Mitofilin in cardiovascular diseases: Insights into the pathogenesis and potential pharmacological interventions.

The impact of mitochondrial dysfunction on the pathogenesis of cardiovascular disease is increasing. However, the precise underlying mechanism remains unclear. Mitochondria produce cellular energy through oxidative phosphorylation while regulating calcium homeostasis, cellular respiration, and the production of biosynthetic chemicals. Nevertheless, problems related to cardiac energy metabolism, defective mitochondrial proteins, mitophagy, and structural changes in mitochondrial membranes can cause cardiovascular diseases via mitochondrial dysfunction. Mitofilin is a critical inner mitochondrial membrane protein that maintains cristae structure and facilitates protein transport while linking the inner mitochondrial membrane, outer mitochondrial membrane, and mitochondrial DNA transcription. Researchers believe that mitofilin may be a therapeutic target for treating cardiovascular diseases, particularly cardiac mitochondrial dysfunctions. In this review, we highlight current findings regarding the role of mitofilin in the pathogenesis of cardiovascular diseases and potential therapeutic compounds targeting mitofilin.

Response to programmed cell death protein 1 antibody in patients with Epstein-Barr virus-associated intrahepatic cholangiocarcinoma.

AIM: Epstein-Barr virus-associated intrahepatic cholangiocarcinoma (EBVaICC) has a distinct genomic profile and increased CD3+ and CD8+ T cells infiltration. However, the efficacy of immunotherapy in EBVaICC remains largely unknown. This study aimed to assess the efficacy of programmed cell death protein 1 (PD-1) antibody therapy in EBVaICC. METHODS: Patients with metastatic biliary tract cancer (BTC) diagnosed at Sun Yat-sen University Cancer Center from January 2016 to December 2021 were identified. In situ hybridisation was performed to detect EBV. Overall survival (OS) and progression-free survival (PFS) were measured. RESULTS: A total of 698 patients with metastatic BTC were identified, of whom 39 (5.6%) had EBVaICC. Among the 136 patients who were not administered PD-1 antibody, the OS was similar between patients with EBVaICC and EBV-negative ICC (median OS 12.5 versus 9.5 months, respectively; P = 0.692). For the 205 patients who were administered PD-1 antibody, patients with EBVaICC had significantly longer OS than patients with EBV-negative ICC (median OS 24.9 versus 11.9 months, respectively; P = 0.004). Seventeen patients with EBVaICC were administered PD-1 antibody. Eight patients (47%) achieved a partial response, and 17 patients achieved disease control. The median PFS was 17.5 months. CONCLUSIONS: This study identified a clinically actionable subset of patients with EBVaICC with a promising response to the PD-1 antibody.

Iron homeostasis in the heart: Molecular mechanisms and pharmacological implications.

Iron is necessary for the life of practically all living things, yet it may also harm people toxically. Accordingly, humans and other mammals have evolved an effective and tightly regulatory system to maintain iron homeostasis in healthy tissues, including the heart. Iron deficiency is common in patients with heart failure, and is associated with worse prognosis in this population; while the prevalence of iron overload-related cardiovascular disorders is also increasing. Therefore, enhancing the therapy of patients with cardiovascular disorders requires a thorough understanding of iron homeostasis. Here, we give readers an overview of the fundamental mechanisms governing systemic iron homeostasis as well as the most recent knowledge about the intake, storage, use, and export of iron from the heart. Genetic mouse models used for investigation of iron metabolism in various in vivo scenarios are summarized and highlighted. We also go through different clinical conditions and therapeutic approaches that target cardiac iron dyshomeostasis. Finally, we conclude the review by outlining the present knowledge gaps and important open questions in this field in order to guide future research on cardiac iron metabolism.

Overview of the preparation method, structure and function, and application of natural peptides and polypeptides.

Natural polypeptides, a kind of molecular polymer with obvious biological activity, are widely existing in nature. They participate in various physiological activities of living organisms and play an important role in promoting human health. They are also widely applied in medicine, food, and cosmetic industries. By searching literature from Pubmed, Google Scholar, Web of Science, Springer Link and Elsevier, this work presents an overview of the preparation methods, the relationship between structure and function, and the application of natural polypeptides. The preparation methods mainly include solvent extraction, enzymatic decomposition, microbiological fermentation, chemical synthesis, genetic engineering recombination, and using cell free system. Natural polypeptide's physiological function mainly includes antioxidative, antibacterial, antihypertensive. This review could provide scientific basis for the research and development of natural polypeptide.

Protection of the Transplant Kidney from Preservation Injury by Inhibition of Matrix Metalloproteinases.

BACKGROUND: Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, play an important role in ischemic injury to the heart, yet it is not known if these MMPs are involved in the injury that occurs to the transplant kidney. We therefore studied the pharmacologic protection of transplant kidneys during machine cold perfusion. METHODS: Human kidney perfusates were analyzed for the presence of injury markers such as cytochrome c oxidase, lactate dehydrogenase, and neutrophil-gelatinase associated lipocalin (NGAL), and MMP-2 and MMP-9 were measured. The effects of MMP inhibitors MMP-2 siRNA and doxycycline were studied in an animal model of donation after circulatory determination of death (DCDD). RESULTS: Markers of injury were present in all analyzed perfusates, with higher levels seen in perfusates from human kidneys donated after controlled DCDD compared to brain death and in perfusate from kidneys with delayed graft function. When rat kidneys were perfused at 4°C for 22 hours with the addition of MMP inhibitors, this resulted in markedly reduced levels of MMP-2, MMP-9 and analyzed injury markers. CONCLUSIONS: Based on our study, MMPs are involved in preservation injury and the supplementation of preservation solution with MMP inhibitors is a potential novel strategy in protecting the transplant kidney from preservation injury.

Crohn disease of small bowel: multidetector row CT with CT enteroclysis, dynamic contrast enhancement, CT angiography, and 3D imaging.

BACKGROUND: CT could be used to evaluate abnormalities in the bowel wall, mesentery, adjacent structures, vasculature, and even the activity of Crohn disease (CD). To our knowledge, few direct comparisons of CD characterization using multidetector row CT with dynamic contrast enhancement, 3D imaging, CT angiography (CTA), and CT-enteroclysis (CT-E) on the same cohort of patients. The purpose of this study was to evaluate the diagnostic value of CD using multidetector helical CT with CT-E, dynamic contrast enhancement, 3D imaging, and CTA. METHODS: Twenty-eight patients known or suspected CD underwent CT-E, dynamic contract enhancement, CTA, and 3D imaging. The multidetector CT series images were performed on eight-slice CT scanner. All the examinations were performed when water was used as an oral contrast starting 25 s after 140 mL of intravenous contrast agent was administered, followed by portal venous phase (60 s), and a 60-70 s delay, then sending 1.25-mm slices to the 3D workstation, CT angiograms and 3D images were reconstructed. All the images were reviewed to detect abnormalities of CD. The abnormalities of the bowel wall, mucosal and submucosal ulceration, prominent perienteric vasculature, sinus tracts or fistulae, abscess were evaluated. RESULTS: Crohn disease was diagnosed in 28 patients by CT images, and 54 inflammatory segments were revealed. In active inflammatory cases, the diseased bowel wall thickened and the enhancement of diseased bowel wall increased significantly in 34 inflammatory segments of 22 cases, the enhancement of diseased bowel wall increased significantly but without the wall thickened in three patients. Prominent vasculature was found in CTA and 3D images in 21 patients with active diseases. In 16 patients, the sharp interface between bowel and mesentery was lost and the attenuation of fat increased. Sinus tracts or fistulae were observed in eight patients, four of 28 patients demonstrated abscesses, all were active inflammatory patients. In three chronic inflammatory patients, normal bowel, bowel lumen stricture, and the normal enhancement of the wall were displayed. CONCLUSION: The abnormalities of CD and its complications can be identified by multidetector CT with CT-E, dynamic enhancement, CTA, and 3D imaging, and they are important methods in diagnosing CD. Complications of CD can be shown better when CT-E is performed.