Transforming growth factor-β1 antisense oligodeoxynucleotides block interstitial fibrosis in unilateral ureteral obstruction

Transforming growth factor-β1 antisense oligodeoxynucleotides block interstitial fibrosis in unilateral ureteral obstruction.BackgroundInterstitial expression of transforming growth factor-β1 (TGF-β1) is important in tubulointerstitial fibrosis, a common process in most progressive renal diseases. However, no effective therapy for progressive interstitial fibrosis is known. Recently, we developed an artificial viral envelope (AVE)-type hemagglutinating virus of Japan (HVJ) liposome-mediated retrograde ureteral gene transfer method, which allowed us to introduce the genetic material selectively into renal interstitial fibroblasts.MethodWe introduced antisense or scrambled oligodeoxynucleotides (ODNs) for TGF-β1 into interstitial fibroblasts in rats with unilateral ureteral obstruction, a model of interstitial fibrosis, to block interstitial fibrosis by retrograde ureteral injection of AVE-type HVJ liposomes.ResultsTGF-β1 and type I collagen mRNA increased markedly in the interstitium of untreated obstructed kidneys, and those were not affected by scrambled ODN transfection. Northern analysis and in situ hybridization revealed that the levels of TGF-β1 and type I collagen mRNA were dramatically decreased in antisense ODN-transfected obstructed kidneys. Consequently, the interstitial fibrotic area of the obstructed kidneys treated with antisense ODN was significantly less than that of the obstructed kidneys untreated or treated with scrambled ODN.ConclusionThe introduction of TGF-β1 antisense ODN into interstitial fibroblasts may be a potential therapeutic maneuver for interstitial fibrosis

Cytokine profiles in an extremely preterm infant with congenital syphilis

We report the cytokine profiles of an infant with congenital syphilis as a first case. This female infant was born by vaginal delivery at a gestational age of 27 weeks during her mother's treatment for syphilis. Elevation of T helper (Th)-1 cytokines (interleukin (IL)-2, IL-12) and IL-17, which supports immunological mechanisms of Th-1, was similar to that in cases of syphilis in adults. IL-6 and granulocyte colony-stimulating factor (G-CSF), the synergistic effects of which cause the leukemoid reaction, were also elevated. The levels of interferon-γ and IL-17 in cerebral spinal fluid, which are elevated in neurosyphilis in adults, were slightly elevated

Seeking Collaborative Instruction Models beyond the Pandemic: Lessons Learned from the JapanKnowledge Workshop Series hosted by the Plains to Pacific Alliance

As the Pandemic disrupted normal communication patterns and networking opportunities, videoconferencing, usually using the Zoom platform, became the preferred method for academic institutions to continue providing instruction to students and supporting researchers. In 2021, the Plains to Pacific Alliance (PPA) developed plans to use this technology to present a workshop series on the JapanKnowledge database that would be open to Japanese studies researchers and students in North America and beyond. This entailed deciding on content, developing instructional materials, promoting the workshops in collaboration with the North American Coordinating Council on Japanese Library Resources, creating a registration system, presenting the workshops through Zoom and analyzing the post-workshop survey results

A Splice Variant of ASC Regulates IL-1β Release and Aggregates Differently from Intact ASC

The apoptosis-associated speck-like protein containing a caspase recruit domain (ASC) is involved in apoptosis and innate immunity and is a major adaptor molecule responsible for procaspase-1 activation. ASC mRNA is encoded by three exons: exons 1 and 3 encode a pyrin domain (PYD) and caspase recruit domain (CARD), respectively, and exon 2 encodes a proline and glycine-rich (PGR) domain. Here, we identified a variant ASC protein (vASC) lacking the PGR domain that was smaller than full length ASC (fASC) derived from fully transcribed mRNA and searched for differences in biochemical and biological nature. Both fASC and vASC were found to activate procaspase-1 to a similar degree, but the efficiency of IL-1β excretion was significantly higher for vASC. There was also a marked structural difference observed in the fibrous aggregates formed by fASC and vASC. These results suggest that although the PGR domain is dispensable for procaspase-1 activation, it plays an important role in the regulation of the molecular structure and activity of ASC

Thrombin Stimulates Synthesis of Macrophage Colony-Stimulating Factor, Granulocyte-Macrophage Colony-Stimulating Factor and Granulocyte Colony-Stimulating Factor by Human Proximal Tubular Epithelial Cells in Culture

Background/Aims: Colony-stimulating factors (CSFs) are well-known hematopoietic growth factors. Although recent studies revealed that CSFs are involved in many inflammatory conditions, the local production of CSFs and its regulation in the kidney is not well elucidated. Therefore, using cultured human proximal tubular epithelial cells (PTEC), we examined the effect of thrombin on CSFs production, since thrombin has been suggested to play an important role in tubulointerstitial injury. Methods: PTEC were incubated with thrombin (0.5–5.0 U/ml) and the effects on the production of macrophage CSF (M-CSF), granulocyte-macrophage CSF (GM-CSF) and granulocyte CSF (G-CSF) were measured in the cell supernatant by enzyme-linked immunosorbent assay, and the expressions of mRNA were analyzed by quantitative real-time reverse transcription polymerase chain reaction. Using argatroban, a direct thrombin inhibitor, we also examined the specific effect of thrombin. Results: Thrombin 5.0 U/ml significantly stimulated the production of M-CSF (p Conclusion: We demonstrated that thrombin significantly increased the production of CSFs by PTEC. These data suggest that the local production of CSFs in the tubulointerstitium may affect tubulointerstitial lesions in kidney injury

Peripheral platelet phagocytosis in an extremely low birth weight infant: a case report

A 768 g female neonate, born at 25 weeks' gestation, developed sepsis due to methicillin-resistant Staphylococcus epidermidis on day 14. Severe thrombocytopenia was observed, and hemophagocytic macrophages were identified in her peripheral blood smear. Cytokine profiles at the time of onset suggested that an inflammatory cytokine storm had activated lymphocytes and macrophages, leading to platelet phagocytosis. After administration of vancomycin for 14 days and immunoglobulin therapy, she improved without any complications. Considering the results of cytokine profiles, early intervention for infection may have prevented progression to hemophagocytic lymphohistiocytosis and reduced the severity of clinical symptoms

Identifying key factors for successful formulation and implementation of healthcare policies on non-communicable diseases: a multinational analysis

Objectives: Non-communicable diseases (NCDs) are a major public health concern that accounts for 74% of global deaths each year. The increasing burden of NCDs exhausts public health resources and threatens the achievement of the 2030 agenda for sustainable development. The purpose of this study is to thematically analyze the contributory factors in the health policy process and reforms to strengthen the prevention of NCDs across borders, as well as the milestones achieved through the process of policy-making, change, and implementation. Method: This study informs and draws on the findings of contributory factors in the health policy process for preventing NCDs across borders: United States, England, Sweden, Bangladesh, Singapore, South Korea, and Thailand. Ten experts from the seven countries were recruited purposively for a semi-structured interview (e-Interview) on the NCD policy-making process in their countries, either through health ministries or the authors’ network. This descriptive qualitative study design is guided by the “Three I’s” framework of public policy (institutions, ideas, and interests). In addition to the information obtained from the interviewee, data were also sourced from relevant documents and homepages suggested by the interviewee, as well as health homepages of the countries. Result: The following themes were generated: (1) environmental policies and social determinants, (2) multistakeholder involvement, (3) interministerial collaboration, (4) independent evidence and review institution, (5) integrated health data, and (6) primary care system. There was a shift from individual-targeted policies to environmental policies and social determinants. Notably, national campaigns were developed through non-governmental organizations (NGOs) for the primary prevention of NCDs. Conclusion: The shift from behavioral modification and treatment to social determinants is important. NCDs are broad and require a multisector and multilevel approach. Establishing an organization or hierarchical body to overlook NCDs could result in increased awareness, focus, and surveillance and enhance the policy process