ABSTRACT
Glucagon-like peptide 1 receptor agonist exenatide (exendin-4) has potential protective capabilities against diabetic kidney disease (DKD). However, the underlying mechanism has not been fully elucidated. The expression of thioredoxin-interacting protein (Txnip) is upregulated during DKD progression by histone acetylation. Sirtuin 1 (SIRT1) is a deacetylase and is decreased in DKD, which indicates that it may regulate Txnip in this disease. Here, we used whole-body heterozygous Sirt1 knockout (Sirt1+/-) and kidney-specific Sirt1 knockout (KSK) mice to investigate whether SIRT1 regulates Txnip via histone deacetylation in DKD and exenatide-alleviated DKD. Exenatide substantially improved renal pathological damage, decreased the albumin-to-creatinine ratio (ACR), upregulated SIRT1 expression, and downregulated Txnip expression in kidneys of high-fat diet-treated C57BL/6J mice. However, these effects diminished in Sirt1+/- and KSK mice under exenatide treatment. The downregulation of Txnip expression by exendin-4 in high-glucose-treated SV40 MES13 cells was hampered during Sirt1 knockdown. These results demonstrate that kidney SIRT1 is indispensable in exenatide-improved DKD and downregulation of Txnip expression. Exendin-4 mechanistically downregulated Txnip histone 3 lysine 9 acetylation (H3K9ac) in a SIRT1-dependent manner and decreased spliced X-box binding protein 1 (XBP1s) recruitment to the Txnip promoter. These findings provide epigenetic evidence elucidating the specific mechanism for exenatide-mediated DKD alleviation and highlight the importance of Txnip as a promising therapeutic target for DKD.
ABSTRACT
BACKGROUND: Early intervention reduces the incidence of postherpetic neuralgia (PHN). Typical shingles are easy to diagnose; however, there is no clear diagnostic method for neuralgia symptoms manifested before the onset of the rash, which can easily cause misdiagnosis. This not only increases the patient's pain, medical expenses, and mental burden, but more importantly, delays the valuable time for early treatment of shingles, and increases the probability of complications and PHN. OBJECTIVE: In this paper, the diagnostic methods of preherpetic neuralgia were summarized and analyzed, and the current challenges were put forward to provide directions for the early diagnosis of herpes zoster (HZ) in the future. METHODS: PubMed, and China National Knowledge Infrastructure (CNKI) libraries were searched using the terms "herpes zoster," "before the blistering," "diagnosis," and "neuralgia." Clinical trials, reviews, and case reports were collected and reviewed. The period of literature search is from 1 January 1980 to 1 October 2022. RESULTS: The early diagnosis of herpes zoster neuralgia can reduce misdiagnosis and mistreatment, and timely and effective intervention can significantly reduce the incidence of PHN. The body may possess a mechanism that limits the local breakthrough of the virus in the skin, causing blistering later than the onset of pain. Changes in the plasma proteins of patients with varicella-zoster virus shingles neuralgia may be used as an early diagnostic indicator in patients with HZ neuralgia before eruption. CONCLUSION: Early diagnosis of HZ neuralgia before eruption can facilitate timely targeted treatment, thereby reducing the incidence of PHN. Proteomic quantitative analysis and validation results can serve as a simple, micro, rapid, and accurate diagnostic method.
ABSTRACT
BACKGROUND: Shoulder is the most injured part in table tennis players, and it takes multiple roles in transmitting power and striking the center of the ball during the stroke. Proprioception is strongly correlated with high level of athletic performance. It is customary to assume that there is a correlation between proprioception and muscle strength and therefore proprioceptive assessment and rehabilitation is often neglected. AIM: To investigate the correlation between isokinetic muscle strength and proprioception in the internal and external rotation muscle groups of elite Chinese male table tennis players, to provide reference for physical training and rehabilitation of elite table tennis players. METHODS: A total of 19 national elite table tennis players from the Chinese National Table Tennis Team were recruited in this research. All of them had more than 10 years training experience and had participated major competitions such as the National Games and World Youth Championships. IsoMed 2000 was used to test the peak torque of internal and external rotation isokinetic concentric contraction of the athletes' bilateral shoulder joints at low speed (60°/s) and high speed (180°/s) respectively; IsoMed 2000 was used to conduct the Joint Position Reproduction test to evaluate the athletes' proprioceptive ability capacity at low speed (60°/s) and high speed (180°/s) respectively. If the data satisfied the normal distribution, the correlation between the differences in peak torque s and angles in different directions was analyzed using a Pearson simple linear model; otherwise, Spearman correlation analysis was used. The comparison of proprioceptive ability between the table tennis racket-holding hand and non-racket-holding hands was performed using independent samples t-test if the data satisfied a normal distribution; otherwise, the Mann-Whitney U test was used. RESULTS: There was no direct linear correlation between the strength and proprioceptive correlation analysis at slow speed (60°/s) and fast speed (180°/s) in the racket-holding hand; At the slow speed (60°/s) and fast speed (180°/s), there was no correlation between muscle strength and proprioception in the non-racket-holding hand except for the internal rotation variable error (VE) and external rotation relative peak torque, which showed a moderate positive correlation (r = 0.477, P < 0.05), (r = 0.554, P < 0.05). The internal rotation's constant error (CE) and VE were 1.06 ± 3.99 and 2.94 ± 2.16, respectively, for the racket-holding hand, and -3.36 ± 2.39 and 1.22 ± 0.93, respectively, for the non-racket-holding hand; the internal rotation's CE, VE of the racket-holding hand was lower than that of the non-racket-holding hand, and there was a highly significant difference (P < 0.01). CONCLUSION: There was no correlation between muscle strength and proprioceptive function in the internal and external rotation of the racket-holding hand's shoulder in elite Chinese male table tennis players. These results may be useful for interventions for shoulder injuries and for the inclusion of proprioceptive training in rehabilitation programs.
ABSTRACT
Increases in several ceramide species have been shown by non-targeted lipid profiling (lipidomics) of the rat hippocampus after kainate lesions (Guan et al. FASEB J 20:1152-1161, 2006). This study was carried out to examine possible effects of ceramide species on exocytosis. Significant increase in membrane capacitance in voltage-clamped rat pheochromocytoma (PC12) cells, an indication of exocytosis, was detected immediately after external application of C2, C6, and C18 ceramide. In contrast, no increase in capacitance was found after addition of C16 and C20 ceramide, or DMSO vehicle. The effect of ceramide on exocytosis was dependent on the integrity of lipid rafts. Treatment of cells with the cholesterol binding agent/disruptor of lipid rafts, methyl beta cyclodextrin, prior to addition of C18 ceramide suppressed the increase in capacitance induced by this lipid species. The ability of C2, C6 and C18 ceramide to trigger exocytosis was confirmed using total internal reflection fluorescence microscopy (TIRFM) experiments. External application of these species caused an exponential decrease in the number of subplasmalemmal neuropeptide Y (NPY)-enhanced green fluorescence protein (EGFP) labeled vesicles, indicating exocytosis. Interestingly, C18 is also the ceramide species that showed the greatest increase in the rat hippocampus after kainate excitotoxicity. It is postulated that C18 ceramide might facilitate exocytosis of glutamate from damaged neurons, thus propagating neuronal injury.
