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3x MANF research articles: Cervical cancer, sleep/Cognition, Hepatitis B
1) Mesencephalic astrocyte-derived neurotrophic factor inhibits cervical cancer progression via regulating macrophage phenotype
Miaomiao Huang et al. Mol Biol Rep. 2024.
Authors from Anhui University, China
https://pubmed.ncbi.nlm.nih.gov/38735002/
Methods and results: Kaplan-Meier curve was used to show the overall survival time of the involved cervical cancer patients with high and low MANF expression in cervical cancer tissues. MANF was highly expressed in peritumoral tissues of cervical carcinoma by using immunohistochemistry and western blot. MANF mRNA level was detected by using qRT-PCR. Dual-labeled immunofluorescence showed MANF was mainly expressed in macrophages of cervical peritumoral tissues. Moreover, MANF-silenced macrophages promoted HeLa and SiHa cells survival, migration, invasion and EMT via NF-κB signaling activation. The results of tumor formation in nude mice indicated MANF-silenced macrophages promoted cervical tumor formation in vivo.
Conclusion: Our study reveals an inhibitory role of MANF in cervical cancer progression, indicating MANF as a new and valuable therapeutic target for cervical cancer treatment
2)Cerebrospinal fluid mesencephalic astrocyte-derived neurotrophic factor: A moderating effect on sleep time and cognitive function
Authors from various Chinese University
https://www.sciencedirect.com/science/article...via%3Dihub
Results
MANF may play a moderating role in the relationship between sleep time and cognition (R2 = 0.06, β = 0.59, p = 0.031). Age showed a negative correlation with MoCA scores (R2 = 0.08, β = −0.18), while education exhibited a positive correlation (β = 0.17, both p < 0.05). Only ≤23 o'clock sleepers exhibited a negative correlation between MANF levels and BMI (r = −0.35, p = 0.005).
Conclusions
This study provides hitherto undocumented evidence of the potential protective effect of CSF MANF on cognitive impairment of late sleepers, which suggests that maintaining a regular sleep schedule may contribute to cognition and overall health, with MANF playing a role in this process.
3)Mesencephalic Astrocyte-derived Neurotrophic Factor Supports Hepatitis B Virus-induced Immunotolerance
Huiyuan Xie et al. Cell Mol Gastroenterol Hepatol. 2024.
https://pubmed.ncbi.nlm.nih.gov/38759839/
From Ningbo University China
Results: Our study revealed that following HBV infection, both myeloid cells and hepatocytes exhibited increased expression of MANF. Moreover, we observed that mice with myeloid-specific MANF knockout (ManfMye-/-) displayed reduced HBV load and improved HBV-specific T cell responses. The decreased HBV-induced tolerance in ManfMye-/- mice was associated with reduced accumulation of myeloid-derived suppressor cells (MDSCs) in the liver. Restoring MDSC levels in ManfMye-/- mice through MDSC adoptive transfer reinstated HBV-induced tolerance. Mechanistically, we found that MANF promoted MDSC expansion by activating the IL-6/STAT3 pathway. Importantly, our study demonstrated the effectiveness of a combination therapy involving an hepatitis B surface antigen vaccine and nanoparticle-encapsulated MANF siRNA in effectively clearing HBV in HBV-carrier mice.
Conclusion: The current study reveals that MANF plays a previously unrecognized regulatory role in liver tolerance by expanding MDSCs in the liver through IL-6/STAT3 signaling, leading to MDSC-mediated CD8+ T cell exhaustion.
1) Mesencephalic astrocyte-derived neurotrophic factor inhibits cervical cancer progression via regulating macrophage phenotype
Miaomiao Huang et al. Mol Biol Rep. 2024.
Authors from Anhui University, China
https://pubmed.ncbi.nlm.nih.gov/38735002/
Methods and results: Kaplan-Meier curve was used to show the overall survival time of the involved cervical cancer patients with high and low MANF expression in cervical cancer tissues. MANF was highly expressed in peritumoral tissues of cervical carcinoma by using immunohistochemistry and western blot. MANF mRNA level was detected by using qRT-PCR. Dual-labeled immunofluorescence showed MANF was mainly expressed in macrophages of cervical peritumoral tissues. Moreover, MANF-silenced macrophages promoted HeLa and SiHa cells survival, migration, invasion and EMT via NF-κB signaling activation. The results of tumor formation in nude mice indicated MANF-silenced macrophages promoted cervical tumor formation in vivo.
Conclusion: Our study reveals an inhibitory role of MANF in cervical cancer progression, indicating MANF as a new and valuable therapeutic target for cervical cancer treatment
2)Cerebrospinal fluid mesencephalic astrocyte-derived neurotrophic factor: A moderating effect on sleep time and cognitive function
Authors from various Chinese University
https://www.sciencedirect.com/science/article...via%3Dihub
Results
MANF may play a moderating role in the relationship between sleep time and cognition (R2 = 0.06, β = 0.59, p = 0.031). Age showed a negative correlation with MoCA scores (R2 = 0.08, β = −0.18), while education exhibited a positive correlation (β = 0.17, both p < 0.05). Only ≤23 o'clock sleepers exhibited a negative correlation between MANF levels and BMI (r = −0.35, p = 0.005).
Conclusions
This study provides hitherto undocumented evidence of the potential protective effect of CSF MANF on cognitive impairment of late sleepers, which suggests that maintaining a regular sleep schedule may contribute to cognition and overall health, with MANF playing a role in this process.
3)Mesencephalic Astrocyte-derived Neurotrophic Factor Supports Hepatitis B Virus-induced Immunotolerance
Huiyuan Xie et al. Cell Mol Gastroenterol Hepatol. 2024.
https://pubmed.ncbi.nlm.nih.gov/38759839/
From Ningbo University China
Results: Our study revealed that following HBV infection, both myeloid cells and hepatocytes exhibited increased expression of MANF. Moreover, we observed that mice with myeloid-specific MANF knockout (ManfMye-/-) displayed reduced HBV load and improved HBV-specific T cell responses. The decreased HBV-induced tolerance in ManfMye-/- mice was associated with reduced accumulation of myeloid-derived suppressor cells (MDSCs) in the liver. Restoring MDSC levels in ManfMye-/- mice through MDSC adoptive transfer reinstated HBV-induced tolerance. Mechanistically, we found that MANF promoted MDSC expansion by activating the IL-6/STAT3 pathway. Importantly, our study demonstrated the effectiveness of a combination therapy involving an hepatitis B surface antigen vaccine and nanoparticle-encapsulated MANF siRNA in effectively clearing HBV in HBV-carrier mice.
Conclusion: The current study reveals that MANF plays a previously unrecognized regulatory role in liver tolerance by expanding MDSCs in the liver through IL-6/STAT3 signaling, leading to MDSC-mediated CD8+ T cell exhaustion.
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