Erratum: Hyperphosphorylation of Tau Protein in Hippocampus of Central Insulin-Resistant Rats is Associated with Cognitive Impairment

<b><i>Background: </i></b>Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. Peripheral insulin resistance increases the risk for memory impairment and the development of AD. <b><i>Objective: </i></b>This study aims to assess changes in cognitive functions and the level of hyperphosphorylated tau proteins in central insulin-resistant rats. <b><i>Methods: </i></b>An <i>in vivo</i> central insulin-resistant (CIR) animal model was generated through intracerebroventricular injection of streptozotocin (STZ) into insulin-resistant (IR) rats that were induced by feeding a high-glucose/-protein/-fat diet. The Morris water maze test was used to assess changes in cognitive functions, pathological changes in the cornu ammonis 1 (CA1) region of the hippocampus were detected by immunohistochemistry, and the phosphorylation levels of tau proteins at specific sites were determined by Western blot analysis. <b><i>Results: </i></b>The escape latency time in the Morris water maze test was significantly prolonged; the number of phosphorylated tau proteins in the CA1 region of the hippocampus was significantly increased; and the phosphorylation levels of tau proteins at Ser199, Thr205, Thr212, Thr217 and Ser396 were significantly elevated in the CIR group compared with the IR and control groups. <b><i>Conclusion: </i></b>This study provides direct evidence that CIR plays an important role in AD pathogenesis by facilitating tau hyperphosphorylation

Supplementary Material for: Faster Macular Vessel Density Loss in More Advanced Primary Open Angle Glaucoma Eyes

Purpose: To characterize and compare the longitudinal change of macular vessel density (VD) in primary open angle glaucoma (POAG) eyes across different disease stages. Methods: This is a sub-analysis of a prospective cohort study. A total of 103 eyes (53 eyes in the mild stage, 50 eyes in the moderate-to-advanced stage) of 75 POAG patients followed for more than 1 year with at least 2 qualified optical coherence tomography (OCT) angiography (OCTA) images were included. The rates of macular VD change were determined by linear regression and compared using the generalized linear mixed models between groups. Mixed effect models were used to evaluate the demographic and ocular parameters associated with the VD loss rate. Results: With a mean follow-up time of 2.36 years, the rates of macular VD change were significantly different from zero in both groups. The rates of macular VD loss were significantly faster in moderate-to-advanced stage group than in mild stage group in whole image (-2.46%/yr vs -1.47%/yr, p=0.002), superior hemifield (-2.42%/yr vs -1.30%/yr, p=0.001), para fovea (-2.35%/yr vs -1.26, p=0.001), superior (-2.20%/yr vs -1.01%/yr, p=0.002), nasal (-2.41%/yr vs -1.04%/yr p=0.001), inferior (-2.46%/yr vs -1.43%/yr, p=0.018) and temporal sectors (-2.32%/yr vs -1.58%/yr, p=0.012). Baseline mean deviation (MD) and OCT parameters were associated with the rates of macular VD loss. Conclusions: OCTA measurements could detect vascular deterioration over time in POAG eyes at different stages. The rates of macular VD loss were significantly faster in more advanced POAG eyes

Supplementary Material for: L-Carnitine Ameliorates Cancer Cachexia in Mice Partly via the Carnitine Palmitoyltransferase-Associated PPAR-γ Signaling Pathway

<b><i>Background:</i></b>L-Carnitine has been demonstrated to ameliorate cachectic symptoms. In the present study, we sought to investigate the role of the peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling pathway in the ameliorative effects of L-carnitine on cancer cachexia in a colon-26 tumor-bearing mouse model. <b><i>Methods:</i></b> The cachectic mice received L-carnitine (p.o.) or etomoxir (i.p.), or pioglitazone hydrochloride (p.o.) or GW9662 (i.p.). The physiological cachexia parameters, biochemical parameters, and serum cytokines were measured. The expression levels of representative molecules in the PPAR-γ signaling pathway were measured by using quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot analysis. <b><i>Results:</i></b> Oral administration of L-carnitine at 9 mg/kg/day improved the cachexia parameters and biochemical parameters in cancer cachectic mice. The elevated serum concentrations of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) were decreased by L-carnitine. These ameliorative effects of L-carnitine were lessened by the carnitine palmitoyltransferase I (CPT I) inhibitor, etomoxir. The mRNA and protein expression levels of PPAR-α and PPAR-γ were decreased in the livers of cancer cachectic mice and increased after L-carnitine administration, which attenuated the increased mRNA expression levels of sterol-regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase (FAS). Similar to pioglitazone, L-carnitine augmented the phosphorylation of PPAR-γ and attenuated the expression levels of phospho-p65 and cyclooxygenase (COX)-2. Additionally, the above-mentioned effects of L-carnitine were reversed by GW9662. <b><i>Conclusion:</i></b>L-Carnitine exerts its ameliorative effects in cancer cachexia in association with the PPAR-γ signaling pathway

Supplementary Material for: Combination Cyclophosphamide/Glucocorticoids Provide Better Tolerability and Outcomes versus Glucocorticoids Alone in Patients with Sjogren’s Associated Chronic Interstitial Nephritis

<b><i>Background:</i></b> Steroid therapy has become an effective option for patients with primary Sjogren’s syndrome with tubulointerstitial nephritis (TIN), while the use of cytotoxic agents is still debated. Our study aimed to compare the clinical outcomes of patients treated with cyclophosphamide (CTX) combined with glucocorticoids with those of patients treated with glucocorticoids alone. <b><i>Methods:</i></b> All patients with primary Sjogren’s syndrome with chronic TIN admitted to the Division of Nephrology, Ruijin Hospital, from January 1, 2002, to April 30, 2016, and treated with steroids alone or combined with CTX were included. The immunological prognosis, improvements of renal function, and acquired tubular defects of the patients were retrospectively compared between the 2 therapeutic groups. <b><i>Results:</i></b> A total of 70 cases were included. Of these, 36 were diagnosed by renal biopsy. A total of 56 patients were treated with glucocorticoids alone, while 14 patients received glucocorticoids combined with CTX. There were no significant differences in clinical characteristics and laboratory parameters between the 2 therapeutic groups at baseline. Compared with patients in the steroid group, patients in the CTX group showed better estimated glomerular filtration rate (eGFR) improvement (21.35 ± 19.63 vs. 2.72 ± 19.11 mL/min/1.73 m², <i>p</i> = 0.006) but a similar decline in immunoglobulin G (IgG; 450 [interquartile range, IQR 910] vs.176 [IQR 1,910] mg/dL, <i>p</i> = 0.93) at 12 months of follow-up. CTX therapy was associated with better eGFR improvement (β = 12.96 [2.95–22.97]) even after adjusting for dry mouth, anti-Sjögren’s-syndrome-related antigen A and anti-Sjögren’s-syndrome-related antigen B positivity, hemoglobin, initial steroid dose, and baseline eGFR by linear regression analyses. Subgroup analyses revealed that the beneficial effects of CTX therapy on renal function were only observed in patients with baseline IgG ≥1,560 mg/dL or eGFR <90 mL/min/1.73 m². The urine α1-microglobulin improvement was better in the CTX group than in the steroid group at 12 months of follow-up (β = 1.29, 95% CI 0.56–2.02, <i>p</i> = 0.001). <b><i>Conclusions:</i></b> CTX therapy is suggested for primary Sjogren’s syndrome patients with chronic TIN, especially those with higher IgG levels and abnormal renal function at baseline