Pentraxin 3 plays a key role in tubular cell senescence and renal fibrosis through inducing ß-catenin signaling.

Renal fibrosis is the common pathological feature of various chronic kidney diseases (CKD). Tubular cell senescence plays a key role in the progression of renal fibrosis. However, the underlying mechanisms are still in mystery. In this study, we identified, Pentraxin 3 (PTX3), belonging to the Pentraxin family, is a new fibrogenic factor. PTX3 was increased in various CKD models. PTX3 was primarily localized in tubular epithelial cells and upregulated, accompanied by mitochondrial dysfunction and cellular senescence. Overexpression of PTX3 aggravated mitochondrial damage and accelerated cell senescence in tubular cells, leading to more severe fibrogenesis in kidneys. However, knockout of PTX3 significantly preserved mitochondrial homeostasis, and blocked cellular senescence in primary cultured tubular cells. Furthermore, KYA1797K, a destabilizer of ß-catenin, greatly inhibited PTX3-induced mitochondrial dysfunction, tubular cell senescence, and renal fibrosis. Overexpression of PTX3 triggered nuclear translocation of ß-catenin, an activating form of ß-catenin. PTX3-induced mitochondrial dysfunction and tubular cell senescence were also significantly inhibited by knockdown of p16INK4A, a senescence-related protein. In a clinical cohort, we found PTX3 was increased in urine and serum in patients with CKD. Urinary PTX3 negatively correlated with eGFR. PTX3 also increased gradually following the severity of diseases, triggering the fibrogenesis. Taken together, our results provide strong evidences that PTX3 is a new fibrogenic factor in the development of renal fibrosis through ß-catenin-induced mitochondrial dysfunction and cell senescence. This study further suggests PTX3 is a new diagnostic factor to renal fibrosis and provides a new therapeutic target against renal fibrosis.

The risk of perchlorate and iodine on the incidence of thyroid tumors and nodular goiter: a case-control study in southeastern China.

BACKGROUND: The incidence rates of thyroid tumors and nodular goiter show an upward trend worldwide. There are limited reports on the risk of perchlorate and iodine on thyroid tumors, but evidence from population studies is scarce, and their impact on thyroid function is still uncertain. Therefore, the objective of this study was to investigate the association of perchlorate and iodine with the risk of nodular goiter (NG), papillary thyroid microcarcinoma (PTMC), and papillary thyroid carcinoma (PTC) and to assess the correlation between perchlorate and iodine with thyroid function indicators. METHODS: A case-control population consisting of 184 pairs of thyroid tumors and nodular goiter matched by gender and age (±2 years) was recruited in this study. Serum and urine samples were collected from each participant. Thyroid function indicators in serum were tested by automatic chemical immunofluorescence, and perchlorate and iodine levels in urine were determined by ultra-high performance liquid chromatography tandem-mass spectrometry and inductively coupled plasma-mass spectrometry, respectively. Conditional logistic regressions and multiple linear regressions were used to analyze the associations. RESULTS: Urinary perchlorate concentration was significantly higher in total cases, NG and PTC than in the corresponding controls (P < 0.05). Perchlorate was positively associated with PTC (OR = 1.058, 95% CI: 1.009, 1.110) in a non-linear dose-response relationship, but there was no association between perchlorate and NG or PTMC. Iodine was not associated with the risk of thyroid tumors and NG and did not correlate with the thyroid function indicators. Furthermore, perchlorate showed a positive correlation with thyroid stimulating hormone (TSH) at iodine adequate levels (P < 0.05), and a negative correlation with free triiodothyronine (FT3) and a positive correlation with thyroglobulin antibody (TgAb) at iodine more than adequate or excess levels (P < 0.05). CONCLUSIONS: Perchlorate can increase the risk of PTC in a non-linear dose-response relationship and disturb the thyroid hormone homeostasis and thyroid autoantibody levels.

Stem/progenitor cell in kidney: characteristics, homing, coordination, and maintenance.

Renal failure has a high prevalence and is becoming a public health problem worldwide. However, the renal replacement therapies such as dialysis are not yet satisfactory for its multiple complications. While stem/progenitor cell-mediated tissue repair and regenerative medicine show there is light at the end of tunnel. Hence, a better understanding of the characteristics of stem/progenitor cells in kidney and their homing capacity would greatly promote the development of stem cell research and therapy in the kidney field and open a new route to explore new strategies of kidney protection. In this review, we generally summarize the main stem/progenitor cells derived from kidney in situ or originating from the circulation, especially bone marrow. We also elaborate on the kidney-specific microenvironment that allows stem/progenitor cell growth and chemotaxis, and comment on their interaction. Finally, we highlight potential strategies for improving the therapeutic effects of stem/progenitor cell-based therapy. Our review provides important clues to better understand and control the growth of stem cells in kidneys and develop new therapeutic strategies.

Do Statins Have a Positive Impact on Patients with Coronary Microvascular Dysfunction on Long-Term Clinical Outcome? A Large Retrospective Cohort Study.

OBJECTIVES: To investigate the influence of statins on major adverse cardiovascular events (MACE) in patients with coronary microvascular dysfunction (CMVD). PARTICIPANTS: 23,494 patients who received coronary angiography (CAG) were included. Thrombolysis in Myocardial Infarction, Myocardial Perfusion Grading (TMPG), a useful angiographic method, was used to evaluate CMVD. RESULTS: Using multivariate analysis, NYHA III/IV (HR, 1.44; 95% CI, 1.03-2.01; P=0.031), PCI history (HR, 3.69; 95% CI, 2.57-5.31; P<0.001), TG (HR, 1.15; 95% CI, 1.06-1.26; P=0.001), creatinine (HR, 1.00; 95% CI, 1.00-1.01; P<0.001), cTnT (HR, 0.98; 95% CI, 0.96-0.99; P<0.001), heart rate (HR, 0.98; 95% CI, 0.97-0.99; P=0.001), ß-blocker (HR, 0.68; 95% CI, 0.51-0.91; P=0.008), aspirin (HR, 0.38; 95% CI, 0.24-0.61; P<0.001), and statins (HR, 0.33; 95% CI, 0.19-0.60; P<0.001) significantly correlated with reduced MACE in CMVD patients. In subgroups analysis, statins decreased MACE overall (HR, 0.33; 95% CI, 0.19-0.59; P<0.001) and in CMVD patients with smoking history (HR, 0.64; 95% CI, 0.43-0.93; P=0.014), diabetes (HR,0.27; 95% CI,0.12-0.61; P=0.002), hypertension (HR, 0.10; 95% CI, 0.03-0.36; P=0.001), and hypertension and diabetes (HR, 0.09; 95% CI, 0.014-0.53; P=0.008). CONCLUSION: Statins could reduce MACE in patients with CMVD.