Chia-Jung Li

New Insights into the Role of Inflammation in the Pathogenesis of Atherosclerosis

Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipids, smooth muscle cell proliferation, cell apoptosis, necrosis, fibrosis, and local inflammation. Immune and inflammatory responses have significant effects on every phase of atherosclerosis, and increasing evidence shows that immunity plays a more important role in atherosclerosis by tightly regulating its progression. Therefore, understanding the relationship between immune responses and the atherosclerotic microenvironment is extremely important. This article reviews existing knowledge regarding the pathogenesis of immune responses in the atherosclerotic microenvironment, and the immune mechanisms involved in atherosclerosis formation and activation.

New Insights into the Role of Autophagy in Tumor Immune Microenvironment

The tumor microenvironment is a complex system that is affected by various factors, including hypoxia, acidosis, and immune and inflammatory responses, which have significant effects on tumor adhesion, invasion, metastasis, angiogenesis, and autophagy. In this hostile tumor microenvironment, autophagy of tumor cells can promote tumor growth and metastasis. As autophagy is a double-edged sword in tumors, treatment of cancer via regulation of autophagy is extremely complicated. Therefore, understanding the relationship between tumor autophagy and the tumor microenvironment is extremely important. As the immune milieu plays an important role in tumor development, immunotherapy has become a promising form of cancer therapy. A multi-pronged treatment approach using immunotherapy and molecular targets may become the major direction for future cancer treatments. This article reviews existing knowledge regarding the immune factors in the tumor microenvironment and the status of tumor autophagy research.

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.

Glycyrrhizic acid induces human MDA-MB-231 breast cancer cell death and autophagy via the ROS-mitochondrial pathway

Glycyrrhizic acid (GA), the main component of licorice root extracts, has been shown to suppress cell proliferation and induce apoptosis in various types of cancers. However, the molecular mechanism of its anticancer activity remains poorly understood and warrants further investigation. MDA-MB‑231 cells were treated with various concentrations of GA and the cytotoxic effects of GA were determined using the CCK-8 assay. Apoptosis and cell cycle status were detected by flow cytometry. Reactive oxygen species (ROS) levels and mitochondrial membrane potential (∆Ψm) were assessed using DCFDA, MitoSOX and JC-1 staining. Western blot analysis was used to quantify the expression of autophagy-related proteins. In the present study, induction of autophagic cell death was observed in GA-treated MDA-MB‑231 cells. Downregulation of p62-xa0and beclinxa01-associated proteins occurred after GA treatment, and, the conversion of LC3 and increased ROS without significant changes in caspase‑associated proteins and intracellular responses were detected. Furthermore, loss of mitochondria and its membrane potential in cells demonstrated that mitochondria were involved in the GA-regulated MDA-MB-231 cell death. The addition of a pan-caspase inhibitor (z-VAD-fmk) did not suppress the GA-induced apoptotic effect, and GA-induced apoptosis was not accompanied by processing of procaspase-8,xa0-9xa0andxa0-3. However, GA triggered the translocation of the apoptosis-inducing factor (AIF) from the mitochondria into the nucleus. In contrast, GA-induced LC3 conversion was significantly inhibited by 3xa0methlyadenine (3MA), an inhibitor of PI3K‑regulated autophagy. Therefore, these results suggest that enhancement of both AIF-xa0andxa0LC3-dependent GA-derived ROS generation plays an important role in the inhibition of the growth of MDA-MB-231 human breast cancer cells.

Dehydroepiandrosterone as a potential agent to slow down ovarian aging

Ovarian aging, which leads to diminished ovarian reserve and decreased oocyte quality, is highly associated with poor reproductive outcomes. It has been suggested that dehydroepiandrosterone (DHEA) might be able to temporarily slow down the aging process. This study attempted to investigate the clinical benefits of DHEA in older patients and the anti‐senescence effect of DHEA on cumulus cells (CC) and human ovarian granulosa cells (HO23 cell line).

Dehydroepiandrosterone Ameliorates Abnormal Mitochondrial Dynamics and Mitophagy of Cumulus Cells in Poor Ovarian Responders

Mitochondrial dysfunction is related to reproductive decline in humans, with consequences for in vitro fertilization (IVF). We assessed whether dehydroepiandrosterone (DHEA) could regulate mitochondrial homeostasis and mitophagy of cumulus cells (CCs) in poor ovarian responders (PORs). A total of 66 women who underwent IVF treatment at the Reproductive Medicine Center of Kaohsiung Veterans General Hospital were included in this study. Twenty-eight normal ovarian responders (NOR) and 38 PORs were enrolled. PORs were assigned to receive DHEA supplementation (n = 19) or not (n = 19) before IVF cycles. DHEA prevents mitochondrial dysfunction by decreasing the activation of DNM1L and MFF, and increasing MFN1 expression. Downregulation of PINK1 and PRKN occurred after DHEA treatment, along with increased lysosome formation. DHEA not only promoted mitochondrial mass but also improved mitochondrial homeostasis and dynamics in the CCs of POR. We also observed effects of alterations in mRNAs known to regulate mitochondrial dynamics and mitophagy in the CCs of POR. DHEA may prevent mitochondrial dysfunction through regulating mitochondrial homeostasis and mitophagy.

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.

Molecular Targets in Hepatocarcinogenesis and Implications for Therapy

Hepatocarcinogenesis comprises of multiple, complex steps that occur after liver injury and usually involve several pathways, including telomere dysfunction, cell cycle, WNT/β-catenin signaling, oxidative stress and mitochondria dysfunction, autophagy, apoptosis, and AKT/mTOR signaling. Following liver injury, gene mutations, accumulation of oxidative stress, and local inflammation lead to cell proliferation, differentiation, apoptosis, and necrosis. The persistence of this vicious cycle in turn leads to further gene mutation and dysregulation of pro- and anti-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-10, IL-12, IL-13, IL-18, and transforming growth factor (TGF)-β, resulting in immune escape by means of the NF-κB and inflammasome signaling pathways. In this review, we summarize studies focusing on the roles of hepatocarcinogenesis and the immune system in liver cancer. In addition, we furnish an overview of recent basic and clinical studies to provide a strong foundation to develop novel anti-carcinogenesis targets 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.