Treatment of Parkinson's disease model with human umbilical cord mesenchymal stem cell-derived exosomes loaded with BDNF.

Aims: Parkinson's disease (PD) is a common neurodegenerative disease that has received widespread attention; however, current clinical treatments can only relieve its symptoms, and do not effectively protect dopaminergic neurons. The purpose of the present study was to investigate the therapeutic effects of human umbilical cord mesenchymal stem cell-derived exosomes loaded with brain-derived neurotrophic factor (BDNF-EXO) on PD models and to explore the underlying mechanisms of these effects.

Main Methods: 6-Hydroxydopamine was used to establish in vivo and in vitro PD models.

SbMYC2 mediates jasmonic acid signaling to improve drought tolerance via directly activating SbGR1 in sorghum.

SbMYC2 functions as a key regulator under JA signaling in enhancing drought tolerance of sorghum through direct activating SbGR1. Drought stress is one of the major threats to crop yield. In response to drought stress, functions of basic helix-loop-helix (bHLH) transcription factors (TFs) have been reported in Arabidopsis and rice, but little is known for sorghum.

The inhibition of YTHDF3/mA/LRP6 reprograms fatty acid metabolism and suppresses lymph node metastasis in cervical cancer.

The lipid synthesis of fatty acid (FA) represents a significant hallmark in the occurrence and progression of malignant tumor, which are associated with lymph node (LN) metastasis. Elucidation of the molecular mechanisms underlying LN metastasis could provide therapeutic strategies for cervical cancer (CCa). N6-Methyladenosine (mA), the most prevalent and abundant RNA modification, exerts specific regulatory control over a series of oncogene expressions.

Programmed Death Ligand-1-Overexpressing Donor Exosomes Mediate Donor-Specific Immunosuppression by Delivering Co-Inhibitory Signals to Donor-Specific T Cells.

Programmed death ligand-1 (PD-L1) and donor antigens are critical for donor immature dendritic cells (DCs) targeting donor-specific T cells to induce transplant tolerance. This study aims to clarify whether DC-derived exosomes (DEX) with donor antigens (H2b) and high levels of PD-L1 expression (DEX ) can help to suppress graft rejection. In this study, it is demonstrated that DEX presents donor antigens, as well as PD-L1 co-inhibitory signals, directly or semi-directly via DCs to H2b-reactive T cells.

FOXD1-dependent RalA-ANXA2-Src complex promotes CTC formation in breast cancer.

Background: Early metastasis is a key factor contributing to poor breast cancer (BC) prognosis. Circulating tumor cells (CTCs) are regarded as the precursor cells of metastasis, which are ultimately responsible for the main cause of death in BC. However, to date molecular mechanisms underlying CTC formation in BC have been insufficiently defined.

Cytoplasm or Supernatant: Where Is the Treasury of the Bioactive Antiaging Factor from Mesenchymal Stem Cells?

Cell-free compounds of mesenchymal stem cells (MSCs) could be a safer and cheaper substitution for MSC transplantation and have gained substantial research interest for antiaging skin treatments. However, whether those bioactive components should be obtained from the cytoplasm or supernatant is yet to be determined. In this study, we examined the ingredients of the MSC cytoplasm extract (MSC-ex) and MSC supernatant (MSC-s) and evaluated their effect in a photoaging model.

Exosomal Delivery of AntagomiRs Targeting Viral and Cellular MicroRNAs Synergistically Inhibits Cancer Angiogenesis.

Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated cancer characterized by a high degree of recurrence, angiogenesis, and metastasis. The importance of alternative pro-angiogenesis pathways including viral factors has emerged after decades of directly targeting various signaling components. Using NPC as a model, we identified an essential oncogenic pathway underlying angiogenesis regulation that involves the inhibition of a tumor suppressor, Spry3, and its downstream targets by EBV-miR-BART10-5p (BART10-5p) and hsa-miR-18a (miR-18a).

Lnc-M2 controls M2 macrophage differentiation via the PKA/CREB pathway.

Long noncoding RNAs (lncRNAs) play an indispensable role in the process of M1 macrophage via regulating the development of macrophages and their responses to bacterial pathogens and viral infections. However, there are few studies on the lncRNA-mediated functions and regulatory mechanisms of M2 macrophage polarization. In this study, we found a number of differentially expressed lncRNAs between human monocyte derived M0 and M2 macrophages according to array analysis and quantitative polymerase chain reaction (qPCR) validation.

Correction: EBV-miR-BART1-5P activates AMPK/mTOR/HIF1 pathway via a PTEN independent manner to promote glycolysis and angiogenesis in nasopharyngeal carcinoma.

[This corrects the article DOI: 10.1371/journal.ppat.

EBV-miR-BART7-3p Imposes Stemness in Nasopharyngeal Carcinoma Cells by Suppressing SMAD7.

Cancer stem-like cells, possessing "stemness" properties, play crucial roles in progression, metastasis, and drug resistance in various cancers. Viral microRNAs (such as EBV-miR-BART7-3p), as exogenous regulators, have been discovered to regulate malignant progression of nasopharyngeal carcinoma (NPC), suggesting a possible role of viral microRNAs in imposing stemness. In this study, we found that EBV-miR-BART7-3p induce stemness of NPC cells.

EBV-miR-BART1-5P activates AMPK/mTOR/HIF1 pathway via a PTEN independent manner to promote glycolysis and angiogenesis in nasopharyngeal carcinoma.

Abnormal metabolism and uncontrolled angiogenesis are two important characteristics of malignant tumors. The occurrence of both events involves many key molecular changes including miRNA. However, EBV encoded miRNAs are rarely mentioned as capable of regulating tumor metabolism and tumor angiogenesis.

Nuclear p27 expression confers a favorable outcome for nasopharyngeal carcinoma patients.

Objective: The purpose of the present study is to explore the correlation between nuclear expression of cyclin-dependent kinase inhibitor 1B (p27) and clinicopathologic features in nasopharyngeal carcinoma (NPC), including patient survival.

Methods: Immunohistochemistry was used to examine the expression of p27 in 130 primary NPC tissues. The relationship between the levels of p27 expression and clinicopathologic characteristics was analyzed.

Nuclear expression of CDK4 correlates with disease progression and poor prognosis in human nasopharyngeal carcinoma.

Aims: The purpose of this study was to examine the correlation between nuclear expression of cyclin-dependent kinase 4 (CDK4) and clinicopathological data in nasopharyngeal carcinoma (NPC), including patient survival.

Methods And Results: Using real-time PCR and immunohistochemistry, the expression of CDK4 was examined in NPC and nasopharyngeal (NP) tissues. We observed that mRNA expression of CDK4 was elevated significantly in NPC tissues compared to NP tissues.

Conserved arginine residue in the membrane-spanning domain of HIV-1 gp41 is required for efficient membrane fusion.

Despite the high mutation rate of HIV-1, the amino acid sequences of the membrane-spanning domain (MSD) of HIV-1 gp41 are well conserved. Arginine residues are rarely found in single membrane-spanning domains, yet an arginine residue, R(696) (the numbering is based on that of HXB2), is highly conserved in HIV-1 gp41. To examine the role of R(696), it was mutated to K, A, I, L, D, E, N, and Q.

Membrane topology analysis of HIV-1 envelope glycoprotein gp41.

Background: The gp41 subunit of the HIV-1 envelope glycoprotein (Env) has been widely regarded as a type I transmembrane protein with a single membrane-spanning domain (MSD). An alternative topology model suggested multiple MSDs. The major discrepancy between the two models is that the cytoplasmic Kennedy sequence in the single MSD model is assigned as the extracellular loop accessible to neutralizing antibodies in the other model.

The membrane-spanning domain of gp41 plays a critical role in intracellular trafficking of the HIV envelope protein.

Background: The sequences of membrane-spanning domains (MSDs) on the gp41 subunit are highly conserved among many isolates of HIV-1. The GXXXG motif, a potential helix-helix interaction motif, and an arginine residue (rare in hydrophobic MSDs) are especially well conserved. These two conserved elements are expected to locate on the opposite sides of the MSD, if the MSD takes a α-helical secondary structure.

Monitoring of HIV-1 envelope-mediated membrane fusion using modified split green fluorescent proteins.

A simple, cell-based, membrane fusion assay system that uses split green fluorescent proteins (spGFPs) as an indicator was developed. The attachment of the pleckstrin homology (PH) domain to the N-termini of each spGFP not only localized the reporter signal to the plasma membrane but also helped the stable expression of the smaller spGFP of seventeen amino acid residues. It was shown that this system allowed real-time monitoring of membrane fusion by HIV-1 envelope protein (Env) without the addition of external substrates.