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OBJECTIVE: To examine the effects of levosimendan on cardiac function, hemodynamics, and body inflammation of patients with acute myocardial infarction and heart failure. METHODS: A retrospective analysis was conducted on 113 acute myocardial infarction patients with heart failure (admitted to Xianyang First People's Hospital from September 2018 to January 2022). According to the treatment plan, patients were categorized into a control group (n = 53) (treated with conventional diuresis and vasodilation) and observation group (n = 60) (treated with levosimendan in addition to the treatment of the control group). Indexes were compared between the two groups before and after treatment, including effectiveness rate, mean pulmonary arterial pressure (PAMP) and pulmonary capillary wedge pressure (PCWP). Left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD) and left ventricular ejection fraction (LVEF) were monitored before and after treatment by color Doppler ultrasonography. Serum high-sensitivity C-reactive protein (hs-CRP) levels were measured before and after treatment. Logistic analysis was applied to screen independent factors affecting treatment efficacy. Adverse reactions and life quality after 6 months of treatment were compared between the two groups. RESULTS: The overall response rate of the observation group was higher than that of the control group (P<0.05). Changes in PAMP and PCWP in the two groups before and after treatment were significantly different. Patients in the observation group had improved indicators compared with the control group (all P<0.05). After treatment, the cardiac function indexes and inflammation-related factors of the observation group were improved more than those of the control group (P<0.05). Patients in the observation group had a lower incidence of adverse reactions and a higher life quality 6 months after treatment compared to the control group (P<0.05). Diabetes and treatment regimen were independent risk factors affecting treatment efficacy by logistic regression analysis. CONCLUSION: The administration of levosimendan helps improve cardiac function, hemodynamics, and body inflammation in patients with acute myocardial infarction and heart failure, with fewer adverse reactions and higher safety.

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Injectable hydrogels have recently emerged as alternatives to sutures for various clinical indications. However, existing injectable hydrogels are unsuitable for hemostasis in minimally invasive surgery because of their weak interfacial adhesion and complex/prolonged processing. Herein, a superwetting injectable hydrogel composed of oppositely charged polysaccharides is developed. The spontaneous spreading of the injectable hydrogel on the surfaces achieves complete wetting and forms tight interfacial contact by absorbing the interfacial water. The superwetting ability and subsequent covalent crosslinking perform fast and ultrastrong wet adhesion (140 kPa) on the tissue surface. Ex vivo porcine and in vivo rat models show that the hydrogel successfully leads to the aggregation of erythrocytes for targeted hemostasis (in less than 12 s) without requiring external adjuncts, and no postsurgical adhesions to the peripheral tissues. This further demonstrates that hydrogel can act as an effective hemostasis agent in laparoscopic surgery in a rabbit model. Overall, the strong wet adhesion, antibacterial properties, and easy operability make this injectable hydrogel a promising candidate for hemostasis applications, as it can successfully combine clinical efficacy and transformation opportunities for minimally invasive surgery.

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BACKGROUND: Our previous study indicated that Ginkgo biloba leaf extract (EGb) could protect against cisplatin-induced acute kidney injury in rabbits. The present study aimed to determine the effects and potential molecular mechanisms of EGb on chronic renal interstitial fibrosis induced by cisplatin using in vivo and in vitro models. METHODS: Rats received a single dose of cisplatin on Day 1, and a subset of rats was intraperitoneally injected with EGb daily between Days 22-40. In vitro, HK-2 cells were treated with cisplatin, and a subset of cells was cultivated with EGb or SIS3 (Smad3 inhibitor) for 48 h. Renal function of rats was assessed by detecting the levels of serum creatinine (Scr), blood urea nitrogen (BUN) and urinary N-acetyl-ß-D-glucosaminidase (NAG). Hematoxylin and eosin staining and Masson's trichrome staining were used to evaluate the damage and fibrosis of renal tissue. Western blotting, immunohistochemistry and immunofluorescence were used to detect the protein levels of fibrosis-associated proteins and signaling pathway-related proteins. RT-qPCR analysis was used to examine the mRNA levels of related indicators. RESULTS: EGb significantly decreased the increased levels of Scr, BUN and urinary NAG and attenuated renal damage and the relative area of renal interstitial fibrosis induced by cisplatin. Additionally, EGb decreased the protein levels of α-SMA, Col I, TGF-ß1, smad2/3, phosphorylated (p)-smad2/3, p38 MAPK, and p-p38 MAPK; the ratio of p-p38 MAPK/p38 MAPK; and the mRNA level of p38 MAPK in renal tissues induced by cisplatin. In agreement with in vivo studies, EGb significantly reduced the increased protein levels of these indicators. Additionally, EGb significantly reduced the increased protein levels of vimentin, TIMP-1, and CTGF, as well as the mRNA levels of α-SMA, vimentin, and TGF-ß1, while it significantly increased the reduced E-cadherin protein level and the MMP-1/TIMP-1 ratio in HK-2 cells induced by cisplatin. It's worth noting that the effects of SIS3 in changing the above indicators were similar to those of EGb. CONCLUSION: Our study demonstrated that EGb improved cisplatin-induced chronic renal interstitial fibrosis, and its mechanisms were associated with inhibiting the epithelial-mesenchymal transition of renal tubular epithelial cells via the Smad3/TGF-ß1 and Smad3/p38 MAPK pathways.

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Cisplatin (CDDP) may induce apoptosis of renal tubular epithelial cells (RTEC) and cause CDDP-induced acute kidney injury (CAKI) during cancer treatment, but yet lack of preventive measures and effective treatment. As a new Chinese herbal preparation, Panax notoginseng saponins (PNS) has been found to mitigate CDDP-induced CAKI through elevating the expression of HIF-1α in the rat model, according to the data from our previous works. However, the underlying link between HIF-1α and apoptosis has not been well elucidated. The current study as a follow-up work, was aimed to reveal if PNS improves CAKI through HIF-1α-dependent apoptosis. A stably HIF-1α-knockdown human proximal tubular epithelial cell (HK-2) line was established by transfecting a HIF-1α-siRNA into HK-2 cells. Cell viability, mitochondrial function, cell apoptosis ratio and the expression of apoptosis-associated proteins (Cyt C, Bcl2, Bax, caspases 3) were determined. In order to elucidate the underlying mechanism, the expression of HIF-1α and BNIP3 were assessed. Our results showed that treatment of PNS rescued the cell viability of CDDP-injured HK-2 or HIF-1α-knockdown HK-2 cells, and increased the expression levels of ATP and MMP in HK-2 or HIF-1α-knockdown HK-2 cells which were reduced by CDDP. Moreover, PNS treatment decreased the CDDP or CDDP plus HIF-1α-knockdown-induced elevation of apoptosis and apoptosis-associated protein expressions. These findings demonstrate that PNS reduces CAKI through increasing HIF-1α to inhibit mitochondrial apoptosis pathway. Hence, we suggest PNS as a protective and therapeutic new drug for CDDP treatment of cancers, which might have significant meaning of further research and application potential.

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Hydrogels could be promising wound healing dressings that maintain a moist environment in the wound site and accelerate wound healing. However, the lack of antibacterial effect, suitable mechanical property and adhesiveness limits their applications. Here, we designed a quaternized chitosan-Matrigel-polyacrylamide (QCS-M-PAM) hydrogel with multi-functions. The morphology, swelling ratio, mechanical test, antimicrobial property, hemostatic performance and biocompatibility of the hybrid hydrogel were investigated in vitro and vivo. The hybrid hydrogel showed a three-dimensional (3D) microporous structure, high swelling ratio, excellent stretchable and compressive property, similar modulus to human skin, good adhesiveness, and low cytotoxicity. The results of histology and molecular testing in vivo demonstrated that the hybrid hydrogel could significantly enhance wound healing, collagen deposition, and induce skin adnexal regeneration by upregulating anti-inflammatory factors, and downregulating proinflammatory factors. Together, the present antibacterial hydrogels with hemostatic and adhesive properties are considered to have promising potential used as wound dressings for full-thickness skin defect.

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Counterion exchange of charged macromolecules has comprehensive implications in biological and synthetic systems such as protein function, biosignaling, ion conducting, and separation, but the correlation between the dynamic ion exchange, polyelectrolyte phase separation, and functionality remains elusive. Here, counterion exchange is exploited as a means to facilitate liquid-liquid phase separation and coacervates featuring higher stability and versatility compared with conventional complex coacervate. Self-coacervation of a cationic polyelectrolyte (polyamidoamine-epichlorohydrin, PAE-Cl) occurs in broader conditions when its original counter anion (Cl- ) is exchanged by bis(trifluoromethane-sulphonyl)imide anion (TFSI- ), as a result of TFSI- counter anions association instead of polyelectrolyte complexation. This coacervate is catechol-free, easy to prepare, and highlights robust wet adhesion strength on diverse submerged surfaces in salty water (pH = 3-11), as demonstrated by its versatile capability of in situ underwater gluing and repairing without any pre-immersive drying.

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Homocysteine- (Hcy-) induced endothelial cell apoptosis has been suggested as a cause of Hcy-dependent vascular injury, while the proposed molecular pathways underlying this process are unclear. In this study, we investigated the adverse effects of Hcy on human umbilical vein endothelial cells (HUVEC) and the underlying mechanisms. Our results demonstrated that moderate-dose Hcy treatment induced HUVEC apoptosis in a time-dependent manner. Furthermore, prolonged Hcy treatment increased the expression of NOX4 and the production of intracellular ROS but decreased the ratio of Bcl-2/Bax and mitochondrial membrane potential (MMP), resulting in the leakage of cytochrome c and activation of caspase-3. Prolonged Hcy treatment also upregulated glucose-regulated protein 78 (GRP78), activated protein kinase RNA-like ER kinase (PERK), and induced the expression of C/EBP homologous protein (CHOP) and the phosphorylation of NF-κb. The inhibition of NOX4 decreased the production of ROS and alleviated the Hcy-induced HUVEC apoptosis and ER stress. Blocking the PERK pathway partly alleviated Hcy-induced HUVEC apoptosis and the activation of NF-κb. Taken together, our results suggest that Hcy-induced mitochondrial dysfunction crucially modulated apoptosis and contributed to the activation of ER stress in HUVEC. The excessive activation of the PERK pathway partly contributed to Hcy-induced HUVEC apoptosis and the phosphorylation of NF-κb.

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