Significance of LIF/LIFR Signaling in the Progression of Obesity-Driven Triple-Negative Breast Cancer.

American women with obesity have an increased incidence of triple-negative breast cancer (TNBC). The impact of obesity conditions on the tumor microenvironment is suspected to accelerate TNBC progression; however, the specific mechanism(s) remains elusive. This study explores the hypothesis that obesity upregulates leukemia inhibitory factor receptor (LIFR) oncogenic signaling in TNBC and assesses the efficacy of LIFR inhibition with EC359 in blocking TNBC progression.

Segregation Between an Ornamental and a Disease Driver Gene Provides Insights Into Pigment Cell Regulation.

Genetic interactions are adaptive within a species. Hybridization can disrupt such species-specific genetic interactions and creates novel interactions that alter the hybrid progeny overall fitness. Hybrid incompatibility, which refers to degenerative genetic interactions that decrease the overall hybrid survival and sterility, is one of the results from combining two diverged genomes in hybrids.

PELP1 Is a Novel Therapeutic Target in Hepatocellular Carcinoma.

Unlabelled: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths in the United States, with a median survival period of approximately 10 months. There is an urgent need for the development of effective targeted therapies for the treatment of HCC. Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) signaling is implicated in the progression of many cancers, although its specific contribution to the progression of HCC is not yet well understood.

Concurrent TB and HIV therapies effectively control clinical reactivation of TB during co-infection but fail to eliminate chronic immune activation.

The majority of Human Immunodeficiency Virus (HIV) negative individuals exposed to () control the bacillary infection as latent TB infection (LTBI). Co-infection with HIV, however, drastically increases the risk to progression to tuberculosis (TB) disease. TB is therefore the leading cause of death in people living with HIV (PLWH) globally.

Integrative multi-omics characterization of hepatocellular carcinoma in Hispanic patients.

Background: The incidence and mortality rates of hepatocellular carcinoma among Hispanic individuals in the United States are much higher than in non-Hispanic White people. We conducted multi-omics analyses to elucidate molecular alterations in hepatocellular carcinoma among Hispanic patients.

Methods: Paired tumor and adjacent nontumor samples were collected from 31 Hispanic hepatocellular carcinomas in South Texas for genomic, transcriptomic, proteomic, and metabolomic profiling.

Degenerative and regenerative peripheral processes are associated with persistent painful chemotherapy-induced neuropathies in males and females.

This study investigated the time course of gene expression changes during the progression of persistent painful neuropathy caused by paclitaxel (PTX) in male and female mouse hindpaws and dorsal root ganglia (DRG). Bulk RNA-seq was used to examine these gene expression changes at 1, 16, and 31 days post-last PTX. At these time points, differentially expressed genes (DEGs) were predominantly related to the reduction or increase in epithelial, skin, bone, and muscle development and to angiogenesis, myelination, axonogenesis, and neurogenesis.

KDM1A/LSD1 inhibition enhances chemotherapy response in ovarian cancer.

Ovarian cancer (OCa) is the deadliest of all gynecological cancers. The standard treatment for OCa is platinum-based chemotherapy, such as carboplatin or cisplatin in combination with paclitaxel. Most patients are initially responsive to these treatments; however, nearly 90% will develop recurrence and inevitably succumb to chemotherapy-resistant disease.

Targeting S6K/NFκB/SQSTM1/Polθ signaling to suppress radiation resistance in prostate cancer.

In this study we have identified POLθ-S6K-p62 as a novel druggable regulator of radiation response in prostate cancer. Despite significant advances in delivery, radiotherapy continues to negatively affect treatment outcomes and quality of life due to resistance and late toxic effects to the surrounding normal tissues such as bladder and rectum. It is essential to develop new and effective strategies to achieve better control of tumor.

Synergistic Antitumor Activity of Talazoparib and Temozolomide in Malignant Rhabdoid Tumors.

Malignant rhabdoid tumors (MRTs) are among the most aggressive and treatment-resistant malignancies affecting infants, originating in the kidney, brain, liver, and soft tissues. The 5-year event-free survival rate for these cancers is a mere 20%. In nearly all cases of MRT, the gene (occasionally )-a pivotal component of the SWI/SNF chromatin remodeling complex-is homozygously deleted, although the precise etiology of these tumors remains unknown.

Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in Synovial Sarcoma.

Synovial Sarcoma (SS) is driven by the SS18::SSX fusion oncoprotein and is ultimately refractory to therapeutic approaches. SS18::SSX alters ATP-dependent chromatin remodeling BAF (mammalian SWI/SNF) complexes, leading to the degradation of canonical (cBAF) complex and amplified presence of an SS18::SSX-containing non-canonical BAF (ncBAF or GBAF) that drives an SS-specific transcription program and tumorigenesis. We demonstrate that SS18::SSX activates the SUMOylation program and SSs are sensitive to the small molecule SAE1/2 inhibitor, TAK-981.

Segregation between an ornamental and a disease driver gene provides insights into pigment cell regulation.

Unlabelled: Genetic interactions are adaptive within a species. Hybridization can disrupt such species-specific genetic interactions and creates novel interactions that alter the hybrid progeny overall fitness. Hybrid incompatibility, which refers to degenerative genetic interactions that decrease the overall hybrid survival, is one of the results from combining two diverged genomes in hybrids.

Pharmacological inhibition of the LIF/LIFR autocrine loop reveals vulnerability of ovarian cancer cells to ferroptosis.

Of all gynecologic cancers, epithelial-ovarian cancer (OCa) stands out with the highest mortality rates. Despite all efforts, 90% of individuals who receive standard surgical and cytotoxic therapy experience disease recurrence. The precise mechanism by which leukemia inhibitory factor (LIF) and its receptor (LIFR) contribute to the progression of OCa remains unknown.

Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in Synovial Sarcoma.

Synovial Sarcoma (SS) is driven by the SS18::SSX fusion oncoprotein. and is ultimately refractory to therapeutic approaches. SS18::SSX alters ATP-dependent chromatin remodeling BAF (mammalian SWI/SNF) complexes, leading to the degradation of canonical (cBAF) complex and amplified presence of an SS18::SSX-containing non-canonical BAF (ncBAF or GBAF) that drives an SS-specific transcription program and tumorigenesis.

Targeting STAT6-mediated synovial macrophage activation improves pain in experimental knee osteoarthritis.

Background: Pain from osteoarthritis (OA) is one of the top causes of disability worldwide, but effective treatment is lacking. Nociceptive factors are released by activated synovial macrophages in OA, but depletion of synovial macrophages paradoxically worsens inflammation and tissue damage in previous studies. Rather than depleting macrophages, we hypothesized that inhibiting macrophage activation may improve pain without increasing tissue damage.

Degenerative and regenerative peripheral processes are associated with persistent painful chemotherapy-induced neuropathies in males and females.

This study aimed to investigate the time course of gene expression changes during the progression of persistent painful neuropathy caused by paclitaxel (PTX) in male and female mouse hind paws and dorsal root ganglia (DRG). Bulk RNA-seq was used to investigate the gene expression changes in the paw and DRG collected at 1, 16, and 31 days post-PTX. At these time points, differentially expressed DEGs were predominantly related to reduction or increase in epithelial, skin, bone, and muscle development and to angiogenesis, myelination, axonogenesis, and neurogenesis.

Expression activation of over 70% of genes during the first hour of infection.

The obligate intracellular bacterium has a unique developmental cycle that alternates between two contrasting cell types. With a hardy envelope and highly condensed genome, the small elementary body (EB) maintains limited metabolic activities yet survives in extracellular environments and is infectious. After entering host cells, EBs differentiate into larger and proliferating reticulate bodies (RBs).

Sex-Specific Impact of Fkbp5 on Hippocampal Response to Acute Alcohol Injection: Involvement in Alterations of Metabolism-Related Pathways.

High levels of alcohol intake alter brain gene expression and can produce long-lasting effects. FK506-binding protein 51 (FKBP51) encoded by is a physical and cellular stress response gene and has been associated with alcohol consumption and withdrawal severity. has been previously linked to neurite outgrowth and hippocampal morphology, sex differences in stress response, and epigenetic modification.

Requirement of GrgA for infectious progeny production, optimal growth, and efficient plasmid maintenance.

Hallmarks of the developmental cycle of the obligate intracellular pathogenic bacterium are the primary differentiation of the infectious elementary body (EB) into the proliferative reticulate body (RB) and the secondary differentiation of RBs back into EBs. The mechanisms regulating these transitions remain unclear. In this report, we developed an effective novel strategy termed dependence on plasmid-mediated expression (DOPE) that allows for the knockdown of essential genes in .

Associations of tissue damage induced inflammatory plasticity in masseter muscle with the resolution of chronic myalgia.

Gene plasticity during myogenous temporomandibular disorder (TMDM) development is largely unknown. TMDM could be modeled by intramuscular inflammation or tissue damage. To model inflammation induced TMDM we injected complete Freund's adjuvant (CFA) into masseter muscle (MM).

Transcriptional profiles of non-neuronal and immune cells in mouse trigeminal ganglia.

Non-neuronal cells constitute 90%-95% of sensory ganglia. These cells, especially glial and immune cells, play critical roles in the modulation of sensory neurons. This study aimed to identify, profile, and summarize the types of trigeminal ganglion (TG) non-neuronal cells in naïve male mice using published and our own data generated by single-cell RNA sequencing, flow cytometry, and immunohistochemistry.

A holistic approach to integrating patient, family, and lived experience voices in the development of the BrainHealth Databank: a digital learning health system to enable artificial intelligence in the clinic.

Artificial intelligence, machine learning, and digital health innovations have tremendous potential to advance patient-centred, data-driven mental healthcare. To enable the clinical application of such innovations, the Krembil Centre for Neuroinformatics at the Centre for Addiction and Mental Health, Canada's largest mental health hospital, embarked on a journey to co-create a digital learning health system called the BrainHealth Databank (BHDB). Working with clinicians, scientists, and administrators alongside patients, families, and persons with lived experience (PFLE), this hospital-wide team has adopted a systems approach that integrates clinical and research data and practices to improve care and accelerate research.

Comprehensive characterization of patient-derived xenograft models of pediatric leukemia.

Patient-derived xenografts (PDX) remain valuable models for understanding the biology and for developing novel therapeutics. To expand current PDX models of childhood leukemia, we have developed new PDX models from Hispanic patients, a subgroup with a poorer overall outcome. Of 117 primary leukemia samples obtained, successful engraftment and serial passage in mice were achieved in 82 samples (70%).