Background: Diabetic nephropathy (DN) is the most common cause of end-stage renal failure. Grape seed proanthocyanidin extracts (GSPE) are powerful antioxidants. However, the role of GSPE on advanced glycation end products (AGEs), receptor for advanced glycation end products (RAGE) and expression of connective tissue growth factor (CTGF) in DN has not been elucidated. Using streptozotocin-induced diabetic rats, we evaluated the effects of GSPE in DN. Methods: Wistar rats were induced into diabetes using streptozotocin injections and diabetic rats were treated with GSPE (dosage: 500 mg·kg^–1·day^–1) for 24 weeks. The renal pathological changes were examined with PAS staining and electron microscope. The mRNA and protein expression of RAGE and CTGF in kidney were detected by RT-PCR, Western blot and immunohistochemical staining. Results: Treated animals showed reduction in serum AGEs (p < 0.01), proteinuria (p < 0.01) and systolic blood pressure (p < 0.01). GSPE reduced the expression of RAGE (p < 0.01) and CTGF (p < 0.01) in the kidney, which were contributing to reversal of extracellular matrix accumulation in DN. Conclusion: Our results suggest that GSPE hold substantial promise for the treatment of DN. GSPE can decrease proteinuria, attenuating the progression of nephropathy in diabetic rats. Renoprotective effects of GSPE are correlated with suppression on AGEs/RAGE axis, downregulating expression of CTGF.

A patient in their 60s presented with a 6-hour history of sudden-onset worsening chest pain associated with shortness of breath and diaphoresis. What is your diagnosis?

SOHLH2 has been demonstrated the downregulation in various cancers and the involvement in tumor growth and metastasis. However, the function of SOHLH2 on tumor angiogenesis and the underlying molecular mechanisms have not been interrogated. IHC staining results revealed that SOHLH2 was negatively associated with microvessel density (MVD), tumor size, histology grade, and metastasis. Overexpression of SOHLH2 inhibited the angiogenic behavior of human umbilical vein endothelial cells (HUVEC) by a tumor cell–mediated paracrine signal, while knockdown of SOHLH2 promoted HUVEC angiogenic behavior. Ectopic SOHLH2 expression remarkably suppressed tumor growth and MVD in xenograft tumors, downregulated the expression of hypoxia inducible factor-1 alpha (HIF1α)-mediated proangiogenic genes in vivo and in vitro, while knockdown of SOHLH2 had an opposite result. Furthermore, we found that upregulation of HIF1α reversed SOHLH2-induced suppression of breast cancer angiogenesis, while KC7F2, the inhibitor of HIF1α, could attenuate the promotion of angiogenesis by SOHLH2 silencing. Using Chromatin immunoprecipitation and luciferase reporter assays, we validated that SOHLH2 could directly bind to HIF1α promoter and repress its transcriptional activity. Collectively, SOHLH2 suppresses breast cancer angiogenesis by downregulating HIF1α transcription and may be a potential biomarker for anti-angiogenesis therapy. Implications: SOHLH2 directly represses HIF1α–mediated angiogenesis and serves as an important inhibitor of angiogenesis in breast cancer.

Hemiplegic paralysis after stroke may augment postural instability and decrease the balance control ability for standing. The center of mass acceleration (COMacc) is considered to be an effective indicator of postural stability for standing balance control. However, it is less studied how the COMacc could be affected by the muscle activities on lower-limbs in post-stroke hemiplegic patients. This study aimed to examine the effects of hemiplegic paralysis in post-stroke individuals on the amplitude and structural variabilities of COMacc and surface electromyography (sEMG) signals during quiet standing. Eleven post-stroke hemiplegic patients and the same number of gender- and age-matched healthy volunteers participated in the experiment. The sEMG signals of tibialis anterior (TA) and lateral gastrocnemius (LG) muscles of the both limbs, and the COMacc in the anterior-posterior direction with and without visual feedback (VF vs. NVF) were recorded simultaneously during quiet standing. The sEMG and COMacc were analyzed using root mean square (RMS) or standard deviation (SD), and a modified detrended fluctuation analysis based on empirical mode decomposition (EMD-DFA). Results showed that the SD and the scale exponent α of EMD-DFA of the COMacc from the patients were significantly higher than the values from the controls under both VF (p < 0.01) and NVF (p < 0.001) conditions. The RMSs of TA and LG on the non-paretic limbs were significantly higher than those on paretic limbs (p < 0.05) for both the patients and controls (p < 0.05). The TA of both the paretic and non-paretic limbs of the patients showed augmented α values than the TA of the controls (p < 0.05). The α of the TA and LG of non-paretic limbs, and the α of COMacc were significantly increased after removing visual feedback in patients (p < 0.05). These results suggested an increased amplitude variability but decreased structural variability of COMacc, associated with asymmetric muscle contraction between the paretic and the non-paretic limbs in hemiplegic paralysis, revealing a deficiency in integration of sensorimotor information and a loss of flexibility of postural control due to stroke.

<p>Table S1: The correlation of sohlh2 expression and clinical characteristics. Figure S1. Sohlh2 suppresses HIF-1α-mediated proangiogenic factors in breast cancer cells. Figure S2. Sohlh2 exerted the inhibition on HIF-1α-mediated proangiogenic signaling pathway in xenografts. Figure S3. Mode: Sohlh2 inhibits breast cancer angiogenesis by tumor cell-mediated paracrine signaling pathway, downregulates HIF-1α transcription and suppresses breast cancer angiogenesis through HIF-1α-mediated proangiogenic axis.</p>