Berberine protects HK-2 cells from hypoxia/reoxygenation induced apoptosis via inhibiting SPHK1 expression

Renal ischemia reperfusion injury (RIRI) refers to the irreversible damage for renal function when blood perfusion is recovered after ischemia for an extended period, which is common in clinical surgeries and has been regarded as a major risk for acute renal failures (ARF) that is accompanied with unimaginably high morbidity and mortality. Hypoxia during ischemia followed by reoxygenation via reperfusion serves as a major event contributing to cell apoptosis, which has been widely accepted as the vital pathogenesis in RIRI. Preventing apoptosis in renal tubular epithelial cell has been considered as effective method for blocking RIRI. In this paper, we established a hypoxia/reoxygenation (H/R) injury model in human proximal tubular epithelial HK-2 cells. Here, we found increased SPHK1 levels in H/R injured HK-2 cells, which could be significantly down regulated after berberine treatment. Berberine has been reported to exert a protective effect on H/R-induced apoptosis of HK-2 cells. So, in our present study, we planned to investigate whether SPHK1 participated in the anti-apoptosis process of berberine in H/R injured HK-2 cells. Our study confirmed the protective effect of berberine against H/R-induced apoptosis in HK-2 cells through promoting cells viability, inhibiting cells apoptosis, and down-regulating p-P38, caspase-3, caspase-9 as well as SPHK1, while up regulating the ratio of Bcl-2/Bax. However, SPHK1 overexpression in HK-2 cells induced severe apoptosis, which can be significantly ameliorated with additional berberine treatment. We concluded that berberine could remarkably prevent H/R-induced apoptosis in HK-2 cells through down-regulating SPHK1 expression levels, and the mechanisms included the suppression of p38 MAPK activation and mitochondrial stress pathways.     

Estimate of reduced glomerular filtration rate by triglyceride-glucose index: insights from a general Chinese population

Objectives: Recent studies have identified triglyceride-glucose index (TyG) as a surrogate of insulin resistance. Since insulin resistance correlates with renal damage, our study aims to investigate the impact of TyG on the risk of reduced eGFR and explore its value to improve the risk stratification and prevention of reduced eGFR.

Methods: This cross-sectional study included 6466 participants (mean age:59.57 years, 60.2% females) from rural areas of northeast China between September 2017 to May 2018. TyG was calculated as ln[fasting triglyceride (mg/dL)×fasting plasma glucose (mg/dL)/2]. Reduced eGFR was defined as eGFR<60ml/min per 1.73m².

Results: The prevalence of reduced eGFR was 2.94%. After full adjustment, each SD increase of TyG caused 42.6% additional risk for reduced eGFR. When dividing TyG into quartiles, the top quartile had a 1.934 times risk than the bottom quartile. Furthermore, the risk of reduced eGFR increased linearly with the increment of TyG. Subgroup analysis also revealed the association was robust to several risk factors of renal damage. Finally, category-free net reclassification index (0.204, 95% CI: 0.060–0.349, p = 0.005) and integrated discrimination index (0.010, 95% CI: 0.005–0.016, p < 0.001) demonstrated the value of TyG to refine the risk stratification of reduced eGFR.

Conclusion: Our work reveals the robust association between TyG and reduced eGFR. Moreover, the present study implicates the potential role of TyG as a risk indicator to optimize the prevention of reduced eGFR. Lastly, the findings also suggest the importance of simultaneous glycemic and lipid control to avoid the development and progression of reduced eGFR.     

Single-incision technique for the internal fixation of distal fractures of the tibia and fibula: a combined anatomic and clinical study

Objectives

To present a novel single anterior-lateral approach for the treatment of distal tibia and fibula fracture via anatomical study and primary clinical application in order to minimize soft tissue complications.

Design

Both a gross anatomic cadaver and retrospective studies of the single-incision technique in patients recruited between June 2004 and January 2010.

Setting

Level I trauma center.

Patients/participants

Twenty-six legs of 14 adult human cadavers and clinical recruitment of 49 patients (29 males, 20 females) with a mean age of 37.6 years (range 11–68) with fracture of distal 1/3 tibia and fibula.

Intervention

A single anterior-lateral incision technique for open reduction and internal fixations of distal tibia and fibula fractures.

Main outcome measures

To identify the anatomic structures at risk in the anterolateral aspect of the lower leg and explicit the safe dissection distance from the extensor digitorum longus (EDL) to tibia and fibula, 26 legs of 14 adult human embalmed specimens were recruited in the anatomical study with the distance between the EDL and the anterior edge of the distal thirds of the tibia, as well as the distance between the EDL and the anterior edge of the distal thirds of the fibula were measured, and their mutual relationships to the surrounding anatomical structures described. Mean average standard deviations were also calculated. As for the clinical study, the quality of bone union and soft tissue healing were noted.

Results

The mean distances between the distal tibia and the EDL were measured to be 2.96 ± 0.46 cm (proximal), 1.85 ± 0.25 cm (middle), and 2.15 ± 0.30 cm (distal), and that between the fibula and the EDL were 1.82 ± 0.28 cm (proximal), 2.09 ± 0.31 cm (middle), and 2.30 ± 0.27 cm (distal), which means the safe gap from the distal tibia to EDL was1.6–3.4 cm and from the EDL to fibula was 1.5–2.6 cm. The anterior tibial vein and artery and the deep fibular nerve lie on the anterior interosseous membrane over the lateral surface of the distal tibia were excellently visualized. Review of clinical outcomes in 49 patients with combined distal tibial and fibular fractures who underwent reduction and fixation with the single-incision technique, revealed uneventful fracture healings in 47 patients; and two cases of superficial wound necrosis which were treated and healed in 4 months. There was no case of delayed union or non-union.

Conclusion

Distal fibula fracture occurring with distal tibia fracture poses a challenge for stable fixation. This has necessitated the need for dual incisions on the distal leg to approach each fracture for reduction and fixation. However, a single anterolateral incision enables the safe approach to the lateral aspects of the distal tibia and fibula thus eliminating the need for two separate incisions and minimizing the soft tissue complication to some extent. Meanwhile, the neurovascular bundle at risk during operation, distal tibia and fibula is clearly exposed in the single anterior-lateral incision.     

结肠癌患者的路径化围手术期中西医结合护理干预

目的探讨路径化围手术期中西医结合护理干预对结肠癌患者术后早期生活质量的影响。方法将60例结肠癌患者随机分为观察组和对照组各30例。对照组实施围手术期常规护理,观察组实施路径化围手术期中西医结合护理干预,比较两组患者术后1周生活质量。结果术后1周观察组躯体功能、情绪功能、社会功能、总生活质量及疲乏、恶心呕吐、疼痛等方面评分显著优于对照组(P<0.05,P<0.01)。结论路径化围手术期中西医结合护理干预可有效改善结肠癌患者术后早期生活质量。     

糖尿病周围神经病变中医药治疗的进展

中医认为,糖尿病周围神经病变与肝、脾、肾三脏关系最为密切,以气虚、阴虚或气阴两虚为本,瘀血、痰浊为标。中医药治疗DPN从整体入手,根据病因病机与辨证论治,进而以辩证分型治疗,或以主要病机为立足点,采取专病专方或单味药治疗,显示中医药的治疗优势。中医复方的实验研究也取得成绩。本文从近年的病因病机、实验研究、辨证论治的中医治疗、中医其他技术方法进行综述。     

Mathematical model of renal interstitial fibrosis

Lupus nephritis (LN) is an autoimmune disease that occurs when autoantibodies complex with self-antigen and form immune complexes that accumulate in the glomeruli. These immune complexes initiate an inflammatory response resulting in glomerular injury. LN often concomitantly affects the tubulointerstitial compartment of the kidney, leading first to interstitial inflammation and subsequently to interstitial fibrosis and atrophy of the renal tubules if not appropriately treated. Presently the only way to assess interstitial inflammation and fibrosis is through kidney biopsy, which is invasive and cannot be repeated frequently. Hence, monitoring of disease progression and response to therapy is suboptimal. In this paper we describe a mathematical model of the progress from tubulointerstitial inflammation to fibrosis. We demonstrate how the model can be used to monitor treatments for interstitial fibrosis in LN with drugs currently being developed or used for nonrenal fibrosis.Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that can affect the kidney. The most common kidney manifestation of SLE is lupus nephritis (LN). LN occurs when autoantibodies complex with self-antigens and form immune complexes that accumulate in the glomeruli, the filtering units of the kidneys. Glomerular immune complexes initiate an inflammatory response that results in the appearance of blood and protein in the urine and impaired kidney function. Rovin et al. (1) recently reviewed the clinical aspects and pathogenesis of LN and noted that, in addition to glomerular injury, LN often concomitantly affects the tubulointerstitial compartment of the kidney. Tubulointerstitial injury is thought to begin as an inflammatory process. If interstitial inflammation is not attenuated it can promote interstitial fibrosis and atrophy of the renal tubules, structural changes that are irreversible, at least with current therapies. Clinically, the prognosis of the kidney in LN is more strongly associated with the degree of tubulointerstitial injury than the original glomerulonephritis (2). LN patients with moderate to severe interstitial inflammation are more likely to progress to chronic or end-stage kidney disease than those with minimal or no interstitial inflammation (3). The prognostic impact of tubulointerstitial injury is not restricted to LN; indeed, it is observed in several other types of immune-mediated glomerular diseases (4–8).The pathogenesis of tubulointerstitial inflammation in LN is not entirely clear, although it is not related to interstitial immune complex deposition (9). It is likely that the injured glomerular compartment communicates with the tubulointerstitial compartment (10). This may occur through production of soluble mediators and/or infiltrating glomerular leukocytes in response to glomerular immune complexes. Monocytes that enter glomeruli from the circulation differentiate into tissue macrophages, and these could escape from damaged glomeruli into the tubulointerstitium. Similarly, soluble proinflammmatory factors could “leak” out of damaged glomeruli and activate tubular epithelial cells (TECs) (11–14). Activated TECs secrete a number of proinflammatory mediators including chemoattractants such as monocyte chemotactic protein-1 (MCP-1) that recruit additional circulating monocytes to the tubulointerstitial space (15–18). Infiltrating monoctyes become activated macrophages and along with activated TECs perpetuate and enhance tubulointerstitial inflammation and facilitate the progression from inflammation to interstitial fibrosis by secreting a number of cytokines and growth factors (Fig. 1). Activated macrophages secrete PDGF, TGF-β, matrix metalloproteinase (MMP), and tissue inhibitor of metalloproteinase (TIMP) (16, 19, 20), all of which are involved in the regulation of tissue fibrosis. TGF-β, along with TEC-derived basic FGF (bFGF), increases the proliferation of interstitial fibroblasts (21–24). PDGF and TGF-β transform fibroblasts to myofibroblasts (16, 19), which together with fibroblasts produce ECM (25, 26). Imbalance between MMP and its inhibitor TIMP facilitates the accumulation of ECM and formation of interstitial fibrosis (17, 20).Open in a separate windowFig. 1.Network of the renal interstitial fibrosis. Arrows indicate activation or induction; hammerheads indicate inhibition or killing.Presently, the only way to clinically assess interstitial inflammation and fibrosis is through a kidney biopsy. Because of the invasive nature of this procedure it cannot be repeated frequently to determine how LN is progressing and whether treatment has been effective. Clinical measurements have been found to poorly reflect histologic changes in the kidneys in LN, and despite very intense immunosuppression renal fibrosis occurs quickly (27). A noninvasive method to follow interstitial injury and detect the effect (or lack thereof) of therapy is an unmet need in the area of LN. We therefore developed a mathematical model of the progression from tubulointerstitial inflammation to fibrosis. We suggest that this model, upon validation and refinement, could be used to clinically follow interstitial injury in LN. The model also allows simulation of interstitial injury and how injury responds to targeting presumed pathogenic pathways. This could be developed into a tool to facilitate and test novel treatments for interstitial damage in LN.     

Andrographolide-loaded silk fibroin nanoparticles

Andrographolide (AP) is a diterpenoid separated from Andrographis paniculata with a wide spectrum of biological activities including anti-inflammatory, anticancer, hepatoprotective, and antihyperlipidemic. However, its poor water solubility and instability result in lower bioavailability, which seriously limit its pharmacological function. In this study, the attempt to use regenerated silk fibroin (RSF) as a drug-carrier to encapsulate AP was reported. The AP-loaded RSF nanoparticles were prepared by a facile and clean method without any toxic agents. Moreover, special attention was paid to the optimization of formulation. Finally, the sizes of the AP-loaded RSF nanoparticles ranged from 200 to 1000 nm, and the nanoparticles were spherically shaped, as seen by transmission electron microscopy. The drug loading and encapsulation efficiency were about 25.9% and 87.3%, respectively. Furthermore, the release time of AP-loaded RSF nanoparticles was about 3 days. The particle size and drug release behaviour could be adjusted by treating with glycol amine. The in vitro cytotoxicity studies demonstrated that the RSF nanoparticles showed negligible cytotoxicity to cells, and the anti-proliferative activity of AP-loaded RSF nanoparticles showed that the AP-loaded RSF nanoparticles can adhere to Hela cells and MDA-MB-231 cells easily. All these results imply that this biomacromolecule drug nanocarrier has great potential for chemotherapy in clinical applications.

Andrographolide (AP) is a diterpenoid separated from Andrographis paniculata with a wide spectrum of biological activities including anti-inflammatory, anticancer, hepatoprotective, and antihyperlipidemic.     

HF(v' = 3) forward scattering in the F + H2 reaction: shape resonance and slow-down mechanism

Crossed molecular beam experiments and accurate quantum dynamics calculations have been carried out to address the long standing and intriguing issue of the forward scattering observed in the F + H(2) --> HF(v' = 3) + H reaction. Our study reveals that forward scattering in the reaction channel is not caused by Feshbach or dynamical resonances as in the F + H(2) --> HF(v' = 2) + H reaction. It is caused predominantly by the slow-down mechanism over the centrifugal barrier in the exit channel, with some small contribution from the shape resonance mechanism in a very small collision energy regime slightly above the HF(v' = 3) threshold. Our analysis also shows that forward scattering caused by dynamical resonances can very likely be accompanied by forward scattering in a different product vibrational state caused by a slow-down mechanism.