Qingshen granule-medicated serum attenuates high glucose-induced epithelial-mesenchymal transition of HK-2 cells via inhibiting oxidative stress-mediated NF-κB signaling pathway / 中国病理生理杂志

AIM:To investigate whether Qingshen granules(QSG)-medicated serum inhibits oxidative stress-mediated NF-κB signaling pathway and attenuates epithelial-mesenchymal transition(EMT)of human proximal tubule epi?thelial HK-2 cells induced by high glucose. METHODS:The active components in QSG were analyzed by HPLC. The HK-2 cells were randomly divided into control group,mannitol group,high glucose group,low-dose QSG group,medium-dose QSG group,high-dose QSG group and pyrrolidine dithiocarbamate(PDTC)group. The morphological changes of the cells were observed by inverted phase contrast microscopy. MTT assay was used to detect the cell viability. Flow cytometry was used to detect the content of reactive oxygen species(ROS)in HK-2 cells. ELISA was used to detect the content of malondi?al dehyde(MDA)and the activity of superoxide dismutase(SOD). The DNA binding activity of nuclear factor-κB(NF-κB) p65 in HK-2 cells was detected by electrophoretic mobility-shift assay(EMSA). The protein expression of NF-κB p65, phosphorylated inhibitor of kappa B alpha(p-IκBα),inhibitor of kappa B kinase alpha(IKKα),monocyte chemoattractant protein-1(MCP-1)and intercellular adhesion molecule-1(ICAM-1)in HK-2 cells was detected by Western blot. Immuno?fluorescence staining was used to detect NF-κB p65 andα-smooth mucle actin(α-SMA)protein expression in HK-2 cells. RESULTS:Chlorogenic acid,berberine hydrochloride,plantamajoside,6,7-dimethoxycoumarin,epiberberine,copti?sine,lithospermicacid B,palmatine,leonurine hydrochloride,rheic acid and tanshinone ⅡA in QSG were preliminarily de?termined by HPLC. Compared with control group,the levels of ROS and MDA in HK-2 cells induced by high glucose in?creased(P<0. 05),while the activity of SOD decreased(P<0. 05). The protein levels of NF-κB p65,p-IκBα,IKKα, MCP-1,ICAM-1 andα-SMA were increased(P<0. 05). After intervened by QSG-medicated serum,the levels of ROS and MDA were decreased(P<0. 05),while the activity of SOD was increased(P<0. 05). The protein levels of NF-κB p65,p-IκBα,IKKα,MCP-1,ICAM-1 andα-SMA were decreased(P<0. 05). CONCLUSION:QSG-medicated serum inhibited oxidative stress-mediated NF-κB signaling pathway,thus attenuating the EMT of HK-2 cells induced by high glucose.

Comparative analysis of visual quality after implantation of Symfony IOL and MF15 IOL / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the visual quality in patients after implantation of extended-range-of-vision(Tecnis Symfony)intraocular lens(IOL)and zonal refractive(Lentis Comfort LS-313 MF15)IOL. METHODS: A prospective clinical study. Collecting 267 cataract patients(305 eyes)who underwent phacoemulsification combined with IOL implantation surgery in our hospital from January 2021 to December 2021,they were divided into the Symfony group(group A, 160 eyes)and MF15 group(group B, 145 eyes)according to the types of implanted IOL. Postoperative visual acuity were observed at 3mo and included uncorrected distance visual acuity(UDVA, 5m), uncorrected intermediate visual acuity(UIVA, 80 cm), uncorrected near visual acuity(UNVA, 40cm), defocus curve, modulation transfer function(MTF)and high-order aberrations(HOAs), including coma, spherical aberration and trefoil aberration, and conducted the Quality of Vision(QoV)questionnaire.RESULTS: There were no significant differences in the preoperative parameters in both groups(P>0.05). There was no significant difference between the UDVA and UNVA in groups A and B(P>0.05); The UIVA was higher in group A than in group B(P<0.05); The MTF value in group A was higher than group B at all spatial frequency, and the difference was statistical significant(P<0.05); The HOAs in group A was lower than that in group B(P<0.05); Defocus curves were plotted 3mo after the operation suggest that the visual acuity of the two groups was similar at 0D, and the visual acuity of the groups A was better than group B from -0.5D to -2.5D, and there was a statistically significant difference at -1.0D and -2.0D(P<0.05). The QoV score in group A was significantly higher than that in group B(P<0.05). The frequency of bad visual interference such as halo and starburst was higher in group A than in group B. CONCLUSION: Both the MF15 and Symfony can provide stable distance and near visual acuity. Compared with MF15, Symfony had better intermediate visual acuity, higher contrast sensitivity and lower HOAs. Compared with Symfony, MF15 IOL had less postoperative bad visual interference symptoms(halo, starburst, etc).

Research progress of three long-acting basic insulin analogues / 药物评价研究

Diabetes is a kind of worldwide chronic disease with high incidence,which threatens people's lives and work.With the development of DNA recombination technology,long-acting basal insulin analogues bring gospel and hope for patients with diabetes.Insulin glargine (IGla),detemir (IDet) and degludec (IDeg),as three basic types of insulin,commonly used in clinical practice that slowly absorbed and distributed by changing the structure,and relatively long acting time,more fit the physiological model of insulin secretion.Therefore,the existing studies of molecular structure,long-acting mechanism,safety evaluation and pharmacodynamic effects of three kinds of insulin preparations are briefly summarized.

Endogenous danger signals trigger hepatic ischemia/reperfusion injury through toll-like receptor 4/nuclear factor-kappa B pathway / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Restoration of blood flow to the ischemic liver lobes may paradoxically exacerbate tissue injury, which is called hepatic ischemia/reperfusion injury (IRI). Toll-like receptor 4 (TLR4), expressed on several liver cell types, and the nuclear factor-kappa B (NF-kappaB) signaling pathway are crucial to mediating hepatic inflammatory response. Because IRI is essentially a kind of profound acute inflammatory reaction evoked by many kinds of danger signals, we investigated TLR4/NF-kappaB signaling pathway activation in a murine model of partial hepatic IRI.</p><p><b>METHODS</b>Wild-type mice (WT, C3H/HeN) or TLR4 mutant mice (C3H/HeJ) were subjected to 45 minutes of partial hepatic ischemia followed by 1 hour, 3 hours of reperfusion. Sham group accepted the same procedure without the obstruction of blood supply. At the end of reperfusion, the compromise of liver function and the histological change of liver sections were measured as the severity of liver injury. The level of endotoxin in the portal vein was measured by limulus assay. NF-kappaB activation was determined by electrophoretic mobility shift assay (EMSA). The levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) in systemic blood after hepatic IRI were assessed by enzyme-linked immunosorbent assay (ELISA).</p><p><b>RESULTS</b>The compromise of liver function and the morphological injuries in mutant mice were relieved more markedly than those in WT mice after partial hepatic IRI. NF-kappaB activation in WT mice was stronger than that in TLR4 mutant mice, and both were stronger than those in the sham operated mice (P < 0.01). Endotoxin in each group was undetectable. The levels of TNF-alpha and IL-1beta in systemic blood were elevated in both strains, but lower in the sham operated group. These mediators were significantly decreased in TLR4 mutant mice compared with those in WT mice (P < 0.01).</p><p><b>CONCLUSIONS</b>The TLR4/NF-kappaB signaling pathway may mediate hepatic IRI triggered by endogenous danger signals. Inhibition of the TLR4/NF-kappaB pathway may be a potential therapeutic target for attenuating ischemia/reperfusion-induced tissue damage in some clinical settings.</p>

Schistosoma japonicum: construction of phage display antibody library and its application in the immunodiagnosis of infection / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>A monoclonal antibody would be an effective tool for the detection of circulating antigens in the serum of patients with schistosomiasis, but the traditional way of producing monoclonal antibodies is not cost-effective. The objective of this study was to find a new method for the large-scale production of monoclonal antibodies against Schistosoma japonicum (Sj).</p><p><b>METHODS</b>A phage display antibody library for Sj was constructed. To obtain a single-chain variable fragment antibody (scFv) against Sj, the library was screened with metabolic antigens from adult Sj worms (Sj-MAg) using enzyme-linked immunosorbent assay. The soluble scFvs selected were used to detect Sj antigens in the serum of acute and chronic schistosomiasis patients.</p><p><b>RESULTS</b>Six positive clones with good reactivity to Sj-MAg were obtained from the phage display antibody library of about 1.07 x 10(6) individual clones. Only two of these six clones bound specifically to Sj-MAg and were chosen for further analysis. Specific soluble anti-Sj-MAg scFvs were produced by inducing the 2 clones with isopropyl-D-thiogalactopyranoside. The characteristics of the scFvs were then determined. The results of Western blot showed that these scFvs could bind to Sj-MAg specifically and had a molecular weight of about 31 kD. When testing serum from schistosomiasis patients with one of the two specific scFvs, its sensitivity was found to be 60% and 37% in acute and chronic patients, respectively, with a specificity of 90%. When the two specific scFvs were combined, their sensitivity was found to be 75% and 57% in acute and chronic patients, respectively, with a specificity of 85%.</p><p><b>CONCLUSIONS</b>The results indicate that the scFvs are potentially useful for the diagnosis of schistosomiasis. The library construction also provides a useful tool for the further screening of other antibodies for both diagnostic and immunotherapeutic applications and for epitope analysis and vaccine design.</p>

Effects of TNF-alpha receptor blocking peptide on adjuvant arthritis in rats / 药学学报

<p><b>AIM</b>To study the effects of TNF receptor blocking peptide on adjuvant arthritis in rats.</p><p><b>METHODS</b>The model of rat adjuvant arthritis was induced by injection of complete Freund's adjuvant. The TNF receptor blocking peptide was injected locally in the ankle. The ankle swelling, the pathologic changes in the ankle joint and the expression of IL-1 beta mRNA and TNF-alpha mRNA by peritoneal macrophages (RT-PCR) were observed.</p><p><b>RESULTS</b>The model of rat adjuvant arthritis induced by injection of complete Freund's adjuvant was similar to human rheumatoid arthritis. The treatment with TNF receptor blocking peptide for 10 days resulted in complete inhibition of joint swelling, a decrease in infiltration of inflammatory cell into joint tissue, an obvious alleviation of inflammatory pathological damages and an apparent decline of TNF-alpha mRNA and IL-1 beta mRNA of peritoneal macrophages of rats.</p><p><b>CONCLUSION</b>The TNF receptor blocking peptide can protect the joint from inflammatory damage induced by adjuvant arthritis by suppression of TNF-alpha and IL-1 production, thereby alleviating the pathological injury of joint and controlling effectively the clinic course of arthritis.</p>