NGF-NGFR communication inefficiency induces T Cell exhaustion impairing PD-1 immunotherapy in hepatocellular carcinoma DOI Creative Commons

Tongwang Yang,

Qingguo Xu,

Chuanshen Xu

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 5, 2023

Abstract The number of T cells that infiltrate tumor tissues in hepatocellular carcinoma (HCC) is significantly low. molecular mechanism underlying cell proliferation poorly understood. present study revealed during the process infiltration from adjacent to tissues, NGF-NGFR communication inefficiency occurred HCC patients. Importantly, cell-secreted NGF interacted with NGFR on membranes infiltrated cells, which promoted these through mitotic spindle signal activation. Mechanistically, activation was mediated by HDAC1 unclear trans-localization-inhibited PREX1 expression. Further, PD-1 mAb acted synergistically suppress progression both mouse model and In addition, NGF–NGFR positively correlated PD-1/PDL-1 However, expressions were low responsible for incursive clinicopathological features disappointing prognosis Collectively, results suggested impaired immunotherapy could, therefore, be utilized as a novel therapeutic target treatment patients clinical practice.

Language: Английский

Computational Prediction of RNA–RNA Interactions between Small RNA Tracks from Betacoronavirus Nonstructural Protein 3 and Neurotrophin Genes during Infection of an Epithelial Lung Cancer Cell Line: Potential Role of Novel Small Regulatory RNA DOI Creative Commons
Alexis Felipe Rojas-Cruz, Clara Isabel Bermudez‐Santana

Viruses, Journal Year: 2023, Volume and Issue: 15(8), P. 1647 - 1647

Published: July 28, 2023

Whether RNA–RNA interactions of cytoplasmic RNA viruses, such as Betacoronavirus, might end in the biogenesis putative virus-derived small RNAs miRNA-like molecules has been controversial. Even more, whether wild animal viruses may act is unknown. Here, we address these issues four ways. First, use conserved structures undergoing negative selection genomes SARS-CoV, MERS-CoV, and SARS-CoV-2 circulating different bat species, intermediate animals, human hosts. Second, a systematic literature review was conducted to identify Betacoronavirus-targeting hsa-miRNAs involved lung cell infection. Third, employed sophisticated long-range refine seed sequence homology with structures. Fourth, used high-throughput sequencing Betacoronavirus-infected epithelial cancer line (Calu-3) validate results. We proposed nine potential RNAs: two vsRNAs SARS-CoV (Bats: SB-vsRNA-ORF1a-3p; SB-vsRNA-S-5p), one vsRNA MERS-CoV MB-vsRNA-ORF1b-3p), six S2B-vsRNA-ORF1a-5p; animals: S2I-vsRNA-ORF1a-5p; humans: S2H-vsRNA-ORF1a-5p, S2H-vsRNA-ORF1a-3p, S2H-vsRNA-ORF1b-3p, S2H-vsRNA-ORF3a-3p), mainly encoded by nonstructural protein 3. Notably, Betacoronavirus-derived targeted 74 differentially expressed genes infected cells, which 55 upregulate molecular mechanisms underlying acute respiratory distress syndrome (ARDS), 19 downregulated be implicated neurotrophin signaling impairment. These results reveal novel RNA-based regulatory mechanism neuropathogenesis that must further studied its therapeutic use.

Language: Английский

Citations

4

Neurological Impact of Respiratory Viruses: Insights into Glial Cell Responses in the Central Nervous System DOI Creative Commons
Valentina P. Mora, Alexis M. Kalergis, Karen Böhmwald

et al.

Microorganisms, Journal Year: 2024, Volume and Issue: 12(8), P. 1713 - 1713

Published: Aug. 20, 2024

Respiratory viral infections pose a significant public health threat, particularly in children and older adults, with high mortality rates. Some of these pathogens are the human respiratory syncytial virus (hRSV), severe acute coronavirus-2 (SARS-CoV-2), influenza viruses (IV), parvovirus B19 (B19V), bocavirus 1 (HBoV1). These cause various symptoms, including cough, fever, bronchiolitis, pneumonia. Notably, can also impact central nervous system (CNS), leading to manifestations such as seizures, encephalopathies, encephalitis, neurological sequelae, long-term complications. The precise mechanisms by which affect CNS not fully understood. Glial cells, specifically microglia astrocytes within CNS, play pivotal roles maintaining brain homeostasis regulating immune responses. Exploring how cells interact pathogens, hRSV, SARS-CoV-2, IVs, B19V, HBoV1, offers crucial insights into on CNS. This review article examines IV, HBoV1 interactions astrocytes, shedding light potential consequences.

Language: Английский

Citations

1

Nerve Growth Factor and Brain-Derived Neurotrophic Factor in COVID-19 DOI Creative Commons
Carla Petrella, Giampiero Ferraguti, Luigi Tarani

et al.

Biology, Journal Year: 2024, Volume and Issue: 13(11), P. 907 - 907

Published: Nov. 7, 2024

Neurotrophins (NTs) constitute a family of small protein messengers that play fundamental role in both the central and peripheral nervous systems. In particular, nerve growth factor (NGF) brain-derived neurotrophic (BDNF) subtle survival, differentiation, functioning neuronal populations, as well fine regulation immune functions. The SARS-CoV-2 infection was characterized by sequela symptoms (serious respiratory pathology, inflammatory storm, neurological discomfort, up to less serious flu-like symptoms), which caused, at end 2023, more than 7 million deaths worldwide. Despite official pandemic, physical psychological consequences are currently object scientific research, acute chronic/long-lasting (Long-COVID-19). Given multifactorial nature outcomes adults children, several studies have investigated potential involvement NGF BDNF systems pathology. This narrative review aims summarize most recent evidence on this crucial topic.

Language: Английский

Citations

1

In silico analysis of genomic landscape of SARS-CoV-2 and its variant of concerns (Delta and Omicron) reveals changes in the coding potential of miRNAs and their target genes DOI Open Access
Sandeep Saini,

Savi Khurana,

Dikshant Saini

et al.

Gene, Journal Year: 2022, Volume and Issue: 853, P. 147097 - 147097

Published: Dec. 5, 2022

Language: Английский

Citations

6

Distinct conformational changes occur within the intrinsically unstructured pro‐domain of pro‐Nerve Growth Factor in the presence of ATP and Mg2+ DOI Creative Commons
Francesca Paoletti, Sonia Covaceuszach, Alberto Cassetta

et al.

Protein Science, Journal Year: 2023, Volume and Issue: 32(2)

Published: Jan. 6, 2023

Nerve growth factor (NGF), the prototypical neurotrophic factor, is involved in maintenance and of specific neuronal populations, whereas its precursor, proNGF, apoptosis. Binding NGF or proNGF to TrkA, p75

Language: Английский

Citations

3

Therapeutic efficacy and pharmacological mechanism of Yindan Xinnaotong soft capsule on acute ischemic stroke: a meta-analysis and network pharmacology analysis DOI
Fangjie Yang, X. Li, Junzi Long

et al.

Metabolic Brain Disease, Journal Year: 2023, Volume and Issue: 39(4), P. 523 - 543

Published: Dec. 29, 2023

Language: Английский

Citations

3

Transcriptomic Profiling of Influenza A Virus-Infected Mouse Lung at Recovery Stage Using RNA Sequencing DOI Creative Commons

Huda A. M. Al-Shalan,

Dailun Hu,

Penghao Wang

et al.

Viruses, Journal Year: 2023, Volume and Issue: 15(11), P. 2198 - 2198

Published: Oct. 31, 2023

Influenza A virus (IAV) is known to cause mild severe respiratory illness. Under some conditions, the infection can lead pneumonia (viral or bacterial), acute distress syndrome, and other complications that be fatal, especially in vulnerable populations such as elderly, young children, individuals with underlying health conditions. Despite previous studies, little about host immune response neuroimmune interactions IAV infection. Using RNA sequencing, we performed transcriptomic analysis of murine lung tissue 21 days post (dpi) (H1N1) order find differentially expression genes (DEGs) related inside during recovery. Among 792 DEGs, 434 were up-regulated, whereas 358 down-regulated. The most prominent molecular functions up-regulated repair, a large proportion down-regulated associated neural functions. Although further molecular/functional studies need for these our results facilitate understanding (from innate immunity adaptive immunity) infected lungs at recovery stage These might have potential uses mechanistic/diagnostic biomarkers represent possible targets anti-IAV therapies.

Language: Английский

Citations

1

Neuropharmacology and neurotherapeutics DOI

Oyetola Oyebanjo,

Babatunde Oluwafemi Adetuyi,

Ayodeji David Adeoye

et al.

Elsevier eBooks, Journal Year: 2024, Volume and Issue: unknown, P. 403 - 425

Published: Jan. 1, 2024

Language: Английский

Citations

0

Wnt/BDNF pathway mediates autism-like behaviors induced by prenatal subclinical hypothyroidism in male neonatal rats DOI Creative Commons

DIJIE LIU,

Kai Tao,

Ying Sun

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 9, 2024

Abstract Epidemiological studies have illuminated that abnormal maternal thyroid function in early pregnancy escalates the risk of autism spectrum disorder (ASD) offspring by nearly fourfold. However, exact mechanism which dysfunction affects ASD remains unknown. Early emerges as a pivotal juncture for fetal brain development, with fetus heavily reliant on hormones its neurological maturation. Our investigation unveils striking correlation: mothers afflicted perinatal subclinical hypothyroidism (SCH) tend to male displaying marked ASD-like behavioral anomalies, typified conspicuous diminution social interactions and repetitive patterns. Furthermore, we discerned substantial reduction neuron count within critical regions among SCH mothers, suggestive underlying neurodegeneration or developmental impediments. Moreover, diminished levels brain-derived neurotrophic factor (BDNF), cAMP response element binding protein (CREB), Bcl-2 were noted hippocampal region offspring, juxtaposed noteworthy upregulation mTOR expression downregulation Wnt. These findings coalesce suggest Wnt-mediated signaling pathway, concert interplay downstream target BDNF, might underpin one mechanisms predisposes autism-like behaviors.

Language: Английский

Citations

0

Immunomodulatory markers and therapies for the management of infant respiratory syncytial virus infection DOI
Ricardo A. Loaiza, Mónica A. Farías, Catalina A. Andrade

et al.

Expert Review of Anti-infective Therapy, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 13, 2024

The human respiratory syncytial virus (hRSV) is one of childhood diseases' most common pathogens and highly associated with lower tract infections. dramatic peak in disease that this single-stranded negative-sense RNA can elicit during outbreaks often a significant burden for healthcare systems worldwide. Despite the recent approval treatments against virus, pathogen remains causative agent infant mortality around world.

Language: Английский

Citations

0