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Huntington’s disease (HD) is an autosomal dominant and fatal neurodegenerative disorder, which is caused by an abnormal CAG repeat in the huntingtin gene. Despite its well-defined genetic origin, the molecular mechanisms of neuronal death are unclear yet, thus there are no effective strategies to block or postpone the process of HD. Ferroptosis, a recently identified iron-dependent cell death, attracts considerable attention due to its putative involvement in neurodegenerative diseases. Accumulative data suggest that ferroptosis is very likely to participate in HD, and inhibition of the molecules and signaling pathways involved in ferroptosis can significantly eliminate the symptoms and pathology of HD. This review first describes evidence for the close relevance of ferroptosis and HD in patients and mouse models, then summarizes advances for the mechanisms of ferroptosis involved in HD, finally outlines some therapeutic strategies targeted ferroptosis. Comprehensive understanding of the emerging roles of ferroptosis in the occurrence of HD will help us to explore effective therapies for slowing the progression of this disease.

Cytokine-induced killer (CIK) cells are a heterogeneous population of effector CD3 CD56 natural killer T cells, which can be easily expanded from peripheral blood mononuclear cells. CIK cells work as pharmacological tools for cancer immunotherapy as they exhibit MHC-unrestricted, safe, and effective antitumor activity. Much effort has been made to improve CIK cells cytotoxicity and treatments of CIK cells combined with other antitumor therapies are applied. This review summarizes some strategies, including the combination of CIK with additional cytokines, dendritic cells, check point inhibitors, antibodies, chemotherapeutic agents, nanomedicines, and engineering CIK cells with a chimeric antigen receptor. Furthermore, we briefly sum up the clinical trials on CIK cells and compare the effect of clinical CIK therapy with other immunotherapies. Finally, further research is needed to clarify the pharmacological mechanism of CIK and provide evidence to formulate uniform culturing criteria for CIK expansion.

Ten-eleven translocation (TET) proteins, the dioxygenase for DNA hydroxymethylation, are important players in nervous system development and diseases. However, their role in myelination and remyelination after injury remains elusive. Here, we identify a genome-wide and locus-specific DNA hydroxymethylation landscape shift during differentiation of oligodendrocyte-progenitor cells (OPC). Ablation of Tet1 results in stage-dependent defects in oligodendrocyte (OL) development and myelination in the mouse brain. The mice lacking Tet1 in the oligodendrocyte lineage develop behavioral deficiency. We also show that TET1 is required for remyelination in adulthood. Transcriptomic, genomic occupancy, and 5-hydroxymethylcytosine (5hmC) profiling reveal a critical TET1-regulated epigenetic program for oligodendrocyte differentiation that includes genes associated with myelination, cell division, and calcium transport. Tet1 -deficient OPCs exhibit reduced calcium activity, increasing calcium activity rescues the differentiation defects in vitro. Deletion of a TET1-5hmC target gene, Itpr2 , impairs the onset of OPC differentiation. Together, our results suggest that stage-specific TET1-mediated epigenetic programming and intracellular signaling are important for proper myelination and remyelination in mice. Myelin formation is regulated by epigenetic mechanisms and ensures proper neuronal function during development and after demyelination. Here, the authors show that TET1, a DNA hydroxymethylase, regulates myelination during development and remyelination in mice.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of myeloid progenitor and precursor cells at different stages of differentiation, which play an important role in tumor immunosuppression. Glioma is the most common and deadliest primary malignant tumor of the brain, and ample evidence supports key contributions of MDSCs to the immunosuppressive tumor microenvironment, which is a key factor stimulating glioma progression. In this review, we summarize the source and characterization of MDSCs, discuss their immunosuppressive functions, and current approaches that target MDSCs for tumor control. Overall, the review provides insights into the roles of MDSC immunosuppression in the glioma microenvironment and suggests that MDSC control is a powerful cellular therapeutic target for currently incurable glioma tumors.

Glioblastoma (GBM) is a deadly disease without effective treatment. Because glioblastoma stem cells (GSCs) contribute to tumor resistance and recurrence, improved treatment of GBM can be achieved by eliminating GSCs through inducing their differentiation. Prior efforts have been focused on studying GSC differentiation towards the astroglial lineage. However, regulation of GSC differentiation towards the neuronal and oligodendroglial lineages is largely unknown. To identify genes that control GSC differentiation to all three lineages, we performed an image-based genome-wide RNAi screen, in combination with single-cell RNA sequencing, and identified ZNF117 as a major regulator of GSC differentiation. Using patient-derived GSC cultures, we show that ZNF117 controls GSC differentiation towards the oligodendroglial lineage via the Notch pathway. We demonstrate that ZNF117 is a promising target for GSC differentiation therapy through targeted delivery of CRISPR/Cas9 gene-editing nanoparticles. Our study suggests a direction to improve GBM treatment through differentiation of GSCs towards various lineages. Improved treatment of glioblastoma (GBM) can be achieved by inducing differentiation of glioblastoma stem cells (GSCs). Here, the authors show that zinc finger protein 117 (ZNF117) is a regulator of GSC differentiation via Notch signaling through interaction with JAG2, and can be targeted for therapy.

Strategies for selectively imaging and delivering drugs to tumours typically leverage differentially upregulated surface molecules on cancer cells. Here, we show that intravenously injected carbon quantum dots, functionalized with multiple paired α-carboxyl and amino groups that bind to the large neutral amino acid transporter 1 (which is expressed in most tumours), selectively accumulate in human tumour xenografts in mice and in an orthotopic mouse model of human glioma. The functionalized quantum dots, which structurally mimic large amino acids and can be loaded with aromatic drugs through π – π stacking interactions, enabled—in the absence of detectable toxicity—near-infrared fluorescence and photoacoustic imaging of the tumours and a reduction in tumour burden after the targeted delivery of chemotherapeutics to the tumours. The versatility of functionalization and high tumour selectivity of the quantum dots make them broadly suitable for tumour-specific imaging and drug delivery. Intravenously injected functionalized carbon quantum dots that bind to the large neutral amino acid transporter 1 and that structurally mimic large amino acids selectively accumulate in human tumours in mice, facilitating targeted theranostics.

In recent years, hydrogel-based cancer drug delivery systems have developed rapidly due to the versatility of hydrogels [...].In recent years, hydrogel-based cancer drug delivery systems have developed rapidly due to the versatility of hydrogels [...].

The aging of the immune system is not only an inevitable result but also an important cause of physical aging. The aging of the immune system is rooted in the aging of hematopoietic cells (HSCs), which manifests as decreasing functionality of the adaptive immune system and the innate immune system. C57BL/6 mice of different ages were collected in this study to better understand the changes in the structures of the innate and adaptive immune systems in individuals of different ages and the distribution and changes in immune cells with stem cell properties. The immune cells of the innate and adaptive immune systems, including DCs, monocytes, macrophages, CD4+ T lymphocytes, CD8+ T lymphocytes, and B lymphocytes, were assessed, and the proportions of cells with stem cell properties among these immune cell populations were also tested. Overall, immune cells in the peripheral blood, spleen, and bone marrow of mice exhibit certain regular properties with increasing age. The trend of changes in immune cells in different immune organs differs with age. The changes in lymphocytes in the peripheral blood are more sensitive. Their proportions increase slowly with age and then decrease rapidly to a very low level (less than 5%) after a certain point (9 or 13 months old). Nine to 13 months of age is the most critical time point for assessing changes in the immune system of mice and the most critical time point for detecting changes in the proportion of stem cells. After 13 months of age, the balance and stability of stem cells in mice are disrupted, and animals begin to age rapidly. The ratio of Ly6A to E+CD117+ cells in the peripheral blood, particularly lymphocytes involved in adaptive immunity, represents a specific marker for predicting immune senescence and body senescence.

Grass plants develop distinct inflorescences and spikelets that determine grain yields. However, the mechanisms underlying the specification of inflorescences and spikelets in grasses remain largely unknown. Here, we report the biological role of one SEPALLATA (SEP)-like gene, OsMADS34, in controlling the development of inflorescences and spikelets in rice (Oryza sativa). OsMADS34 encodes a MADS box protein containing a short carboxyl terminus without transcriptional activation activity in yeast cells. We demonstrate the ubiquitous expression of OsMADS34 in roots, leaves, and primordia of inflorescence and spikelet organs. Compared with the wild type, osmads34 mutants developed altered inflorescence morphology, with an increased number of primary branches and a decreased number of secondary branches. In addition, osmads34 mutants displayed a decreased spikelet number and altered spikelet morphology, with lemma/leaf-like elongated sterile lemmas. Moreover, analysis of the double mutant osmads34 osmads1 suggests that OsMADS34 specifies the identities of floral organs, including the lemma/palea, lodicules, stamens, and carpel, in combination with another rice SEP-like gene, OsMADS1. Collectively, our study suggests that the origin and diversification of OsMADS34 and OsMADS1 contribute to the origin of distinct grass inflorescences and spikelets.

Glioblastoma (GBM) is the most aggressive tumor of the central nervous system and remains universally lethal due to lack of effective treatment options and their inefficient delivery to the brain. Here the development of multifunctional polymeric nanoparticles (NPs) for effective treatment of GBM is reported. The NPs are synthesized using a novel glutathione (GSH)‐reactive poly (2,2″‐thiodiethylene 3,3″‐dithiodipropionate) (PTD) polymer and engineered for brain penetration through neutrophil elastase‐triggered shrinkability, iRGD‐mediated targeted delivery, and lexiscan‐induced autocatalysis. It is found that the resulting lexiscan‐loaded, iRGD‐conjugated, shrinkable PTD NPs, or LiPTD NPs, efficiently penetrate brain tumors with high specificity after intravenous administration. Furthermore, it is demonstrated that LiPTD NPs are capable of efficient encapsulation and delivery of chemotherapy doxorubicin and sonosensitizer chlorin e6 to achieve combined chemotherapy and sonodynamic therapy (SDT). It is demonstrated that the capability of GSH depletion of LiPTD NPs further augments the tumor cell killing effect triggered by SDT. As a result, treatment with LiPTD NPs effectively inhibits tumor growth and prolongs the survival of tumor‐bearing mice. This study may suggest a potential new approach for effective GBM treatment. Glutathione (GSH)‐reactive polymer‐based nanoparticles (NPs), which can target drug delivery to the brain tumor through the integration of neutrophil elastase‐triggered shrinkability, ligand‐mediated interaction, and lexiscan‐induced blood–brain barrier modulation. The resulting NPs with excellent penetration capability can efficiently deliver chemotherapy drug doxorubicin and sonosensitizer chlorin e6 to tumors in the brain for effective chemo‐sonodynamic combination therapy.