Protective Effect of Silent Mating Type Information Regulation 2 Homolog 1 on TGF-β1 Pathway via mTOR in Diabetic Nephropathy

Objective: To demonstrate whether the expression of silent mating type information regulation 2 homolog 1 (SIRT1) affects the level of TGF-β1 and Smad3 in HEK293 cells through regulating mTOR. Methods: First, recombinant plasmids DNA (rSIRT1) and siRNA targeting SIRT1 were constructed which were transfected into Human Embryonic Kidney 293 cell (HEK293) cells, respectively. Then, the generation of intracellular ROS in cells was examined by flow cytometry using the oxidation-sensitive probe. Last, the expressions of TGF-β1, smad3, P53, mTOR, p-mTOR, LC3-I and LC3-II in cells were detected to observe the effect of SIRT1 on TGF-β1 Pathway by western blot analysis. Results: We demonstrated that overexpressing of SIRT1 may decrease TGF-β1 and Smad3 expression in HEK293 cells through regulating mTOR. In addition, the result is the opposite when SIRT1 was silent in HEK293 cells. Conclusions: SIRT1 is closely related to TGF-β1/Smad3 pathway that correlates with the regulation of mTOR and ROS generation and causes diabetic nephropathy. The available evidence implies that SIRT1 has great potential as a clinical target for the prevention and treatment of renal fibrosis in the development of DN.

Optimizing profile line interval for enhanced accuracy in rock joint morphology and shear strength assessments

2D profile lines play a critical role in cost-effectively evaluating rock joint properties and shear strength.However, the interval(ΔI_(L)) between these lines significantly impacts roughness and shear strength assessments. A detailed study of 45 joint samples using four statistical measures across 500 different ΔI_(L)values identified a clear line interval effect with two stages: stable and fluctuation-discrete.Further statistical analysis showed a linear relationship between the error bounds of four parameters,shear strength evaluation, and their corresponding maximum ΔI_(L)values, where the gradient k of this linear relationship was influenced by the basic friction angle and normal stress. Accounting for these factors,lower-limit linear models were employed to determine the optimal ΔI_(L)values that met error tolerances(1%–10%) for all metrics and shear strength. The study also explored the consistent size effect on joints regardless of ΔI_(L)changes, revealing three types of size effects based on morphological heterogeneity.Notably, larger joints required generally higher ΔI_(L)to maintain the predefined error limits, suggesting an increased interval for large joint analyses. Consequently, this research provides a basis for determining the optimal ΔI_(L), improving accuracy in 2D profile line assessments of joint characteristics.

Pharmacological Monitoring of Capecitabine in a Gastric Cancer Patient with Hyperbilirubinemia

Objective: To examine therapeutic drug monitoring in managing hyperbilirubinemia caused by capecitabine in patients with gastric adenocarcinoma with extensive liver metastases. Results: The initial liver function tests showed an elevation of transaminases (aspartate amino transferase 615 UI/l, alanine aminotransferase 385.9 UI/l), hyperbilirubinemia (total bilirubin at 246.1 μmol/l), and alkaline phosphatase at 694.6 UI/l. We initiated capecitabine based combination chemotherapy, and the clinical pharmacist conducted a full-course medication monitoring of the patient’s treatment including design of individualized dosing regimens and monitoring of bilirubin, infection, cancer pain, parenteral nutrition support and adverse events. After 21 days of supervision by clinical pharmacist and clinicians, the patient’s bilirubin and transaminase decreased progressively, with aspartate aminotransferase, total bilirubin and alkaline phosphatase falling back to 57 UI/l, 69.8 μmol/l, 307.2 UI/l, respectively. The patient’s condition improved significantly at the time of discharge, with the jaundice subsided, and the bloating relieved. Conclusion: Due to adverse reactions, capecitabine requires medication monitoring during use. The relationship between effectiveness and adverse effects is controversial. Adverse reactions should not be the sole criterion for the use of drugs. Clinical pharmacists can improve the safety and effectiveness of patients’ medications and promote rational drug use by monitoring patients, which may be useful to help the doctors identify the high-risk patients for taking efficient treatment strategy decisions.