SARS-CoV-2 Nsp14 activates NF-κB signaling and induces IL-8 upregulation

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to NF-{kappa}B activation and induction of pro-inflammatory cytokines, though the underlying mechanism for this activation is not fully understood. Our results reveal that the SARS-CoV-2 Nsp14 protein contributes to the viral activation of NF-{kappa}B signaling. Nsp14 caused the nuclear translocation of NF-{kappa}B p65. Nsp14 induced the upregulation of IL-6 and IL-8, which also occurred in SARS-CoV-2 infected cells. IL-8 upregulation was further confirmed in lung tissue samples from COVID-19 patients. A previous proteomic screen identified the putative interaction of Nsp14 with host Inosine-5-monophosphate dehydrogenase 2 (IMPDH2) protein, which is known to regulate NF-{kappa}B signaling. We confirmed the Nsp14-IMPDH2 protein interaction and found that IMPDH2 knockdown or chemical inhibition using ribavirin (RIB) and mycophenolic acid (MPA) abolishes Nsp14-mediated NF-{kappa}B activation and cytokine induction. Furthermore, IMDPH2 inhibitors (RIB, MPA) efficiently blocked SARS-CoV-2 infection, indicating that IMDPH2, and possibly NF-{kappa}B signaling, is beneficial to viral replication. Overall, our results identify a novel role of SARS-CoV-2 Nsp14 in causing the activation of NF-{kappa}B.

FACT subunit SUPT16H associates with BRD4 and contributes to silencing of antiviral interferon signaling

Summary/AbstractFACT (FAcilitates Chromatin Transcription) is a heterodimeric protein complex composed of SUPT16H and SSRP1, and a histone chaperone participating in chromatin remodeling during gene transcription. FACT complex is profoundly regulated, and contributes to both gene activation and suppression. Here we reported that SUPT16H, a subunit of FACT, is acetylated at lysine 674 (K674) of middle domain (MD), which involves TIP60 histone acetyltransferase. Such acetylation of SUPT16H is recognized by bromodomain protein BRD4, which promotes protein stability of SUPT16H. We further demonstrated that SUPT16H-BRD4 associates with histone modification enzymes (EZH2, HDAC1) and affects histone marks (H3K9me3, H3K27me3 and H3ac). BRD4 is known to profoundly regulate interferon (IFN) signaling, while such function of SUPT16H has never been explored. Surprisingly, our results revealed that SUPT16H genetic knockdown via RNAi or pharmacological inhibition by using its inhibitor, curaxin 137 (CBL0137), results in the induction of IFNs and interferon-stimulated genes (ISGs). Through this mechanism, CBL0137 is shown to efficiently inhibit infection of multiple viruses, including Zika, influenza, and SARS-CoV-2. Furthermore, we demonstrated that CBL0137 also causes the remarkable activation of IFN signaling in natural killer (NK) cells, which promotes the NK-mediated killing of virus-infected cells in a co-culture system using human primary NK cells. Overall, our studies unraveled the previously un-appreciated role of FACT complex in regulating IFN signaling in both epithelial and NK cells, and also proposed the novel application of CBL0137 to treat viral infections.

Clinical retrospective analysis in delayed graft function morbidity of kidney transplantation recipients and gender factors in both donors and recipients / 中华器官移植杂志

Objective To explore the effects of donor/recipients' gender on delayed graft function (DGF) .Methods A retrospective analysis was performed for clinical data of donors (n=174) and recipients (n=265) during renal transplantation between May 1 ,2012 and December 31 ,2017 . Types of China donation after citizen's death ,age ,last creatinine level ,height ,weight ,body mass index (BMI) and protopathy of donors were collected .And pre-dialysis method ,dialysis time ,HLA mismatch ,post-creatine at Day 7 ,whether dialysis after transplantation ,height ,weight and BMI of recipients were analyzed .The data were checked by t and chi square tests and P<0 .05 was deemed as statistically significant .Results Donor gender had no correlation with DGF occurrence rate ( P=0 .689) while DGF occurrence rate among female recipients was evidently lower than that among males (P=0 .036);Female recipients selected peritoneal dialysis therapy more than male recipients (P=0 .023);Cerebral hemorrhage female donors were more than male donors (P= 0 .034);BMI (P<0 .001) and postoperative creatinine (P= 0 .001) among female recipients were evidently lower than that among males .Conclusions DGF occurrence rate is significantly lower among female receptors than that among males after kidney transplantation .

Clinical observation of integrated traditional Chinese and western medicine in the treatment of intractable hiccup caused by cerebrovascular disease Medicine / 中国基层医药

Objective To explore the clinical effect of integrated traditional Chinese and western medicine in the treatment of intractable hiccup caused by cerebrovascular disease.Methods A total of 74 patients with intractable hiccup caused by cerebrovascular disease were selected.The patients were randomly divided into observation group and control group according to random number table method.28 patients in the control group were given simple western medicine treatment.46 patients in the observation group were treated with integrated traditional Chinese and western medicine.The total effective rate and symptom improvement were observed after treatment.Results The total effective rate of observation group was 94.48%,that was 78.57% in the control group,the difference was statistically significant(x2=2.0,P<0.05).Conclusion Combined traditional Chinese and western medicine can significantly reduce intractable hiccup caused by cerebrovascular disease,improve total efficacy,improve the quality of life.

Application of Computer Aided Design/Computer Aided Manufacturing System for Tele-process of Lower-limb Prosthesis / 中国康复理论与实践

Objective To explore the feasibility of professional computer-aided design prosthetic software and processing systems for tele-process of lower-limb prosthesis. Methods The residual limb size data of 8 leg-amputation patients in prosthetic clinical reception were transferred to the computer prosthetic processing center. The appropriate lower-limb prosthetic socket mouth circles were selected in the soft-ware data model library, and were modified in accordance with the size table, and then they were processed and sent to the prosthetic clinical reception for the patients. The clinical function of lower-limb prosthesis was evaluated after try-on. Results The clinical function met the re-quirements in 7 patients wearing the prosthesis. Conclusion It is possible to design and tele-process lower-limb prosthesis through elaborate dimensional measurement, which can be a mode to serve lower-limb prosthesis to remote areas.

Application of Computer Aided Design/Computer Aided Manufacturing System for Tele-process of Lower-limb Prosthesis / 中国康复理论与实践

@#Objective To explore the feasibility of professional computer-aided design prosthetic software and processing systems for tele-process of lower-limb prosthesis. Methods The residual limb size data of 8 leg-amputation patients in prosthetic clinical reception were transferred to the computer prosthetic processing center. The appropriate lower-limb prosthetic socket mouth circles were selected in the software data model library, and were modified in accordance with the size table, and then they were processed and sent to the prosthetic clinical reception for the patients. The clinical function of lower-limb prosthesis was evaluated after try-on. Results The clinical function met the requirements in 7 patients wearing the prosthesis. Conclusion It is possible to design and tele-process lower-limb prosthesis through elaborate dimensional measurement, which can be a mode to serve lower-limb prosthesis to remote areas.

Application of Computer Aided Design/Computer Aided Manufacturing System for Tele-process of Lower-limb Prosthesis / 中国康复理论与实践

@#Objective To explore the feasibility of professional computer-aided design prosthetic software and processing systems for tele-process of lower-limb prosthesis. Methods The residual limb size data of 8 leg-amputation patients in prosthetic clinical reception were transferred to the computer prosthetic processing center. The appropriate lower-limb prosthetic socket mouth circles were selected in the software data model library, and were modified in accordance with the size table, and then they were processed and sent to the prosthetic clinical reception for the patients. The clinical function of lower-limb prosthesis was evaluated after try-on. Results The clinical function met the requirements in 7 patients wearing the prosthesis. Conclusion It is possible to design and tele-process lower-limb prosthesis through elaborate dimensional measurement, which can be a mode to serve lower-limb prosthesis to remote areas.

Application of Computer Aided Design/Computer Aided Manufacturing System for Tele-process of Lower-limb Prosthesis / 中国康复理论与实践

@#Objective To explore the feasibility of professional computer-aided design prosthetic software and processing systems for tele-process of lower-limb prosthesis. Methods The residual limb size data of 8 leg-amputation patients in prosthetic clinical reception were transferred to the computer prosthetic processing center. The appropriate lower-limb prosthetic socket mouth circles were selected in the software data model library, and were modified in accordance with the size table, and then they were processed and sent to the prosthetic clinical reception for the patients. The clinical function of lower-limb prosthesis was evaluated after try-on. Results The clinical function met the requirements in 7 patients wearing the prosthesis. Conclusion It is possible to design and tele-process lower-limb prosthesis through elaborate dimensional measurement, which can be a mode to serve lower-limb prosthesis to remote areas.

Effects of ankle-foot orthoses on muscle fatigue of the lower limbs / 中国组织工程研究

BACKGROUND:At present, there is no relevant systematic research about the effects of ankle-foot orthoses on lower limb muscles. OBJECTIVE:To extract the main features of the surface electromyography signals of the lower limbs from normal people with ankle-foot orthoses and to analyze the effects of the fixed ankle-foot orthoses on lower limb muscle fatigue. METHODS:Each of five male healthy young adults was respectively required to walk with and without special ankle-foot orthoses for three times. (1) Group 1, walking in a nature gait without orthoses. (2) Group 2, walking in a natural gait with ankle-foot orthoses (the ankle center was packaged over 1.0 cm by the orthoses that was recorded 1.0 cm); wearing the same orthoses but 1.0 cm in the ankle was removed and the ankle plastic edge was just through the ankle center to colect the data (recorded as 0 cm); after 1.0 cm was removed again in the ankle, walking in a natural gait (recorded as-1.0 cm). (3) Group 3, wearing 1.5 cm heel-height ankle-foot orthoses and walking in a natural gait; wearing the same orthoses but with 1.0 cm and 2.0 cm heel-height and walking in a natural gait. During walking, surface electromyography signals were colected from the biceps femoris muscle, rectus femoris muscle, tibialis anterior muscle, and gastrocnemius of the lower limbs. RESULTS AND CONCLUSION: (1) Without orthoses, the surface electromyography signals were the weakest. (2) For any muscle, the electrical activity of subjects without orthoses was weaker than that of subjects wearing orthoses at different hardness. (3) For the biceps femoris muscle, the integral electrical value without orthoses was very close to that wearing orthoses with normal heel height. Meanwhile, these two values were lower than that wearing orthoses with abnormal heel height. These findings indicate that the fixed plastic ankle-foot orthoses could cause the fatigue of the biceps femoris muscle, rectus femoris muscle, tibialis anterior muscle, and gastrocnemius; and the orthoses with abnormal heel height can further increase the fatigue of the biceps femoris muscle.

ESI fragmentation studies of six unusual nucleotide sugars / 药学学报

Unusual dTDP-sugars are key intermediate in many pathogenic bacteria. In this study, negative-ion electrospray tandem mass spectrometry (ESI-MS-MS) with collision-induced dissociation (CID) was used to study the fragmentation characteristics of six unusual nucleotide diphosphate sugars. The results indicated the major fragment of the six unusual nucleoside sugars observed in the ESI-MS-MS spectra resulted from cleavage of diphosphate moiety and their characteristic fragment ions at m/z 401, 383, and 321, correspond to [TDP-H] together with fragment ions resulting from the loss of water and phosphate moiety, respectively. Furthermore, 4-position substituted change of unusual sugar rings affected the stability of two important characteristic fragment ions of [glycosyl-1"-PO3](-) and [glycosyl-1"-P2O6](-).

Structure Elucidation of Product of β-1,3-Glucosyltransferase Encoded by wfgD Gene in Escherichia Coli O152 Using Mass Spectrometry / 分析化学

The O152 antigens of Escherichia coli contains a Glc-β-1,3-GlcNAc linkage within the repeating unit. The wfgD gene in E. coli O152 O antigen gene cluster had been demonstrated utilizing NMR technique to encode a glucosyltransferase which is responsible for the synthesis of Glc-β-1,3-GlcNAc linkage. In this study, a synthetic substrate analog of the natural acceptor substrate undecaprenol-pyrophosphate-lipid [GlcNAc-α-PO_3-PO_3-(CH_2)_(11))-O-phenyl]) was used as an acceptor and UDP-Glc as a donor substrate, and electrospray ionization tandem mass spectrometry(ESI-MS-MS) was used for the detailed structural characte-)rization) of the enzyme product. A systematic study was conducted on product to allow rationalization of the fragmentation) processes. The major fragments observed in the ESI-MS-MS spectra result from cleavage of glycosidic) bond and diphosphate moiety. The fragment originating from the nonreducing end of the product yields information on sequence). Cross-ring cleavages, which are very informative of the linkages of the monosaccharide residues constituting) the product, and "internal" cleavage ions which are derived from elimination of substituents from around) the pyranose ring, were also observed. This extensive fragmentation was shown that the expected Glc-β-1,3-GlcNAc linkage in the product, confirming that wfgD is in the form of UDP-Glc: GlcNAc-pyrophosphate-lipid β-1,3-glucosyltransferase.)

Effects of Sinomenine on the expression of cytoskeleton and MMP-2, MMP-9 in renal tubular epithelial cells / 中华肾脏病杂志

Objective To explore the effects of Sinomenine (Sin) on phenotype transdifferentiation in renal tubular epithelial cells. Methods Mice primary tubular epithelial cells and cell line (MCT) were cultured in vitro. Model group cells were stimulated by IL-1?(10 ng/ml). The cells of Sin group were co-incubated with Sin(10, 100 ,500?mol/L) simultaneously. The cells without IL-1?and Sin treatment were regarded as control group. The protein expression of?-smooth muscle actin (SMA) and Vimentin was assessed by immunohistochemistry and Western blotting. The mRNA expression of?-SMA and Vimentin was examined by RT-PCR. Secretion of matrix metalloproteinases was determined by zymography. Results The mRNA expression and protein level of?-SMA and Vimentin, and the enzyme activity of MMP-2 and MMP-9 in tubular epithelial cells stimulated with IL-1?were significantly higher than those in the controls. Sinomenine significantly reduced the expression levels of protein and mRNA of?-SMA and Vimentin. At the same time, the MMP-2 and MMP-9 activities were reduced markedly. Conclusion Sinomenine can decrease the transdifferentiation in renal tubular epithelial cells stimulated by inflammatory factor IL-1?and prevent renal interstitial fibrosis.

Effects of Tripterygium Wlilfordii on renal interstitial fibrosis and inflamed lesion in UUO mice kidney / 中国免疫学杂志

Objective:To investigate the effects of Tripterygium Wlilfordii on renal interstitial fibrosis and the expression of inflammatory factor in mice kidney with the Unilateral Ureteral Obstruction(UUO).Methods:Mice were randomly assigned to shame operation group(shame proup), UUO group, Tripterygium Wlilfordii and ACEI treatment group after UUO. The protein expression of ?-SMA,ICAM-1 were assessed by immunohistochemistry or Western blot; MCP-1 mRNA were detected by reverse transcription-polymerase chain reaction analyses(RT-PCR). And the change of renal pathology was observed at the same time.Results:In comparison with the shame group, the protein levels of ?-SMA, ICAM-1 and the mRNA expression of MCP-1 in UUO mice and treatment groups increased significantly, meanwhile Tripterygium Wlilfordii and ACEI could significantly reduce the expression of ?-SMA, ICAM-and MCP-1 on levels of protein and gene. The effects of Tripterygium Wlilfordii on ICAM-1 and MCP-1 were more significant than ACEI.Conclusion:Tripterygium Wlilfordii could reduce the transdifferentiation of renal interstitial cells and prevent renal interstitial inflammatory injury.