Transcriptome sequencing of medical herb Salvia Rosmarinus (Rosemary) revealed the phenylpropanoid biosynthesis pathway genes and their phylogenetic relationships.

BACKGROUND: The Salvia rosmarinus spenn. (rosemary) is considered an economically important ornamental and medicinal plant and is widely utilized in culinary and for treating several diseases. However, the procedure behind synthesizing secondary metabolites-based bioactive compounds at the molecular level in S. rosmarinus is not explored completely. METHODS AND RESULTS: We performed transcriptomic sequencing of the pooled sample from leaf and stem tissues on the Illumina HiSeqTM X10 platform. The transcriptomics analysis led to the generation of 29,523,608 raw reads, followed by data pre-processing which generated 23,208,592 clean reads, and de novo assembly of S. rosmarinus obtained 166,849 unigenes. Among them, nearly 75.1% of unigenes i.e., 28,757 were interpreted against a non-redundant protein database. The gene ontology-based annotation classified them into 3 main categories and 55 sub-categories, and clusters of orthologous genes annotation categorized them into 23 functional categories. The Kyoto Encyclopedia of Genes and Genomes database-based pathway analysis confirmed the involvement of 13,402 unigenes in 183 biochemical pathways, among these unigenes, 1,186 are involved in the 17 secondary metabolite production pathways. Several key enzymes involved in producing aromatic amino acids and phenylpropanoids were identified from the transcriptome database. Among the identified 48 families of transcription factors from coding unigenes, bHLH, MYB, WRKYs, NAC, C2H2, C3H, and ERF are involved in flavonoids and other secondary metabolites biosynthesis. CONCLUSION: The phylogenetic analysis revealed the evolutionary relationship between the phenylpropanoid pathway genes of rosemary with other members of Lamiaceae. Our work reveals a new molecular mechanism behind the biosynthesis of phenylpropanoids and their regulation in rosemary plants.

Formulation, optimization, hemocompatibility and pharmacokinetic evaluation of PLGA nanoparticles containing paclitaxel.

OBJECTIVE: Paclitaxel (PTX)-loaded polymer (Poly(lactic-co-glycolic acid), PLGA)-based nanoformulation was developed with the objective of formulating cremophor EL-free nanoformulation intended for intravenous use. SIGNIFICANCE: The polymeric PTX nanoparticles free from the cremophor EL will help in eliminating the shortcomings of the existing delivery system as cremophor EL causes serious allergic reactions to the subjects after intravenous use. METHODS AND RESULTS: Paclitaxel-loaded nanoparticles were formulated by nanoprecipitation method. The diminutive nanoparticles (143.2 nm) with uniform size throughout (polydispersity index, 0.115) and high entrapment efficiency (95.34%) were obtained by employing the Box-Behnken design for the optimization of the formulation with the aid of desirability approach-based numerical optimization technique. Optimized levels for each factor viz. polymer concentration (X1), amount of organic solvent (X2), and surfactant concentration (X3) were 0.23%, 5 ml %, and 1.13%, respectively. The results of the hemocompatibility studies confirmed the safety of PLGA-based nanoparticles for intravenous administration. Pharmacokinetic evaluations confirmed the longer retention of PTX in systemic circulation. CONCLUSION: In a nutshell, the developed polymeric nanoparticle formulation of PTX precludes the inadequacy of existing PTX formulation and can be considered as superior alternative carrier system of the same.

Preparation, characterization, and in vivo evaluation of nano formulations of ferulic acid in diabetic wound healing.

Diabetes mellitus is most common disorder characterize by hyperglycemia. Chronic hyperglycemia may lead to over production of free radicals thereby results in oxidative stress which impaired healing of wounds. Ferulic acid (FA) has been shown to have antidiabetic and antioxidant properties. The aim of the present study was to develop Ferulic acid nanoparticles and to study its hypoglycemic and wound healing activities. Ferulic acid-poly(lactic-co-glycolic acid) (FA-PLGA) nanoparticles were prepared by nano precipitation method. The prepared FA-PLGA nanoparticles had an average size of 240 nm. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) analysis showed the prepared FA-PLGA nanoparticles were spherical in shape. Drug encapsulation assay showed that 88.49% FA was encapsulated in PLGA. Carbopol 980 was used to formulate FA-PLGA nanoparticles loaded hydrogel. FA-loaded polymeric nanoparticles dispersion (oral administration) and FA-loaded polymeric nanoparticles based hydrogel (topical administration) treated wounds were found to epithelize faster as compared with diabetic wound control group. The hydroxyproline content increased significantly when compared with diabetic wound control. Therefore, the results indicate that FA significantly promotes wound healing in diabetic rats.

Biobased Nanomaterials: Pioneering Innovations for Biomedical Advancements.

The purpose of this review article is to provide a complete overview of the fastdeveloping topic of biobased nanomaterials and the various uses that they have. An extensive study into the utilization of biological resources for nanotechnology has been motivated by the growing demand for materials that are both sustainable and favorable to the environment. In this review, the different uses of biobased nanomaterials across a variety of fields are investigated. When it comes to drug delivery systems, biosensors, nanocarriers, and catalysts, biobased nanomaterials are interesting choices because of their unique qualities. These properties include biocompatibility, programmable surface chemistry, and inherent functionality. Also, in the biomedical field, biobased nanomaterials offer promising prospects for revolutionizing medical diagnostics and therapies. Their biocompatibility, tunable surface chemistry, and inherent functionalities make them attractive candidates for applications such as targeted drug delivery, imaging contrast agents, and tissue engineering scaffolds. In addition, the study discusses the current difficulties and potential future developments in the industry, emphasizing the necessity of interdisciplinary collaboration and ongoing innovation. The incorporation of nanomaterials derived from biological sources into conventional applications holds tremendous potential for the advancement of sustainable development and provides solutions to global concerns. For the purpose of providing researchers, scientists, and professionals with a complete grasp of the synthesis, characterization, and applications of biobased nanomaterials, the purpose of this review is to serve as a helpful resource.

Natural products in the management of neurodegenerative diseases.

Neurodegenerative diseases represent one of the utmost imperative well-being health issues and apprehensions due to their escalating incidence of mortality. Natural derivatives are more efficacious in various preclinical models of neurodegenerative illnesses. These natural compounds include phytoconstituents in herbs, vegetables, fruits, nuts, and marine and freshwater flora, with remarkable efficacy in mitigating neurodegeneration and enhancing cognitive abilities in preclinical models. According to the latest research, the therapeutic activity of natural substances can be increased by adding phytoconstituents in nanocarriers such as nanoparticles, nanogels, and nanostructured lipid carriers. They can enhance the stability and specificity of the bioactive compounds to a more considerable extent. Nanotechnology can also provide targeting, enhancing their specificity to the respective site of action. In light of these findings, this article discusses the biological and therapeutic potential of natural products and their bioactive derivatives to exert neuroprotective effects and some clinical studies assessing their translational potential to treat neurodegenerative disorders.

The fetal cardiovascular response to increased placental vascular impedance to flow determined with 4-dimensional ultrasound using spatiotemporal image correlation and virtual organ computer-aided analysis.

OBJECTIVE: We sought to determine if increased placental vascular impedance to flow is associated with changes in fetal cardiac function using spatiotemporal image correlation and virtual organ computer-aided analysis. STUDY DESIGN: A cross-sectional study was performed in fetuses with umbilical artery pulsatility index >95th percentile (abnormal [ABN]). Ventricular volume (end-systole, end-diastole), stroke volume, cardiac output (CO), adjusted CO, and ejection fraction were compared to those of 184 normal fetuses. RESULTS: A total of 34 fetuses were evaluated at a median gestational age of 28.3 (range, 20.6-36.9) weeks. Mean ventricular volumes were lower for ABN than normal cases (end-systole, end-diastole) with a proportionally greater decrease for left ventricular volume (vs right). Mean left and right stroke volume, CO, and adjusted CO were lower for ABN (vs normal) cases. Right ventricular volume, stroke volume, CO, and adjusted CO exceeded the left in ABN fetuses. Mean ejection fraction was greater for ABN than normal cases. Median left ejection fraction was greater (vs right) in ABN fetuses. CONCLUSION: Increased placental vascular impedance to flow is associated with changes in fetal cardiac function.

Natural Products-based Drugs: Potential Drug Targets Against Neurological Degeneration.

Phytochemicals or natural products have been studied extensively for their potential in the treatment of neurodegenerative diseases (NDs) like Parkinson's disease, Alzheimer's disease, etc. The neuronal structure loss and progressive dysfunction are the main characteristics of these diseases. In spite of impressive and thorough knowledge of neurodegenerative molecular pathways, little advancement has been found in the treatment of the same. Moreover, it was proved that natural products can be used efficiently in the treatment of NDs while certain issues regarding the patient's safety and clinical data are still existing. As ND is a bunch of diseases and it will start the myriad of pathological processes, active targeting of the molecular pathway behind ND will be the most efficient strategy to treat all ND-related diseases. The targeting pathway must prevent cell death and should restore the damaged neurons. In the treatment of ND and related diseases, natural products are playing the role of neuroprotective agents. This review will target the therapeutic potential of various phytochemicals which shows neuroprotective action.

The Experiences of Black Community-Based Doulas as They Mitigate Systems of Racism: A Qualitative Study.

INTRODUCTION: Black pregnant individuals endure a disproportionate burden of preventable morbidity and mortality due to persistent, racially mediated social and systemic inequities. As patient advocates, Black community-based doulas help address these disparities via unique services not provided by conventional doulas. However, Black doulas themselves may encounter obstacles when providing care to Black perinatal clients. We characterized the barriers encountered by Black community-based doulas in Los Angeles, California. METHODS: We partnered with a Black community-based doula program to conduct semistructured interviews with its community doulas and program directors, covering the following topics: motivations for becoming a doula, services provided, and challenges faced as a Black doula in perinatal settings. Interview transcripts were reviewed via directed content analysis, with attention to the influence of systemic racism on service provision. Additionally, our research team used Camara Jones' Levels of Racism, which describes race-associated differences in health outcomes to code data. RESULTS: We interviewed 5 Black community-based doulas and 2 program directors, who all shared experiences of inequitable care and bias against Black clients that could be addressed with the support and advocacy of culturally congruent doulas. The community doulas shared experiences of stigma as Black doulas, compounded by racial prejudice. Interviewees noted sources of structural racism affecting program development, instances of interpersonal racism as they interacted with the health care system, and internalized racism that was revealed during culturally based doula trainings. Additionally, the doulas emphasized the importance of cultural concordance, or a shared identity with clients, which they considered integral to providing equitable care. CONCLUSION: Despite facing institutionalized, interpersonal, and internalized forms of racism, Black community-based doulas provide avenues for Black birthing individuals to navigate systemic racism experienced during the perinatal process. However, these forms of racism need to be addressed for Black community doulas to flourish.

Silibinin: an inhibitor for a high-expressed BCL-2A1/BFL1 protein, linked with poor prognosis in breast cancer.

Breast cancer (BC) accounts for 30% of all diagnosed cases of cancer in women and remains a leading cause of cancer-related deaths among women worldwide. The current study looks for a protein from the anti-apoptotic/pro-survival BCL-2 family whose overexpression reduces survivability in BC patients and a potential inhibitor for the protein. We found BCL-2A1/BFL1 protein with high expression linked to low survivability in BC. The protein shows prognosis in 8 out of 29 categories, whereas no other family member manifests this property. Out of 7379 compounds, three small molecules (CHEMBL9509, CHEMBL2104550 and CHEMBL3545011) form an H-bond with BCL-2A1/BFL1 protein's unique residue Cys55. Of the three small molecules, we found CHEMBL9509 (Silibinin) to be a potent inhibitor. The compound forms a stable H-bond with the residue Cys55 with the lowest binding energy compared to the other two compounds. It remains stable in the BH3 binding region for more than 100 ns, whereas the other two detach from the region. Additionally, the compound is found to be better than Venetoclax and Nematoclax. We firmly believe in the compound CHEMBL9509 potency to halt BC's progression by inhibiting the BCL-2A1/BFL1 protein, increasing patients' survivability.Communicated by Ramaswamy H. Sarma.

Multi-omics therapeutic perspective on ACVR1 gene: from genetic alterations to potential targeting.

Activin A receptor type I (ACVR1), a transmembrane serine/threonine kinase, belongs to the transforming growth factor-ß superfamily, which signals via phosphorylating the downstream effectors and SMAD transcription factors. Its central role in several biological processes and intracellular signaling is well known. Genetic variation in ACVR1 has been associated with a rare disease, fibrodysplasia ossificans progressive, and its somatic alteration is reported in rare cancer diffuse intrinsic pontine glioma. Furthermore, altered expression or variation of ACVR1 is associated with multiple pathologies such as polycystic ovary syndrome, congenital heart defects, diffuse idiopathic skeletal hyperostosis, posterior fossa ependymoma and other malignancies. Recent advancements have witnessed ACVR1 as a potential pharmacological target, and divergent promising approaches for its therapeutic targeting have been explored. This review highlights the structural and functional characteristics of receptor ACVR1, associated signaling pathways, genetic variants in several diseases and cancers, protein-protein interaction, gene expression, regulatory miRNA prediction and potential therapeutic targeting approaches. The comprehensive knowledge will offer new horizons and insights into future strategies harnessing its therapeutic potential.

Breast Cancer Therapeutics and Hippo Signaling Pathway: Novel MicroRNA-Gene-Protein Interaction Networks.

The Hippo signaling pathway is a master regulator of development, cell proliferation, and apoptosis in particular, and it plays an important role in tissue regeneration, controlling organ size, and cancer suppression. Dysregulation of the Hippo signaling pathway has been implicated in breast cancer, a highly prevalent cancer affecting 1 out of every 15 women worldwide. While the Hippo signaling pathway inhibitors are available, they are suboptimal, for example, due to chemoresistance, mutation, and signal leakage. Inadequate knowledge about the Hippo pathway connections and their regulators limits our ability to uncover novel molecular targets for drug development. We report here novel microRNA (miRNA)-gene and protein-protein interaction networks in the Hippo signaling pathway. We employed the GSE miRNA dataset for the present study. The GSE57897 dataset was normalized and searched for differentially expressed miRNAs, and their targets were searched using the miRWalk2.0 tool. From the upregulated miRNAs, we observed that the hsa-miR-205-5p forms the biggest cluster and targets four genes involved in the Hippo signaling pathway. Interestingly, we found a novel connection between two Hippo signaling pathway proteins, angiomotin (AMOT) and mothers against decapentaplegic homolog 4 (SMAD4). From the downregulated miRNAs, hsa-miR-16-5p, hsa-miR-7g-5p, hsa-miR-141-3p, hsa-miR-103a-3p, hsa-miR-21-5p, and hsa-miR-200c-3p, target genes were present in the pathway. We found that PTEN, EP300, and BTRC were important cancer-inhibiting proteins, form hubs, and their genes interact with downregulating miRNAs. We suggest that targeting proteins from these newly unraveled networks in the Hippo signaling pathway and further research on the interaction of hub-forming cancer-inhibiting proteins can open up new avenues for next-generation breast cancer therapeutics.

Unlocking the power of nanomedicine: the future of nutraceuticals in oncology treatment.

Cancer, an intricate and multifaceted disease, is characterized by the uncontrolled proliferation of cells that can lead to serious health complications and ultimately death. Conventional therapeutic strategies mainly target rapidly dividing cancer cells, but often indiscriminately harm healthy cells in the process. As a result, there is a growing interest in exploring novel therapies that are both effective and less toxic to normal cells. Herbs have long been used as natural remedies for various diseases and conditions. Some herbal compounds exhibit potent anti-cancer properties, making them potential candidates for nutraceutical-based treatments. However, despite their promising efficacy, there are considerable limitations in utilizing herbal preparations due to their poor solubility, low bioavailability, rapid metabolism and excretion, as well as potential interference with other medications. Nanotechnology offers a unique platform to overcome these challenges by encapsulating herbal compounds within nanoparticles. This approach not only increases solubility and stability but also enhances the cellular uptake of nutraceuticals, allowing for controlled and targeted delivery of therapeutic agents directly at tumor sites. By harnessing the power of nanotechnology-enabled therapy, this new frontier in cancer treatment presents an opportunity to minimize toxicity while maximizing efficacy. In conclusion, this manuscript provides compelling evidence for integrating nanotechnology with nutraceuticals derived from herbal sources to optimize cancer therapy outcomes. We explore the roadblocks associated with traditional herbal treatments and demonstrate how nanotechnology can help circumvent these issues, paving the way for safer and more effective cancer interventions in future oncological practice.

Nanomedicine: Innovative Strategies and Recent Advances in Targeted Cancer Therapy.

Nanomedicine's application of nanotechnology in medicine holds tremendous potential for diagnosing and treating life-threatening diseases such as cancer. Unlike conventional therapies, nanomedicine offers a promising strategy to enhance clinical outcomes while minimizing severe side effects. The principle of drug targeting enables specific delivery of therapeutic agents to their intended sites, making it a more precise and effective therapy. Combination strategies, such as the co-delivery of chemotherapeutic drugs with nucleic acids or receptor-specific molecules, are being employed to enhance therapeutic outcomes. Nanocarriers and drug delivery systems designed using these approaches offer resourceful co-delivery of therapeutic agents for anticancer therapy. Targeted drug delivery via nanotechnology-based techniques has become an urgent need and has shown significant improvements in therapeutic implications, pharmacokinetics, specificity, reduced toxicity, and biocompatibility. This review discusses the extrapolation of nanomaterials for developing innovative and novel drug delivery systems for effective anticancer therapy. Additionally, we explore the role of nanotechnology-based concepts in drug delivery research.

Celiac disease: Pathogenesis, disease management and new insights into the herbal-based treatments.

Celiac disease (CD) is a gluten intolerance autoimmune disorder which its symptoms involve the gastrointestinal tract and sometimes the other organs. It is one of the most prevalent health problems rising in many populations as statistics show that in every 100 people about one person is suffering from CD. It has been observed that the persons who genetically contain the human leukocyte antigen (HLA) DQ2 and HLA DQ8 genes involved in the immune system haplotypes are more prone to develop an allergy to gluten. The only treatment currently available for CD is a strict gluten-free diet. However, recent research has shown promising new insights into the herbal-based treatments of CD. New insight on CD is now offering various prospects to manage its treatment, diagnosis, and serving in the development of advanced therapies. Several herbs and botanical extracts have demonstrated anti-inflammatory, immunomodulatory, and gut-healing properties that make them potential candidates for the management of CD. Here, we provide an updated review on pathogeneses and managements of CD. In particular, we summarize the current understandings of herbal-based treatments for CD and highlights their potential benefits.

A Review on Natural Antioxidants for Their Role in the Treatment of Parkinson's Disease.

The neurodegenerative condition known as Parkinson's disease (PD) is brought on by the depletion of dopaminergic neurons in the basal ganglia, which is the brain region that controls body movement. PD occurs due to many factors, from which one of the acknowledged effects of oxidative stress is pathogenic pathways that play a role in the development of Parkinson's disease. Antioxidants, including flavonoids, vitamins E and C, and polyphenolic substances, help to reduce the oxidative stress brought on by free radicals. Consequently, this lowers the risk of neurodegenerative disorders in the long term. Although there is currently no cure for neurodegenerative illnesses, these conditions can be controlled. The treatment of this disease lessens its symptoms, which helps to preserve the patient's quality of life. Therefore, the use of naturally occurring antioxidants, such as polyphenols, which may be obtained through food or nutritional supplements and have a variety of positive effects, has emerged as an appealing alternative management strategy. This article will examine the extent of knowledge about antioxidants in the treatment of neurodegenerative illnesses, as well as future directions for research. Additionally, an evaluation of the value of antioxidants as neuroprotective agents will be provided.

Theoretical design for covering Engeletin with functionalized nanostructure-lipid carriers as neuroprotective agents against Huntington's disease via the nasal-brain route.

Objective: To propose a theoretical formulation of engeletin-nanostructured lipid nanocarriers for improved delivery and increased bioavailability in treating Huntington's disease (HD). Methods: We conducted a literature review of the pathophysiology of HD and the limitations of currently available medications. We also reviewed the potential therapeutic benefits of engeletin, a flavanol glycoside, in treating HD through the Keap1/nrf2 pathway. We then proposed a theoretical formulation of engeletin-nanostructured lipid nanocarriers for improved delivery across the blood-brain barrier (BBB) and increased bioavailability. Results: HD is an autosomal dominant neurological illness caused by a repetition of the cytosine-adenine-guanine trinucleotide, producing a mutant protein called Huntingtin, which degenerates the brain's motor and cognitive functions. Excitotoxicity, mitochondrial dysfunction, oxidative stress, elevated concentration of ROS and RNS, neuroinflammation, and protein aggregation significantly impact HD development. Current therapeutic medications can postpone HD symptoms but have long-term adverse effects when used regularly. Herbal medications such as engeletin have drawn attention due to their minimal side effects. Engeletin has been shown to reduce mitochondrial dysfunction and suppress inflammation through the Keap1/NRF2 pathway. However, its limited solubility and permeability hinder it from reaching the target site. A theoretical formulation of engeletin-nanostructured lipid nanocarriers may allow for free transit over the BBB due to offering a similar composition to the natural lipids present in the body a lipid solubility and increase bioavailability, potentially leading to a cure or prevention of HD. Conclusion: The theoretical formulation of engeletin-nanostructured lipid nanocarriers has the potential to improve delivery and increase the bioavailability of engeletin in the treatment of HD, which may lead to a cure or prevention of this fatal illness.

miR-210 targets iron-sulfur cluster scaffold homologue in human trophoblast cell lines: siderosis of interstitial trophoblasts as a novel pathology of preterm preeclampsia and small-for-gestational-age pregnancies.

This study was performed to assess the biological significance of miR-210 in preeclampsia and small-for-gestational-age (SGA) pregnancies. Placental miR-210 expression was evaluated by quantitative RT-PCR (RT-qPCR) in the following groups: i) appropriate-for-gestational-age pregnancies (n = 72), ii) preeclampsia (n = 52), iii) SGA (n = 66), and iv)preeclampsia with SGA (n = 31). The effects of hypoxia (1% O(2)) on miR-210 and iron-sulfur cluster scaffold homologue (ISCU) expressions and miR-210 binding to ISCU 3' UTR were examined in Swan 71 and BeWo cell lines. Perls' reaction (n = 229) and electron microscopy (n = 3) were conducted to verify siderosis of trophoblasts. miR-210 expression was increased in preeclampsia and SGA cases and was decreased with birth weight and gestational age. In both cell lines, miR-210 was induced by hypoxia, whereas ISCU expression was decreased. The luciferase assay confirmed miR-210 binding to ISCU mRNA 3' UTR. RNA interference knockdown of ISCU expression in Swan 71, but not in BeWo, cells resulted in autophagosomal and siderosomal iron accumulation and a fourfold decrease of Matrigel invasion (P = 0.004). Placental ISCU expression was decreased in preeclampsia (P = 0.002) and SGA (P = 0.002) cases. Furthermore, hemosiderin-laden trophoblasts were more frequent in the placental bed of preterm preeclampsia and/or SGA births than in control cases (48.7% versus 17.9%; P = 0.004). Siderosis of interstitial trophoblasts is a novel pathological feature of preeclampsia and SGA. The findings herein suggest that ISCU down-regulation by miR-210 perturbing trophoblast iron metabolism is associated with defective placentation.

Chronic chorioamnionitis displays distinct alterations of the amniotic fluid proteome.

Acute chorioamnionitis of infectious origin and chronic chorioamnionitis of immunological origin are two major placental lesions of spontaneous preterm birth with elevated amniotic fluid interleukin-6 and CXCL10 concentrations, respectively. The changes in the amniotic fluid proteome associated with intra-amniotic infection and acute chorioamnionitis are well defined, yet alterations unique to chronic chorioamnionitis remain to be elucidated. This study was conducted to determine those amniotic fluid proteins changing specifically in the presence of chronic chorioamnionitis. Amniotic fluid obtained from acute chorioamnionitis, chronic chorioamnionitis and gestational age-matched controls were analysed by two-dimensional (2D) difference in gel electrophoresis and MALDI-TOF analyses. The type of histological inflammation was used to define each condition in preterm labour cases (n = 125) and term not in labour cases (n = 22), and the amniotic fluid concentrations of interleukin-6, CXCL8, CXCL10 and prostaglandin F(2α) were also measured by specific immunoassays. Among preterm labour cases, 31 differentially expressed proteins were identified in chronic chorioamnionitis cases as compared to both acute chorioamnionitis and control cases. Importantly, glycodelin-A, which maintains maternal tolerance against an allogeneic fetus, was decreased in chronic chorioamnionitis, while haptoglobin was increased. We report the amniotic fluid proteome of chronic chorioamnionitis for the first time, and the findings herein strongly suggest that there is a pathophysiological association between the changes of immunomodulatory proteins in the amniotic fluid and chronic chorioamnionitis, a histological manifestation of maternal anti-fetal allograft rejection.

Surfactant protein-A as an anti-inflammatory component in the amnion: implications for human pregnancy.

The mechanism of mouse parturition is thought to involve myometrial infiltration by amniotic fluid (AF) macrophages, activated by surfactant protein-A (SP-A). In humans, the concentration of AF SP-A decreases during labor, and no fetal macrophages are found in the myometrium after labor. Therefore, it appears that the mechanisms of labor in mice and humans are different. We investigated a potential role for SP-A in human pregnancy and parturition by examining SP-A expression patterns in AF and amnion. High molecular mass (>250 kDa) oligomeric SP-A was increased in AF with advancing gestation. Interestingly, these oligomers were more abundant in placental amnion before labor at term, while they increased primarily in reflected amnion during labor (p < 0.05). Immunoblotting showed a binding of high molecular mass SP-A in AF to amnion. In C57BL/6 mice, oligomeric SP-A was also readily detected in AF from E15 onwards, but not in amnion. Macrophage density in mice myometrium did not change with advancing gestational age. Microarray analysis of human amnion explants incubated with SP-A revealed a molecular signature of inhibited cytokine-cytokine receptor interaction with downregulation of IL-1beta, CXCL2, and CXCL5 mRNA expression. The findings in this study strongly suggest that SP-A signals amniotic anti-inflammatory response via AF during pregnancy. We propose that an SP-A interaction among AF, placental amnion, and reflected amnion is a unique mechanism for immunoregulation in human pregnancy akin to that established in lung biology. However, AF SP-A and fetal macrophages by themselves do not seem to be exclusive effectors of parturition in humans.