Diabetic peripheral neuropathy (DPN) is caused by hyperglycemia, which induces oxidative stress and inflammatory responses that damage nerve tissue. Excessive generation of reactive oxygen species (ROS) and NOD-like receptor protein 3 (NLRP3) inflammasome activation trigger the inflammation and pyroptosis in diabetes. Schwann cell dysfunction further promotes DPN progression. Loganin has been shown to have antioxidant and anti-inflammatory neuroprotective activities. This study evaluated the neuroprotective effect of loganin on high-glucose (25 mM)-induced rat Schwann cell line RSC96 injury, a recognized in vitro cell model of DPN. RSC96 cells were pretreated with loganin (0.1, 1, 10, 25, 50 μM) before exposure to high glucose. Loganin’s effects were examined by CCK-8 assay, ROS assay, cell death assay, immunofluorescence staining, quantitative RT–PCR and western blot. High-glucose-treated RSC96 cells sustained cell viability loss, ROS generation, NF-κB nuclear translocation, P2 × 7 purinergic receptor and TXNIP (thioredoxin-interacting protein) expression, NLRP3 inflammasome (NLRP3, ASC, caspase-1) activation, IL-1β and IL-18 maturation and gasdermin D cleavage. Those effects were reduced by loganin pretreatment. In conclusion, we found that loganin’s antioxidant effects prevent RSC96 Schwann cell pyroptosis by inhibiting ROS generation and suppressing NLRP3 inflammasome activation.

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Endoplasmic reticulum stress occurs in a variety of patho-physiological mechanisms and there has been great interest in managing this pathway for the treatment of clinical diseases. Autophagy is closely interconnected with endoplasmic reticulum stress to counteract the possible injurious effects related with the impairment of protein folding. Studies have shown that glomerular podocytes exhibit high rate of autophagy to maintain as terminally differentiated cells. In this study, podocytes were exposed to tunicamycin and thapsigargin to induce endoplasmic reticulum stress. Thapsigargin/tunicamycin treatment induced a significant increase in endoplasmic reticulum stress and of cell death, represented by higher GADD153 and GRP78 expression and propidium iodide flow cytometry, respectively. However, thapsigargin/tunicamycin stimulation also enhanced autophagy development, demonstrated by monodansylcadaverine assay and LC3 conversion. To evaluate the regulatory effects of autophagy on endoplasmic reticulum stress-induced cell death, rapamycin (Rap) or 3-methyladenine (3-MA) was added to enhance or inhibit autophagosome formation. Endoplasmic reticulum stress-induced cell death was decreased at 6 h, but was not reduced at 24 h after Rap+TG or Rap+TM treatment. In contrast, endoplasmic reticulum stress-induced cell death increased at 6 and 24 h after 3-MA+TG or 3-MA+TM treatment. Our study demonstrated that thapsigargin/tunicamycin treatment induced endoplasmic reticulum stress which resulted in podocytes death. Autophagy, which counteracted the induced endoplasmic reticulum stress, was simultaneously enhanced. The salvational role of autophagy was supported by adding Rap/3-MA to mechanistically regulate the expression of autophagy and autophagosome formation. In summary, autophagy helps the podocytes from cell death and may contribute to sustain the longevity as a highly differentiated cell lineage.

BACKGROUND: C-arm cone-beam computed tomography (CBCT) is a comparatively novel modality for guiding percutaneous transthoracic lung biopsies (PTLBs), and despite its potential advantages over conventional computed tomography (CCT), a head-to-head comparison of the two techniques has yet to be reported in the literature. This study aims to evaluate the diagnostic value and safety of CBCT-guided PTLB compared to CCT-guided biopsy, with cases performed in a single hospital. METHODS: A total of 104 PTLB patients were retrospectively analyzed in this study. 35 PTLBs were performed under CBCT guidance, and 69 PTLBs were performed under CCT guidance. Diagnostic accuracy, sensitivity, and specificity for malignancy as well as procedure time, radiation dose of patients, and complication rate in the two groups were compared. RESULTS: Total procedure time was significantly lower in the CBCT group (32 ± 11 minutes) compared to the CCT group (38 ± 9.7 minutes; P = .009), especially among patients ≥ 70 years of age (CBCT: 33 ± 12 minutes, CCT: 42 ± 13, P = .022). For lesions in the lower lobes, the CBCT-guided group received significantly reduced effective radiation dose (2.9 ± 1.6 mSv) than CCT-guided patients (3.7 ± 0.80; P = .042). Diagnostic accuracy, sensitivity, and specificity for malignancy were comparable between the two groups, as were post-biopsy complication rates. CONCLUSION: CBCT guidance significantly reduces the procedure time and radiation exposure for PTLBs compared with CCT, and should be considered in clinical settings that may be difficult or time-consuming to perform under CCT.

Proteinuria is a major hallmark of glomerular nephropathy and endoplasmic reticulum (ER) stress plays an important role in glomerular nephropathy. The protein levels of integrin-β1 in podocytes are found to be negative correlation with amount of proteinuria. This study investigated whether urinary protein, particularly albumin, induced ER stress that consequently reduced integrin-β1 expression. All experiments were performed using primary cultured rat podocyte. Protein and mRNA expression were measured by western blotting and semiquantified reverse transcriptase polymerase chain reaction. Albumin uptake was found at 1 h after albumin addition. Albumin reduced precursor and mature forms of integrin-β1, but did not change mRNA levels of integrin-β1. Albumin induced reactive oxygen species (ROS) generation and ER stress. Antioxidant (N-acetylcysteine) suppressed albumin-induced ER stress and decrements in precursor and mature forms of integrin-β1. Then, ER stress inhibitors (4-phenylbutyrate and salubrinal) also inhibited albumin-induced decrements in precursor and mature forms of integrin-β1. The potent ER stress inducers (thapsigargin and tunicamycin) directly decreased precursor and mature forms of integrin-β1 and led appearance of unglycosylated core protein of integrin-β1. Our results show that in proteinuric disease, albumin decreases precursor and mature forms of integrin-β1 through ROS-ER stress pathway in podocytes.

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