Indoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme that plays a pivotal role in immune regulation by metabolizing tryptophan into kynurenine, leading to T cell suppression and promoting immune tolerance. However, persistent activation of IDO1 can lead to prolonged immune stimulation in inflammatory conditions such as skin diseases and chronic inflammation. In this study, we developed modified peptide nucleic acids (PNAs) conjugated with cationic lipid chains to target IDO1 pre-mRNA and evaluated their anti-inflammatory effects in human keratinocytes. The modified PNAs demonstrated enhanced solubility, robust binding affinity, and effective penetration into keratinocytes. Quantitative PCR results showed significant downregulation of IDO1 and pro-inflammatory cytokines such as IL-6, IL-8, and PTGS2 in interferon γ (IFNγ)-treated keratinocytes. These findings suggest that cell-penetrating PNAs targeting IDO1 hold potential as a therapeutic approach for inflammatory skin disorders and chronic inflammation.

Indoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme that plays a pivotal role in immune regulation by metabolizing tryptophan into kynurenine, leading to T cell suppression and promoting immune tolerance. However, persistent activation of IDO1 can lead to prolonged immune stimulation in inflammatory conditions such as skin diseases and chronic inflammation. In this study, we developed modified peptide nucleic acids (PNAs) conjugated with cationic lipid chains to target IDO1 pre-mRNA and evaluated their anti-inflammatory effects in human keratinocytes. The modified PNAs demonstrated enhanced solubility, robust binding affinity, and effective penetration into keratinocytes. Quantitative PCR results showed significant downregulation of IDO1 and pro-inflammatory cytokines such as IL-6, IL-8, and PTGS2 in interferon γ (IFNγ)-treated keratinocytes. These findings suggest that cell-penetrating PNAs targeting IDO1 hold potential as a therapeutic approach for inflammatory skin disorders and chronic inflammation.

Indoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme that plays a pivotal role in immune regulation by metabolizing tryptophan into kynurenine, leading to T cell suppression and promoting immune tolerance. However, persistent activation of IDO1 can lead to prolonged immune stimulation in inflammatory conditions such as skin diseases and chronic inflammation. In this study, we developed modified peptide nucleic acids (PNAs) conjugated with cationic lipid chains to target IDO1 pre-mRNA and evaluated their anti-inflammatory effects in human keratinocytes. The modified PNAs demonstrated enhanced solubility, robust binding affinity, and effective penetration into keratinocytes. Quantitative PCR results showed significant downregulation of IDO1 and pro-inflammatory cytokines such as IL-6, IL-8, and PTGS2 in interferon γ (IFNγ)-treated keratinocytes. These findings suggest that cell-penetrating PNAs targeting IDO1 hold potential as a therapeutic approach for inflammatory skin disorders and chronic inflammation.

Neuroendocrine carcinoma of colon is a rare disease entity that is histologically poorly differentiated and immunochemically synaptophysin positive, enabling it to be confirmed by an immunohistochemical stain. Neuroendocrine carcinomas, in almost all cases, have poor prognosis due to a tendency of early metastasis and lack of standardized treatment. The concurrent diagnosis of neuroendocrine carcinoma and adenocarcinoma is extremely rare. The relation of these two disease entities is not understood. We experienced a patient with a colonic neuroendocrine carcinoma concurrent with adenocarcinoma. A 65-year-old male presented with abdominal pain. Emergent computed tomography suggested a malignant tumor of the ascending colon. Colonoscopy showed an infiltrative lesion in the ascending colon with a luminal narrowing, a large pedunculated lesion at the splenic flexure, and multiple small polyps in the descending colon. The patient underwent a right hemicolectomy including the pedunculated lesion. The pathology confirmed advanced neuroendocrine carcinoma in the ascending colon, adenocarcinoma in proximal descending colon, and multiple metastatic lymph nodes of neuroendocrine carcinomas on abdomen. The patient underwent the postoperative chemotherapy but did not tolerate it well and expired a year after diagnosis. We report this rare case with a review of the literature.
Abdomen ; Abdominal Pain ; Adenocarcinoma ; Carcinoma, Neuroendocrine ; Colon ; Colon, Ascending ; Colon, Descending ; Colon, Transverse ; Colonic Neoplasms ; Colonoscopy ; Humans ; Lymph Nodes ; Male ; Neoplasm Metastasis ; Phenobarbital ; Polyps ; Prognosis ; Rare Diseases ; Synaptophysin