivotal role energy immune modulation, we propose modulating homeostasis could bolster host's defensive capabilities against virus. article reviews scientific rationale behind targeting pathways benefit, utilizing precursor supplementation enzyme inhibition to modulate function. While preliminary data are encouraging, challenge lies optimizing these interventions clinical use. Future research should aim unravel intricate roles key metabolites elucidate their specific mechanisms action. This will be essential developing targeted therapies, potentially transforming management setting a precedent addressing other infectious diseases.

Язык: Английский

The Significance of MAPK Signaling Pathway in the Diagnosis and Subtype Classification of Intervertebral Disc Degeneration DOI Creative Commons
Yong Liu, Xueyan Chen,

Jingwen Chen

и другие.

JOR Spine, Год журнала: 2025, Номер 8(1)

Опубликована: Март 1, 2025

ABSTRACT Background Intervertebral disc degeneration (IDD) is a human aging disease related mainly to inflammation, cellular senescence, RNA/DNA methylation, and ECM. The mitogen‐activated protein kinase (MAPK) signaling pathway engaged in multiple biological functions by phosphorylating specific serine threonine residues on target proteins through phosphorylation cascade effects, but the role mechanisms of MAPK IDD are still unclear. Methods We identified 20 MAPK‐related differential genes analysis GSE124272 GSE150408 datasets from GEO database. To explore these humans, we performed GO KEGG analyses. Additionally, applied PPI networks, LASSO analysis, RF algorithm, SVM‐RFE algorithm identify core genes. Finally, conducted further validation using clinical samples. Results ultimately validated four pivotal genes, namely, KRAS, JUN, RAP1B, TNF, samples, constructed ROC curves evaluate predictive accuracy hub A nomogram model was subsequently developed based predict prevalence IDD. Based classified patients into two MAP clusters applying consensus clustering method 1916 DEGs analyzing differences between clusters. Further same approach allowed us gene DEGs. used PCA determine score for each sample discovered that cluster had higher scores, suggesting greater sensitivity pathway‐associated agents subtype. displayed differing expression levels across their relationship with immune cell infiltration highlight distinctions B. Conclusion In summary, pathway‐related could be diagnosis subtype classification benefit prevention treatment

Язык: Английский

Процитировано

0
CHK1 inhibition overcomes gemcitabine resistance in non-small cell lung cancer cell A549 DOI Creative Commons

Zhi-Yin Ke,

Tian Fu,

Xuechun Wang

и другие.

Molecular & Cellular Oncology, Год журнала: 2025, Номер 12(1)

Опубликована: Апрель 9, 2025

The purpose of the study is mainly to investigate anti proliferation non-small cell lung cancer A549 cells and its mechanism by inhibition CHK1 expression combined with gemcitabine. mRNA protein levels genes were analyzed RT-qPCR Western blot, respectively. Cell viability was detected CCK-8 assay clone formation assay. detection cycle used Annexin V/7-amino-actinomycin D apoptosis kit. Analysis DNA damage done immunofluorescence alkaline comet results showed that gemcitabine combination significantly reduced ability two lines. We also revealed degradation full-length PARP Bcl-2/Bax ratio on increased apoptosis. Inhibition leads damage, induces phosphorylation γ-H2AX, affects repair homologous recombination through Rad51. Mechanistically, phosphorylation-ATR phosphorylation-CHK1, indicating activation system ATR-CHK1-CDC25A pathway. resulted in synthesis CDK2/Cyclin A2 E1 complexes, more entered subsequent cycle, leading S phase arrest mitotic catastrophe. identified as a potential treatment for NSCLC confirmed this kinase could overcome acquired resistance.

Язык: Английский

Процитировано

0
Receptor-Based Strategies for Overcoming Resistance in Cancer Therapy DOI Creative Commons
Naresh Sah,

Abdul Althaf Shaik,

Ganesh Acharya

и другие.

Receptors, Год журнала: 2024, Номер 3(4), С. 425 - 443

Опубликована: Сен. 24, 2024

This review article explores the fundamental role of receptor targeting in overcoming drug resistance cancer therapy, an area critical concern given persistently high rates morbidity and mortality globally. We highlight how biology intersects with development therapeutic a specific focus on anti-angiogenic agents, immune checkpoint inhibitors, monoclonal antibodies, which directly or indirectly influence pathways. also explore other tyrosine kinases can initially suppress tumor growth, yet often lead to resistance, underscoring need for novel combinatorial approaches that incorporate advanced modulation techniques. Further, delves into mechanisms by microenvironment system via pathways overcome traditional immunotherapies. Additionally, emerging technologies receptor-targeted nanomedicine are highlighted, showcasing their potential revolutionize delivery improve outcomes interactions. Ultimately, this calls deeper understanding dynamics develop more precise interventions, including insights from various healthcare settings prevent circumvent thus enhancing patient oncology.

Язык: Английский

Процитировано

1
PARG inhibitor sensitivity correlates with accumulation of single-stranded DNA gaps in preclinical models of ovarian cancer DOI Creative Commons
Ramya Ravindranathan, Ozge Somuncu, Alexandre André Balieiro Anastácio da Costa

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(47)

Опубликована: Ноя. 15, 2024

Poly (ADP-ribose) glycohydrolase (PARG) is a dePARylating enzyme which promotes DNA repair by removal of poly (PAR) from PARylated proteins. Loss or inhibition PARG results in replication stress and sensitizes cancer cells to DNA-damaging agents. inhibitors are now undergoing clinical development for patients having tumors with homologous recombination deficiency (HRD), such as germline somatic

Язык: Английский

Процитировано

1
Suppression of ADP-ribosylation reversal triggers cell vulnerability to alkylating agents DOI
Rocco Caggiano, Evgeniia Prokhorova, Lena Duma

и другие.

Neoplasia, Год журнала: 2024, Номер 59, С. 101092 - 101092

Опубликована: Ноя. 30, 2024

Язык: Английский

Процитировано

0
LEF1 is associated with immunosuppressive microenvironment of patients with lung adenocarcinoma DOI Creative Commons
Xiaoqing Liu,

C.Y. Wang,

Xiaoling Zhang

и другие.

Medicine, Год журнала: 2024, Номер 103(41), С. e39892 - e39892

Опубликована: Окт. 11, 2024

Wnt/β-Catenin pathway plays an important role in the occurrence and progression of malignant tumors, especially PD-L1 -mediated tumor immune evasion. However, TCF/LEF , member Wnt/β-catenin pathway, immunosuppressive microenvironment lung adenocarcinoma (LUAD) remains unknown. LUAD tissue-coding RNA expression data from The Cancer Genome Atlas TIMER databases were used to analyze transcription factors their correlation with various cell infiltration. Immunohistochemistry immunofluorescence detect tissue protein staining 105 patients LUAD. LEF1, TCF7, TCF7L1 TCF7L2 all aberrantly expressed tissues (TCGA) database, estimation resource (TIMER) database results immunohistochemistry, but only LEF1 was associated 5-year overall survival patients. advanced node metastasis (TNM) stage, lymphatic local invasion cases At same time, mRNA also TCGA database. Results immunohistochemistry showed that there a positively between infiltration M2 macrophages Treg cells. highly patients,

Язык: Английский

Процитировано

0
Emerging strategies to overcome ovarian cancer: advances in immunotherapy DOI Creative Commons
Tatiana Massariol Pimenta, Josiany Carlos de Souza, Bárbara da Silva Martins

и другие.

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Ноя. 5, 2024

Ovarian cancer is the second most common malignant neoplasm of gynecological origin and leading cause death from in female reproductive system worldwide. This scenario largely due to late diagnoses, often advanced stages, development chemoresistance by cells. These challenges highlight need for alternative treatments, with immunotherapy being a promising option. Cancer involves triggering an anti-tumor immune response developing immunological memory eliminate cells, prevent recurrence, inhibit metastasis. Some ongoing research investigate potentially advancements field vaccines, checkpoint blockade, CAR-T cell, other strategies.

Язык: Английский

Процитировано

0
Decoding NAD+ Metabolism in COVID-19: Implications for Immune Modulation and Therapy DOI Creative Commons
Shixu Song,

Jianhong Gan,

Qiuyue Long

и другие.

Vaccines, Год журнала: 2024, Номер 13(1), С. 1 - 1

Опубликована: Дек. 24, 2024

The persistent threat of COVID-19, particularly with the emergence new variants, underscores urgency for innovative therapeutic strategies beyond conventional antiviral treatments. Current immunotherapies, including IL-6/IL-6R monoclonal antibodies and JAK inhibitors, exhibit suboptimal efficacy, necessitating alternative approaches. Our review delves into significance NAD+ metabolism in COVID-19 pathology, marked by decreased levels upregulated NAD+-consuming enzymes such as CD38 poly (ADP-ribose) polymerases (PARPs). Recognizing NAD+'s pivotal role energy immune modulation, we propose modulating homeostasis could bolster host's defensive capabilities against virus. article reviews scientific rationale behind targeting pathways benefit, utilizing precursor supplementation enzyme inhibition to modulate function. While preliminary data are encouraging, challenge lies optimizing these interventions clinical use. Future research should aim unravel intricate roles key metabolites elucidate their specific mechanisms action. This will be essential developing targeted therapies, potentially transforming management setting a precedent addressing other infectious diseases.

Язык: Английский

Процитировано

0