Apart and back again: Reestablished neuronal connections restore walking after paralysis.

Despite significant strides promoting axon regeneration after spinal cord injury (SCI), meaningful functional recovery remains elusive. Using a combination of approaches, Squair et al. elegantly demonstrate that axons damaged after SCI must be reconnected with their natural targets to recover lost neurological functions.

Transplantation of Human Induced Pluripotent Stem Cell-Derived Neural Progenitor Cells Promotes Forelimb Functional Recovery after Cervical Spinal Cord Injury.

Locomotor function after spinal cord injury (SCI) is critical for assessing recovery. Currently, available means to improve locomotor function include surgery, physical therapy rehabilitation and exoskeleton. Stem cell therapy with neural progenitor cells (NPCs) transplantation is a promising reparative strategy.

Establishment of a mouse model for ovarian cancer-associated venous thromboembolism.

Patients with ovarian cancer are at increased risk of venous thromboembolism (VTE), and the cumulative incidence is high, particularly at advanced stages of this disease. Nevertheless, it is challenging to investigate the molecular mechanisms of ovarian cancer-associated VTE (OC-VTE), mainly due to the lack of a well-developed animal model for this disease. We generated a mouse model for developing OC-VTE using ovarian cancer cell injection in combination with the inferior vena cava stenosis method.

Investigation of the Potential Mechanisms Underlying Nuclear F-Actin Organization in Ovarian Cancer Cells by High-Throughput Screening in Combination With Deep Learning.

Increasing evidence supports the notion that filamentous actin (F-actin) and globular actin exist in the nuclei of somatic cells, and are involved in chromatin remodeling, gene transcription regulation and DNA damage repair. However, the underlying mechanisms of how nuclear F-actin are polymerized in cells remain incompletely understood. Here, we identify potential kinase targets that participate in nuclear F-actin polymerization in ovarian cancer cells using small-molecule inhibitor library screening in combination with a deep learning approach.

MS: Wip1 suppresses angiogenesis through the STAT3-VEGF signalling pathway in serous ovarian cancer.

Multifaceted functions of the so-called "oncogene" Wip1 have been reported in a previous study, while its actual role remains to be explored in serous ovarian cancer (SOC). In this study, by performing bioinformatic analysis with a public database and immunohistochemical staining of Wip1 in tumour tissue from SOC, we concluded that decreased expression of Wip1 was associated with a higher rate of tumour metastasis and platinum-based therapy resistance and increased ascites volume, which led to poorer prognosis in SOC patients. We also found that overexpression of Wip1 in SKOV3 cells decreased the levels of several cytokines, including VEGF, by secretome profiling analysis, and Wip1 overexpression suppressed angiogenesis both in vitro and in vivo.

SOX17 and PAX8 constitute an actionable lineage-survival transcriptional complex in ovarian cancer.

Müllerian tissue-specific oncogenes, prototyped by PAX8, underlie ovarian tumorigenesis and represent unique molecular vulnerabilities. Further delineating such lineage-dependency factors and associated therapeutic implications would provide valuable insights into ovarian cancer biology and treatment. In this study, we identified SOX17 as a new lineage-survival master transcription factor, which shared co-expression pattern with PAX8 in epithelial ovarian carcinoma.

Systematic analysis of purified astrocytes after SCI unveils Zeb2os function during astrogliosis.

Spinal cord injury (SCI) is one of the most devastating neural injuries without effective therapeutic solutions. Astrocytes are the predominant component of the scar. Understanding the complex contributions of reactive astrocytes to SCI pathophysiologies is fundamentally important for developing therapeutic strategies.

Reaching and Grasping Training Improves Functional Recovery After Chronic Cervical Spinal Cord Injury.

Previous studies suggest locomotion training could be an effective non-invasive therapy after spinal cord injury (SCI) using primarily acute thoracic injuries. However, the majority of SCI patients have chronic cervical injuries. Regaining hand function could significantly increase their quality of life.

The Repertoire of Serous Ovarian Cancer Non-genetic Heterogeneity Revealed by Single-Cell Sequencing of Normal Fallopian Tube Epithelial Cells.

The inter-differentiation between cell states promotes cancer cell survival under stress and fosters non-genetic heterogeneity (NGH). NGH is, therefore, a surrogate of tumor resilience but its quantification is confounded by genetic heterogeneity. Here we show that NGH in serous ovarian cancer (SOC) can be accurately measured when informed by the molecular signatures of the normal fallopian tube epithelium (FTE) cells, the cells of origin of SOC.

An evolving story of the metastatic voyage of ovarian cancer cells: cellular and molecular orchestration of the adipose-rich metastatic microenvironment.

Metastasis is a complex multistep process that involves critical interactions between cancer cells and a variety of stromal components in the tumor microenvironment, which profoundly influence the different aspects of the metastatic cascade and organ tropism of disseminating cancer cells. Ovarian cancer is the most lethal gynecological malignancy and is characterized by peritoneal disseminated metastasis. Evidence has demonstrated that ovarian cancer possesses specific metastatic tropism for the adipose-rich omentum, which has a pivotal role in the creation of the metastatic tumor microenvironment in the intraperitoneal cavity.

Tuning microtubule dynamics to enhance cancer therapy by modulating FER-mediated CRMP2 phosphorylation.

Though used widely in cancer therapy, paclitaxel only elicits a response in a fraction of patients. A strong determinant of paclitaxel tumor response is the state of microtubule dynamic instability. However, whether the manipulation of this physiological process can be controlled to enhance paclitaxel response has not been tested.

Apolipoprotein E as a novel therapeutic neuroprotection target after traumatic spinal cord injury.

Apolipoprotein E (apoE), a plasma lipoprotein well known for its important role in lipid and cholesterol metabolism, has also been implicated in many neurological diseases. In this study, we examined the effect of apoE on the pathophysiology of traumatic spinal cord injury (SCI). ApoE-deficient mutant (apoE) and wild-type mice received a T9 moderate contusion SCI and were evaluated using histological and behavioral analyses after injury.

Loss of PFKFB4 induces cell death in mitotically arrested ovarian cancer cells.

Taxanes represent some of the most commonly used chemotherapeutic agents for ovarian cancer treatment. However, they are only effective in approximately 40% of patients. Novel therapeutic strategies are required to potentiate their effect and improve patient outcome.

The systematic analysis of coding and long non-coding RNAs in the sub-chronic and chronic stages of spinal cord injury.

Spinal cord injury (SCI) remains one of the most debilitating neurological disorders and the majority of SCI patients are in the chronic phase. Previous studies of SCI have usually focused on few genes and pathways at a time. In particular, the biological roles of long non-coding RNAs (lncRNAs) have never been characterized in SCI.

Human neural progenitors derived from integration-free iPSCs for SCI therapy.

As a potentially unlimited autologous cell source, patient induced pluripotent stem cells (iPSCs) provide great capability for tissue regeneration, particularly in spinal cord injury (SCI). However, despite significant progress made in translation of iPSC-derived neural progenitor cells (NPCs) to clinical settings, a few hurdles remain. Among them, non-invasive approach to obtain source cells in a timely manner, safer integration-free delivery of reprogramming factors, and purification of NPCs before transplantation are top priorities to overcome.

Response to di-functionalized hyaluronic acid with orthogonal chemistry grafting at independent modification sites in rodent models of neural differentiation and spinal cord injury.

Hyaluronic acid (HA) with one reactive moiety grafted to the backbone is a commonly used matrix in tissue engineering. The addition of a second orthogonal moiety to the backbone allows for greater control in bioactive signal tethering and gelation. In this study, thiol and azide functional groups were grafted to the HA backbone at separate modification sites.

Salt-Inducible Kinase 2 Couples Ovarian Cancer Cell Metabolism with Survival at the Adipocyte-Rich Metastatic Niche.

The adipocyte-rich microenvironment forms a niche for ovarian cancer metastasis, but the mechanisms driving this process are incompletely understood. Here we show that salt-inducible kinase 2 (SIK2) is overexpressed in adipocyte-rich metastatic deposits compared with ovarian primary lesions. Overexpression of SIK2 in ovarian cancer cells promotes abdominal metastasis while SIK2 depletion prevents metastasis in vivo.

Arabidopsis actin-depolymerizing factor7 severs actin filaments and regulates actin cable turnover to promote normal pollen tube growth.

Actin filaments are often arranged into higher-order structures, such as the longitudinal actin cables that generate the reverse fountain cytoplasmic streaming pattern present in pollen tubes. While several actin binding proteins have been implicated in the generation of these cables, the mechanisms that regulate their dynamic turnover remain largely unknown. Here, we show that Arabidopsis thaliana actin-depolymerizing factor7 (ADF7) is required for turnover of longitudinal actin cables.

RNA-seq characterization of spinal cord injury transcriptome in acute/subacute phases: a resource for understanding the pathology at the systems level.

Spinal cord injury (SCI) is a devastating neurological disease without effective treatment. To generate a comprehensive view of the mechanisms involved in SCI pathology, we applied RNA-Sequencing (RNA-Seq) technology to characterize the temporal changes in global gene expression after contusive SCI in mice. We sequenced tissue samples from acute and subacute phases (2 days and 7 days after injury) and systematically characterized the transcriptomes with the goal of identifying pathways and genes critical in SCI pathology.

Apolipoprotein E Mimetic Promotes Functional and Histological Recovery in Lysolecithin-Induced Spinal Cord Demyelination in Mice.

Objective: Considering demyelination is the pathological hallmark of multiple sclerosis (MS), reducing demyelination and/or promoting remyelination is a practical therapeutic strategy to improve functional recovery for MS. An apolipoprotein E (apoE)-mimetic peptide COG112 has previously demonstrated therapeutic efficacy on functional and histological recovery in a mouse experimental autoimmune encephalomyelitis (EAE) model of human MS. In the current study, we further investigated whether COG112 promotes remyelination and improves functional recovery in lysolecithin induced focal demyelination in the white matter of spinal cord in mice.

Transplantation of D15A-expressing glial-restricted-precursor-derived astrocytes improves anatomical and locomotor recovery after spinal cord injury.

The transplantation of neural stem/progenitor cells is a promising therapeutic strategy for spinal cord injury (SCI). In this study, we tested whether combination of neurotrophic factors and transplantation of glial-restricted precursor (GRPs)-derived astrocytes (GDAs) could decrease the injury and promote functional recovery after SCI. We developed a protocol to quickly produce a sufficiently large, homogenous population of young astrocytes from GRPs, the earliest arising progenitor cell population restricted to the generation of glia.

Oryza sativa actin-interacting protein 1 is required for rice growth by promoting actin turnover.

Rapid actin turnover is essential for numerous actin-based processes. However, how it is precisely regulated remains poorly understood. Actin-interacting protein 1 (AIP1) has been shown to be an important factor by acting coordinately with actin-depolymerizing factor (ADF)/cofilin in promoting actin depolymerization, the rate-limiting factor in actin turnover.