Impact of non-emergency surgical timing on postoperative recovery quality in mild or asymptomatic SARS-CoV-2 infected patients: a grouped cohort study.

OBJECTIVE: To explore the relationship between the timing of non-emergency surgery in mild or asymptomatic SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infected individuals and the quality of postoperative recovery from the time of confirmed infection to the day of surgery. METHODS: We retrospectively reviewed the medical records of 300 cases of mild or asymptomatic SARS-CoV-2 infected patients undergoing elective general anaesthesia surgery at Yijishan Hospital between January 9, 2023, and February 17, 2023. Based on the time from confirmed SARS-CoV-2 infection to the day of surgery, patients were divided into four groups: ≤2 weeks (Group A), 2-4 weeks (Group B), 4-6 weeks (Group C), and 6-8 weeks (Group D). The primary outcome measures included the Quality of Recovery-15 (QoR-15) scale scores at 3 days, 3 months, and 6 months postoperatively. Secondary outcome measures included postoperative mortality, ICU admission, pulmonary complications, postoperative length of hospital stay, extubation time, and time to leave the PACU. RESULTS: Concerning the primary outcome measures, the QoR-15 scores at 3 days postoperatively in Group A were significantly lower compared to the other three groups (P < 0.05), while there were no statistically significant differences among the other three groups (P > 0.05). The QoR-15 scores at 3 and 6 months postoperatively showed no statistically significant differences among the four groups (P > 0.05). In terms of secondary outcome measures, Group A had a significantly prolonged hospital stay compared to the other three groups (P < 0.05), while other outcome measures showed no statistically significant differences (P > 0.05). CONCLUSION: The timing of surgery in mild or asymptomatic SARS-CoV-2 infected patients does not affect long-term recovery quality but does impact short-term recovery quality, especially for elective general anaesthesia surgeries within 2 weeks of confirmed infection. Therefore, it is recommended to wait for a surgical timing of at least greater than 2 weeks to improve short-term recovery quality and enhance patient prognosis.

Paraventricular thalamus controls consciousness transitions during propofol anaesthesia in mice.

BACKGROUND: The neuronal mechanisms underlying propofol-induced modulation of consciousness are poorly understood. Neuroimaging studies suggest a potential role for non-specific thalamic nuclei in propofol-induced loss of consciousness. We investigated the contribution of the paraventricular thalamus (PVT), a midline thalamic nucleus that has been implicated in arousal control and general anaesthesia with inhaled anaesthetics, to loss and recovery of consciousness during propofol anaesthesia. METHODS: Polysomnographic recordings and righting reflex test were used to determine the transitions of loss and recovery of righting reflex, used as a measure of consciousness in mice, during propofol anaesthesia in mice under conditions mimicking clinical propofol administration. PVT neuronal activities were monitored using fibre photometry and regulated using optogenetic and chemogenetic methods. RESULTS: Population activities of PVT glutamatergic neurones began to decrease before propofol-induced loss of consciousness and rapidly increased to a peak at the onset of recovery of consciousness. Chemogenetic inhibition of PVT calretinin-expressing (PVTCR) neurones shortened onset (from 176 [35] to 127 [26] s; P=0.001) and prolonged return (from 1568 [611] to 3126 [1616] s; P=0.002) of righting reflex. Conversely, chemogenetic activation of PVTCR neurones exerted opposite effects. Furthermore, optogenetic silencing of PVTCR neurones accelerated transitions to loss of consciousness (from 205 [35] to 158 [44] s; P=0.027) and slowed transitions to recovery of consciousness (from 230 [78] to 370 [99] s; P=0.041). During a steady period of unconsciousness maintained with continuous propofol infusion, brief optical activation of PVTCR neurones restored cortical activity and arousal with a latency of about 5 s. CONCLUSIONS: The paraventricular thalamus contributes to the control of consciousness transitions in propofol anaesthesia in mice. This provides a potential neuroanatomical target for controlling consciousness to reduce anaesthetic dose requirements and side effects.

Knockdown of lncRNA TTTY15 alleviates myocardial ischemia-reperfusion injury through the miR-374a-5p/FOXO1 axis.

Myocardial ischemia/reperfusion (I/R) injury greatly contributes to myocardial tissue damage in patients with coronary disease, which eventually leads to heart failure. Long noncoding RNAs (lncRNAs) have an emerging role in the process of myocardial I/R injury. Our previous work revealed the protective role of miR-374a-5p against myocardial I/R injury. In this study, we explored the role of lncRNA TTTY15 and its potential interaction mechanisms with miR-374a-5p in myocardial I/R injury. The expression of TTTY15 was increased both in vitro and in vivo after myocardial I/R injury models according to quantitative real-time polymerase chain reaction. Various assays were conducted to evaluate the regulatory relationship among TTTY15, miR-374a-5p, FOXO1, and autophagy in H9c2 and HL-1 cells. The results showed that TTTY15 suppresses autophagy and myocardial I/R injury by targeting miR-374a-5p. We found that TTTY15 regulates miR-374a-5p, thus affecting FOXO1 expression and autophagy in myocytes during I/R. Furthermore, in an in vivo mouse model of myocardial I/R injury, suppression of TTTY15 successfully alleviated myocardial I/R injury. Our results reveal a novel feedback mechanism in which TTTY15 regulates miRNA processing and a potential target in myocardial I/R injury. TTTY15 is a promising therapeutic target for treating myocardial I/R injury.

Autologous blood transfusion stimulates wound healing in diabetic mice through activation of the HIF-1α pathway by improving the blood preservation solution.

Transfusion of autologous blood is a timesaving, convenient, safe, and effective therapy from a clinical perspective, and often employed for the treatment of diabetic patients. Stabilization of HIF-1α has been widely reported to be a critical factor in the improvement of wound healing in diabetes. Therefore, our study reveals the roles of improved autologous blood in wound healing in diabetes, through autologous blood transfusion in a mouse model. Initially, BALB/c mice were subjected to streptozotocin for diabetic mouse model establishment. Diabetic mice were transfused with improved or standard autologous blood in perfusion culture system. Roles of improved autologous blood in mediating HIF-1α pathway were determined by measuring expression of VEGF, EGF, HIF-1α, and HSP-90. In order to assess the detailed regulatory mechanism of improved autologous blood in perspective of wound healing, cell proliferation, migration and cell cycle, fibroblasts isolated from diabetic mice were transfected with HIF-1α siRNA. Mice transfused with improved autologous blood exhibited increased levels of CD31 and α-SMA in skin tissues, and reduced TNF-α, IL-1ß, and IL-6 levels, indicating that improved autologous blood promoted wound healing ability and reduced the release of inflammatory factors. Diabetic mice transfused with improved autologous blood presented activated HIF-1α pathway. The survival rate, proliferation, and migration of fibroblasts were elevated via activation of the HIF-1α pathway. Taken together, improved blood preservation solution could enhance the oxygen carrying capacity of red blood cells and wound healing in mice with diabetes, which is achieved through regulation of HIF-1α pathway.

Ethyl ferulate protects against lipopolysaccharide-induced acute lung injury by activating AMPK/Nrf2 signaling pathway.

Ethyl ferulate (EF) is abundant in Rhizoma Chuanxiong and grains (e.g., rice and maize) and possesses antioxidative, antiapoptotic, antirheumatic, and anti-inflammatory properties. However, its effect on lipopolysaccharide (LPS)-induced acute lung injury (ALI) is still unknown. In the present study, we found that EF significantly alleviated LPS-induced pathological damage and neutrophil infiltration and inhibited the gene expression of proinflammatory cytokines (TNF-α, IL-1ß, and IL-6) in murine lung tissues. Moreover, EF reduced the gene expression of TNF-α, IL-1ß, IL-6, and iNOS and decreased the production of NO in LPS-stimulated RAW264.7 cells and BMDMs. Mechanistic experiments revealed that EF prominently activated the AMPK/Nrf2 pathway and promoted Nrf2 nuclear translocation. AMPK inhibition (Compound C) and Nrf2 inhibition (ML385) abolished the beneficial effect of EF on the inflammatory response. Furthermore, the protective effect of EF on LPS-induced ALI was not observed in Nrf2 knockout mice. Taken together, the results of our study suggest that EF ameliorates LPS-induced ALI in an AMPK/Nrf2-dependent manner. These findings provide a foundation for developing EF as a new anti-inflammatory agent for LPS-induced ALI/ARDS therapy.

Autologous blood transfusion augments impaired wound healing in diabetic mice by enhancing lncRNA H19 expression via the HIF-1α signaling pathway.

BACKGROUND: Impaired wound healing frequently occurs in diabetes mellitus (DM) and is implicated in impaired angiogenesis. Long non-coding RNA (lncRNA) H19 has been reported as being reduced in DM and played a critical role in inducing angiogenesis. Thus, we hypothesized that H19 may affect impaired wound healing in streptozotocin (STZ)-induced diabetic mice transfused with autologous blood preserved in standard preservative fluid or modified preservative fluid. METHODS: Fibroblasts in injured skin were isolated and cultured in vitro. After location of H19 in fibroblasts using fluorescence in situ hybridization (FISH), RNA-pull down, RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), Co immunoprecipitation (COIP) and dual luciferase reporter gene assay were used to verify the binding of H19 to HIF-1α. RESULTS: The modified preservative fluid preserved autologous blood increased the H19 expression in fibroblasts, and maintained better oxygen-carrying and oxygen release capacities as well as coagulation function. Furthermore, H19 promoted HIF-1α histone H3K4me3 methylation and increased HIF-1α expression by recruiting EZH2. H19 promoted fibroblast activation by activating HIF-1α signaling pathway in fibroblasts and enhanced wound healing in diabetic mice. CONCLUSIONS: Taken together, H19 accelerated fibroblast activation by recruiting EZH2-mediated histone methylation and modulating the HIF-1α signaling pathway, whereby augmenting the process of modified preservative fluid preserved autologous blood enhancing the postoperative wound healing in diabetic mice.

In vitro effects of reprogramming factors on the expressions of pluripotent genes and CD34 gene in human acute promyelocytic leukemia HL-60 cells.

OBJECTIVE: Our study aims to explore the in vitro effects of reprogramming factors on the expressions of pluripotent genes and CD34 gene in HL-60 cells. METHODS: According to the construction of lentiviral vector LV-OSCK of reprogramming factors (Oct-4, Sox2, Klf4, c-Myc), 293T cells were transfected to detect virus titer. The endogenous pluripotent genes (Oct4, SOX2, c-Myc and Klf4) and CD34 mRNA and protein expressions were detected by AP staining, immunofluorescence staining, qRT-PCR and flow cytometry. RESULTS: Expressions of Oct4, SOX2, c-Myc and Klf4 were 0.220±0.013, 0.186±0.009, 0.287±0.015 and 0.153±0.007. These levels were significantly higher in the experimental group than the control and blank groups. CD34 protein expression in the experimental group was also discovered to be significantly higher than the other two groups. CONCLUSION: The reprogramming factors could increase the expressions of pluripotent genes and CD34 gene in HL-60 cells.

The Construction and Identification of Induced Pluripotent Stem Cells Derived from Acute Myelogenous Leukemia Cells.

OBJECTIVE: The present study aimed to establish an induced pluripotent stem cell (iPSC) line from acute myelogenous leukemia (AML) cells in vitro and identify their biological characteristics. METHODS: Cells from the AML-infiltrated skin from an M6 patient were infected with a lentivirus carrying OCT4, SOX2, KLF4 and C-MYC to induce iPSCs. The characteristics of the iPSCs were confirmed by alkaline phosphatase (ALP) staining. The proliferation ability of iPSCs was detected with a CCK-8 assay. The expression of pluripotency markers was measured by immunostaining, and the expression of stem cell-related genes was detected by qRT-PCR; distortion during the induction process was detected by karyotype analysis; the differentiation potential of iPSCs was determined by embryoid body-formation and teratoma-formation assays. ALP staining confirmed that these cells exhibited positive staining and had the characteristics of iPSCs. RESULTS: The CCK-8 assay showed that the iPSCs had the ability to proliferate. Immunostaining demonstrated that iPSC clones showed positive expression of NANOG, SSEA-3, SSEA-4, TRA-1-60 and TRA-1-81. qRT-PCR results revealed that the mRNA expression of Nanog, Lin28, Cripto, FOX3, DNMT3b, DPPA2, and DPPA4 significantly increased in iPSCs. Karyotype analysis found no chromosome aberration in the iPSCs. The results of the embryoid body-formation and teratoma-formation assays indicated that the iPSCs had the potential to differentiate into all three germ layers. CONCLUSION: Our study provided evidence that an iPSC line derived from AML cells was successfully established.

Lack of Association between MYO9B Gene Polymorphisms and Susceptibility to Coeliac Disease in Caucasians: Evidence from a Meta-Analysis.

OBJECTIVE: Coeliac disease (CD) is a complex disorder influenced by environmental and genetic factors. Recently, a number of studies reported MYO9B gene is associated with CD, but the results are controversial. The aim of this study is to clarify this dispute by means of a meta-analysis. METHODS: The databases of PubMed, Web of Science, and Embase updated to August 2015 were retrieved. Crude odds ratio (OR) and corresponding 95% confidence interval (95%CI) as effect size were calculated by fixed or random effect model according to the heterogeneity. RESULTS: A total of 8 studies including 2272 cases and 5419 controls were enrolled in this meta-analysis. There was no significant association both in allele and genotype comparisons between the MYO9B (rs2305764, rs2305767, rs1457092) polymorphism and CD in Caucasian populations. No publication bias was detected in this meta-analysis. CONCLUSIONS: This meta-analysis indicates that MYO9B gene polymorphisms might be not associated with CD susceptibility in Caucasians. Further studies are still needed for definitive conclusions.

Circulating exosomal miR-16-5p and let-7e-5p are associated with bladder fibrosis of diabetic cystopathy.

Diabetic cystopathy (DCP) is a prevalent etiology of bladder dysfunction in individuals with longstanding diabetes, frequently leading to bladder interstitial fibrosis. Research investigating the initial pathological alterations of DCP is notably scarce. To comprehend the development of fibrosis and find effective biomarkers for its diagnosis, we prepared streptozotocin-induced long-term diabetic SD rats exhibiting a type 1 diabetes phenotype and bladder fibrosis in histology detection. After observing myofibroblast differentiation from rats' primary bladder fibroblasts with immunofluorescence, we isolated fibroblasts derived exosomes and performed exosomal miRNA sequencing. The co-differentially expressed miRNAs (DEMis) (miR-16-5p and let-7e-5p) were screened through a joint analysis of diabetic rats and long-term patients' plasma data (GES97123) downloaded from the GEO database. Then two co-DEMis were validated by quantitative PCR on exosomes derived from diabetic rats' plasma. Following with a series of analysis, including target mRNAs and transcription factors (TFs) prediction, hubgenes identification, protein-protein interaction (PPI) network construction and gene enrichment analysis, a miRNA-mediated genetic regulatory network consisting of two miRNAs, nine TFs, and thirty target mRNAs were identified in relation to fibrotic processes. Thus, circulating exosomal miR-16-5p and let-7e-5p are associated with bladder fibrosis of DCP, and the crucial genes in regulatory network might hold immense significance in studying the pathogenesis and molecular mechanisms of fibrosis, which deserves further exploration.

The effect of parecoxib sodium on postoperative delirium in elderly patients with hip arthroplasty.

Objective: This study aimed to clarify the effect of parecoxib sodium on the occurrence of postoperative delirium and to investigate its possible mechanism. Methods: A total of 80 patients who underwent elective hip arthroplasty in our hospital between December 2020 and December 2021 were selected and randomly divided into two groups: a parecoxib sodium group (group P, n = 40) and a control group (group C, n = 40). Patients in group P were intravenously injected with 40 mg of parecoxib sodium 30 min before anesthesia and at the end of the surgery. Patients in group C were intravenously injected with the same volume of normal saline at the same time points. The primary endpoint was the incidence of POD, and the secondary endpoints were the levels of inflammatory factors (tumor necrosis factor- α [TNF-α], interleukin [IL]-1ß, IL-6, and IL-10), nerve injury-related factors (brain-derived neurotrophic factor [BDNF], S-100ß protein, neuron-specific enolase [NSE], and neurofilament light chain [NfL]), and antioxidant factors (heme oxygenase-1 [HO-1]), as well as the Visual Analogue Scale (VAS) and Confusion Assessment Method-Chinese Reversion (CAM-CR) scores. Results: The incidence of POD was 10% in group P and 27.5% in group C. Intergroup comparison revealed that the levels of TNF-α, IL-1ß, S-100ß, NfL, and NSE were lower, and BDNF was higher, in group P than in group C at each postoperative time point. The levels of IL-6 were lower, and the levels of IL-10 and HO-1 were higher, in group P than in group C at 1 h and 1 day postoperatively (p < 0.05). Three days after surgery, the differences in the levels of IL-6, IL-10, and HO-1 were not statistically significant between the two groups (p > 0.05). The VAS and CAM-CR scores were lower at each postoperative time point in group P than in group C (p < 0.05). Conclusion: Parecoxib sodium could reduce postoperative pain, decrease the plasma levels of inflammatory and nerve injury-related factors, upregulate HO-1 levels, and reduce the incidence of POD. The results of this study suggest that parecoxib sodium may reduce the occurrence of POD through the effects of anti-inflammation, analgesia, and antioxidants.

[Effects of stellate ganglion block on blood pressure in spontaneously hypertensive rats].

OBJECTIVE: To investigate the effects of stellate ganglion block (SGB) on blood pressure in spontaneously hypertensive rats(SHRs). METHODS: Thirty-two 10-week-old male spontaneously hypertensive rats(SHRs) were assigned randomly into four groups: left stellate ganglion block group(Group LS), right stellate ganglion block group(Group RS), captopril group(Group D) and control group(Group C). Arterial systolic blood pressure(SBP) was measured, and endothelin (ET-1) and endothelial nitric oxide synthase(eNOS) in blood vessels were detected by radioimmunoassay. RESULTS: Compared with baseline value, the blood pressure of Group LS gradually increased significantly (P<0.05 or P <0.01); however, the blood pressure of Group RS was stable(P >0.05) and increased only at week 2(P <0.05).The blood pressure of Group D decreased significantly at week 2 and week 4, and it remained stable compared with baseline value (P<0.05). The blood pressure of Group C gradually increased at weeks 2-10, compared with baseline values (P <0.01). Compared with Group LS and Group C, the expression of eNOS in blood vessels of Group RS significantly increased (P <0.05), and ET-1 decreased (P <0.05). CONCLUSION: The right stellate ganglion block can significantly lower blood pressure, down-regulate ET-1 and up-regulate eNOS protein expression.

Simultaneous Presentation of Multiple Myeloma and Lung Cancer: Case Report and Gene Bioinformatics Analysis.

Patients diagnosed with more than one cancer generally develop the individual tumors sequentially. There are a few cases of co-occurring multiple myeloma and lung cancer reported in the literature. Here, we report two cases of co-occurring multiple myeloma and lung cancer in patients who presented with the chief complaint of pain. The diagnoses of multiple myeloma and lung cancer were supported by hematologic and biochemical investigations, as well as bone marrow and lung histopathologic examination. We provided suitable interventions for both two patients. The patients are still currently undergoing treatment and followed up closely. We first performed a bioinformatic analysis to determine commonly shared genes and pathways in the two types of cancer types. Fortunately, we identified the hub gene mitochondrial trans-2-enoyl-CoA reductase (MECR), which was overexpressed in both tumors. Survival analysis correlated higher MECR expression with poorer overall survival. Signaling pathway analysis suggested possible transduction pathways implicated in the co-occurrence of both tumors. The clinical cases combined with bioinformatic analysis may provide insight for the pathogenesis of synchronous tumors.

Retraction Notice to: lncRNA MALAT1 Accelerates Wound Healing of Diabetic Mice Transfused with Modified Autologous Blood via the HIF-1α Signaling Pathway.

[This retracts the article DOI: 10.1016/j.omtn.2019.05.020.].

Epidemiological characteristics of hand, foot, and mouth disease in China: A meta-analysis.

BACKGROUND: To study the epidemic features of hand-foot-mouth disease (HFMD) in mainland China through systematic review and meta-analysis so as to provide evidence for the future prevention and control of HFMD. METHODS: Articles on the epidemic features of HFMD in mainland China, written in English or Chinese and released between January 1, 2015 and January 1, 2020, were searched from English literature databases including Embase, Web of Science, PubMed, Cochrane library, Google academic, and Chinese literature databases including China national knowledge infrastructure (CNKI), Wanfang, and China Biology Medicine (CBM). Papers were selected according to the inclusion and exclusion criteria, and quality scoring was performed. Meta-analysis, sensitivity analysis, and identification of publication bias were finished through STATA version 12.0 software. RESULTS: A total of 23 articles were included in this study, the total number of cases was 377,083, of which the total number of male cases was 231,798 and the total number of female cases was 145,285, the sex ratio was about 1.6:1, and the incidence of HFMD in China was 1.61‰ (95% confidence interval [CI]: 1.21‰-1.94‰). The results of the subgroup analysis showed that the incidence of HFMD in mainland China was the highest in South China, in 2014, in 1-year-old group and in other types of enteroviruses, respectively, with the rate of 3.48‰ (95% CI: 1.22‰-5.73‰), 1.81‰ (95% CI: 1.06‰-2.57‰), 15.20‰ (95% CI: 5.00‰-25.30‰), and 1.83‰ (95% CI: 1.32‰-2.33‰), respectively. The differences among the above 4 subgroups were statistically significant (P < .05). There were no publication bias in this study, and the sensitivity analysis results suggested that the meta-analysis results were robust. CONCLUSION: There were differences in the distribution of region, time, population, and etiology of HFMD in mainland China. Health departments should adopt key strategies and measures for key populations in key areas to prevent and control the development of HFMD, and improve the ability of pathogen detection and typing in laboratories.

Treatment for CD57-negative γδ T-cell large granular lymphocytic leukemia with pure red cell aplasia: A case report.

BACKGROUND: T-cell large granular lymphocytic leukemia (T-LGLL) is a rare type of aplastic anemia with diverse clinical manifestations. Concomitant diseases are often present at the first manifestation. We describe the treatment of a patient with CD57-negative γδT-LGLL with pure red cell aplasia (PRCA). CASE SUMMARY: A 34-year-old woman with a 20-year history of anemia visited our hospital owing to severe dizziness and was admitted. Her condition was diagnosed as CD57-negative γδT-LGLL with PRCA through bone marrow cytology, bone marrow pathology, bone marrow flow cytometry, bone marrow multiplex polymerase chain reaction combined with fluorescent fragment analysis, and other tests. Treatment with prednisone, methotrexate, and subcutaneous erythropoietin did not significantly change her hemoglobin level. After treatment with oral cyclophosphamide for 3 mo, her hemoglobin level increased to approximately 100 g/L. After 5 mo of treatment, the patient could perform activities of daily living independently. CONCLUSION: The treatment of CD57-negative γδT-LGLL with PRCA with cyclophosphamide helps to improve prognosis.

Adequate expression of neuropeptide Y is essential for the recovery of zebrafish motor function following spinal cord injury.

In strong contrast to limited repair within the mammalian central nervous system, the spinal cord of adult zebrafish is capable of almost complete recovery following injury. Understanding the mechanism underlying neural repair and functional recovery in zebrafish may lead to innovative therapies for human spinal cord injury (SCI). Since neuropeptide Y (NPY) plays a protective role in the pathogenesis of several neurological diseases, in the present study, we evaluated the effects of NPY on neuronal repair and subsequent recovery of motor function in adult zebrafish following SCI. Real-time quantitative PCR (qRT-PCR), in situ hybridization and immunostaining for NPY revealed decreased NPY expression at 12 hours (h), 6 and 21 days (d) after SCI. Double-immunostaining for NPY and islet-1, a motoneuron marker, showed that NPY was expressed in spinal cord motoneurons. Morpholino (MO) treatment for suppressing the expression of NPY inhibited supraspinal axon regrowth and locomotor recovery, in which double-staining for proliferating cell nuclear antigen (PCNA) and islet-1 showed a reduction in motoneuron proliferation. Similarly, a downregulated mRNA level of Y1 receptor of NPY (NPY1R) was also detected at 12 h, 6 and 21 d after injury. Immunostaining for NPY and in situ hybridization for NPY1R revealed that NPY1R was co-localized with NPY. Collectively, the results suggest that NPY expression in motoneurons promotes descending axon regeneration and locomotor recovery in adult zebrafish after SCI, possibly by regulating motoneuron proliferation through activation of NPY1R.

Sophoricoside attenuates lipopolysaccharide-induced acute lung injury by activating the AMPK/Nrf2 signaling axis.

Sophoricoside (SOP), an isoflavone glycoside isolated from seed of Sophora japonica L., has been reported to have various pharmacological activities, including anti-cancer, anti-allergy and anti-inflammation. However, the effect of SOP on lipopolysaccharides (LPS)-acute lung injury (ALI) is completely unclear. Here, we found that SOP pretreatment significantly ameliorated LPS-induced pathological damage, tissue permeability, neutrophil infiltration and the production of pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6) in a murine model of ALI. Besides, SOP reduced the production of pro-inflammatory mediators such as iNOS, NO and inflammatory cytokines including TNF-α, IL-1ß and IL-6 in LPS-stimulated RAW264.7 cells and bone marrow derived macrophages. Interestingly, treatment with SOP exhibited no effect on the activation of NF-κB and MAPKs in macrophages but prominently accelerated the expression and nuclear translocation of Nrf2. By using ML385, a specific Nrf2 inhibitor, we found that inhibition of Nrf2 abolished the inhibitory effect of SOP on LPS-induced iNOS expression, NO production as well as pro-inflammatory cytokine generation. SOP also activated AMPK, an upstream protein of Nrf2, under LPS stimuli. Furthermore, we demonstrated that the accelerated expression of Nrf2 induced by SOP was reversed by interference with the AMPK inhibitor Compound C. Taken together, our results suggested that SOP attenuated LPS-induced ALI in AMPK/Nrf2 dependent manner and indicated that SOP might be a potential therapeutic candidate for treating ALI/ARDS.

Stabilization of the single-chain fragment variable by an interdomain disulfide bond and its effect on antibody affinity.

The interdomain instability of single-chain fragment variable (scFv) might result in intermolecular aggregation and loss of function. In the present study, we stabilized H4-an anti-aflatoxin B(1) (AFB(1)) scFv-with an interdomain disulfide bond and studied the effect of the disulfide bond on antibody affinity. With homology modeling and molecular docking, we designed a scFv containing an interdomain disulfide bond between the residues H44 and L100. The stability of scFv (H4) increased from a GdnHCl(50) of 2.4 M to 4.2 M after addition of the H44-L100 disulfide bond. Size exclusion chromatography revealed that the scFv (H44-L100) mutant existed primarily as a monomer, and no aggregates were detected. An affinity assay indicated that scFv (H4) and the scFv (H44-L100) mutant had similar IC(50) values and affinity to AFB(1). Our results indicate that interdomain disulfide bonds could stabilize scFv without affecting affinity.

Genome-Wide Analysis of the Malaria Parasite Plasmodium falciparum Isolates From Togo Reveals Selective Signals in Immune Selection-Related Antigen Genes.

Malaria is a public health concern worldwide, and Togo has proven to be no exception. Effective approaches to provide information on biological insights for disease elimination are therefore a research priority. Local selection on malaria pathogens is due to multiple factors including host immunity. We undertook genome-wide analysis of sequence variation on a sample of 10 Plasmodium falciparum (Pf) clinical isolates from Togo to identify local-specific signals of selection. Paired-end short-read sequences were mapped and aligned onto > 95% of the 3D7 Pf reference genome sequence in high fold coverage. Data on 266 963 single nucleotide polymorphisms were obtained, with average nucleotide diversity π = 1.79 × 10-3. Both principal component and neighbor-joining tree analyses showed that the Togo parasites clustered according to their geographic (Africa) origin. In addition, the average genome-wide diversity of Pf from Togo was much higher than that from other African samples. Tajima's D value of the Togo isolates was -0.56, suggesting evidence of directional selection and/or recent population expansion. Against this background, within-population analyses identifying loci of balancing and recent positive selections evidenced that host immunity has been the major selective agent. Importantly, 87 and 296 parasite antigen genes with Tajima's D values > 1 and in the top 1% haplotype scores, respectively, include a significant representation of membrane proteins at the merozoite stage that invaded red blood cells (RBCs) and parasitized RBCs surface proteins that play roles in immunoevasion, adhesion, or rosetting. This is consistent with expectations that elevated signals of selection due to allele-specific acquired immunity are likely to operate on antigenic targets. Collectively, our data suggest a recent expansion of Pf population in Togo and evidence strong host immune selection on membrane/surface antigens reflected in signals of balancing/positive selection of important gene loci. Findings from this study provide a fundamental basis to engage studies for effective malaria control in Togo.