Primary Arthrodesis with Retrograde Hindfoot Nail for Elderly Patients with Tibia Pilon Fractures and Psychiatric Illness.

BACKGROUND: Management of tibial pilon fracture in elderly patients with psychiatric illness remains challenging for orthopedic doctors because of patients' poor bone quality and inability for self-care. This study aimed to ascertain the viability and reliability of primary arthrodesis by using retrograde hindfoot nail for these difficult cases. METHODS: We retrospectively reviewed eight elderly consecutive patients (age older than 65 years) with tibial pilon fractures and psychiatric illness from January of 2012 to December of 2019 in our institute. Primary tibiotalocalcaneal arthrodesis with retrograde hindfoot nail was used as a definitive procedure. The bone union time, wound complication rate, ankle alignment, necessity for narcotic agents, and ambulation status were evaluated. RESULTS: The average length of follow-up was 22.25 months (range, 15-36 months). Additional bone grafting surgery was performed for one patient because of fusion-site nonunion 6 months postoperatively. Another patient required debridement and removal of posterior calcaneal screw because of implant prominence and local infection. Osseous union with angular deformity less than 10° was achieved in all patients finally. The average bone union time was 6.6 months (range, 4-12 months). In terms of walking ability, six patients were capable of outdoor ambulation (classes 2 and 3). Two patients required oral pain medication at the final visit. CONCLUSIONS: The current study involved only a small number of patients, and two of the eight cases encountered undesired complications (one local infection and one bone nonunion); however, we believe that our method may serve as a valuable alternative for the treatment of tibial pilon fractures in elderly patients with psychiatric illness, considering the specificity of this fragile population.

Erratum: Exosomal miR-125b-5p deriving from mesenchymal stem cells promotes tubular repair by suppression of p53 in ischemic acute kidney injury: Erratum.

[This corrects the article DOI: 10.7150/thno.54550.].

External Pressure in Polymer-Based Lithium Metal Batteries: An Often-Neglected Criterion When Evaluating Cycling Performance?

Solid-state batteries based on lithium metal anodes, solid electrolytes, and composite cathodes constitute a promising battery concept for achieving high energy density. Charge carrier transport within the cells is governed by solid-solid contacts, emphasizing the importance of well-designed interfaces. A key parameter for enhancing the interfacial contacts among electrode active materials and electrolytes comprises externally applied pressure onto the cell stack, particularly in the case of ceramic electrolytes. Reports exploring the impact of external pressure on polymer-based cells are, however, scarce due to overall better wetting behavior. In this work, the consequences of externally applied pressure in view of key performance indicators, including cell longevity, rate capability, and limiting current density in single-layer pouch-type NMC622||Li cells, are evaluated employing cross-linked poly(ethylene oxide), xPEO, and cross-linked cyclodextrin grafted poly(caprolactone), xGCD-PCL. Notably, externally applied pressure substantially changes the cell's electrochemical cycling performance, strongly depending on the mechanical properties of the considered polymers. Higher external pressure potentially enhances electrode-electrolyte interfaces, thereby boosting the rate capability of pouch-type cells, despite the fact that the cell longevity may be reduced upon plastic deformation of the polymer electrolytes when passing beyond intrinsic thresholds of compressive stress. For the softer xGCD-PCL membrane, cycling of cells is only feasible in the absence of external pressure, whereas in the case of xPEO, a trade-off between enhanced rate capability and minimal membrane deformation is achieved at cell pressures of ≤0.43 MPa, which is considerably lower and more practical compared to cells employing ceramic electrolytes with ≥5 MPa external pressure.

Roxadustat Versus Erythropoietin: The Comparison of Efficacy in Reversing Ventricular Remodeling in Dialysis Patients with Anaemia.

Background: Renal anaemia and left ventricular hypertrophy are the main complications of chronic kidney disease and are shared among dialysis patients. This retrospective study aimed to compare the efficacies of the hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat and recombinant human erythropoietin in reversing ventricular remodeling in dialysis patients with renal anaemia. Methods: A total of 204 participants underwent baseline examinations, including echocardiograms and laboratory tests, before being administered either treatment for at least 24 weeks from January 2018 to October 2021, after which follow-up examinations were conducted at 6 months. Propensity score matching based on key variables included age, gender, cardiovascular diseases, cardiovascular medications, dialysis course and the vascular access at baseline was performed to include populations with similar characteristics between groups. Results: In total, 136 patients were included with roxadustat or recombinant human erythropoietin. The left ventricular mass index after treatment with roxadustat and recombinant human erythropoietin both significantly decreased after 6 months, but there was no significant difference in the change in left ventricular mass index between the two groups. In addition, the left ventricular end-diastolic diameters and left ventricular wall thickness, systolic blood pressure, and diastolic blood pressure significantly decreased in the roxadustat group. Roxadustat and recombinant human erythropoietin also increased haemoglobin significantly, but there was no significant difference in the change in haemoglobin between the two groups. The results of multiple linear regression showed that the change in haemoglobin was independent factor affecting the improvement of left ventricular mass index. Conclusions: The increase of haemoglobin was associated with improving left ventricular hypertrophy in dialysis patients. However, the beneficial effects between roxadustat and recombinant human erythropoietin on left ventricular mass index did not show clear superiority or inferiority in six months.

ITGAM-mediated macrophages contribute to basement membrane damage in diabetic nephropathy and atherosclerosis.

BACKGROUND: Diabetic nephropathy (DN) and atherosclerosis (AS) are prevalent and severe complications associated with diabetes, exhibiting lesions in the basement membrane, an essential component found within the glomerulus, tubules, and arteries. These lesions contribute significantly to the progression of both diseases, however, the precise underlying mechanisms, as well as any potential shared pathogenic processes between them, remain elusive. METHODS: Our study analyzed transcriptomic profiles from DN and AS patients, sourced from the Gene Expression Omnibus database. A combination of integrated bioinformatics approaches and machine learning models were deployed to identify crucial genes connected to basement membrane lesions in both conditions. The role of integrin subunit alpha M (ITGAM) was further explored using immune infiltration analysis and genetic correlation studies. Single-cell sequencing analysis was employed to delineate the expression of ITGAM across different cell types within DN and AS tissues. RESULTS: Our analyses identified ITGAM as a key gene involved in basement membrane alterations and revealed its primary expression within macrophages in both DN and AS. ITGAM was significantly correlated with tissue immune infiltration within these diseases. Furthermore, the expression of genes encoding core components of the basement membrane was influenced by the expression level of ITGAM. CONCLUSION: Our findings suggest that macrophages may contribute to basement membrane lesions in DN and AS through the action of ITGAM. Moreover, therapeutic strategies that target ITGAM may offer potential avenues to mitigate basement membrane lesions in these two diabetes-related complications.

Ellagic acid protects against angiotensin II-induced hypertrophic responses through ROS-mediated MAPK pathway in H9c2 cells.

The early myocardial response of hypertension is an elevation of angiotensin-II (Ang-II) concentration, leading to heart failure and cardiac hypertrophy. This hypertrophic event of the heart is mediated by the interaction of Ang type 1 receptors (AT-R1), thereby modulating NADPH oxidase activity in cardiomyocytes, which alters redox status in cardiomyocytes. Ellagic acid (EA) has anti-inflammatory and anti-oxidative capacities. Thus, EA has potential preventive effects on cardiovascular diseases and diabetes. In the last decades, because the protective effect of EA on Ang-II-induced hypertrophic responses is unclear, this study aims to investigate the protective effect of EA in cardiomyocytes. H9c2 cells were treated to Ang-II 1 µM for 24 h to induce cellular damage. We found that EA protected against Ang-II-increased cell surface area and pro-hypertrophic gene expression in H9c2. EA reduced Ang-II-caused AT-R1 upregulation, thereby inhibiting oxidative stress NADPH oxidase activation. EA mitigated Ang-II-enhanced p38 and extracellular-signal-regulated kinase (ERK) phosphorylation. Moreover, EA treatment under Ang-II stimulation also reversed NF-κB activity and iNOS expression. This study shows that EA protects against Ang-II-induced myocardial hypertrophy and attenuates oxidative stress through reactive oxygen species-mediated mitogen-activated protein kinase signaling pathways in H9c2 cells. Thus, EA may be an effective compound for preventing Ang-II-induced myocardial hypertrophy.

Acetyl-CoA synthetase 2 promotes diabetic renal tubular injury in mice by rewiring fatty acid metabolism through SIRT1/ChREBP pathway.

Diabetic nephropathy (DN) is characterized by chronic low-grade renal inflammatory responses, which greatly contribute to disease progression. Abnormal glucose metabolism disrupts renal lipid metabolism, leading to lipid accumulation, nephrotoxicity, and subsequent aseptic renal interstitial inflammation. In this study, we investigated the mechanisms underlying the renal inflammation in diabetes, driven by glucose-lipid metabolic rearrangement with a focus on the role of acetyl-CoA synthetase 2 (ACSS2) in lipid accumulation and renal tubular injury. Diabetic models were established in mice by the injection of streptozotocin and in human renal tubular epithelial HK-2 cells cultured under a high glucose (HG, 30 mmol/L) condition. We showed that the expression levels of ACSS2 were significantly increased in renal tubular epithelial cells (RTECs) from the diabetic mice and human diabetic kidney biopsy samples, and ACSS2 was co-localized with the pro-inflammatory cytokine IL-1ß in RTECs. Diabetic ACSS2-deficient mice exhibited reduced renal tubular injury and inflammatory responses. Similarly, ACSS2 knockdown or inhibition of ACSS2 by ACSS2i (10 µmol/L) in HK-2 cells significantly ameliorated HG-induced inflammation, mitochondrial stress, and fatty acid synthesis. Molecular docking revealed that ACSS2 interacted with Sirtuin 1 (SIRT1). In HG-treated HK-2 cells, we demonstrated that ACSS2 suppressed SIRT1 expression and activated fatty acid synthesis by modulating SIRT1-carbohydrate responsive element binding protein (ChREBP) activity, leading to mitochondrial oxidative stress and inflammation. We conclude that ACSS2 promotes mitochondrial oxidative stress and renal tubular inflammation in DN by regulating the SIRT1-ChREBP pathway. This highlights the potential therapeutic value of pharmacological inhibition of ACSS2 for alleviating renal inflammation and dysregulation of fatty acid metabolic homeostasis in DN. Metabolic inflammation in the renal region, driven by lipid metabolism disorder, is a key factor in renal injury in diabetic nephropathy (DN). Acetyl-CoA synthetase 2 (ACSS2) is abundantly expressed in renal tubular epithelial cells (RTECs) and highly upregulated in diabetic kidneys. Deleting ACSS2 reduces renal fatty acid accumulation and markers of renal tubular injury in diabetic mice. We demonstrate that ACSS2 deletion inhibits ChREBP-mediated fatty acid lipogenesis, mitochondrial oxidative stress, and inflammatory response in RTECs, which play a major role in the progression of diabetic renal tubular injury in the kidney. These findings support the potential use of ACSS2 inhibitors in treating patients with DN.

The ratio of neutrophils to lymphocytes effectively predicts clinical outcomes in idiopathic membranous nephropathy.

BACKGROUND: Systemic inflammatory indicators are important in the prognoses of various diseases. Such indicators, including the neutrophil-to-lymphocyte ratio (NLR), can be meaningful in predicting the clinical outcome in patients diagnosed with idiopathic membranous nephropathy (IMN). MATERIALS AND METHODS: 112 IMN patients diagnosed by renal biopsy were recruited retrospectively. The endpoint was defined as a combination of partial and complete remission. Statistical analysis determined the independent factors associated with clinical remission and the predictive utility of NLR. RESULTS: Within the 12-month follow-up period, 72 patients achieved clinical remission after treatment. Univariate analysis identified significant differences in serum albumin, estimated glomerular filtration rate (eGFR), proteinuria, neutrophil count, and NLR between the remission group and the non-remission group (all p < 0.05). Cox proportional hazards indicated that elevated eGFR (HR 1.022, 95% CI (1.009 - 1.035), p = 0.001), lower NLR (HR 0.345, 95% CI (0.237 - 0.501), p = 0.0001), and decreased proteinuria (HR 0.826, 95% CI (0.693 - 0.984), p = 0.032) were protective elements for remission. With an optimal cut-off value of 2.61, the pre-treatment NLR had an excellent ability to identify the remission (area under the curve (AUC), 0.785). Participants were separated into low- and high-NLR groups by using 2.61. Kaplan-Meier survival curves revealed significantly higher remission rates in the lower group (p < 0.0001). CONCLUSION: The NLR is an effective indicator for predicting clinical remission in patients with IMN.

Application of cloud server-based machine learning for assisting pathological structure recognition in IgA nephropathy.

BACKGROUND: Machine learning (ML) models can help assisting diagnosis by rapidly localising and classifying regions of interest (ROIs) within whole slide images (WSIs). Effective ML models for clinical decision support require a substantial dataset of 'real' data, and in reality, it should be robust, user-friendly and universally applicable. METHODS: WSIs of primary IgAN were collected and annotated. The H-AI-L algorithm which could facilitate direct WSI viewing and potential ROI detection for clinicians was built on the cloud server of matpool, a shared internet-based service platform. Model performance was evaluated using F1-score, precision, recall and Matthew's correlation coefficient (MCC). RESULTS: The F1-score of glomerular localisation in WSIs was 0.85 and 0.89 for the initial and pretrained models, respectively, with corresponding recall values of 0.79 and 0.83, and precision scores of 0.92 and 0.97. Dichotomous differentiation between global sclerotic (GS) and other glomeruli revealed F1-scores of 0.70 and 0.91, and MCC values of 0.55 and 0.87, for the initial and pretrained models, respectively. The overall F1-score of multiclassification was 0.81 for the pretrained models. The total glomerular recall rate was 0.96, with F1-scores of 0.68, 0.56 and 0.26 for GS, segmental glomerulosclerosis and crescent (C), respectively. Interstitial fibrosis/tubular atrophy lesion similarity between the true label and model predictions was 0.75. CONCLUSIONS: Our results underscore the efficacy of the ML integration algorithm in segmenting ROIs in IgAN WSIs, and the internet-based model deployment is in favour of widespread adoption and utilisation across multiple centres and increased volumes of WSIs.

Activation of acetyl-CoA synthetase 2 mediates kidney injury in diabetic nephropathy.

Albuminuria and podocyte injury are the key cellular events in the progression of diabetic nephropathy (DN). Acetyl-CoA synthetase 2 (ACSS2) is a nucleocytosolic enzyme responsible for the regulation of metabolic homeostasis in mammalian cells. This study aimed to investigate the possible roles of ACSS2 in kidney injury in DN. We constructed an ACSS2-deleted mouse model to investigate the role of ACSS2 in podocyte dysfunction and kidney injury in diabetic mouse models. In vitro, podocytes were chosen and transfected with ACSS2 siRNA and ACSS2 inhibitor and treated with high glucose. We found that ACSS2 expression was significantly elevated in the podocytes of patients with DN and diabetic mice. ACSS2 upregulation promoted phenotype transformation and inflammatory cytokine expression while inhibiting podocytes' autophagy. Conversely, ACSS2 inhibition improved autophagy and alleviated podocyte injury. Furthermore, ACSS2 epigenetically activated raptor expression by histone H3K9 acetylation, promoting activation of the mammalian target of rapamycin complex 1 (mTORC1) pathway. Pharmacological inhibition or genetic depletion of ACSS2 in the streptozotocin-induced diabetic mouse model greatly ameliorated kidney injury and podocyte dysfunction. To conclude, ACSS2 activation promoted podocyte injury in DN by raptor/mTORC1-mediated autophagy inhibition.

The Neuroprotective Effect of Isotetrandrine on Parkinson's Disease via Anti-Inflammation and Antiapoptosis In Vitro and In Vivo.

Parkinson's disease (PD) is one of the most influential diseases in the world, and the current medication only can relieve the clinical symptoms but not slow the progression of PD. Therefore, we intend to examine the neuroprotective activity of plant-derived compound isotetrandrine (ITD) in vitro and in vivo. In vitro, cells were cotreated with ITD and LPS to detect the inflammatory-related protein and mRNA. In vivo, zebrafish were pretreated with ITD and inhibitors prior to 6-OHDA treatment. Then, the behavior was monitored at 5 dpf. Our result showed ITD inhibited LPS-induced upregulation of iNOS, COX-2 protein expression, and iL-6, inos, cox-2, and cd11b mRNA expression in BV2 cells. The data in zebrafish also demonstrated a significant improvement of ITD on the 6-OHDA-induced locomotor deficiency. ITD also improved 6-OHDA-induced apoptosis in zebrafish PD. We also pharmacologically validated the mechanism with three inhibitors, including LY294002, PI3K inhibitor; LY32141996, ERK inhibitor, SnPP, and HO-1 inhibitors. All of these inhibitors could abolish the neuroprotective effect of ITD partially in locomotor activity. Besides, the molecular level also showed the same trend. Treatment of these inhibitors could significantly abolish ITD-induced antineuroinflammatory and antioxidative stress effects in zebrafish PD. Our study showed ITD possessed a neuroprotective activity in zebrafish PD. The mRNA level also supported our arguments. The neuroprotection of ITD might be through antineuroinflammation and antiapoptosis pathways via PI3K, ERK, and HO-1.

Synthesis of Two-Dimensional (Cu-S)n Metal-Organic Framework Nanosheets Applied as Peroxidase Mimics for Detection of Glutathione.

Facilely synthesized peroxidase-like nanozymes with high catalytic activity and stability may serve as effective biocatalysts. The present study synthesizes peroxidase-like nanozymes with multinuclear active sites using two-dimensional (2D) metal-organic framework (MOF) nanosheets and evaluates them for their practical applications. A simple method involving a one-pot bottom-up reflux reaction is developed for the mass synthesis of (Cu-S)n MOF 2D nanosheets, significantly increasing production quantity and reducing reaction time compared to traditional autoclave methods. The (Cu-S)n MOF 2D nanosheets with the unique coordination of Cu(I) stabilized in Cu-based MOFs demonstrate impressive activity in mimicking natural peroxidase. The active sites of the peroxidase-like activity of (Cu-S)n MOF 2D nanosheets were predominantly verified as Cu(I) rather than Cu(II) of other Cu-based MOFs. The cost-effective and long-term stability of (Cu-S)n MOF 2D nanosheets make them suitable for practical applications. Furthermore, the inhibition of the peroxidase-like activity of (Cu-S)n MOF nanosheets by glutathione (GSH) could provide a simple strategy for colorimetric detection of GSH against other amino acids. This work remarkably extends the utilization of (Cu-S)n MOF 2D nanosheets in biosensing, revealing the potential for 2D (Cu-S)n MOFs.

Effect of pelvic floor muscles exercises by extracorporeal magnetic innervations on the bladder neck and urinary symptoms.

BACKGROUND: This study aimed to investigate the changes in the bladder neck (BN) and urinary symptoms using extracorporeal magnetic innervation (ExMI) therapy before and after performing passive pelvic floor exercises. METHODS: Twenty women with stress urinary incontinence (SUI) were assessed by transperineal ultrasound and questionnaires before and after the ExMI therapy from January 2011 to February 2021. RESULTS: The incidence of urinary frequency and SUI were significantly decreased after the therapy (McNemar test, p < 0.01). The therapeutic efficacy of SUI was 75%. A significant decrease was noted in pad test results (paired t test, p < 0.05). At the same time, there was a considerable difference in Urinary Distress Inventory-6 scale measures (paired t test, p < 0.001). However, results for the Incontinence Impact Questionnaire-7 showed a marginally significant difference (paired t test, p = 0.066). Three domains of lubrication, orgasm, and satisfaction in the Female Sexual Function Index showed significant differences (paired t test, p < 0.05). Transperineal ultrasound found that BN mobility and Q-tip straining angle were not statistically significant (paired t test, p > 0.05). CONCLUSION: The ExMI is effective for SUI by strengthening the pelvic floor muscle without significantly decreasing BN mobility.

Mangiferin Protects against Angiotensin-II-Enhanced Hypertrophic Markers and Apoptosis in H9c2 Cardiomyocytes.

Hypertrophic cardiomyopathy accompanies numerous cardiovascular diseases, and the intervention of cardiac hypertrophy is an important issue to prevent detrimental consequences. Mangiferin (MGN) is a glucosylxanthone found in Mangifera indica, which exhibits anti-oxidant and anti-inflammatory properties. Various studies have demonstrated the cardioprotective potential of MGN, but the mechanisms behind its beneficial effects have not been fully revealed. Here, angiotensin-II (Ang-II) was used to induce cardiac hypertrophy, and we examined cell size, expression of hypertrophy markers (e.g., ANP, BNP, and [Formula: see text]-MHC), and oxidative stress (e.g., the ratio of NADPH/NADP[Formula: see text], the expression of p22phox and p67phox, and ROS and SOD production) of cardiomyocytes. Moreover, we assessed the activation of mitogen-activated protein kinase (MAPK) signaling (e.g., p38 and ERK) and the NF-[Formula: see text]Bp65/iNOS axis. Additionally, an annexin V/PI assay was employed to evaluate whether MGN administration can attenuate Ang-II-elicited apoptosis. Lastly, the expression of Ang-II type 1 receptor (AT1) was measured to confirm its involvement in MGN-mediated protection. Our results showed that treatment with MGN attenuated the Ang-II-induced cell size, expression of hypertrophy markers, and oxidative stress in cardiomyocytes. MGN also abrogated the activation of MAPK signaling and the NF-[Formula: see text]Bp65/iNOS axis. Additionally, MGN prevented apoptosis and downregulated the elevation of AT1 in cardiomyocytes that had been exposed to Ang-II. Altogether, these results demonstrated the potential of using MGN to ameliorate the Ang-II-associated cardiac hypertrophy, which may be due to its anti-oxidant and anti-inflammatory effects through suppression of MAPK signaling and the NF-[Formula: see text]Bp65/iNOS axis.

Outer membrane vesicles derived from gut microbiota mediate tubulointerstitial inflammation: a potential new mechanism for diabetic kidney disease.

Rationale: Chronic tubulointerstitial inflammation is a common pathological process in diabetic kidney disease (DKD). However, its underlying mechanism is largely unknown. This study aims at investigating the role of gut microbiota-derived outer membrane vesicles (OMVs) in tubulointerstitial inflammation in DKD. Methods: Gut microbiota in diabetes mellitus rats was manipulated by microbiota depletion and fecal microbiota transplantation to explore its role in tubulointerstitial inflammation. To check the direct effects of OMVs, fecal bacterial extracellular vesicles (fBEVs) were administrated to mice orally and HK-2 cells in vitro. For mechanistic investigations, HK-2 cells were treated with small interfering RNA against caspase-4 and fBEVs pre-neutralized by polymyxin B. Results: By performing gut microbiota manipulation, it was confirmed that gut microbiota mediated tubulointerstitial inflammation in DKD. In diabetic rats, gut microbiota-derived OMVs were increased and were clearly detected in distant renal tubulointerstitium. Diabetic fBEVs directly administered by gavage translocated into tubular epithelial cells and induced tubulointerstitial inflammation and kidney injury. In vitro, OMVs were internalized through various endocytic pathways and triggered cellular inflammatory response. Mechanistically, it was revealed that OMVs-derived lipopolysaccharide induced tubular inflammation, which was mediated by the activation of the caspase-11 pathway. Conclusions: Increased OMVs due to dysbiosis translocated through leaky gut barrier into distant tubulointerstitium and induced cellular inflammation and renal tubulointerstitial injury in DKD. These findings enrich the mechanism understanding of how gut microbiota and its releasing OMVs influence the development and progression of kidney disease.

Swimming exercise attenuates mechanical hypersensitivity and mitigates peripheral nerve degeneration in rats with painful diabetic neuropathy (PDN).

BACKGROUND: This study aimed to assess the effectiveness of swimming exercise in alleviating mechanical hypersensitivity and peripheral nerve degeneration associated with a pre-clinical model of painful diabetic neuropathy (PDN). METHODS: This study is a pre-clinical study conducted using the streptozocin (STZ)-induced PDN rat model. Rats were randomly allocated to three groups: a vehicle group of non-diabetic rats (Vehicle, n = 9), a group of rats with PDN (PDN, n = 8), and a group of rats with PDN that performed a swimming exercise program (PDN-SW, n = 10). The swimming exercise program included daily 30-minute swimming exercise, 5 days per week for 4 weeks. Von Frey testing was used to monitor hindpaw mechanical sensitivity over 4 weeks. Assessment of cutaneous peripheral nerve fiber integrity was performed after the 4-week study period via immunohistochemistry for protein gene product 9.5-positive (PGP9.5+) intra-epidermal nerve fiber density (IENFD) in hind-paw skin biopsies by a blinded investigator. RESULTS: The results showed that swimming exercise mitigated but did not fully reverse mechanical hypersensitivity in rats with PDN. Immunohistochemical testing revealed that the rats in the PDN-SW group retained higher PGP9.5+ IENFD compared to the PDN group but did not reach normal levels of the Vehicle group. CONCLUSIONS: The results of this study indicate that swimming exercise can mitigate mechanical hypersensitivity and degeneration of peripheral nerve fibers in rats with experimental PDN.

Relationship between Q-Tip Test and Urethral Hypermobility on Perineal Ultrasound.

BACKGROUND: The aim of this study was to assess the correlation between the overall rest-stress distance measured by transperineal ultrasound (TPUS) and Q-tip test angle in women with urodynamic stress incontinence (USI), and determine a cut-off value of rest-stress distance for predicting urethral hypermobility (UH). METHODS: Women with USI scheduled for mid-urethral sling surgery were retrospectively recruited. UH was defined as a Q-tip angle more than or equal to 30 degrees. Ultrasonic measurement of the overall rest-stress distance was defined as the linear distance of bladder-neck position change from resting status to maximal strain. RESULTS: Among the 132 enrolled women, the Pearson correlation coefficient between the overall rest-stress distance in TPUS and Q-tip test angle was 0.9104 (95% CI, 0.8758-0.9357, p < 0.001). In receiver-operating-characteristic-curve analysis, a rest-stress distance of more than 13.3 mm was an optimal cut-off value to predict UH (sensitivity = 76.47%, specificity = 93.3%; area = 0.937, 95% confidence interval: 0.881-0.972). CONCLUSIONS: The overall rest-stress distance in TPUS correlated well with the Q-tip test angle, indicating that it can be an alternative method for the assessment of USI. A rest-stress distance of more than 13.3 mm was an optimal cut-off value to predict UH in women with USI.

Schisanhenol Attenuates OxLDL-Induced Endothelial Dysfunction via an AMPK-Dependent Mechanism.

Atherosclerotic cardiovascular diseases, commonly known as the formation of fibrofatty lesions in the artery wall, are the leading causes of death globally. Oxidized low-density lipoprotein (oxLDL) is one of the major components of atherosclerotic plaques. It is evident that dietary supplementation containing sources of antioxidants can prevent atherogenic diseases. Schisanhenol (SAL), a dibenzocyclooctene lignin, has been shown to attenuate oxLDL-induced apoptosis and the generation of reactive oxygen species (ROS) in endothelial cells. However, the underlying molecular mechanisms are still largely unknown. In this study, human umbilical vein endothelial cells (HUVECs) were pre-treated with SAL and oxLDL. Our results showed that adenosine monophosphate-activated protein kinase (AMPK) phosphorylation was enhanced in cells pre-treated with SAL in time-dependent and dose-dependent manners. Subsequently, oxLDL-induced AMPK dephosphorylation and protein kinase C (PKC) phosphorylation were significantly reversed in the presence of SAL. In addition, SAL treatment led to an inhibiting effect on the oxLDL-induced membrane assembly of NADPH oxidase subunits, and a similar effect was observed in ROS generation. This effect was further confirmed using knockdown AMPK with small interfering RNA (siRNA) and pharmaceutical reagents, such as the AMPK activator (AICAR), PKC inhibitor (Gö 6983), and ROS inhibitor (DPI). Furthermore, the oxLDL-induced intracellular calcium rise and the potential collapse of the mitochondrial membrane reduced the Bcl-2/Bax ratio, and released cytochrome c from the mitochondria, leading to the subsequent activation of caspase-3 in HUVECs, which were also markedly suppressed by SAL pretreatment. The results mentioned above may provide additional insights into the possible molecular mechanisms underlying the cardiovascular protective effects of SAL.

Cisplatin triggers oxidative stress, apoptosis and pro-inflammatory responses by inhibiting the SIRT1-mediated Nrf2 pathway in chondrocytes.

Although the height of the proliferating layer that was suppressed in the growth plate has been recognized as an adverse effect of cisplatin in pediatric cancer survivors, the detailed pathological mechanism has not been elucidated. Sirtuin-1 (SIRT1) has been reported as an essential modulator of cartilage homeostasis, but its role in cisplatin-induced damage of chondrocytes remains unclear. In this study, we examined how cisplatin affected the expression of SIRT1 and cell viability. Next, we showed downregulation of SIRT1 after cisplatin treatment resulted in suppression of Peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α), leading to inhibition of Nrf2 nuclear translocation and subsequently decreased Heme oxygenase-1(HO-1) and NAD(P)H Quinone Dehydrogenase 1(NQO-1) expression. Blockage of the SIRT1/ PGC-1α axis not only increased oxidative stress with lower antioxidant SOD and GSH, but also contributed to mitochondrial dysfunction evidenced by the collapse of membrane potential and repression of mitochondrial DNA copy number and ATP. We also found that Cisplatin up-regulated the p38 phosphorylation, pro-inflammatory events and matrix metalloproteinases (MMPs) in chondrocytes through the SIRT1-modulated antioxidant manner. Collectively, our findings suggest that preservation of SIRT1 in chondrocytes may be a potential target to ameliorate growth plate dysfunction for cisplatin-receiving pediatric cancer survivors.