scholarly journals The biological mechanisms regulating sperm selection by the ovine cervix

Reproduction ◽  
2019 ◽  
Vol 158 (1) ◽  
pp. R1-R13 ◽  
Author(s):  
S Fair ◽  
K G Meade ◽  
K Reynaud ◽  
X Druart ◽  
S P de Graaf
Keyword(s):  
Innate Immune ◽  
Cervical Mucus ◽  
Sperm Selection ◽  
Biological Mechanisms ◽  
Mucus Production ◽  
Assisted Reproduction Techniques ◽  
Complex Anatomy ◽  
Breed Differences ◽  
Semen Processing ◽  
The Impact

In species where semen is deposited in the vagina, the cervix has the unique function of facilitating progress of spermatozoa towards the site of fertilisation while also preventing the ascending influx of pathogens from the vagina. For the majority of species, advances in assisted reproduction techniques facilitate the bypassing of the cervix and therefore its effect on the transit of processed spermatozoa has been largely overlooked. The exception is in sheep, as it is currently not possible to traverse the ovine cervix with an inseminating catheter due to its complex anatomy, and semen must be deposited at the external cervical os. This results in unacceptably low pregnancy rates when frozen-thawed or liquid stored (>24 h) semen is inseminated. The objective of this review is to discuss the biological mechanisms which regulate cervical sperm selection. We assess the effects of endogenous and exogenous hormones on cervical mucus composition and discuss how increased mucus production and flow during oestrus stimulates sperm rheotaxis along the crypts and folds of the cervix. Emerging results shedding light on the sperm-cervical mucus interaction as well as the dialogue between spermatozoa and the innate immune system are outlined. Finally, ewe breed differences in cervical function and the impact of semen processing on the success of fertilisation, as well as the most fruitful avenues of further investigation in this area are proposed.

scholarly journals Orchestration of Neutrophil Extracellular Traps (Nets), a Unique Innate Immune Function during Chronic Obstructive Pulmonary Disease (COPD) Development

Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 53
Author(s):  
Anjali Trivedi ◽  
Meraj A. Khan ◽  
Geetanjali Bade ◽  
Anjana Talwar
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Neutrophil Extracellular Traps ◽  
Innate Immune ◽  
Chronic Obstructive ◽  
Tissue Destruction ◽  
Mucus Production ◽  
Obstructive Pulmonary Disease ◽  
Extracellular Traps ◽  
Endothelial Cell Death

Morbidity, mortality and economic burden caused by chronic obstructive pulmonary disease (COPD) is a significant global concern. Surprisingly, COPD is already the third leading cause of death worldwide, something that WHO had not predicted to occur until 2030. It is characterized by persistent respiratory symptoms and airway limitation due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles of gases. Neutrophil is one of the key infiltrated innate immune cells in the lung during the pathogenesis of COPD. Neutrophils during pathogenic attack or injury decide to undergo for a suicidal death by releasing decondensed chromatin entangled with antimicrobial peptides to trap and ensnare pathogens. Casting neutrophil extracellular traps (NETs) has been widely demonstrated to be an effective mechanism against invading microorganisms thus controlling overwhelming infections. However, aberrant and massive NETs formation has been reported in several pulmonary diseases, including chronic obstructive pulmonary disease. Moreover, NETs can directly induce epithelial and endothelial cell death resulting in impairing pulmonary function and accelerating the progression of the disease. Therefore, understanding the regulatory mechanism of NET formation is the need of the hour in order to use NETs for beneficial purpose and controlling their involvement in disease exacerbation. For example, DNA neutralization of NET proteins using protease inhibitors and disintegration with recombinant human DNase would be helpful in controlling excess NETs. Targeting CXC chemokine receptor 2 (CXCR2) would also reduce neutrophilic inflammation, mucus production and neutrophil-proteinase mediated tissue destruction in lung. In this review, we discuss the interplay of NETs in the development and pathophysiology of COPD and how these NETs associated therapies could be leveraged to disrupt NETopathic inflammation as observed in COPD, for better management of the disease.

128 Development of an M1-polarized, non-viral chimeric antigen receptor macrophage (CAR-M) platform for cancer immunotherapy

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A141-A141
Author(s):  
Yumi Ohtani ◽  
Kayleigh Ross ◽  
Aditya Dandekar ◽  
Rashid Gabbasov ◽  
Michael Klichinsky
Keyword(s):  
Cancer Immunotherapy ◽  
Chimeric Antigen Receptor ◽  
Scale Up ◽  
Antigen Receptor ◽  
Innate Immune ◽  
List Type ◽  
M1 Phenotype ◽  
The Impact ◽  
Anti Tumor Activity ◽  
Immunosuppressive Factors

BackgroundWe have previously developed CAR-M as a novel cell therapy approach for the treatment of solid tumors.1 CAR-M have the potential to overcome key challenges that cell therapies face in the solid tumor setting – tumor infiltration, immunosuppression, lymphocyte exclusion – and can induce epitope spreading to overcome target antigen heterogeneity. While macrophages transduced with the adenoviral vector Ad5f35 (Ad CAR-M) traffic to tumors, provide robust anti-tumor activity, and recruit and activate T cells, we sought to identify a robust non-viral method of macrophage engineering in order to reduce the cost of goods, manufacturing complexity, and potential immunogenicity associated with viral vectors.MethodsAs innate immune cells, macrophages detect exogenous nucleic acids and respond with inflammatory and apoptotic programs. Thus, we sought to identify a means of mRNA delivery that avoids recognition by innate immune sensors. We screened a broad panel of mRNA encoding an anti-HER2 CAR comprising multiplexed 5’Cap and base modifications using an optimized and scalable electroporation approach and evaluated the impact of interferon-β priming on CAR-M phenotype and function.ResultsWe identified the optimal multiplexed mRNA modifications that led to maximal macrophage viability, transfection efficiency, intensity of CAR expression, and duration of expression. Non-viral HER2 CAR-M phagocytosed and killed human HER2+ tumor cells. Unlike Ad CAR-M, mRNA CAR-M were not skewed toward an M1 state by mRNA electroporation. Priming non-viral CAR-M with IFN-β induced a durable M1 phenotype, as shown by stable upregulation of numerous M1 markers and pathways. IFN-β priming significantly enhanced the anti-tumor activity of CAR but not control macrophages. IFN-β primed mRNA CAR-M were resistant to M2 conversion, maintaining an M1 phenotype despite challenge with various immunosuppressive factors, and converted bystander M2 macrophages toward M1. Interestingly, priming mRNA CAR-M with IFN-β significantly enhanced the persistence of CAR expression, overcoming the known issue of rapid mRNA turnover. RNA-seq analysis revealed that IFN-β priming affected pathways involved in increasing translation and decreasing RNA degradation in human macrophages.ConclusionsWe have established a novel, optimized non-viral CAR-M platform based on chemically modified mRNA and IFN-β priming. IFN-β priming induced a durable M1 phenotype, improved CAR expression, improved CAR persistence, led to enhanced anti-tumor function, and rendered resistance to immunosuppressive factors. This novel platform is amenable to scale-up, GMP manufacturing, and represents an advance in the development of CAR-M.ReferenceKlichinsky M, Ruella M, Shestova O, et al. Human chimeric antigen receptor macrophages for cancer immunotherapy. Nat Biotechnol 2020;38(8):947–953.

scholarly journals Impact on actual clinical practice of the latest evidence for percutaneous closure of patent foramen ovale associated with stroke. A single center experience

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
L Carnero Montoro ◽  
M Ruiz Ortiz ◽  
N Paredes Hurtado ◽  
M Delgado Ortega ◽  
A Rodriguez Almodovar ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Patent Foramen Ovale ◽  
Cryptogenic Stroke ◽  
Percutaneous Closure ◽  
Publication Date ◽  
Foramen Ovale ◽  
Complex Anatomy ◽  
The Mean ◽  
The Impact

Abstract Funding Acknowledgements Type of funding sources: None. Background and aims Since september 14th, 2017. Three large clinical trials demonstrated that, in selected patients, percutaneous closure of patent foramen ovale (PFO) was associated with lower recurrence in patients with cryptogenic stroke (CS). Our aim was to determine the impact of these findings on routine  clinical practice in a tertiary hospital. Methods Patients with percutaneous closure of PFO due to CS (January 2001-January 2020) were included. The clinical characteristics were analyzed individually and grouped in the RoPE score, before and after the publication date. Complex anatomy (CA) defined as interatrial septum aneurysm or basal wide bubble passage was evaluated in both periods. Results 293 patients were included. The mean age was 49 ± 11 years, 15% were older than 60 years, 60% men, 26% hypertensive, 28% smokers and 7%diabetics. The median RoPEscore was 6 [p25-75, 5-7] and 75% met CA criteria. Since september 14th, 2017, the frequency of CA and the mean age of the patients were significantly higher (89% vs. 69% p <0.0005 and 51 ± 11 vs. 48 ± 11 years, p = 0.02, respectively), and RoPEscore, significantly lower (5 [5-7] vs. 6 [5-7], p = 0.02). Conclusion The publication of clinical trials wich demonstrated the benefit of percutaneous closure of PFO in CS had a significant impact on the daily clinical practice of our institution, with an increase in indications for CA, despite a clinical profile suggestive of lower causal probability of PFO.

scholarly journals Sperm Selection by Magnetic-Activated Cell Sorting Before Microinjection of Autologous Oocytes Increases Cumulative Live Birth Rates with Limited Clinical Impact: A Retrospective Study in Unselected Males

Biology ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 430
Author(s):  
María Gil Juliá ◽  
Irene Hervás ◽  
Ana Navarro-Gómez Lechón ◽  
Fernando Quintana ◽  
David Amorós ◽  
...  
Keyword(s):  
Live Birth ◽  
Clinical Impact ◽  
Sperm Selection ◽  
Reproductive Outcomes ◽  
Birth Rates ◽  
Multicenter Observational Study ◽  
Live Birth Rates ◽  
Cumulative Live Birth ◽  
The Impact ◽  
Autologous Oocytes

The application of MACS non-apoptotic sperm selection in infertility clinics is controversial since the published literature does not agree on its effect on reproductive outcomes. Therefore, it is not part of the routine clinical practice. Classical measures of reproductive success (pregnancy or live birth rates per ovarian stimulation) introduce a bias in the evaluation of a technique’s effect, since only the best embryo is transferred. This retrospective, multicenter, observational study evaluated the impact of MACS on reproductive outcomes, measuring results in classical parameters and cumulative live birth rates (CLBR). Data from ICSI cycles using autologous oocyte in Spanish IVIRMA fertility clinics from January 2008 to February 2020 were divided into two groups according to their semen processing: standard practice (reference: 46,807 patients) versus an added MACS sperm selection (1779 patients). Only when measured as CLBR per embryo transferred and per MII oocyte used was the difference between groups statistically significant. There were no significant differences between MACS and reference groups on pregnancy and live birth rates. In conclusion, results suggest that non-apoptotic sperm selection by MACS on unselected males prior to ICSI with autologous oocytes has limited clinical impact, showing a subtle increase in CLBR per embryo transferred.

scholarly journals Antimicrobial peptides in patients with anorexia nervosa: comparison with healthy controls and the impact of weight gain

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Marie-Christin Bendix ◽  
Michael Stephan ◽  
Mariel Nöhre ◽  
Wally Wünsch-Leiteritz ◽  
Hagen Schmidt ◽  
...  
Keyword(s):  
Anorexia Nervosa ◽  
Weight Gain ◽  
Antimicrobial Peptides ◽  
Pathogenic Bacteria ◽  
Innate Immune ◽  
Effect Sizes ◽  
Healthy Controls ◽  
Clinical Observations ◽  
The Impact

AbstractClinical observations show that patients with anorexia nervosa (AN) are surprisingly free from infectious diseases. There is evidence from studies in Drosophila melanogaster that starvation leads to an increased expression of antimicrobial peptides (AMPs). AMPs are part of the innate immune system and protect human surfaces from colonization with pathogenic bacteria, viruses and fungi. We compared the expression of AMPs between patients with AN and healthy controls (HC) and investigated the influence of weight gain. Using a standardized skin rinsing method, quantitative determination of the AMPs psoriasin and RNase 7 was carried out by ELISA. Even though non-significant, effect sizes revealed slightly higher AMP concentrations in HC. After a mean weight gain of 2.0 body mass index points, the concentration of psoriasin on the forehead of patients with AN increased significantly. We could not confirm our hypotheses of higher AMP concentrations in patients with AN that decrease after weight gain. On the contrary, weight gain seems to be associated with increasing AMP concentrations.

scholarly journals The impact of bacterial contamination of the ejaculate and extender on the quality of swine semen doses

2017 ◽  
Vol 38 (5) ◽  
pp. 3095 ◽  
Author(s):  
Ana Maria Groehs Goldberg ◽  
Marisa Cardoso ◽  
Mari Lourdes Bernardi ◽  
Ivo Wentz ◽  
Fernando Pandolfo Bortolozzo
Keyword(s):  
Bacterial Contamination ◽  
Sperm Morphology ◽  
No Reduction ◽  
Degree Of Contamination ◽  
Colony Forming Units ◽  
Semen Processing ◽  
Semen Extender ◽  
Contamination Levels ◽  
The Impact

The aim of this study was to verify the influence of the degree of bacterial contamination of boar ejaculate and semen extender on the quality of semen doses. The experiment was conducted in four boar studs, from which raw semen and two semen doses from each ejaculate were collected to evaluate the number of colony-forming units (CFU), pH, sperm morphology and motility. Extender samples were also evaluated for CFU. Ejaculates that had higher levels of contamination ( > 220 CFU mL-1) resulted in semen doses with a greater degree of bacterial contamination but with no reduction in motility or alteration in pH. When the semen doses were classified according to the degree of contamination of the extender, a decrease in motility was observed after 108 and 168 h of storage (P < 0.05) in the group whose extender had ? 14,000 CFU mL-1 versus the group whose extender had ? 330 CFU mL-1. The pH remained stable during 168 h of storage in semen doses with extender that had lower contamination levels, but decreased from 7.2 to 6.0 between 24 and 168 h of storage (P < 0.05) in the group with extender that had higher levels of contamination. A higher number of abnormal acrosomes (P < 0.05) were observed after 168 h of storage in the semen doses whose extender was highly contaminated. The production of semen doses with low bacterial contamination and high sperm cell viability will only be possible with a strict hygienic control in semen processing, primarily with respect to the extender, combined with minimal contamination during collection.

scholarly journals Detection of A-to-I RNA Editing in SARS-COV-2

Genes ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 41
Author(s):  
Ernesto Picardi ◽  
Luigi Mansi ◽  
Graziano Pesole
Keyword(s):  
Rna Editing ◽  
Time Course ◽  
Vero Cells ◽  
Innate Immune ◽  
Therapeutic Interventions ◽  
Clinical Samples ◽  
Transcriptome Data ◽  
Host Interactions ◽  
Rnaseq Data ◽  
The Impact

ADAR1-mediated deamination of adenosines in long double-stranded RNAs plays an important role in modulating the innate immune response. However, recent investigations based on metatranscriptomic samples of COVID-19 patients and SARS-COV-2-infected Vero cells have recovered contrasting findings. Using RNAseq data from time course experiments of infected human cell lines and transcriptome data from Vero cells and clinical samples, we prove that A-to-G changes observed in SARS-COV-2 genomes represent genuine RNA editing events, likely mediated by ADAR1. While the A-to-I editing rate is generally low, changes are distributed along the entire viral genome, are overrepresented in exonic regions, and are (in the majority of cases) nonsynonymous. The impact of RNA editing on virus–host interactions could be relevant to identify potential targets for therapeutic interventions.

scholarly journals Impact of Ringer’s Solution Challenge Stress to Immunostimulatory Experiment, Insights From Japanese Flounder

2020 ◽  
Vol 11 ◽  
Author(s):  
Jinxiang Liu ◽  
Zan Li ◽  
Yujue Wang ◽  
Quanqi Zhang
Keyword(s):  
Immune Response ◽  
Intraperitoneal Injection ◽  
Expression Profiles ◽  
Paralichthys Olivaceus ◽  
Metabolic Process ◽  
Japanese Flounder ◽  
Innate Immune ◽  
Fundamental Information ◽  
Immune Related Genes ◽  
The Impact

Ringer’s or phosphate buffer saline (PBS) solution buffer usually was used as dilution butter in intraperitoneal injection. Stress could activate immune response, inflammatory response and glycogen metabolic process. The impact of solution buffer as a stressor to immune system was ignored in immunostimulatory experiment. In this report, we tested the hypothesis that the innate immune response and glycogen metabolic process were altered when it were challenged with Ringer’s in Japanese flounder (Paralichthys olivaceus). RNA-seq was performed after challenge with Ringer’s at 8 h and 48 h. The data revealed that the expression profiles of blood, gill, and kidney were significantly changed. Differentially expressed genes (DEGs) were identified, and energy metabolic and immune-related genes were up-regulated or down-regulated obviously. GO and KEGG analyses showed that DEGs were mainly enriched in innate immune terms and pathways. Weighted gene co-expression networks analysis (WGCNA) also indicated the highest association module with stress. A total of 16 genes were detected in the gray module, which were immune-related and metabolic-related genes. These results provided fundamental information on intraperitoneal injection with solution buffer. It offered useful clues to further explore the functional mechanism of stress and immunity.

Applications of a microfabricated device for evaluating sperm function

1993 ◽  
Vol 39 (9) ◽  
pp. 1944-1947 ◽  
Author(s):  
L J Kricka ◽  
O Nozaki ◽  
S Heyner ◽  
W T Garside ◽  
P Wilding
Keyword(s):  
Hyaluronic Acid ◽  
Cervical Mucus ◽  
Sperm Function ◽  
Sperm Selection ◽  
Igg Antibody ◽  
Feature Size ◽  
Specific Antibodies ◽  
Branching Structures ◽  
Mesoscale Structures ◽  
Simultaneous Assessment

Abstract Mesoscale structures (microns dimensions, nL-pL volumes) have been designed and fabricated in silicon for use in various analytical tasks. We studied sperm motility and performed sperm selection in channels (80 microns wide x 20 microns deep), branching structures (40 microns wide x 20 microns deep, eight bifurcations), and channels containing barriers (7 microns feature size). Sperm-cervical mucus and sperm-hyaluronic acid interactions were assessed by using appropriate microchannel-chamber structures filled with either cervical mucus or hyaluronic acid. Simultaneous assessment of the potency of different spermicides (e.g., nonoxynol-9, C13G) and spermicide concentrations was achieved with structures comprising chambers containing spermicide connected via channels to a central chamber into which semen was introduced. Semen was also tested for the presence of sperm-specific antibodies by using microchannels filled with human anti-IgG antibody-coated microbeads.

The impact of rising sea temperature on innate immune parameters in the tropical subtidal sea urchin Lytechinus variegatus and the intertidal sea urchin Echinometra lucunter

2013 ◽  
Vol 92 ◽  
pp. 95-101 ◽  
Author(s):  
Paola Cristina Branco ◽  
João Carlos Shimada Borges ◽  
Marinilce Fagundes Santos ◽  
Bernard Ernesto Jensch Junior ◽  
José Roberto Machado Cunha da Silva
Keyword(s):  
Sea Urchin ◽  
Innate Immune ◽  
Lytechinus Variegatus ◽  
Sea Temperature ◽  
Immune Parameters ◽  
The Impact
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