Meng-Yu Wu

Current Mechanistic Concepts in Ischemia and Reperfusion Injury

Ischemia-reperfusion injury is associated with serious clinical manifestations, including myocardial hibernation, acute heart failure, cerebral dysfunction, gastrointestinal dysfunction, systemic inflammatory response syndrome, and multiple organ dysfunction syndrome. Ischemia-reperfusion injury is a critical medical condition that poses an important therapeutic challenge for physicians. In this review article, we present recent advances focusing on the basic pathophysiology of ischemia-reperfusion injury, especially the involvement of reactive oxygen species and cell death pathways. The involvement of the NADPH oxidase system, nitric oxide synthase system, and xanthine oxidase system are also described. When the blood supply is re-established after prolonged ischemia, local inflammation and ROS production increase, leading to secondary injury. Cell damage induced by prolonged ischemia-reperfusion injury may lead to apoptosis, autophagy, necrosis, and necroptosis. We highlight the latest mechanistic insights into reperfusion-injury-induced cell death via these different processes. The interlinked signaling pathways of cell death could offer new targets for therapeutic approaches. Treatment approaches for ischemia-reperfusion injury are also reviewed. We believe that understanding the pathophysiology ischemia-reperfusion injury will enable the development of novel treatment interventions.

Molecular Regulation of Bone Metastasis Pathogenesis

Distant metastases are the major cause of mortality in cancer patients. Bone metastases may cause bone fractures, local pain, hypercalcemia, bone marrow aplasia, and spinal cord compression. Therefore, the management of bone metastases is important in cancer treatment. Normal bone remodeling is regulated by osteoprotegerin ligand (OPGL), receptor activator of NF-κB ligand (RANKL), parathyroid hormone-related protein (PTHrP), and other cytokines. In the tumor microenvironment, tumor cells induce a vicious cycle that promotes osteoblastic and osteolytic lesions. Studies support the idea that distant metastases may occur due to the immunosuppressive function of myeloid-derived suppressor cells (MDSCs). These cells inhibit T cells and natural killer (NK) cells and differentiate into tumor-associating macrophages (TAMs), monocytes, and dendritic cells (DCs). In this review, we summarize studies focusing on the role of MDSCs in bone metastasis and provide a strong foundation for developing anticancer immune treatments and anticancer therapies, in general.

New Insights into the Immune Molecular Regulation of the Pathogenesis of Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome is an inflammatory disease characterized by dysfunction of pulmonary epithelial and capillary endothelial cells, infiltration of alveolar macrophages and neutrophils, cell apoptosis, necroptosis, NETosis, and fibrosis. Inflammatory responses have key effects on every phase of acute respiratory distress syndrome. The severe inflammatory cascades impaired the regulation of vascular endothelial barrier and vascular permeability. Therefore, understanding the relationship between the molecular regulation of immune cells and the pulmonary microenvironment is critical for disease management. This article reviews the current clinical and basic research on the pathogenesis of acute respiratory distress syndrome, including information on the microenvironment, vascular endothelial barrier and immune mechanisms, to offer a strong foundation for developing therapeutic interventions.

The Oxidative Stress and Mitochondrial Dysfunction during the Pathogenesis of Diabetic Retinopathy

Diabetic retinopathy is one of the most serious microvascular complications induced by hyperglycemia via five major pathways, including polyol, hexosamine, protein kinase C, and angiotensin II pathways and the accumulation of advanced glycation end products. The hyperglycemia-induced overproduction of reactive oxygen species (ROS) induces local inflammation, mitochondrial dysfunction, microvascular dysfunction, and cell apoptosis. The accumulation of ROS, local inflammation, and cell death are tightly linked and considerably affect all phases of diabetic retinopathy pathogenesis. Furthermore, microvascular dysfunction induces ischemia and local inflammation, leading to neovascularization, macular edema, and neurodysfunction, ultimately leading to long-term blindness. Therefore, it is crucial to understand and elucidate the detailed mechanisms underlying the development of diabetic retinopathy. In this review, we summarized the existing knowledge about the pathogenesis and current strategies for the treatment of diabetic retinopathy, and we believe this systematization will help and support further research in this area.

The Emerging Role of Pathogenesis of IgA Nephropathy

IgA nephropathy is an autoimmune disease induced by fthe ormation of galactose-deficient IgA1 and anti-glycans autoantibody. A multi-hit hypothesis was promoted to explain full expression of IgA nephropathy. The deposition of immune complex resulted in activation of the complement, increasing oxidative stress, promoting inflammatory cascade, and inducing cell apoptosis via mesangio-podocytic-tubular crosstalk. The interlinked signaling pathways of immune-complex-mediated inflammation can offer a novel target for therapeutic approaches. Treatments of IgA nephropathy are also summarized in our review article. In this article, we provide an overview of the recent basic and clinical studies in cell molecular regulation of IgAN for further treatment interventions.

Clinical Outcome and Management for Geriatric Traumatic Injury: Analysis of 2688 Cases in the Emergency Department of a Teaching Hospital in Taiwan

Geriatric traumatic injuries in emergency departments are frequent and associated with higher mortality rates and catastrophic functional outcomes. Several prediction scores have been established to manage traumatic patients, including the shock index (SI), revised trauma score (RTS), injury severity score (ISS), trauma injury severity score (TRISS), and new injury severity score (NISS). However, it was necessary to investigate the effectiveness and efficiency of care for the geriatric traumatic population. In addition, image studies such as computed tomography and magnetic resonance imaging play an important role in early diagnosis and timely intervention. However, few studies focus on this aspect. The association between the benefit of carrying out more image studies and clinical outcomes remains unclear. In this study, we included a total of 2688 traumatic patients and analyzed the clinical outcomes and predicting factors in terms of geriatric trauma via pre-hospital and in-hospital analysis. Our evaluation revealed that a shock index ≥1 may be not a strong predictor of geriatric trauma due to the poor physical response in the aging population. This should be modified in geriatric patients. Other systems, like RTS, ISS, TRISS, and NISS, were significant in terms of predicting the clinical outcome.

Septic Pulmonary Emboli or Pulmonary Metastasis in a Patient with Diabetes Mellitus

Emphysematous pyelonephritis is a rare but life-threatening infection characterized by an accumulation of gas in the renal parenchyma. A high mortality rate was reported, and timely administration of broad-spectrum antibiotics for enteric gram-negative bacilli, such as Escherichia coli, Enterobacter, and Klebsiella pneumoniae, was recommended for improving the clinical outcome. Computed tomography is a useful tool for identifying gas accumulation within the perirenal space. Abdominal ultrasound and abdominal plain film are alternative options with lower accuracy rates. Here, we present the case of a 49-year-old male patient who presented with acute-onset progressive abdominal cramping pain and dysuria. Diffuse bilateral opacities over the lung field and a heterogeneous mass with air density in the abdomen were found on radiological examination. Multiple septic pulmonary emboli and emphysematous pyelonephritis were diagnosed using computed tomography. After emergency percutaneous nephrostomy and administration of broad-spectrum antibiotics, the patient was discharged in a stable condition and followed up at the outpatient department. This report also describes the clinical and imaging features of emphysematous pyelonephritis and highlights that early diagnosis and timely administration of broad-spectrum antibiotics may help avoid a potentially devastating outcome.

Epithelial-Mesenchymal Transition with Malignant Transformation Leading Multiple Metastasis from Disseminated Peritoneal Leiomyomatosis

Disseminated peritoneal leiomyomatosis (DPL) is a rare condition that is characterized by the presence of multiple subperitoneal or peritoneal smooth muscle nodules of varying sizes on the omentum and peritoneal surfaces, grossly mimicking disseminated carcinoma. DPL usually develops in premenopausal women with a benign course, and it is often found incidentally during abdominal surgery. Malignant transformation is a rare clinical course of DPL. Only a few studies have focused on DPL transformation into a leiomyosarcoma. Herein, we describe the case of a 61-year-old woman with a history of recurrent leiomyoma of the uterus who presented with intermittent progressive abdominal pain. The imaging study revealed a huge heterogeneous density mass in the pelvic region with pulmonary and hepatic metastases. Exploratory laparotomy and debulking surgery were performed, and showed the coexistence of DPL and leiomyosarcoma. She died approximately one month after the diagnosis because of rapid progression of pleural effusion due to malignancy. This case highlights the clinical features of DPL and its malignant transformation and metastasis so physicians can make an early diagnosis and provide timely management.