Design of an Artificial Peptide Inspired by Transmembrane Mitochondrial Protein for Escorting Exogenous DNA into the Mitochondria to Restore their Functions by Simultaneous Multiple Gene Expression

新規ミトコンドリア膜貫通ペプチドによる遺伝子送達 --ミトコンドリア内部で効率的な多重遺伝子発現を達成--. 京都大学プレスリリース. 2023-11-02.Mitochondria are vital organelles regulating essential cellular functions. Human mitochondrial DNA (mtDNA) consists of 37 genes, 13 of which encode mitochondrial proteins, and the remaining 24 genes encode two ribosomal RNAs and 22 transfer RNAs needed for the translation of the mtDNA-encoded 13 proteins. However, mtDNA often impairs the expression and function of these genes due to various mutations, ultimately causing mitochondrial dysfunction. To recover from this desperate condition, developing the technology to supply all mitochondrial proteins encoded by mtDNA at once is an urgent task, but there is no established strategy for this purpose. In this study, a simple yet effective mitochondrial gene delivery system is proposed comprising an artificial peptide inspired by a transmembrane mitochondrial membrane protein. The designed mitochondria-targeting peptides presented on the carrier surface effectively guide the encapsulated plasmid to the mitochondria, facilitating mitochondrial uptake and gene expression. The developed system successfully delivers exogenous mtDNA to mtDNA-depleted cells and leads to simultaneous multigene expression, ultimately restoring mitochondrial functions, including the mitochondrial respiration rate. The established multiple gene expression system in each mitochondrion is a game-changing technology that can accelerate the development of mitochondrial engineering technologies as well as clinical applications for mitochondrial diseases

Role of cyclooxygenase-2-mediated prostaglandin E2-prostaglandin E receptor 4 signaling in cardiac reprogramming

Direct cardiac reprogramming from fibroblasts can be a promising approach for disease modeling, drug screening, and cardiac regeneration in pediatric and adult patients. However, postnatal and adult fibroblasts are less efficient for reprogramming compared with embryonic fibroblasts, and barriers to cardiac reprogramming associated with aging remain undetermined. In this study, we screened 8400 chemical compounds and found that diclofenac sodium (diclofenac), a non-steroidal anti-inflammatory drug, greatly enhanced cardiac reprogramming in combination with Gata4, Mef2c, and Tbx5 (GMT) or GMT plus Hand2. Intriguingly, diclofenac promoted cardiac reprogramming in mouse postnatal and adult tail-tip fibroblasts (TTFs), but not in mouse embryonic fibroblasts (MEFs). Mechanistically, diclofenac enhanced cardiac reprogramming by inhibiting cyclooxygenase-2, prostaglandin E2/prostaglandin E receptor 4, cyclic AMP/protein kinase A, and interleukin 1β signaling and by silencing inflammatory and fibroblast programs, which were activated in postnatal and adult TTFs. Thus, anti-inflammation represents a new target for cardiac reprogramming associated with aging

Magnetic torque and heat capacity measurements on TPP[Fe(Pc)(CN)2]2

Magnetic torque and heat capacity measurements on TPP[Fe(Pc)(CN)2]2 are reported. The torque curves for the magnetic field rotated within the ab plane have a fourfold symmetry, exhibiting inversions around 13 and 27K. The heat capacity exhibits a broad peak around T=16.5K. By applying the magnetic field along the c axis, the maximum value of the heat capacity is enhanced below 20K. These results, as well as the magnetic susceptibility, were analyzed by employing a numerical calculation based on the anisotropic Heisenberg model in one dimension. The analyses revealed that: (i) the peak in the magnetic-susceptibility data around 25K is due to an antiferromagnetic short-range order (SRO) formation associated with d electrons, and (ii) π electrons fall into an antiferromagnetic state below 13K. The spin-flop field of π electrons is approximately 80kOe at 9K

Anaplastic carcinoma associated with a mucinous cystic neoplasm of the pancreas during pregnancy: Report of a case and a review of the literature

Oncogenesis of anaplastic carcinoma of the pancreas is a subject of controversy, because it shows sarcomatous nature with extremely poor prognosis. We herein report an unusual case of anaplastic carcinoma occurring with a recurrent mucinous cystic neoplasm in a 38-year-old female. A 10-cm retroperitoneal cystic mass was pointed out in the first pregnancy and a probable diagnosis of mucinous cystic neoplasm was made in October 2000. She refused surgery first and delivered her baby uneventfully. During her second pregnancy in 2002, however, she presented hematemesis and underwent urgent distal pancreatectomy, splenectomy and partial resection of the gastric wall where the tumor perforated. A diagnosis of borderline-type mucinous cystic neoplasm with ovarian-like stroma was made. Nine months later, CT visualized a recurrent cystic tumor near the pancreatic stump, which was subsequently resected. Pathology revealed that the tumor was composed of two different components of borderline-type mucinous cystic neoplasm and anaplastic carcinoma. The latter was intensely positive for vimentin, CD68, p53 and focally for cytokeratin, suggesting both sarcomatous and carcinomatous differentiation. She survived four years after the second surgery without tumor recurrence. Although the origin of anaplastic carcinoma has not been determined yet, it should be remembered that anaplastic carcinoma can occur in association with mucinous cystic neoplasm of more benign histology

A case of invasive hemolymphangioma of the pancreas

Hemolymphangioma of the pancreas is a very rare benign tumor. There were only five reports of this disease until March 2008. Herein, we report a case of hemolymphangioma of the pancreas with gastrointestinal bleeding due to duodenal invasion. A 53-year-old man had been admitted a referral hospital because of severe anemia due to gastrointestinal bleeding in December 2005. He was then transferred to our institute with a diagnosis of a tumor of the head of the pancreas with duodenal invasion in January 2006. No abnormalities were revealed except for anemia in laboratory data including CEA and CA19-9. Gastrointestinal endoscopy revealed bleeding at the duodenum. Computed tomography also demonstrated a heterogenous mass at the pancreatic head and suspected invasion to the duodenal wall. Ultrasonography showed a huge mass at the pancreatic head with a mixture of high and low echoic areas. Pylorous-preserving pancreatoduodenectomy was performed. The pancreatic tumor was soft and had invaded to the duodenum. The pathological diagnosis was a hemolymphangioma of the pancreas invaded to the duodenum. His postoperative course was uneventful and he was discharged on the 26th d after surgery. Hemolymphangioma of the pancreas is a very rare benign tumor. In a literature review until March 2008, we found five case reports. Major symptoms are abdominal pain and distension due to the enlarged tumor. However, we experienced a case of hemolymphangioma of the pancreas with gastrointestinal bleeding due to invasion to the duodenum. This disease is a very rare entity, but should be considered when patients have gastrointestinal bleeding

An easier method for performing a pancreaticojejunostomy for the soft pancreas using a fast-absorbable suture

AIM: To clarify the usefulness of a new method for performing a pancreaticojejunostomy by using a fast-absorbable suture material irradiated polyglactin 910, and a temporary stent tube for a narrow pancreatic duct with a soft pancreatic texture

Cycle and rate properties of mesoporous tin anode for lithium ion secondary batteries

A mesoporous Sn anode was electrodeposited in the presence of lyotropic liquid crystals made of nonionic surfactants. The introduction of mesoporous structure was effective for the accommodation of volume change of Sn during charge and discharge cycling of Li ions. The discharge capacity of the mesoporous Sn anode at 1 C rate was as high as 425 mA h g(-1) at the 100th cycle, and that was as high as 320 mA It g(-1) at the 100th cycle even though at 5 degrees C rate

Hemosuccus pancreaticus: Problems and pitfalls in diagnosis and treatment

Hemosuccus pancreaticus is a rare cause of intermittent upper gastrointestinal bleeding. We report two cases of hemosuccus pancreaticus with multiple episodes of upper gastrointestinal bleeding. The causes of hemorrhage were rupture of pseudoaneurysm of the splenic artery and bleeding from the wall of pancreatic pseudocyst. Interventional radiology is the first modality for early diagnosis and possible treatment of hemosuccus pancreaticus. When angiography shows no abnormal findings or interventional radiological therapy can not be successful, surgery should be considered without delay. Our patients herein underwent surgery without recurrence or sequelae. Intraoperative ultrasonography and pancreatoscopy were helpful modalities for confirming the source of hemorrhage and determining the cutting line of the pancreas. When we encounter intermittent upper gastrointestinal bleeding with an obscure source, hemosuccus pancreaticus should be included in differential diagnoses especially in patients with chronic pancreatitis, which would lead to a prompt and proper treatment

Intraoperative ultrasound as an educational guide for laparoscopic biliary surgery

AIM: To analyze the efficacy of routine intraoperative ultrasound (IOUS) as a guide for understanding biliary tract anatomy, to avoid bile duct injury (BDI) after laparoscopic cholecystectomy (LC), as well as any burden during the learning period