Translational research : the journal of laboratory and clinical medicine
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Acute kidney injury (AKI) is a complex and heterogeneous disease with high incidence and mortality, posing a serious threat to human life and health. Usually, in clinical practice, AKI is caused by crush injury, nephrotoxin exposure, ischemia-reperfusion injury, or sepsis. Therefore, most AKI models for pharmacological experimentation are based on this. ⋯ These approaches can promote renal repair and improve systemic hemodynamics after renal injury by reducing oxidative stress, inflammatory response, organelles damage, and cell death, or activating cytoprotective mechanisms. However, no candidate drugs for AKI prevention or treatment have been successfully translated from bench to bedside. This article summarizes the latest progress in AKI biotherapy, focusing on potential clinical targets and novel treatment strategies that merit further investigation in future pre-clinical and clinical studies.
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Chronic heart failure (CHF) as a long-term disease is highly prevalent in elder people worldwide. Early diagnosis and treatments are crucial for preventing the development of CHF. Herein, we aimed to identify novel diagnostic biomarker, therapeutic target and drug for CHF. ⋯ What's more, RUS can effectively improve cardiac function, myocardial fibrosis and morphological damage. Collectively, this study provided a potential metabolic marker CMPF and novel target OAT1/3 for CHF, which were demonstrated to be involved in FAO. And RUS was identified as a potential anti-FAO drug for CHF by regulating OAT1/3.
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Cutaneous neurofibromas (cNFs) are a hallmark of patients with the neurofibromatosis type 1 (NF1) genetic disorder. These benign nerve sheath tumors, which can amount to thousands, develop from puberty onward, often cause pain and are considered by patients to be the primary burden of the disease. Mutations of NF1, encoding a negative regulator of the RAS signaling pathway, in the Schwann cell (SCs) lineage are considered to be at the origin of cNFs. ⋯ Using this model, we found that cNFs development is a singular event and goes through 3 successive stages: initiation, progression, and stabilization characterized by changes in the proliferative and MAPK activities of tumor SCs. We found that skin trauma accelerated the development of cNFs and further used this model to explore the efficacy of the MEK inhibitor binimetinib to cure these tumors. We showed that while topically delivered binimetinib has a selective and minor effect on mature cNFs, the same drug prevents their development over long periods.
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Ongoing research on cellular heterogeneity of Cancer stem cells (CSCs) and its synergistic involvement with tumor milieu reveals enormous complexity, resulting in diverse hindrance in immune therapy. CSCs has captured attention for their contribution in shaping of tumor microenvironment and as target for therapeutic intervention. Recent studies have highlighted cell-extrinsic and intrinsic mechanisms of reciprocal interaction between tumor stroma constituents and CSCs. ⋯ Detail understanding of CSC and TME resident immune cells interaction can shape new avenues for cancer immune therapy. In this review, we have tried to summarize the development of knowledge on cellular, molecular and functional interaction between CSCs and tumor microenvironment immune cells, highlighting immune-mediated therapeutic strategies aimed at CSCs. We also discussed developing a potential CSC and TME targeted therapeutic avenue.
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Testing of microsatellite instability is not only used as a triage for possible Lynch syndrome, but also to predict immunotherapy treatment response. The aim of this study was to assess the frequency of mismatch repair deficiency (MMR-D)/microsatellite instability (MSI) in 400 cases of non-endometrioid ovarian tumors (high-grade serous, low-grade serous, mucinous and clear cell), to compare different methodological approaches of testing, and to assess the optimal approach for next generation sequencing (NGS) MSI testing. For all tumors, we evaluated immunohistochemical (IHC) expression of MMR proteins and assessed microsatellite markers by PCR-based method. ⋯ Our study shows that MSI occurs in 7% of CCC while it is rare or absent in other nonendometrioid ovarian neoplasms. Lynch syndrome was present in 2% of patients with CCC. However, some cases with MSH6 mutation can evade all testing methods, including IHC, PCR, and NGS-MSI.