Novel approaches to assess diet and kidney health risk

Chronic kidney disease (CKD) is a global public health problem. CKD is ultimately resulting in kidney failure and is an important cause of premature mortality and cardiovascular morbidity. The diet plays an important role in the development and progression of CKD and kidney function decline. This thesis describes several new approaches to assess the association between diet and kidney health, taking into account the complexity of overall diet and dietary intake in real life. Through observational prospective Lifelines cohort studies, spatial differences in kidney function are observed in the Northern Netherlands, which may be related to the neighborhood-level dietary intake. Higher adherence to a high-quality diet underlying the 2015 Dutch Dietary Guidelines is associated with a lower risk of incident CKD or kidney function decline in the general population. Kidney-specific dietary patterns are identified and are strongly linked with kidney health risk, thus, they can be considered to design tailored and targeted measures to prevent kidney health risk in the general population and kidney transplant recipients. Ultra-processed foods as modern industrial products become increasingly prominent in the food supplies and dietary patterns. We found that they are associated with a higher kidney health risk. In conclusion, achieving healthier dietary habits is a main strategy for the prevention of CKD and its complications (including cardiovascular disease). Novel approaches, addressing the complexity of diet in daily life, provide important insights and opportunities to guide the prevention of CKD by dietary measures in the future

Epstein-Barr Virus-Positive Natural Killer/T-Cell Lymphoma

Extranodal natural killer/T-cell lymphoma, nasal type (ENKL), is a rare malignancy of Non-Hodgkin lymphoma characterized by an aggressive clinical course and poor prognosis. It shows strong association with Epstein-Barr virus infection and occurs more commonly in Asia and Latin America. Various genetic alterations have been identified in ENKL by gene expression profiling and sequencing techniques. The frequent deletion of chromosome 6q21 was reported to lead to the silence of several tumor suppressor genes. Also, there have been novel genetic mutations that were recently uncovered and were found to frequently activate several oncogenic pathways, including the JAK/STAT, NF-κB, and MAPK pathways. Besides, we believe that deregulated single genes and epigenetic dysregulation might be relevant to the mechanism of this disease and thus, may have the potential to shed lights on the development of new therapeutic strategies. The consensus on the standard treatment for ENKL has not yet been currently established. For localized ENKL patients, radiotherapy with concurrent chemotherapy and sequential patterns of chemotherapy and radiotherapy are recommended as first-line therapy. As for advanced or relapsed/refractory ENKL patients, the application of non-anthracycline-containing regimens have significantly improved the clinical outcome, contributing to higher response rate, longer overall survival and progression-free survival. Hematopoietic stem cell transplantation is widely recommended for consolidation after a complete remission or partial remission has been achieved. The anti-programmed death 1 antibody, an immune checkpoint inhibitor, has demonstrated favorable results in treating relapsed or refractory ENKL. Of the current ENKL treatment, researchers are still striving to validate how radiotherapy and chemotherapy should be optimally combined and which of the non-anthracycline-containing regimens is superior. In this review, we summarize the main genetic alterations frequently found in ENKL and their role in providing new insights into the therapeutic targets of this disease, and highlight the recent findings regarding new biologic markers, novel therapeutic strategies applied to this intriguing neoplasm

Shikonin suppresses the proliferation and colony formation of gastric cancer cells by regulating miR96/SOCS4 pathway

Purpose: To investigate whether shikonin is able to inhibit cell proliferation and colony formation in gastric cancer (GC) cells and to elucidate the molecular mechanism. Methods: Gastric cancer (GC) cell line SGC-7901 was used. The effects of shikonin on SGC-7901 cells were evaluated using Cell Counting Kit-8 (CCK-8) and soft-agar colony formation assays, respectively. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was employed to measure miR-96 expression levels. The regulatory effect of miR-96 on SOCS4 was determined by luciferase activity assay, while the effect of shikonin and miR-96 overexpression on proliferating cell nuclear antigen (PCNA), cyclin D1, suppressor of cytokine signaling 4 (SOCS4), and JAK/STAT pathwayrelated protein expression levels were analyzed by western blots. Results: The results show that shikonin dose-dependently suppressed the proliferation and colony formation of SGC-7901 cells. Western blot analysis revealed that PCNA and cyclin D1 were downregulated by shikonin treatment. Luciferase activity assay demonstrated that miR-96 is directly bound to SOCS4. Further results showed that miR-96 mimics reversed the effects of shikonin on SOCS4 and JAK/STAT pathway-related protein expression levels. Conclusion: Shikonin suppresses proliferation and colony formation by regulating miR-96/SOCS4 pathway in SGC-7901 cells, providing a potential therapeutic target for GC