Predicting preterm birth within 2 weeks in asymptomatic women with a short cervix: Combined effects of cervicovaginal fluid cytokine levels and fetal fibronectin test.

AIMS: To predict preterm birth (PTB) accurately, we conducted a comprehensive cytokine assay using cervicovaginal fluid (CVF) and evaluated the additive effects of cytokine levels on the fetal fibronectin (fFN) test. METHODS: A total of 645 CVF samples were collected from 256 asymptomatic pregnant women between 24 and 35 weeks gestation, exhibiting short cervix. After selection based on specific criteria, 17 cytokines in 105 CVF samples were simultaneously measured using multiplex assay. Multivariate logistic regression analysis was performed to evaluate the association between cytokine levels and impending PTB, which is defined as PTB within 2 weeks after CVF collection. Moreover, receiver operating characteristic (ROC) analysis was performed in women with positive fFN results, which was validated using another set of 65 CVF samples. RESULTS: In positive fFN women, the CCL2 level was significantly higher in the impending PTB group than the other group (p < 0.01) and a predictor of impending PTB (adjusted odds ratio 1.020, 95% confidence interval [95% CI] 1.003-1.038, p = 0.020). The cutoff value of CCL2 was 64.8 pg/mL (are under the curve 0.726, p = 0.004, 95% CI 0.593-0.859, sensitivity 45.2%, specificity 91.7%). Additionally, the reliable classification performance of proposed ROC model could be validated. However, measuring cytokine levels could not help in predicting impending PTB in women with negative fFN or normal labor onset in healthy-term women. CONCLUSION: Comprehensive analysis of CVF cytokines revealed that the CCL2 level significantly improves the prediction of impending PTB in asymptomatic fFN-positive women with a short cervix, which may contribute to better clinical management.

Identification of Short-Chain Fatty Acids for Predicting Preterm Birth in Cervicovaginal Fluid Using Mass Spectrometry.

Preterm birth (PTB) refers to delivery before 37 weeks of gestation. Premature neonates exhibit higher neonatal morbidity and mortality rates than term neonates; therefore, predicting and preventing PTB are important. In this study, we investigated the potential of using short-chain fatty acid (SCFA) levels, specific vaginal microbiota-derived metabolites, as a biomarker in predicting PTB using gas chromatography/mass spectrometry. Cervicovaginal fluid (CVF) was collected from 89 pregnant women (29 cases of PTB vs. 60 controls) without evidence of other clinical infections, and SCFA levels were measured. Furthermore, the PTB group was divided into two subgroups based on birth timing after CVF sampling: delivery ≤ 2 days after sampling (n = 10) and ≥2 days after sampling (n = 19). The concentrations of propionic acid, isobutyric acid, butyric acid, valeric acid, hexanoic acid, and heptanoic acid were significantly higher in the PTB group than in the term birth (TB) group (p < 0.05). In particular, the concentrations of propionic acid, isobutyric acid, hexanoic acid, and heptanoic acid were continuously higher in the PTB group than in the TB group (p < 0.05). In the delivery ≤ 2 days after sampling group, the propionic acid, isobutyric acid, hexanoic acid, and heptanoic acid levels were significantly higher than those in the other groups (p < 0.05). This study demonstrated a significant association between specific SCFAs and PTB. We propose these SCFAs as potential biomarkers for the prediction of PTB.

Measuring the nonselective effects of motor inhibition using isometric force recordings.

Inhibition is a key cognitive control mechanism humans use to enable goal-directed behavior. When rapidly exerted, inhibitory control has broad, nonselective motor effects, typically demonstrated using corticospinal excitability measurements (CSE) elicited by transcranial magnetic stimulation (TMS). For example, during rapid action-stopping, CSE is suppressed at both stopped and task-unrelated muscles. While such TMS-based CSE measurements have provided crucial insights into the fronto-basal ganglia circuitry underlying inhibitory control, they have several downsides. TMS is contraindicated in many populations (e.g., epilepsy or deep-brain stimulation patients), has limited temporal resolution, produces distracting auditory and haptic stimulation, is difficult to combine with other imaging methods, and necessitates expensive, immobile equipment. Here, we attempted to measure the nonselective motor effects of inhibitory control using a method unaffected by these shortcomings. Thirty male and female human participants exerted isometric force on a high-precision handheld force transducer while performing a foot-response stop-signal task. Indeed, when foot movements were successfully stopped, force output at the task-irrelevant hand was suppressed as well. Moreover, this nonselective reduction of isometric force was highly correlated with stop-signal performance and showed frequency dynamics similar to established inhibitory signatures typically found in neural and muscle recordings. Together, these findings demonstrate that isometric force recordings can reliably capture the nonselective effects of motor inhibition, opening the door to many applications that are hard or impossible to realize with TMS.

Four Chemotherapeutic Compounds That Limit Blood-Brain-Barrier Invasion by Toxoplasma gondii.

BACKGROUND: Toxoplasma gondii, an intracellular protozoan parasite, exists in the host brain as cysts, which can result in Toxoplasmic Encephalitis (TE) and neurological diseases. However, few studies have been conducted on TE, particularly on how to prevent it. Previous proteomics studies have showed that the expression of C3 in rat brains was up-regulated after T. gondii infection. METHODS: In this study, we used T. gondii to infect mice and bEnd 3 cells to confirm the relation between T. gondii and the expression of C3. BEnd3 cells membrane proteins which directly interacted with C3a were screened by pull down. Finally, animal behavior experiments were conducted to compare the differences in the inhibitory ability of TE by four chemotherapeutic compounds (SB290157, CVF, NSC23766, and Anxa1). RESULTS: All chemotherapeutic compounds in this study can inhibit TE and cognitive behavior in the host. However, Anxa 1 is the most suitable material to inhibit mice TE. CONCLUSION: T. gondii infection promotes TE by promoting host C3 production. Anxa1 was selected as the most appropriate material to prevent TE among four chemotherapeutic compounds closely related to C3.

Dynamic Alteration in the Vaginal Secretory Proteome across the Early and Mid-Trimesters of Pregnancy.

Pregnancy is characterized by intense physiological and structural alterations in the vagina, cervix, and overlying fetal membranes. High vaginal fluid (HVF) is a proximal fluid that covers the lower part of the female reproductive system and the severity of vaginal pathology often adversely affects pregnancy outcomes. To identify the correlation of vaginal fluid proteome dynamics and physiological changes during the progression of pregnancy, a longitudinal study was performed on 20 pregnant women who delivered a baby in >37 weeks without any complications. SWATH-MS-based label-free quantitative proteomics was performed to profile the HVF proteome at three time points defined as V1 (7-12 weeks), V2 (18-20 weeks), and V3 (26-28 weeks). Linear mixed-effect models were used to estimate protein abundance as a function of the period of gestational age. In this study, we identified 1015 HVF proteins and 61 of them were significantly altered until late second trimester. Our result demonstrates that the HVF proteins reveal gestational age-specific expression patterns and the function of these proteins is associated with tissue remodeling, organ development, and microbial defense. Our study provides an opportunity to monitor the underlying physiology of pregnancy that may be further probed for the biomarker identification in pregnancy-related adverse outcomes. Data are available via ProteomeXchange with identifiers PXD014846 and PXD021811.

A unique presentation of Colovesical fistula.

A colovesical fistula (CVF) is a pathological connection between the colon and the urinary bladder. Although they are uncommon, consequences can severely affect quality of life and mortality. Diverticula are the most common cause of CVF. This case details a patient's CVF diagnosis in the emergency department with unremitting gastrointestinal and urinary symptoms. A 78-year-old male patient with recent hospitalization for stroke and left carotid endarterectomy complicated by urinary retention treated with a Foley catheter presented to the Emergency Department with a chief complaint of hematuria and unremitting diarrhea. Foley exchange resulted in improved urinary retention and diarrhea during hospitalization. One day following hospital discharge, the patient presented again with a blocked Foley catheter and diarrhea. Foley irrigations resulting in near immediate diarrhea and lack of bladder filling on bladder scan portended to a diagnosis of colovesical fistula despite no history diverticula or colon malignancy. An abdominal/pelvic computed tomography scan and cystogram confirmed a colovesical fistula. This case highlights the need for consideration of colovesical fistula in a seemingly simple ED complaint of urinary retention. It is prudent to closely follow bladder scan volumes when flushing a Foley catheter. Given the significant comorbidities such as urosepsis and health care impact of repeat ED visits and hospitalizations, CVF can and should be entertained and rapidly diagnosed in the emergency department. Our case highlights the need for consideration of a vesico-colic fistula despite the absence of initial relevant risk factors.

Evaluation of the RNA Silencing Suppression Activity of Three Cherry Virus F-Encoded Proteins.

Cherry virus F (CVF) is a newly emerged sweet cherry virus. CVF has been identified in a small number of countries and it has not been associated with discrete symptomatology. RNA silencing is a natural defense mechanism of plants against invaders that degrades viral RNA in a sequence-specific manner. As a counter-defense, plant viruses encode one or more RNA silencing suppressors (RSSs) interfering with the silencing pathway via several mechanisms. To identify putative RSSs, the three proteins (MP, CPL, CPS) encoded by the RNA2 of CVF were selected and separately cloned into the binary vector pART27. The clones were used for transient expression experiments in Nicotiana benthamiana leaves, using co-agroinfiltration with a GFP-expressing vector. In both CPL and CPS, a rapid decrease in fluorescence was recorded, comparable to the negative control, whereas the MP of CVF retained the GFP's fluorescence for a few days longer even though this was observed in a small number of infiltrated leaves. Further experiments have shown that the protein was not able to inhibit the cell-to-cell spread of the silencing signal; however, a putative interference with systemic silencing was recorded especially when the induction was carried out with double-stranded GFP RNA. Overall, our results indicate that the MP of CVF is putatively implicated in the suppression of RNA silencing, though further experimentation is needed to unveil the exact mode of action.

Cerebrospinal Venous Fistula Presenting with Cognitive Decline: Systematic Literature Review and Report of Two Cases.

OBJECTIVE: A cerebrospinal fluid (CSF) venous fistula (CVF) is an aberrant connection between the subarachnoid space and a vein resulting in CSF loss. The presentation and management of CVF with cognitive decline is incompletely understood. METHODS: A systematic review was completed following the PRISMA guidelines. Articles that included at least 1 case of imaging-confirmed CVF with details on patient treatment were included. A separate review of cases of patients with spontaneous intracranial hypotension (SIH) with frontotemporal dementia (FTD) or dementia symptoms was also completed. RESULTS: Ten CVF articles (69 patients; average age, 51.5 years) and 5 SIH with FTD or dementia articles (n = 41; average age, 55.9 years) were identified. Only 1 patients with CVF with cognitive abnormalities was identified. The most common symptom was headache in both reviews. Brain sag was identified in all patients, whereas CSF leak was identified in only 2 patients with SIH with FTD or dementia (4.9%). An epidural blood or fibrin glue patch was used in all patients with CVF and in 33 patients with SIH with FTD or dementia. Fifty-five patients with CVF (79.7%) and 27 patients with SIH with FTD or dementia (65.9%) had surgery. CONCLUSIONS: The 2 cases and literature reviews show the difficulty in diagnosis and treatment of CVF with cognitive decline. Novel imaging techniques should be used in patients with cognitive decline in whom a CSF leak is suspected. Transvenous embolization or surgery should be considered before patching for treatment of CVF-induced brain sag and resulting dementia.

TCF7L1 Accelerates Smooth Muscle Cell Phenotypic Switching and Aggravates Abdominal Aortic Aneurysms.

Phenotypic switching of vascular smooth muscle cells is a central process in abdominal aortic aneurysm (AAA) pathology. We found that knockdown TCF7L1 (transcription factor 7-like 1), a member of the TCF/LEF (T cell factor/lymphoid enhancer factor) family of transcription factors, inhibits vascular smooth muscle cell differentiation. This study hints at potential interventions to maintain a normal, differentiated smooth muscle cell state, thereby eliminating the pathogenesis of AAA. In addition, our study provides insights into the potential use of TCF7L1 as a biomarker for AAA.

Development of a New Biomarker Model for Predicting Preterm Birth in Cervicovaginal Fluid.

Preterm birth (PTB) is a social problem that adversely affects not only the survival rate of the fetus, but also the premature babies and families, so there is an urgent need to find accurate biomarkers. We noted that among causes, eubiosis of the vaginal microbial community to dysbiosis leads to changes in metabolite composition. In this study, short chain fatty acids (SCFAs) representing dysbiosis were derivatized using (N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide, MTBSTFA) and targeted analysis was conducted in extracted organic phases of cervicovaginal fluid (CVF). In residual aqueous CVF, polar metabolites produced biochemistry process were derivatized using methoxyamine and N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA), and non-targeted analysis were conducted. Nine SCFAs were quantified, and 58 polar metabolites were detected in 90 clinical samples using gas chromatography/mass spectrometry (GC/MS). The criteria of statistical analysis and detection rate of clinical sample for development of PTB biomarkers were presented, and 19 biomarkers were selected based on it, consisting of 1 SCFA, 2 organic acids, 4 amine compounds, and 12 amino acids. In addition, the model was evaluated as a suitable indicator for predicting PTB without distinction between sample collection time. We hope that the developed biomarkers based on microbiota-derived metabolites could provide useful diagnostic biomarkers for actual patients and pre-pregnancy.

Co-existing fast CSF leaks and CSF-venous fistulas on dynamic CT myelography.

Spontaneous intracranial hypotension can be caused by spinal dural tears or CSF-venous fistulas. It is rare for patients to have more than one type of leak at any given time. Here, we illustrate 3 examples of dural tears that co-existed with CSF-venous fistulas, with both being seen on dynamic CT myelography. To our knowledge, coexistent CSF-venous fistulas and dural tears have not been previously illustrated on dynamic CT myelography, even though this is one of the most commonly used modalities to work-up patients with CSF leaks. We discuss the clinical importance of the rare co-occurrence of these leaks with regard to diagnosis and treatment, as well as implications for understanding and classifying CSF leaks.

Insights on Proteomics-Driven Body Fluid-Based Biomarkers of Cervical Cancer.

Cervical cancer is one of the top malignancies in women around the globe, which still holds its place despite being preventable at early stages. Gynecological conditions, even maladies like cervical cancer, still experience scrutiny from society owing to prevalent taboo and invasive screening methods, especially in developing economies. Additionally, current diagnoses lack specificity and sensitivity, which prolong diagnosis until it is too late. Advances in omics-based technologies aid in discovering differential multi-omics profiles between healthy individuals and cancer patients, which could be utilized for the discovery of body fluid-based biomarkers. Body fluids are a promising potential alternative for early disease detection and counteracting the problems of invasiveness while also serving as a pool of potential biomarkers. In this review, we will provide details of the body fluids-based biomarkers that have been reported in cervical cancer. Here, we have presented our perspective on proteomics for global biomarker discovery by addressing several pertinent problems, including the challenges that are confronted in cervical cancer. Further, we also used bioinformatic methods to undertake a meta-analysis of significantly up-regulated biomolecular profiles in CVF from cervical cancer patients. Our analysis deciphered alterations in the biological pathways in CVF such as immune response, glycolytic processes, regulation of cell death, regulation of structural size, protein polymerization disease, and other pathways that can cumulatively contribute to cervical cancer malignancy. We believe, more extensive research on such biomarkers, will speed up the road to early identification and prevention of cervical cancer in the near future.

New and High Virulent Pathotypes of Sunflower Downy Mildew (Plasmopara halstedii) in Seven Countries in Europe.

Downy mildew of sunflower, caused by Plasmopara halstedii (Farl.) Berl. et de Toni, is a relevant disease of this crop. High virulent pathotypes have been identified in several countries, while there are few data on the spread of P. halstedii pathotypes in some important sunflower-growing areas of Europe. The goal of this study was to give up-to-date information on the pathotype structure of P. halstedii in Hungary and provide some actual data on the virulence phenotype of the pathogen for six European countries. Infected leaves of different sunflower hybrids and volunteers were collected in seven countries (Hungary, Bulgaria, Serbia, Turkey, Greece, Romania, and Italy) between 2012 and 2019. A universally accepted nomenclature was used with a standardized set of sunflower differential lines for pathotype characterization of isolates. The virulence pattern of the isolates was determined by a three-digit code (coded virulence formula, CVF). A total of 109 P. halstedii isolates were characterized. As a result of our survey, 18 new P. halstedii pathotypes were identified in Europe. Two out of the eighteen pathotypes were detected from the Asian part of Turkey. The detailed distribution of pathotypes in Hungary is also discussed.

Myocardial extracellular volume fraction quantification in an animal model of the doxorubicin-induced myocardial fibrosis: a synthetic hematocrit method using 3T cardiac magnetic resonance.

BACKGROUND: Visualization of diffuse myocardial fibrosis is challenging and mainly relies on histology. Cardiac magnetic resonance (CMR), which uses extracellular contrast agents, is a rapidly developing technique for measuring the extracellular volume (ECV). The objective of this study was to evaluate the feasibility of the synthetic myocardial ECV fraction based on 3.0 T CMR compared with the conventional ECV fraction. METHODS: This study was approved by the local animal care and ethics committee. Fifteen beagle models with diffuse myocardial fibrosis, including 12 experimental and three control subjects, were generated by injecting doxorubicin 30 mg/m2 intravenously every three weeks for 24 weeks. Short-axis (SAX) and 4-chamber long-axis (LAX) T1 maps were acquired for both groups. The association between hematocrit (Hct) and native T1blood was derived from 9 non-contrast CMR T1 maps of 3 control beagles using regression analysis. Synthetic ECV was then calculated using the synthetic Hct and compared with conventional ECV at baseline and the 16th and 24th week after doxorubicin administration. The collagen volume fraction (CVF) value was measured on digital biopsy samples. Bland-Altman plots were used to analyze the agreement between conventional and synthetic ECV. Correlation analyses were performed to explore the association among conventional ECV, synthetic ECV, CVF, and left ventricular ejection fraction (LVEF). RESULTS: The regression model synthetic Hct = 816.46*R1blood - 0.01 (R2=0.617; P=0.012) was used to predict the Hct from native T1blood values. The conventional and synthetic ECV fractions of experimental animals at the 16th and 24th week after modeling were significantly higher than those measured at the baseline (31.4%±2.2% and 36.3%±2.1% vs. 22.9%±1.7%; 29.9%±2.4% and 36.1%±2.6% vs. 22.0%±2.4%; all with P<0.05). Bland-Altman plots showed a bias (1.0%) between conventional and synthetic ECV with 95% limits of agreement of -2.5% to 4.4% in the per-subject analysis (n=21) and a bias (1.0%) between conventional and synthetic ECV with 95% limits of agreement of -2.4% to 4.3% in the per-segment analysis (n=294). Conventional and synthetic ECV were well correlated with CVF (r=0.937 and 0.925, all with P<0.001, n=10). CONCLUSIONS: Our study showed promising results for using synthetic ECV compared with the conventional ECV for providing accurate quantification of myocardial ECV without the need for blood sampling.

Endoscopic management of colovaginal fistulas in advanced cancer patients.

BACKGROUND AND AIMS: Colovaginal fistula (CVF) in cancer patients can cause significant morbidity. In addition to causing local symptoms and infections, the constant stool leakage contributes to a poor quality of life, psychological distress, and possible social isolation. Patients with CVFs often have advanced disease, poor nutrition, and complex anatomy, making them poor candidates for major surgical interventions. Advancement in endoscopic tools has made endoscopic management possible. Endoscopic management is less invasive, is associated with prompt recovery, and can significantly improve the quality of life of patients and possibly allow them to resume systemic therapy. METHODS: In this video case series, 3 cases of CVF patients treated endoscopically are presented to demonstrate the use of the currently available tools and techniques. The strategy used for the closure of the 3 CVFs was dependent on the size and etiology of the fistulas. RESULTS: Technical and clinical success was achieved in all 3 situations. There were no procedure-related adverse events. CONCLUSION: These cases demonstrate the use of the cap to perform vaginal endoscopy; the use of the over-the-scope clips, covered stents, and endoscopic suturing; and how they can facilitate the closure of fistulas in patients who are poor surgical candidates.

Cardiac Nuclear High-Mobility Group Box 1 Ameliorates Pathological Cardiac Hypertrophy by Inhibiting DNA Damage Response.

High-mobility group box 1 (HMGB1) is a deoxyribonucleic acid (DNA)-binding protein associated with DNA repair. Decreased nuclear HMGB1 expression and increased DNA damage response (DDR) were observed in human failing hearts. DNA damage and DDR as well as cardiac remodeling were suppressed in cardiac-specific HMGB1 overexpression transgenic mice after angiotensin II stimulation as compared with wild-type mice. In vitro, inhibition of HMGB1 increased phosphorylation of extracellular signal-related kinase 1/2 and nuclear factor kappa B, which was rescued by DDR inhibitor treatment. DDR inhibitor treatment provided a cardioprotective effect on angiotensin II-induced cardiac remodeling in mice.

CDC childhood physical activity strategies fail to show sustained fitness impact in middle school children.

An increasing number of children are now obese and fail to meet minimum recommendations for physical activity (PA). Schools play a critical role in impacting children's activity behaviors, including PA. Our objective was to assess whether CDC-based school-centered strategies to promote PA increase long-term cardiovascular fitness (CVF) levels in students in schools. A prospective observational trial was conducted in 26 middle schools to implement CDC school-based strategies to increase PA for 3 years. Students had CVF assessed by Fitnessgram (PACER), a 20-meter shuttle run, at the start and end of each school year. A post-study questionnaire was administered to assess each school's strategy adherence. At baseline, 2402 students with a mean age 12.2 ±â€¯1.1 years showed a mean CVF measured by PACER of 33.2 ±â€¯19.0 laps (estimated VO2max 44.3 ±â€¯5.3 ml/kg/min). During the first year, there was a significant increase in the mean PACER score (Δ = 3, 95% CI: 2-4.1 laps, p < 0.001) and PACER z-score (Δ = 0.09, 95% CI: 0.04-0.14, p = 0.001). Subsequently, however, a significant negative trend in PACER z-scores occurred (ß = -0.02, p < 0.0001) so that over the 3-year study period, the intervention did not increase overall CVF. This effort to implement CDC school-based PA strategies in middle schools did not result in sustained increase in CVF over 3 years. It remains to be clarified whether this limited efficacy indicates that CDC physical activity strategies are not sufficiently robust to meaningfully impact health outcomes and/or additional support is needed in schools to improve fidelity of implementation.

[Systemic inflammatory profile of smokers with and without COPD]. / Profil inflammatoire systémique des fumeurs atteints de BPCO comparés aux fumeurs indemnes de BPCO.

INTRODUCTION: Studies comparing the systemic inflammatory profiles of smokers with and without COPD present discordant findings. AIM: To compare the systemic inflammatory profile of smokers with and without COPD. METHODS: This is a cross-sectional comparative study. Two groups of active smokers of more than 10 pack-years were included: 56 consecutives stable COPD (postbronchodilator FEV1/FVC<0.70) and 32 consecutives non-COPD (postbronchodilator FEV1/FVC≥0.70). Smoking and clinical, anthropometric and spirometric data were noted. The following blood biomarkers were identified: leukocytes, hemoglobin, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR). According to the levels (normal/abnormal) of these markers, two groups of smokers were formed. Quantitative and qualitative data were expressed, respectively, as means±SD and percentages. RESULTS: Compared to the non-COPD group, the COPD group was older (56±12 vs. 65±8 years) and had a higher smoking consumption (30±18 vs. 52±31 pack-years). Compared to the non-COPD group, the COPD group had higher values of CRP (2.06±1.24 vs. 11.32±11.03mg/L), of ESR (9.59±8.29 vs. 15.96±11.56), of IL-6 (9.28±4.69 vs. 20.27±5.31ng/L) and of TNF-α (18.38±7.98ng/L vs. 8.62±3.72ng/L). Compared to the non-COPD group, the COPD group included higher percentages of smokers with elevated CRP (0 % vs. 32 %), with leukocytosis (6 % vs. 16 %), with higher levels of IL-6 (81 % vs. 98 %) or TNF-α (91 % vs. 100 %). CONCLUSION: Smokers with COPD, compared to smokers free from COPD, have a marked systemic inflammation.

Ly6G-mediated depletion of neutrophils is dependent on macrophages.

Antibody-mediated depletion of neutrophils is commonly used to study neutropenia. However, the mechanisms by which antibodies deplete neutrophils have not been well defined. We noticed that mice deficient in complement and macrophages had blunted neutrophil depletion in response to anti-Ly6G monoclonal antibody (MAb) treatment. In vitro, exposure of murine neutrophils to anti-Ly6G MAb in the presence of plasma did not result in significant depletion of cells, either in the presence or absence of complement. In vivo, anti-Ly6G-mediated neutrophil depletion was abrogated following macrophage depletion, but not complement depletion, indicating a requirement for macrophages to induce neutropenia by this method. These results inform the use and limitations of anti-Ly6G antibody as an experimental tool for depleting neutrophils in various immunological settings.

Complement depletion with humanised cobra venom factor: efficacy in preclinical models of vascular diseases.

The complement system is an intrinsic part of the immune system and has important functions in both innate and adaptive immunity. On the other hand, inadvertent or misdirected complement activation is also involved in the pathogenesis of many diseases, contributing solely or significantly to tissue injury and disease development. Multiple approaches to develop pharmacological agents to inhibit complement are currently being pursued. We have developed a conceptually different approach of not inhibiting but depleting complement, based on the complement-depleting activities of cobra venom factor (CVF), a non-toxic cobra venom component with structural and functional homology to complement component C3. We developed a humanised version of CVF by creating human complement component C3 derivatives with complement-depleting activities of CVF (humanised CVF) as a promising therapeutic agent for diseases with complement pathogenesis. Here we review the beneficial therapeutic effect of humanised CVF in several murine models of vascular diseases such as reperfusion injury.