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Cytokine Jul 2023The induction of maternal inflammation in mice leads to fetal injury that is believed to be IL-6 dependent. The fetal inflammatory response, defined by elevated fetal or...
BACKGROUND
The induction of maternal inflammation in mice leads to fetal injury that is believed to be IL-6 dependent. The fetal inflammatory response, defined by elevated fetal or amniotic fluid IL-6, has been described as a potential mechanism for subsequent fetal injury. The role of maternal IL-6 production and signaling in the fetal IL-6 response is currently unclear.
METHODS
Genetic and anti-IL-6 antibody strategies were used to systematically block the maternal IL-6 response during inflammation. Chorioamnionitis was induced using intraperitoneal injection of lipopolysaccharide (LPS) at mid gestation (E14.5) and late gestation (E18.5). This model was used in pregnant C57Bl/6 dams, IL6 dams, C57Bl/6 dams treated with anti-IL-6 (blocks both classical and trans-signaling) or anti-gp130 antibodies (blocks trans-signaling only) and IL6 dams. Six hours following LPS injection, maternal serum, placental tissue, amniotic fluid and fetal tissue or serum were collected. A bead-based multiplex assay was used to evaluate levels of IL-6, KC, IL-1β, TNF, IL-10, IL-22, IFN-γ, IL-13 and IL-17A.
RESULTS
Chorioamnionitis in C57Bl/6 dams was characterized by elevated maternal serum levels of IL-6, KC and IL-22 with litter loss during mid gestation. The fetal response to maternal inflammation in C57Bl/6 mice was primarily characterized by elevated levels of IL-6, KC and IL-22 in the placenta, amniotic fluid and fetus during both mid and late gestation. A global IL-6 knockout (IL6) eradicated the maternal, placental, amniotic fluid and fetal IL-6 response to LPS during mid and late gestation and improved litter survival, while minimally influencing the KC or IL-22 responses. Blocking maternal classical IL-6 signaling in C57Bl/6 dams at the time of LPS exposure diminished the maternal, placental, amniotic fluid and fetal IL-6 response during mid and late gestation, while blocking maternal IL-6 trans-signaling only affected fetal IL-6 expression. To evaluate whether maternal IL-6 was crossing the placenta and reaching the fetus, IL-6 dams were utilized in the chorioamnionitis model. IL-6 dams mounted a systemic inflammatory response following injection with LPS, characterized by elevated IL-6, KC and IL-22. IL-6 pups born to IL6 dams had decreased amniotic fluid levels of IL-6 and undetectable levels of fetal IL-6 compared to IL-6 littermate controls.
CONCLUSION
The fetal response to systemic maternal inflammation is dependent upon maternal IL-6 signaling, but maternal IL-6 is not crossing the placenta and reaching the fetus at detectable levels.
Topics: Animals; Female; Mice; Pregnancy; Amniotic Fluid; Chorioamnionitis; Disease Models, Animal; Fetal Diseases; Inflammation; Interleukin-6; Lipopolysaccharides; Placenta
PubMed: 37130487
DOI: 10.1016/j.cyto.2023.156210 -
Pathogens (Basel, Switzerland) Apr 2024Female genital tract infections (FGTIs) include vaginal infections (e.g., bacterial vaginosis [BV]), endometritis, pelvic inflammatory disease [PID], and... (Review)
Review
Female genital tract infections (FGTIs) include vaginal infections (e.g., bacterial vaginosis [BV]), endometritis, pelvic inflammatory disease [PID], and chorioamnionitis [amniotic fluid infection]. They commonly occur in women of reproductive age and are strongly associated with multiple adverse health outcomes including increased risk of HIV/sexually transmitted infection acquisition and transmission, infertility, and adverse birth outcomes such as preterm birth. These FGTIs are characterized by a disruption of the cervicovaginal microbiota which largely affects host immunity through the loss of protective, lactic acid-producing spp. and the overgrowth of facultative and strict anaerobic bacteria. species (spp.), anaerobic Gram-negative rods, are implicated in the pathogenesis of multiple bacterial FGTIs. Specifically, , , and have unique virulence factors in this setting, including resistance to antibiotics commonly used in treatment. Additionally, evidence suggests that the presence of spp. in untreated BV cases can lead to infections of the upper female genital tract by ascension into the uterus. This narrative review aims to explore the most common spp. in FGTIs, highlight their important role in the pathogenesis of FGTIs, and propose future research in this area.
PubMed: 38787215
DOI: 10.3390/pathogens13050364 -
Animals : An Open Access Journal From... Jul 2023The aim of the study was to investigate the potential of cell-based regenerative therapy for elbow joints affected by osteoarthritis. Interest was focused on two...
The aim of the study was to investigate the potential of cell-based regenerative therapy for elbow joints affected by osteoarthritis. Interest was focused on two intra-articular applications of amnion-derived mesenchymal stem cells (A-MSCs) to a group of different breeds of dogs with elbow osteoarthritis (13 joints). Two injections were performed 14 days apart. We evaluated synovial fluid biomarkers, such as IFN-γ, IL-6, IL-15, IL-10, MCP-1, TNF-α, and GM-CSF, by multiplex fluorescent micro-bead immunoassay in the treated group of elbows (n = 13) (day 0, day 14, and day 28) and in the control group of elbows (n = 9). Kinematic gait analysis determined the joint range of motion (ROM) before and after each A-MSCs application. Kinematic gait analysis was performed on day 0, day 14, and day 28. Kinematic gait analysis pointed out improvement in the average range of motion of elbow joints from day 0 (38.45 ± 5.74°), day 14 (41.7 ± 6.04°), and day 28 (44.78 ± 4.69°) with statistical significance ( < 0.05) in nine elbows. Correlation analyses proved statistical significance ( < 0.05) in associations between ROM (day 0, day 14, and day 28) and IFN-γ, IL-6, IL-15, MCP-1, TNF-α, and GM-CSF concentrations (day 0, day 14, and day 28). IFN-γ, IL-6, IL-15, MCP-1, GM-CSF, and TNF- α showed negative correlation with ROM at day 0, day 14, and day 28, while IL-10 demonstrated positive correlation with ROM. As a consequence of A-MSC application to the elbow joint, we detected a statistically significant ( < 0.05) decrease in concentration levels between day 0 and day 28 for IFN-γ, IL-6, and TNF-α and statistically significant increase for IL-10. Statistical significance ( < 0.05) was detected in TNF-α, IFN-γ, and GM-CSF concentrations between day 14 and the control group as well as at day 28 and the control group. IL-6 concentrations showed statistical significance ( < 0.05) between day 14 and the control group.
PubMed: 37443993
DOI: 10.3390/ani13132195 -
ACS Applied Bio Materials Mar 2024Scaffolds can be introduced as a source of tissue in reconstructive surgery and can help to improve wound healing. Amniotic membranes (AMs) as scaffolds for tissue...
Scaffolds can be introduced as a source of tissue in reconstructive surgery and can help to improve wound healing. Amniotic membranes (AMs) as scaffolds for tissue engineering have emerged as promising biomaterials for surgical reconstruction due to their regenerative capacity, biocompatibility, gradual degradability, and availability. They also promote fetal-like scarless healing and provide a bioactive matrix that stimulates cell adhesion, migration, and proliferation. The aim of this study was to create a tissue-engineered AM-based implant for the repair of vesicovaginal fistula (VVF), a defect between the bladder and vagina caused by prolonged obstructed labor. Layers of AMs (with or without cross-linking) and electrospun poly-4-hydroxybutyrate (P4HB) (a synthetic, degradable polymer) scaffold were joined together by fibrin glue to produce a multilayer scaffold. Human vaginal fibroblasts were seeded on the different constructs and cultured for 28 days. Cell proliferation, cell morphology, collagen deposition, and metabolism measured by matrix metalloproteinase (MMP) activity were evaluated. Vaginal fibroblasts proliferated and were metabolically active on the different constructs, producing a distributed layer of collagen and proMMP-2. Cell proliferation and the amount of produced collagen were similar across different groups, indicating that the different AM-based constructs support vaginal fibroblast function. Cell morphology and collagen images showed slightly better alignment and organization on the un-cross-linked constructs compared to the cross-linked constructs. It was concluded that the regenerative capacity of AM does not seem to be affected by mechanical reinforcement with cross-linking or the addition of P4HB and fibrin glue. An AM-based implant for surgical repair of internal organs requiring load-bearing functionality can be directly translated to other types of surgical reconstruction of internal organs.
Topics: Female; Humans; Tissue Engineering; Tissue Scaffolds; Fibrin Tissue Adhesive; Amnion; Collagen; Polymers
PubMed: 38391263
DOI: 10.1021/acsabm.3c00765 -
Renal Failure Dec 2023Calciphylaxis is a rare cutaneous vascular disease that manifests with intolerable pains, non-healing skin wounds, histologically characterized by calcification,...
Calciphylaxis is a rare cutaneous vascular disease that manifests with intolerable pains, non-healing skin wounds, histologically characterized by calcification, fibrointimal hyperplasia, and microvessel thrombosis. Currently, there are no standardized guidelines for this disease. Recent studies have recognized a high prevalence of thrombophilias and hypercoagulable conditions in calciphylaxis patients. Here, we report a case of uremic calciphylaxis patient whom was refractory to conventional treatments and then received a salvage strategy with intravenous and local hAMSC application. In order to investigate the therapeutic mechanism of hAMSCs from the novel perspective of hypercoagulability, coagulation-related indicators, wound status, quality of life and skin biopsy were followed up. Polymerase chain reaction (PCR) was performed to determine the distribution of hAMSCs in multiple tissues including lung, kidney and muscle after infusion of hAMSCs for 24 h, 1 week and 1 month in mice aiming to investigate whether hAMSCs retain locally active roles after intravenous administration. Improvement of hypercoagulable condition involving correction of platelet, D-dimer and plasminogen levels, skin regeneration and pain alleviation were revealed after hAMSC administration over one-year period. Skin biopsy pathology suggested regenerative tissues after 1 month hAMSC application and full epidermal regeneration after 20 months hAMSC treatment. PCR analysis indicated that hAMSCs were homing in lung, kidney and muscle tissues of mice even until tail vein injection of hAMSCs for 1 month. We propose that hypercoagulability is a promising therapeutic target of calciphylaxis patients, which can be effectively improved by hAMSC treatment.
Topics: Humans; Mice; Animals; Amnion; Calciphylaxis; Quality of Life; Thrombophilia; Mesenchymal Stem Cells
PubMed: 37293809
DOI: 10.1080/0886022X.2023.2218483 -
The Journal of Maternal-fetal &... Dec 2023Intra-amniotic inflammation (IAI), associated with either microbe (infection) or danger signals (sterile), plays a major role in the pathophysiology of preterm labor and...
OBJECTIVE
Intra-amniotic inflammation (IAI), associated with either microbe (infection) or danger signals (sterile), plays a major role in the pathophysiology of preterm labor and delivery. Coiled-Coil-Helix-Coiled-Coil-Helix Domain Containing 2 (CHCHD2) [also known as Mitochondrial Nuclear Retrograde Regulator 1 (MNRR1)], a mitochondrial protein involved in oxidative phosphorylation and cell survival, is capable of sensing tissue hypoxia and inflammatory signaling. The ability to maintain an appropriate energy balance at the cellular level while adapting to environmental stress is essential for the survival of an organism. Mitochondrial dysfunction has been observed in acute systemic inflammatory conditions, such as sepsis, and is proposed to be involved in sepsis-induced multi-organ failure. The purpose of this study was to determine the amniotic fluid concentrations of CHCHD2/MNRR1 in pregnant women, women at term in labor, and those in preterm labor (PTL) with and without IAI.
METHODS
This cross-sectional study comprised patients allocated to the following groups: (1) mid-trimester ( = 16); (2) term in labor ( = 37); (3) term not in labor ( = 22); (4) PTL without IAI who delivered at term ( = 25); (5) PTL without IAI who delivered preterm ( = 47); and (6) PTL with IAI who delivered preterm ( = 53). Diagnosis of IAI (amniotic fluid interleukin-6 concentration ≥2.6 ng/mL) included cases associated with microbial invasion of the amniotic cavity and those of sterile nature (absence of detectable bacteria, using culture and molecular microbiology techniques). Amniotic fluid and maternal plasma CHCHD2/MNRR1 concentrations were determined with a validated and sensitive immunoassay.
RESULTS
(1) CHCHD2/MNRR1 was detectable in all amniotic fluid samples and women at term without labor had a higher amniotic fluid CHCHD2/MNRR1 concentration than those in the mid-trimester ( = 0.003); (2) the amniotic fluid concentration of CHCHD2/MNRR1 in women at term in labor was higher than that in women at term without labor ( = 0.01); (3) women with PTL and IAI had a higher amniotic fluid CHCHD2/MNRR1 concentration than those without IAI, either with preterm ( < 0.001) or term delivery ( = 0.01); (4) women with microbial-associated IAI had a higher amniotic fluid CHCHD2/MNRR1 concentration than those with sterile IAI ( < 0.001); (5) among women with PTL and IAI, the amniotic fluid concentration of CHCHD2/MNRR1 correlated with that of interleukin-6 (Spearman's Rho = 0.7; < 0.001); and (6) no correlation was observed between amniotic fluid and maternal plasma CHCHD2/MNRR1 concentrations among women with PTL.
CONCLUSION
CHCHD2/MNRR1 is a physiological constituent of human amniotic fluid in normal pregnancy, and the amniotic concentration of this mitochondrial protein increases during pregnancy, labor at term, and preterm labor with intra-amniotic infection. Hence, CHCHD2/MNRR1 may be released into the amniotic cavity by dysfunctional mitochondria during microbial-associated IAI.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Interleukin-6; Cross-Sectional Studies; Mitochondrial Proteins; Chorioamnionitis; Obstetric Labor, Premature; Inflammation; Amniotic Fluid; Sepsis; Gestational Age; Fetal Membranes, Premature Rupture; DNA-Binding Proteins; Transcription Factors
PubMed: 36941246
DOI: 10.1080/14767058.2023.2183088 -
Indian Journal of Ophthalmology Aug 2023The use of human amniotic membrane transplantation is rapidly increasing for the management of various ocular surface disorders. Despite its numerous advantages,...
BACKGROUND
The use of human amniotic membrane transplantation is rapidly increasing for the management of various ocular surface disorders. Despite its numerous advantages, amniotic membrane is not widely available due to the lack of awareness among ophthalmologists regarding its preparation and preservation techniques.
PURPOSE
To provide an instructional video demonstrating the technique of harvesting, preparation, preservation of human amniotic membrane, and its uses in the management of ocular surface diseases.
SYNOPSIS
The amniotic membrane is the innermost layer of the human placenta. Properties of the amniotic membrane, like the presence of various growth factors, anti-inflammatory and anti-angiogenic factors, and its low immunogenicity, contribute to its ability to promote epithelial growth and differentiation with the reduction in fibrosis during healing. To harvest amniotic membrane, informed consent is obtained from a patient undergoing an elective caesarian section, and the donor is screened to exclude the risk of infections. Under sterile precautions, the amniotic membrane is separated from the chorion and washed free of blood clots. With the epithelial surface up, the amniotic membrane is spread uniformly without folds or tears on individually sterilized 0.22 μm nitrocellulose filter papers of the required sizes. The prepared filter paper with the adherent amniotic membrane is placed in freshly prepared Dulbecco's Modified Eagle's Medium and stored at -80°C. The amniotic membrane can be used for surgical procedures like symblepharon release, pterygium or dermoid excision, perforated ulcers, nonhealing epithelial defects, etc.
HIGHLIGHTS
Instructional videos demonstrating the preparation and preservation of amniotic membrane are very sparse. This video clearly explains how any ophthalmologist can learn to prepare and preserve the human amniotic membrane and gives a glimpse of its properties, advantages, and scope of use.
VIDEO LINK
https://youtu.be/8HfSjXUKoiY.
Topics: Pregnancy; Female; Humans; Amnion; Eye Diseases; Conjunctiva; Plastic Surgery Procedures; Pterygium
PubMed: 37530302
DOI: 10.4103/IJO.IJO_674_23 -
The Journal of Maternal-fetal &... Dec 2023Intra-amniotic infections increase the risk of preterm delivery and short- and long-term fetal morbidity; however, no consensus exists on the choice of antimicrobial...
OBJECTIVE
Intra-amniotic infections increase the risk of preterm delivery and short- and long-term fetal morbidity; however, no consensus exists on the choice of antimicrobial agents as treatment for these infections. We aimed to examine the efficacy of intravenous administration of sulbactam/ampicillin (SBT/ABPC) and azithromycin (AZM) for intra-amniotic infection in patients with preterm premature rupture of membranes (PPROM).
METHODS
This study followed a single-centered retrospective cohort design. We compared changes in interleukin 6 (IL-6) levels and the load of species DNA in the amniotic fluid between singleton pregnancy patients with intra-amniotic infection (Group A) and without either intra-amniotic inflammation (IAI) or microbial invasion of the amniotic cavity (MIAC) (Group B) who developed PPROM between week 22, day 0 and week 33, day 6 of gestation and maintained pregnancy for ≥7 d after diagnosis (August 2014 to April 2020). Patients in Group A were treated with SBT/ABPC and AZM, whereas those in Group B were treated with ABPC and AZM or clarithromycin.
RESULTS
Thirty-one patients with IAI and 48 patients without either IAI or MIAC at diagnosis of PPROM underwent pregnancy/delivery management at our hospital. Following the study population selection, we evaluated six patients in Group A and 13 patients in Group B. Amniotic fluid IL-6 concentrations at the initial amniocentesis were high, ranging from 11.7 ng/mL to 139.2 ng/mL, indicating a state of severe IAI in all six patients in Group A. In five of the six patients in Group A, the amniotic fluid cultures during the first amniocentesis included species only. In both groups, the amniotic fluid IL-6 concentration at the follow-up amniocentesis was lower than that at the initial amniocentesis (Group A: follow-up median 3.06 ng/mL [quartiles, 1.75-6.74], initial median 30.53 ng/mL [quartiles, 15.60-67.07], =.03; Group B: follow-up median 0.40 ng/mL [quartiles, 0.18-0.69], initial median 0.96 ng/mL [quartiles, 0.65-1.42], =.005); Group A showed a greater decrease than Group B ( < .001). No difference was found between the microbial loads of species DNA in the initial and follow-up amniocentesis ( = .13).
CONCLUSIONS
In patients with PPROM and intra-amniotic infection, IL-6 levels in the amniotic fluid decreased significantly from before antimicrobial administration to day 7. This decrease is thought to be mainly due to the effects of intravenous AZM. The efficacy of AZM in patients with PPROM needs to be further confirmed randomized controlled studies in the future.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Chorioamnionitis; Retrospective Studies; Premature Birth; Interleukin-6; Fetal Membranes, Premature Rupture; Anti-Bacterial Agents; Inflammation; Amniotic Fluid; Ureaplasma; DNA; Gestational Age
PubMed: 38016702
DOI: 10.1080/14767058.2023.2286189 -
Journal of Reproductive Immunology Aug 2023The pandemic linked to SARS-CoV-2 has profoundly disrupted the health systems and many studies have led to a better understanding of this virus, which is responsible for... (Review)
Review
The pandemic linked to SARS-CoV-2 has profoundly disrupted the health systems and many studies have led to a better understanding of this virus, which is responsible for severe disease, particularly during pregnancy. Pregnancy is a risk factor for severe COVID-19. Term of pregnancy and vaccination status is the main risk factor in addition to classic comorbidities like general population. COVID-19 during pregnancy is responsible for more maternal death, stillbirth, pre-eclampsia spontaneous and induced prematurity. Vaccination is therefore strongly recommended for pregnant patients. In addition, the COVID-19 pandemic has highlighted a psychological and social dimension that should not be neglected in the management of a pregnant patient. Correlation between immunological changes and clinical impact are described in this review. Many conclusions can now be made and are summarized in this article in order to discuss possible future research.
Topics: Pregnancy; Humans; Female; COVID-19; Obstetrics; SARS-CoV-2; Pandemics; Pregnancy Complications, Infectious; Pregnant Women; Premature Birth; Pregnancy Outcome
PubMed: 37390631
DOI: 10.1016/j.jri.2023.103981 -
Polymers Jul 2023Gel dressings, composed of polymers both natural and synthetic, are successfully used in the treatment of burn wounds. They protect the burn wound site against adverse...
Gel dressings, composed of polymers both natural and synthetic, are successfully used in the treatment of burn wounds. They protect the burn wound site against adverse external factors, ensure an adequate level of tissue hydration, have soothing and pain-relieving properties, and also support the healing process and reduce the risk of pathological scars. Another promising material that can be used in the wound-healing process is an amnion membrane. Due to its valuable properties such as protecting the body against bacterial infections and permeability to nutrition, it has found usage in different brands of medicine. In this work, we have combined the beneficial properties of hydrogels and amnion in order to make the laminar dressing that may serve for wound healing. For that purpose, the physically crosslinked cryogel of poly(vinyl alcohol) (PVA) was covered with an amnion membrane. Subsequently, gamma irradiation was performed, leading to the simultaneous internal crosslinking of the hydrogel, its permanent bonding with the amnion, and dressing sterilization. The physicochemical properties of the dressing including gel fraction, swelling, and hardness were studied. Biological tests such as the MTT assay, antimicrobial activity, and histopathological examination confirmed that the obtained material constituted a promising candidate for further, more in-depth studies aiming at wound dressing application.
PubMed: 37447600
DOI: 10.3390/polym15132955