separation-avian-preovulatory-follicle-granulosa-theca-cell-layers

Separation of Avian Preovulatory Follicle Granulosa and Theca Cell Layers for Downstream Applications

Layer hens (egg-laying chickens) and broiler breeders (breeding stock for meat-producing chickens) are crucial to the world's food supply as a reliable ...

University of Delaware

Mitochondria provide the first line of defense against the tumor-promoting effects of oxidative stress. Here we show that the prostate-specific homeoprotein NKX3.1 suppresses prostate cancer initiation by protecting mitochondria from oxidative stress. Integrating analyses of genetically engineered mouse models, human prostate cancer cells, and human prostate cancer organotypic cultures, we find that, in response to oxidative stress, NKX3.1 is imported to mitochondria via the chaperone protein HSPA9, where it regulates transcription of mitochondrial-encoded electron transport chain (ETC) genes, thereby restoring oxidative phosphorylation and preventing cancer initiation. Germline polymorphisms of  associated with increased cancer risk fail to protect from oxidative stress or suppress tumorigenicity. Low expression levels of  combined with low expression of mitochondrial ETC genes are associated with adverse clinical outcome, whereas high levels of mitochondrial NKX3.1 protein are associated with favorable outcome. This work reveals an extranuclear role for NKX3.1 in suppression of prostate cancer by protecting mitochondrial function. SIGNIFICANCE: Our findings uncover a nonnuclear function for NKX3.1 that is a key mechanism for suppression of prostate cancer. Analyses of the expression levels and subcellular localization of NKX3.1 in patients at risk of cancer progression may improve risk assessment in a precision prevention paradigm, particularly for men undergoing active surveillance...

NKX3.1 Localization to Mitochondria Suppresses Prostate Cancer Initiation.

Micro-sized magnetic particles (also known as microrobots [MRs]) have recently been shown to have potential applications for numerous biomedical applications like drug delivery, microengineering, and single cell manipulation. Interdisciplinary studies have demonstrated the ability of these tiny particles to actuate under the action of a controlled magnetic field that not only drive MRs in a desired trajectory but also precisely deliver therapeutic payload to the target site. Additionally, optimal concentrations of therapeutic molecules can also be delivered to the desired site which is cost-effective and safe especially in scenarios where drug dose-related side effects are a concern. In this study, MRs are used to deliver anticancer drugs (doxorubicin) to cancer cells and subsequent cell death is evaluated in different cell lines (liver, prostate, and ovarian cancer cells). Cytocompatibility studies show that MRs are well-tolerated and internalized by cancer cells. Doxorubicin (DOX) is chemically conjugated with MRs (DOX-MRs) and magnetically steered toward cancer cells using the magnetic controller. Time-lapsed video shows that cells shrink and eventually die when MRs are internalized by cells. Taken together, this study confirms that microrobots are promising couriers for targeted delivery of therapeutic biomolecules for cancer therapy and other non-invasive procedures that require precise control.

Doxorubicin-Loaded Microrobots for Targeted Drug Delivery and Anticancer Therapy.

The antidiabetic drug metformin has known anticancer effects related to its antioxidant activity; however, its clinical benefit for prostate cancer (PCa) has thus far been inconclusive. Here, we investigate whether the efficacy of metformin in PCa is related to the expression status of NKX3.1, a prostate-specific homeobox gene that functions in mitochondria to protect the prostate from aberrant oxidative stress.

Metformin Overcomes the Consequences of NKX3.1 Loss to Suppress Prostate Cancer Progression.

Developmental stuttering is a complex neurodevelopmental disorder characterized by disfluent speech. It has been associated with mutations in genes involved in lysosomal enzyme trafficking. Mice with mutations in one such gene, Gnptab, exhibit atypical vocalizations analogous to stuttering in humans. This mouse model has enabled the study of various molecular mechanisms related to the disorder. Simultaneously, an increasing number of reports have suggested the role of gut microbiota in altered brain function and development in neurological disorders. In this study, we compared gut microbiota profiles from Gnptab mutant mice to wildtype control mice. Microbiome analysis demonstrated a distinct microbiota profile in Gnptab mutant mice. The most significant alteration was an increased relative abundance of Akkermansia, a genus of mucin degrading bacteria, which has previously been associated with multiple neurological disorders. Moreover, the altered microbiota profile of these mice was predicted to result in differences in abundance of several metabolic pathways, including short chain fatty acid and lipopolysaccharide synthesis. These pathways may play a role in the onset, progression and persistence of developmental stuttering. This is the first study to show a potential link between developmental stuttering and changes in the gut microbiota, laying the groundwork for a new research direction.

Article	Year
NKX3.1 Localization to Mitochondria Suppresses Prostate Cancer Initiation. Cancer discovery\| PubMed ID: 33893149	2021
Doxorubicin-Loaded Microrobots for Targeted Drug Delivery and Anticancer Therapy. Advanced healthcare materials\| PubMed ID: 37378647	2023
Metformin Overcomes the Consequences of NKX3.1 Loss to Suppress Prostate Cancer Progression. European urology\| PubMed ID: 37659962	2024
Atypical gut microbiota composition in a mouse model of developmental stuttering. Scientific reports\| PubMed ID: 39379558	2024

Aditya Dutta

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