The renoprotective effect of Tibolone in sepsis-induced acute kidney injury.

INTRODUCTION: Sepsis-induced acute kidney injury (AKI) remains a major challenge in intensive care, contributing significantly to morbidity and mortality. Tibolone, known for its neuroprotective and hormonal properties, has not been explored for its potential in AKI management. This study investigates the protective effects of Tibolone and its underlying mechanisms involving Sirtuin-1 (SIRT1) and Yes-Associated Protein (YAP) in a rat sepsis model. MATERIALS AND METHODS: Thirty-six female Wistar albino rats underwent cecal ligation and puncture (CLP) to induce sepsis. They were randomly assigned to control, CLP+Saline, and CLP+Tibolone groups. Tibolone was administered intraperitoneally. Biomarkers, including Sirtuin (SIRT1), Yes-associated protein (YAP), Tumor necrosis factor (TNF-α), High mobility group box 1 (HMGB1), malondialdehyde (MDA), creatinine, and urea, were assessed. Histopathological examination evaluated renal damage. RESULTS: Tibolone administration significantly reduced plasma TNF-α, HMGB1, MDA, creatinine, and urea levels compared to the CLP+Saline group. Moreover, Tibolone elevated SIRT1 and YAP levels in kidney tissues. Histopathological examination demonstrated a significant decrease in tubular epithelial necrosis, luminal debris, dilatation, hemorrhage, and interstitial inflammation in Tibolone-treated rats. CONCLUSION: This study unveils the protective role of Tibolone against sepsis-induced AKI in rats. The improvements in inflammatory and oxidative biomarkers and histological evidence suggest Tibolone's potential as a therapeutic intervention in sepsis-associated kidney injury. The upregulation of SIRT1 and YAP indicates their involvement in Tibolone's renoprotective mechanisms. Further investigations are warranted to explore Tibolone's translational potential in human sepsis-induced AKI.

MicroRNA-216a is essential for cardiac angiogenesis.

While it is experimentally supported that impaired myocardial vascularization contributes to a mismatch between myocardial oxygen demand and supply, a mechanistic basis for disruption of coordinated tissue growth and angiogenesis in heart failure remains poorly understood. Silencing strategies that impair microRNA biogenesis have firmly implicated microRNAs in the regulation of angiogenesis, and individual microRNAs prove to be crucial in developmental or tumor angiogenesis. A high-throughput functional screening for the analysis of a whole-genome microRNA silencing library with regard to their phenotypic effect on endothelial cell proliferation as a key parameter, revealed several anti- and pro-proliferative microRNAs. Among those was miR-216a, a pro-angiogenic microRNA which is enriched in cardiac microvascular endothelial cells and reduced in expression under cardiac stress conditions. miR-216a null mice display dramatic cardiac phenotypes related to impaired myocardial vascularization and unbalanced autophagy and inflammation, supporting a model where microRNA regulation of microvascularization impacts the cardiac response to stress.

Long-Read Nanopore Sequencing Validated for Human Leukocyte Antigen Class I Typing in Routine Diagnostics.

Matching of human leukocyte antigen (HLA) gene polymorphisms by high-resolution DNA sequence analysis is the gold standard for determining compatibility between patient and donor for hematopoietic stem cell transplantation. Single-molecule sequencing (PacBio or MinION) is a newest (third) generation sequencing approach. MinION is a nanopore sequencing platform, which provides long targeted DNA sequences. The long reads provide unambiguous phasing, but the initial high error profile prevented its use in high-impact applications, such as HLA typing for HLA matching of donor and recipient in the transplantation setting. Ongoing developments on instrumentation and basecalling software have improved the per-base accuracy of 1D2 nanopore reads tremendously. In the current study, two validation panels of samples covering 70 of the 71 known HLA class I allele groups were used to compare third field sequences obtained by MinION, with Sanger sequence-based typing showing a 100% concordance between both data sets. In addition, the first validation panel was used to set the acceptance criteria for the use of MinION in a routine setting. The acceptance criteria were subsequently confirmed with the second validation panel. In summary, the present study describes validation and implementation of nanopore sequencing HLA class I typing method and illustrates that nanopore sequencing technology has advanced to a point where it can be used in routine diagnostics with high accuracy.

Interplay of N acetyl cysteine and melatonin in regulating oxidative stress-induced cardiac hypertrophic factors and microRNAs.

Early and specific diagnosis of oxidative stress linked diseases as cardiac heart diseases remains a major dilemma for researchers and clinicians. MicroRNAs may serve as a better tool for specific early diagnostics and propose their utilization in future molecular medicines. We aimed to measure the microRNAs expressions in oxidative stress linked cardiac hypertrophic condition induced through stimulants as Endothelin and Isoproterenol. Cardiac hypertrophic animal models were confirmed by BNP, GATA4 expression, histological assays, and increased cell surface area. High oxidative stress (ROS level) and decreased antioxidant activities were assessed in hypertrophied groups. Enhanced expression of miR-152, miR-212/132 while decreased miR-142-3p expression was observed in hypertrophic condition. Similar pattern of these microRNAs was detected in HL-1 cells treated with H2O2. Upon administration of antioxidants, the miRNAs expression pattern altered from that of the cardiac hypertrophied model. Present investigation suggests that oxidative stress generated during the cardiac pathology may directly or indirectly regulate anti-hypertrophy pathway elements through microRNAs including antioxidant enzymes, which need further investigation. The down-regulation of free radical scavengers make it easier for the oxidative stress to play a key role in disease progression.