Heme oxygenase­1 inhibits renal tubular epithelial cell pyroptosis by regulating mitochondrial function through PINK1.

Endotoxin-induced acute kidney injury (AKI) is commonly observed in clinical practice. Renal tubular epithelial cell (RTEC) pyroptosis is one of the main factors leading to the development of endotoxin-induced AKI. Mitochondrial dysfunction can lead to pyroptosis. However, the biological pathways involved in the potential lipopolysaccharide (LPS)-induced pyroptosis of RTECs, notably those associated with mitochondrial dysfunction, are poorly understood. Previous studies have demonstrated that heme oxygenase (HO)-1 confers cell protection via the induction of PTEN-induced putative kinase 1 (PINK1) expression through PTEN to regulate mitochondrial fusion/fission during endotoxin-induced AKI in vivo. Therefore, the present study investigated the role of HO-1/PINK1 in maintaining mitochondrial function and inhibiting the pyroptosis of RTECs exposed to LPS. Primary cultures of RTECs were obtained from wild-type (WT) and PINK1-knockout (PINK1KO) rats. An in vitro model of endotoxin-associated RTEC injury was established following treatment of the cells with LPS. The WT RTECs were divided into the control, LPS, Znpp + LPS and Hemin + LPS groups, and the PINK1KO RTECs were divided into the control, LPS and Hemin + LPS groups. RTECs were exposed to LPS for 6 h to assess cell viability, inflammation, pyroptosis and mitochondrial function. In the LPS-treated RTECs, the mRNA and protein expression levels of HO-1 and PINK1 were upregulated. Cell viability, adenosine triphosphate (ATP) levels and the mitochondrial oxygen consumption rate were decreased, whereas the inflammatory response, pyroptosis and mitochondrial reactive oxygen species (ROS) levels were increased. The cell inflammatory response and the induction of pyroptosis were inhibited, whereas the levels of mitochondrial ROS were decreased. In addition, the cell viability and ATP levels were increased in the WT RTECs following the upregulation of HO-1 expression. These effects were reversed by the downregulation of HO-1 expression. However, no statistically significant differences were noted between the LPS and the Hemin + LPS groups in the PINK1KO RTECs. Collectively, the findings of the present study indicate that HO-1 inhibits inflammation and regulates mitochondrial function by inhibiting the pyroptosis of LPS-exposed RTECs via PINK1.

Comparison of comfort and complications of Implantable Venous Access Port (IVAP) with ultrasound guided Internal Jugular Vein (IJV) and Axillary Vein/Subclavian Vein (AxV/SCV) puncture in breast cancer patients: a randomized controlled study.

BACKGROUND: Axillary vein/subclavian vein (AxV/SCV) and Internal jugular vein (IJV) are commonly used for implantable venous access port (IVAP) implantation in breast cancer patients for chemotherapy. Previous research focused on comparison of complications while patient comfort was ignored. This study aims to compare patient comfort, surgery duration and complications of IVAP implantation between IJV and AxV/SCV approaches. METHODS: Two hundred forty-eight breast cancer patients were enrolled in this randomized controlled study from August 2020 to June 2021. Patients scheduled to undergo IVAP implantation were randomly and equally assigned to receive central venous catheters with either AxV /SCV or IJV approaches. All patients received comfort assessment using a comfort scale table at day 1, day 2 and day 7 after implantation. Patient comfort, procedure time of operation as well as early complications were compared. RESULTS: Patient comfort was significantly better in the AxV/SCV group than that of IJV group in day 1 (P < 0.001), day 2 (P < 0.001) and day 7(P = 0.023). Procedure duration in AxV/SCV group was slightly but significantly shorter than IJV group (27.14 ± 3.29 mins vs 28.92 ± 2.54 mins, P < 0.001). More early complications occurred in AxV/SCV group than IJV group (11/124 vs 2/124, P = 0.019). No difference of complications of artery puncture, pneumothorax or subcutaneous hematoma between these two groups but significantly more catheter misplacement in AxV/SCV group than IJV group (6/124 vs 0/124, P = 0.029). Absolutely total risk of complications was rather low in both groups (8.87% in AxV/SCV group and 1.61% in IJV group). CONCLUSIONS: Our study indicates that patients with AxV/SCV puncture have higher comfort levels than IJV puncture. AxV/SCV puncture has shorter procedure duration but higher risk of early complications, especially catheter misplacement. Both these two approaches have rather low risk of complications. Consequently, our study provides an alternative choice for breast cancer patients to reach better comfort.

Comparison of comfort and complications in breast cancer patients of implantable venous access port (IVAP) with ultrasound guided internal jugular vein (IJV) and axillary vein/subclavian vein (AxV/SCV) puncture: a randomized controlled study protocol.

BACKGROUND: Internal jugular vein (IJV) and axillary vein/subclavian vein (AxV/SCV) are commonly used for implantable venous access port (IVAP) implantation in breast cancer (BC) patients with chemotherapy. Previous studies focused on complications between these different approaches and ignored patient comfort. In this study, we aim to compare patient comfort between IJV and AxV/SCV approaches, as well as surgery duration and complications. METHODS: This is a single-center prospective randomized controlled clinical trial. A total of 200 patients diagnosed with invasive BC will be enrolled in this study. After signing written informed consent, patients schedule to undergo IVAP implantation will be randomized at a 1:1 ratio to receive central venous catheters (CVC) with either IJV or AxV/SCV approaches. Baseline as well as demographic data and procedure time of port implantation will be recorded. All patients will receive assessment of comfort with a comfort scale table at days 1, 2 and 7 after implantation surgery. Patients will be followed up and complications will be recorded until devices are removed at the end of the treatment period, or in case of complications. Patient comfort, procedure time of implantation and complications will be compared and analyzed between these two arms. DISCUSSION: To the best of our knowledge, this is the first study to compare patient comfort as primary outcome measure between IJV and AxV/SCV puncture. This study will further confirm the benefits of ultrasound guidance and may provide a better choice of IVAP implantation for BC patients. TRIAL REGISTRATION: This study has been registered at Chinese Clinical Trial Registry (ChiCTR, www. chictr.org.cn) and Chinese Ethics Committee of Registering Clinical Trials (No. ChiCTR2000034986).

HO-1/PINK1 Regulated Mitochondrial Fusion/Fission to Inhibit Pyroptosis and Attenuate Septic Acute Kidney Injury.

BACKGROUND: Endotoxin-associated acute kidney injury (AKI), a disease characterized by marked oxidative stress and inflammation disease, is a major cause of mortality in critically ill patients. Mitochondrial fission and pyroptosis often occur in AKI. However, the underlying biological pathways involved in endotoxin AKI remain poorly understood, especially those related to mitochondrial dynamics equilibrium disregulation and pyroptosis. Previous studies suggest that heme oxygenase- (HO-) 1 confers cytoprotection against AKI during endotoxic shock, and PTEN-induced putative kinase 1 (PINK1) takes part in mitochondrial dysfunction. Thus, in this study, we examine the roles of HO-1/PINK1 in maintaining the dynamic process of mitochondrial fusion/fission to inhibit pyroptosis and mitigate acute kidney injury in rats exposed to endotoxin. METHODS: An endotoxin-associated AKI model induced by lipopolysaccharide (LPS) was used in our study. Wild-type (WT) rats and PINK1 knockout (PINK1KO) rats, respectively, were divided into four groups: the control, LPS, Znpp+LPS, and Hemin+LPS groups. Rats were sacrificed 6 h after intraperitoneal injecting LPS to assess renal function, oxidative stress, and inflammation by plasma. Mitochondrial dynamics, morphology, and pyroptosis were evaluated by histological examinations. RESULTS: In the rats with LPS-induced endotoxemia, the expression of HO-1 and PINK1 were upregulated at both mRNA and protein levels. These rats also exhibited inflammatory response, oxidative stress, mitochondrial fission, pyroptosis, and decreased renal function. After upregulating HO-1 in normal rats, pyroptosis was inhibited; mitochondrial fission and inflammatory response to oxidative stress were decreased; and the renal function was improved. The effects were reversed by adding Znpp (a type of HO-1 inhibitor). Finally, after PINK1 knockout, there is no statistical difference in the LPS-treated group and Hemin or Znpp pretreated group. CONCLUSIONS: HO-1 inhibits inflammation response and oxidative stress and regulates mitochondria fusion/fission to inhibit pyroptosis, which can alleviate endotoxin-induced AKI by PINK1.

Comparison of the Humphrey Field Analyser and Humphrey Matrix Perimeter for the evaluation of glaucoma patients.

AIMS: To compare the Humphrey Matrix Perimeter (HMP) with the Humphrey Field Analyser (HFA) in visual-field examinations of patients with glaucoma or suspected glaucoma. METHODS: One hundred and forty-nine patients with suspected glaucoma or glaucoma were recruited. All patients underwent visual-field examinations with the Swedish Interactive Threshold Algorithm standard, the central 30-2 threshold test with the HFA, and the frequency doubling technique 30-2 threshold test with the HMP. The examination times, mean deviations (MDs) and pattern standard deviations (PSDs) of both perimeters were compared in all patients and according to the patient's diagnosis or the severity of their visual-field defects (VFDs). The paired 2-tailed t test and Pearson's correlation coefficients were used for statistical analyses. RESULTS: Overall, the examination times were significantly shorter with the HMP than with the HFA. There was a positive correlation between the HFA and HMP measurements of MD and PSD. In patients with suspected glaucoma, the PSDs measured with the HMP were significantly higher than those measured with the HFA. In patients with mild VFDs (MD >-4.0 dB), PSDs measured with the HMP were significantly higher than those measured with the HFA. In patients with severe VFDs (MD <-12.0 dB), MDs measured with the HMP were significantly higher than those measured with the HFA, whereas PSDs measured with the HMP were significantly lower than those measured with the HFA. CONCLUSIONS: The HMP is more time efficient than the HFA in visual-field examinations. The HMP tends to overestimate mild VFDs and underestimate severe VFDs.

Clinical evaluation of the intraocular pressure in patients with glaucoma or ocular hypertension by a self-assessable tonometer.

PURPOSE: To investigate the clinical efficacy of a new patient-operated intraocular pressure tool, the Proview eye pressure monitor (PEPM; Bausch & Lomb, Inc., Rochester, NY), for monitoring intraocular pressure (IOP) in patients with glaucoma or ocular hypertension. PATIENTS AND METHODS: One hundred and forty eyes of 70 Taiwanese patients from the Tri-Service General Hospital (Taiwan, Republic of China) who had been diagnosed with ocular hypertension or glaucoma were studied. After being fully trained during an initial clinic visit, patients measured their own IOP with the PEPM at home. The IOPs were measured again using a Haag-StreitBern Goldmann tonometer (GT; Haag-Streit, Köniz, Switzerland) during subsequent outpatient visits. The training time, assessment of the patients' ease of PEPM use, and accuracy of measured PEPM IOPs in relation to GT IOPs were recorded and analyzed. RESULTS: Relative to GT readings, PEPM readings tended to be overestimated at lower pressure (<10 mmHg) and underestimated at higher pressure (>20 mmHg). Between 10 to 20 mmHg, PEPM measurements did not significantly differ from GT measurements. Up to 80% of the PEPM measurements fell within +/- 3 mmHg of the corresponding GT readings. When consideration was limited to GT readings of > or =21 mmHg, PEPM measured IOPs of > or =21 mmHg with a sensitivity of 80% and a specificity of 90%. The mean satisfaction rating of PEPM use was 88.3 +/- 2.0 (maximum, 100). The mean training time for appropriate use of PEPM was 17.9 +/- 4.0 minutes. The older the patients, the longer the training time that was required. CONCLUSION: Our data suggest that after appropriate training: (1) PEPM and GT measurements correspond well between 10 mmHg and 20 mmHg and (2) PEPM could offer patients with glaucoma or ocular hypertension an easy-to-use, substantially reliable means of selfmonitoring IOP.

Neural progenitor cells resist excitatory amino acid-induced neurotoxicity.

The applications of neural progenitor cells in clinical therapy for neural degeneration, such as Parkinson's disease, Huntington's disease, and cerebral infarction, have long been explored widely. It had been suggested that these cells may block the apoptosis of ischemia-induced neuronal damage and may themselves resist neurotoxic factors. In the present study, neural progenitor cells derived from the cortex of rodent embryos were cultured with the mitogenic agent epidermal growth factor. It was observed that these progenitor cells could self-renew and differentiate into a number of types of neurons and glial cells. By using sodium nitroprusside, glutamate, and N-methyl-D-aspartate, these neural progenitor cells were shown to have a higher resistance to neurotoxicity induced by these drugs compared with primary neuronal cells. However, the release of nitric oxide in response to glutamate by these neural progenitor cells was similar to the released by primary neuronal cells. Also, when the glutamate-stimulated increase in intracellular free Ca(2+) concentration was measured, stimulation of the glutamate receptors could not induce a significant influx of Ca(2+) into these progenitor cells until they differentiated. Our results suggest that the resistance of neural progenitor cells to neurotoxicity may be partially due to a lack of response to glutamate. In addition, some progenitor-generated neurotrophic factors may contribute to the resistance of these cells to nitric oxide-induced neurotoxicity.