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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. Common mechanisms, therapeutic targets, and molecular pathogenesis of neurodegeneration. It is focused on the biological and therapeutic potential of natural products and their bioactive derivatives to exert a neuroprotective effect on the pathologies of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Activin A receptor type I (ACVR1), a transmembrane serine/threonine kinase, belongs to the transforming growth factor-β 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. [ABSTRACT FROM AUTHOR]

Background: Extracts of medicinal plant like lemongrass offer a new choice for optional antimicrobial therapy against various oral microorganisms. The objective of this study was to assess, verify, and compare the antimicrobial effectiveness of locally administered 2% lemongrass gel and 10% doxycycline hyclate gel as an adjunct to scaling and root planing (SRP) in treating chronic periodontitis. Method: This is a double-blind parallel arm randomized controlled study. Forty subjects were randomly divided into Group A and B for 2% lemongrass gel and 10% doxycycline hyclate gel, respectively. The clinical assessments of Gingival Index (GI), Plaque Index (PI), Probing Pocket Depth (PPD), and Clinical Attachment Level (CAL) together with microbial colony counts for Porphyromonas gingivalis, Actinomyces naeslundii, and Prevotella intermedia were done at baseline, 1st month, and 3rd month follow-ups. Results: The results showed there was a significant reduction in the mean scores of GI, PPD, and CAL clinical indices from baseline to the 1st and 3rd month follow-ups in both the 2% lemongrass gel and 10% doxycycline gel groups (p < 0.05). Similarly, there was significant reduction in mean CFU scores for all periodontal pathogens from baseline to 1st and 3rd month follow-ups in both the 2% lemongrass gel and 10% doxycycline gel groups (p < 0.05). Conclusions: It could be concluded that the local delivery of 2% lemongrass gel as an adjunct to scaling and root planing is effective and comparable to 10% doxycycline gel in the treatment of chronic periodontitis. [ABSTRACT FROM AUTHOR]

Apoptosis, a major hallmark of cancer cells, regulates cellular fate and homeostasis. BCL-2 (B-cell CLL/Lymphoma 2) protein family is popularly known to mediate the intrinsic mode of apoptosis, of which MCL-1 is a crucial member. Myeloid cell leukemia 1 (MCL-1) is an anti-apoptotic oncoprotein and one of the most investigated members of the BCL-2 family. It is commonly known to be genetically altered, aberrantly overexpressed, and primarily associated with drug resistance in various human cancers. Recent advancements in the development of selective MCL-1 inhibitors and evaluating their effectiveness in cancer treatment establish its popularity as a molecular target. The overall aim is the selective induction of apoptosis in cancer cells by using a single or combination of BCL-2 family inhibitors. Delineating the precise molecular mechanisms associated with MCL-1-mediated cancer progression will certainly improve the efficacy of clinical interventions aimed at MCL-1 and hence patient survival. This review is structured to highlight the structural characteristics of MCL-1, its specific interactions with NOXA, MCL-1-regulatory microRNAs, and at the same time focus on the emerging therapeutic strategies targeting our protein of interest (MCL-1), alone or in combination with other treatments. • Myeloid cell leukemia 1 (MCL-1), an anti-apoptotic oncoprotein, possess several distinct structural characteristics. • Binding specificity between MCL-1 and NOXA, and associated mechanisms provide insights into MCL-1 inhibition. • Several microRNAs have emerged as potential regulators of MCL-1 mRNA expression. • MCL-1-targeting PROTACs have emerged as an innovative strategy for targeted protein degradation and inhibition. • Combination therapies and dual inhibitors of MCL-1 might help in overcoming resistance to pan-BCL-2 inhibitors. [ABSTRACT FROM AUTHOR]

Dendrimers are nanosized, symmetrical molecules in which a small atom or group of atoms is surrounded by the symmetric branches known as dendrons. The structure of dendrimers possesses the greatest impact on their physical and chemical properties. They grow outwards from the core-shell which further reacts with monomers having one reactive or two dormant molecules. Dendrimers' unique characteristics such as hyperbranching, well-defined spherical structure, and high compatibility with the biological systems are responsible for their wide range of applications including medical and biomedical areas. Particularly, the dendrimers' three-dimensional structure can incorporate a wide variety of drugs to form biologically active drug conjugates. In this review, we focus on the synthesis, mechanism of drug encapsulations in dendrimers, and their wide applications in drug delivery. [ABSTRACT FROM AUTHOR]

Quercetin (Qu), is a flavonoid known to have anti-diabetic effects owing to its antioxidant property, thus promoting regeneration of the pancreatic islets, ultimately increasing insulin secretion. But the therapeutic application of Qu is hampered by its low oral bioavailability and its unfavourable physicochemical characteristics. The present work aimed at formulation of Quercetin loaded Soluplus® micelles (SMs) so as to enhance its bioavailability and provide prolonged release for the management of diabetes. Box-Behnken response surface methodology was employed to optimize the formulation prepared using co-solvent evaporation method. Physicochemical characterization confirmed the nano-spherical nature of Quercetin loaded Soluplus® micelles (Qu-SMs) with average particle size ranging from 85-108nm, encapsulation efficiency of 63-77%. Solid state characterization confirmed the encapsulation of Qu in the micelles without any incompatibilities. Moving forward, the results of in vitro study revealed prolonged and slow release of Qu from the developed formulations. The in vivo pharmacokinetic study revealed improved bioavailability by enveloping the drug in SMs. Moreover, the study performed to evaluate the efficiency in diabetes treatment revealed an enhanced anti-diabetic effect. Thus, Qu-SMs can serve as potential carriers aimed at improving the anti-diabetic property of Qu. [ABSTRACT FROM AUTHOR]

This research was motivated due to substantial requirement of improved treatment for breast cancer which accounts for over 0.52 million deaths annually worldwide. Utilizing nanoparticles carrying active medicaments as targeted delivery carrier is emerging as a promising approach. For a drug to be clinically effective, it needs to be suitably protected in the biological fluid till it is delivered to the targeted site. Keeping above in mind, we prepared and optimized polymeric nanoparticles by polyhydroxybutyrate-co-hydroxyvalerate (PHBV) a biodegradable polymer utilizing modified emulsification solvent evaporation method. The optimized formulation had particle size of 349 ± 3.51 nm with entrapment efficiency of 69 ± 1.28%. Nanoparticle formation and its surface morphology were confirmed by various electron microscopes. The in vitro and pharmacokinetic studies demonstrated a sustained release of drug in a non-biological system and into rat's bloodstream respectively. Also, the in vitro cytotoxicity and in vivo toxicological evaluation at the therapeutic dose demonstrated the safety and antitumor efficacy of the formulation. Due to formulation characteristic properties, it was found to be effective in enveloping and chaperoning the drug to the suitable site of action. The PHBV-TPGS combination causes the drug to be released in controlled and sustained modes, thereby reducing drug dose and toxicity. [ABSTRACT FROM AUTHOR]

Long-circulating nanoparticles (NPs) are promising drug delivery vehicles which target solid tumors via enhanced permeation and retention effect. Plackett–Burman (PBD) and Box–Behnken (BBD) designs were adopted to study the effects of factors viz. polymer concentration, surfactant concentration, homogenizer speed, homogenization time and ultrasonication time on responses. A graphical and numerical optimization technique was used to obtain predicted value of the response. The drug entrapment efficiency was approximately 39 ± 0.85%. The particle size of the nanoparticles was found to be 260 ± 2.85 nm, while the zeta potential was −18 ± 2.12 mV, indicating more stable particles. SEM, TEM, and AFM were used for characterization of surface morphology and the physicochemical characters of NPs. A pharmacokinetic evaluation carried out intravenous administration in healthy Charles Foster rats displayed enhanced systemic bioavailability and plasma drug concentration. The in vivo-in silico assessment by GastroPlus™ showed good prediction accuracy and presented best-fit model. Nanoparticles were also studied for stability testing and were found to be stable concerning their drug content and physical characters. In vitro cytotoxicity was assessed using MCF-7 for percentage inhibition of human breast cancer cell line. Anticancer studies of optimized NPs showed a significant increase in efficacy as observed by relative tumor volume up to 30 days. [ABSTRACT FROM AUTHOR]

In the present research an attempt was made to develop and optimize docetaxel-loaded polyhydroxybutyrate- co -hydroxyvalerate (PHBV) nanoparticles, using modified emulsification solvent evaporation technique and design of experiment (DOE) methodology. Formulation of docetaxel-loaded PHBV nanoparticles was conducted by factor screening studies with Plackett-Burman design (PBD) followed by Box-Behnken experimental design (BBD) to evaluate the effect of independent variables on responses. Five most important independent variables were screened out, which were obtained from failure mode effect analysis (FMEA) and factor screening studies. The effect of formulation parameters on selected responses was depicted by 2-D and 3-D response surface methodology (RSM). The final optimized batch was evaluated by various in vitro characterizations. The observed particle size, zeta potential and entrapment efficiency of optimized formulation was found to be 283 ± 2.79 nm, − 17 ± 2.64 mV and 44 ± 0.59% respectively. Morphological studies demonstrated the smooth and spherical shape of nanoparticles. In vitro drug release follows the Peppas-Korsmeyer model of drug release kinetics. Cytotoxicity study was assessed using MCF-7 for percentage inhibition of human breast cancer cell line. These results indicate that the PHBV Nanoparticles could be a promising drug delivery system for efficient prolong drug release. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Chronic diseases such as hypertension, diabetes, and obesity pose unique reproductive challenges for women. Preconception health results in improved reproductive outcomes. We designed an interventional study testing the use of a reproductive life plan to improve knowledge of preconception and contraception health in women with chronic diseases. Methods: Primarily underserved, English- and Spanish-speaking women aged 18 to 40 years with active diabetes, hypertension, or obesity were recruited. We developed a revised reproductive life plan specific to these diseases. Two resident physicians performed reproductive plan counseling. Pre- and postcounseling surveys were administered to evaluate knowledge and attitudes about chronic disease and the effects on a potential pregnancy. Results: Twenty-seven women (average age = 31 years) were surveyed. Of the subjects, 85.2% were obese, 29.6% had hypertension, and 7.4% had diabetes. Significant increases were reported in understanding risks of pregnancy associated with diabetes (p < 0.001), hypertension (p < 0.001), and obesity (p < 0.01). After counseling, women increased their knowledge about a reproductive plan (p < 0.001) and increased support and information to make reproductive health choices (p = 0.001 and p < 0.01, respectively). The largest improvements in postcounseling variables occurred in women with the lowest precounseling test scores and in women without children. Conclusion: A reproductive life plan is a brief, cost-effective preconception and contraception counseling tool in the primary care setting for women with chronic diseases. This tool increases knowledge about reproductive health and enables women with chronic diseases to make informed decisions about their reproductive future. [ABSTRACT FROM AUTHOR]

Objectives: In vitro preparations have provided evidence suggesting that acute and chronic exposure to very high glucose concentrations can lead to embryonic demise via disruption of the extra-celomic membranes and yolk sac. In this study, we sought to determine, in vivo, if an acute increase in extra-embryonic fluid glucose concentration could cause spontaneous abortion. Materials and methods: We employed a pregnant non-human primate model and ultrasound-guided celocentesis at 38-42 days from conception. In three control animals, partial replacement of the extra-embryonic celomic fluid was performed using normal saline containing 0.6 mg/mL of glucose. In four study animals, the extra-celomic fluid was replaced with a similar solution containing high glucose concentrations. All animals were then followed until delivery. Results: Immediately after celocentesis, the estimated celomic fluid glucose concentration in experimental animals ranged between 5 mg/mL and 83.8 mg/mL (8-140 times the physiologic glucose concentration of 0.6 mg/mL). All animals delivered live newborns at term without congenital abnormalities. Conclusions: These findings suggest that transitory increases in the extra-celomic fluid glucose concentration are not likely to cause a spontaneous abortion detectable with the sample size of our study. [ABSTRACT FROM AUTHOR]

Aims: To characterize the transcriptome of human myometrium during spontaneous labor at term. Methods: Myometrium was obtained from women with (n=19) and without labor (n=20). Illumina® HumanHT-12 microarrays were utilized. Moderated t-tests and false discovery rate adjustment of P-values were applied. Real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was performed for a select set of differentially expressed genes in a separate set of samples. Enzyme-linked immunosorbent assay and Western blot were utilized to confirm differential protein production in a third sample set. Results: 1) Four hundred and seventy-one genes were differentially expressed; 2) gene ontology analysis indicated enrichment of 103 biological processes and 18 molecular functions including: a) inflammatory response; b) cytokine activity; and c) chemokine activity; 3) systems biology pathway analysis using signaling pathway impact analysis indicated six significant pathways: a) cytokine-cytokine receptor interaction; b) Jak-STAT signaling; and c) complement and coagulation cascades; d) NOD-like receptor signaling pathway; e) systemic lupus erythematosus; and f) chemokine signaling pathway; 4) qRT-PCR confirmed over-expression of prostaglandin-endoperoxide synthase-2, heparin binding epidermal growth factor (EGF)-like growth factor, chemokine C-C motif ligand 2 (CCL2/MCP1), leukocyte immunoglobulin-like receptor, subfamily A member 5, interleukin (IL)-8, IL-6, chemokine C-X-C motif ligand 6 (CXCL6/GCP2), nuclear factor of kappa light chain gene enhancer in B-cells inhibitor zeta, suppressor of cytokine signaling 3 (SOCS3) and decreased expression of FK506 binding-protein 5 and aldehyde dehydrogenase in labor; 5) IL-6, CXCL6, CCL2 and SOCS3 protein expression was significantly higher in the term labor group compared to the term not in labor group. Conclusions: Myometrium of women in spontaneous labor at term is characterized by a stereotypic gene expression pattern consistent with over-expression of the inflammatory response and leukocyte chemotaxis. Differential gene expression identified with microarray was confirmed with qRT-PCR using an independent set of samples. This study represents an unbiased description of the biological processes involved in spontaneous labor at term based on transcriptomics. [ABSTRACT FROM AUTHOR]

Objective. Aquaporin 9 (AQP9) is a water channel protein characterized by its high permeability to nutrients such as lactate and glycerol, as well as urea and other small solutes. These unique properties of AQP9 suggest that this molecule may play a role in the modulation of nutrient flux through the fetal membranes in conditions associated with increased metabolic demand, such as spontaneous labor and inflammation. The objective of this study was to determine the expression of AQP9 in the chorioamniotic membranes from women with and without term labor, as well as those with preterm prelabor rupture of membranes (PPROM) with and without histologic chorioamnionitis. Study design. A cross-sectional study was performed which included patients in the following groups: (1) term not in labor (TNL; n = 14); (2) term, spontaneous labor ( n = 14); and (3) PPROM with ( n = 20) and without ( n = 17) histologic chorioamnionitis. AQP9 mRNA expression in fetal membranes was quantified using quantitative real-time reverse transcription-polymerase chain reaction and analyzed with a linear model including gestational age as a covariate. Results. (1) AQP9 mRNA expression was identified in all chorioamniotic membrane specimens; (2) AQP9 expression in fetal membranes was significantly higher in spontaneous term labor when compared with TNL (fold change 3.6; p = 0.01); and (3) Among patients with PPROM, the presence of histologic chorioamnionitis was associated with a higher expression of AQP9 in the chorioamniotic membranes compared with those from women without histologic chorioamnionitis (fold change 8.7; p < 0.001). Conclusion. Aquaporin 9 mRNA expression is higher in the fetal membranes from patients with spontaneous term labor and those with PPROM and histologic chorioamnionitis. These findings are novel, and suggest a role for aquaporin 9 in membrane-mediated transfer of nutrients to support the increased metabolic demands associated with the host immune response of the terminal pathway of parturition and histologic chorioamnionitis. [ABSTRACT FROM AUTHOR]

Problem CXCL6 is a potent pro-inflammatory neutrophil chemoattractant and activator whose activity during pregnancy is not well-established. The purpose of this study was to determine if CXCL6 is present in amniotic fluid (AF) and if CXCL6 concentrations in AF change with labor (pre-term and term) or intra-amniotic infection/inflammation (IAI). Method of study A cross-sectional study was designed including the following groups: (1) mid-trimester ( n = 65); (2) term no labor ( n = 20); (3) term labor ( n = 44); (4) patients with pre-term labor (PTL) with subsequent term delivery ( n = 57); (5) PTL without IAI who delivered pre-term ( n = 47); and (6) PTL with IAI ( n = 62). AF CXCL6 concentrations were determined by ELISA. Results CXCL6 was present in all term samples, but undetectable in 64/65 mid-trimester specimens. Patients with PTL and IAI had a significantly higher median AF CXCL6 concentration than those with PTL without IAI [228.9 pg/mL (0.0–8344.8) versus 55.7 pg/mL (0–454.4); P < 0.05] and those with PTL and term delivery [41.5 pg/mL (0–279.0); P < 0.05]. The median AF CXCL6 concentration did not change with spontaneous term labor [term no labor: 81.1 pg/mL (8.5–201.7) versus term labor: 75.2 pg/mL (6.7–378.7): P = 0.7]. Conclusion (1) CXCL6 is detectable in AF and its concentration increases with gestational age; (2) IAI results in increased AF CXCL6 concentrations, suggesting that CXCL6 plays a role in the deployment of an inflammatory response; (3) In contrast to related chemokines, specifically IL-8, AF CXCL6 does not appear to be involved in spontaneous term parturition. These observations are novel, and suggest a role for CXCL6 in the innate immune response to microbial invasion of the amniotic cavity. [ABSTRACT FROM AUTHOR]

Objectives: Placental growth hormone (PGH) is a pregnancy-specific protein produced by syncytiotrophoblast and extravillous cytotrophoblast. No other cells have been reported to synthesize PGH Maternal. PGH Serum concentration increases with advancing gestational age, while quickly decreasing after delivery of the placenta. The biological properties of PGH include somatogenic, lactogenic, and lipolytic functions. The purpose of this study was to determine whether the maternal serum concentrations of PGH change in women with preeclampsia (PE), women with PE who deliver a small for gestational age neonate (PE + SGA), and those with SGA alone.Study Design: This cross-sectional study included maternal serum from normal pregnant women (n = 61), patients with severe PE (n = 48), PE + SGA (n = 30), and SGA alone (n = 41). Fetal cord blood from uncomplicated pregnancies (n = 16) and PE (n = 16) was also analyzed. PGH concentrations were measured by ELISA. Non-parametric statistics were used for analysis.Results: (1) Women with severe PE had a median serum concentration of PGH higher than normal pregnant women (PE: median 23,076 pg/mL (3473-94 256) vs. normal pregnancy: median 12 157 pg/mL (2617-34 016); p < 0.05), pregnant women who delivered an SGA neonate (SGA: median 10 206 pg/mL (1816-34 705); p < 0.05), as well as pregnant patients with PE and SGA (PE + SGA: median 11 027 pg/mL (1232-61 702); p < 0.05). (2) No significant differences were observed in the median maternal serum concentration of PGH among pregnant women with PE and SGA, SGA alone, and normal pregnancy (p > 0.05). (3) Compared to those of the control group, the median umbilical serum concentration of PGH was significantly higher in newborns of preeclamptic women (PE: median 356.1 pg/mL (72.6-20 946), normal pregnancy: median 128.5 pg/mL (21.6-255.9); p < 0.01). (4) PGH was detected in all samples of cord blood.Conclusions: (1) PE is associated with higher median concentrations of PGH in both the maternal and fetal circulation compared to normal pregnancy. (2) Patients with PE + SGA had lower maternal serum concentrations of PGH than preeclamptic patients without SGA. (3) Contrary to previous findings, PGH was detectable in the fetal circulation. The observations reported herein are novel and suggest that PGH may play a role in the mechanisms of disease in preeclampsia and fetal growth restriction. [ABSTRACT FROM AUTHOR]

Cytochrome P450s (CYPs) are a versatile group of enzymes and one of the largest families of proteins, controlling various physiological processes via biosynthetic and detoxification pathways. CYPs perform multiple roles through a critical irreversible enzymatic reaction in which an oxygen atom is inserted within hydrophobic molecules, converting them into the reactive and hydro soluble components. During evolution, plants have acquired significantly more number of CYPs and represent about 1% of the encoded genes. CYPs are highly conserved proteins involved in growth, development and tolerance against biotic and abiotic stresses. Furthermore, CYPs reinforce plants' molecular and chemical defense mechanisms by regulating the biosynthesis of secondary metabolites, enhancing reactive oxygen species (ROS) scavenging and controlling biosynthesis and homeostasis of phytohormones, including abscisic acid (ABA) and jasmonates. Thus, they are the critical targets of metabolic engineering for enhancing plant defense against environmental stresses. Additionally, CYPs are also used as biocatalysts in the fields of pharmacology and phytoremediation. Herein, we highlight the role of CYPs in plant stress tolerance and their applications for human welfare. [ABSTRACT FROM AUTHOR]

The objective of the present study was to explore the anti-acne activity of herbal drug extracts of curcumin by making complexes with varying concentrations of soya lecithin using the phase inversion technique. The preformulation studies were performed and indicated that using the resultant formulation FIM4 shows the maximum potency outcomes. The characterization and evaluation were carried using Fourier Transform Infrared Spectroscopy (FTIR) and using various parameters such as appearance, texture, pH determination, viscosity, spreadability, stability, drug content, saponification value, irritation, antibacterial activity and in vitro diffusion. From the study, it was concluded that the optimized formulation FIM4 show the best resulting potency with antimicrobial properties. [ABSTRACT FROM AUTHOR]

The article focuses on a study which described the use of a parent-centered group-care model in providing well-child care. The Centering Parenting model emphasizes continuing positive support by valuing achievements within groups started during pregnancy. Three residents participated in this study. Results of the study showed that there was significant improvement in physicians' skills and knowledge. The study also observed closer relationships between patients and physicians.

Presents the poem "Pale Green," by Pooja Mittal. First Line: Here in the rainy season; Last Line: Tomorrow...

Presents the poem "Drought Relief," by Pooja Mittal. First Line: she carries her thighs; Last Line: it was.

An open wound is highly susceptible to microbial infection leading to elevated level of inflammatory response. For prompt healing, a wound requires a biomimetic dressing material with ideal hydrophilicity and tensile strength, possessing antimicrobial and antioxidant property. Although PCL-based nanofibers have sufficient tensile strength and biocompatibility, it lacks in terms of optimum hydrophilicity and biodegradation. Therefore, we fabricated a PCL-gelatin based electrospun nanofibers, enriched with quercetin and ciprofloxacin hydrochloride (CH). The average diameter of developed nanofibers was 725.943 ± 201.965 nm, and devoid of chemical interaction between two drugs and polymers. CH and quercetin exhibited biphasic in-vitro release in phosphate buffer (pH 7.4). The in-vitro antibacterial and antioxidant property of scaffolds were evaluated by film-diffusion against Staphylococcus aureus and DPPH assay, respectively. The addition of gelatin along with CH and quercetin enhanced the hydrophilicity (contact angle = 48.8 ± 2.95°) and biodegradation rate of the nanofibers. In-vitro biocompatibility of scaffold was examined by hemocompatibility and fibroblast viability using MTT assay. The results confirm the direct application of scaffold in the wounded area. Further, complete closure of full-thickness wound within 16 days, and regulation of hydroxyproline, SOD and catalase level in granulation tissues following treatment with scaffold, confirmed its application for accelerated wound healing. [ABSTRACT FROM AUTHOR]

Plant‐derived protease inhibitors (PIs) are a promising defensin for crop improvement and insect pest management. Although agronomist made significant efforts in utilizing PIs for managing insect pests, the potentials of PIs are still obscured. Insect ability to compensate nutrient starvation induced by dietary PI feeding using different strategies, that is, overexpression of PI‐sensitive protease, expression of PI‐insensitive proteases, degradation of PI, has made this innumerable collection of PIs worthless. A practical challenge for agronomist is to identify potent PI candidates, to limit insect compensatory responses and to elucidate insect compensatory and resistance mechanisms activated upon herbivory. This knowledge could be further efficiently utilized to identify potential targets for RNAi‐mediated pest control. These vital genes of insects could be functionally annotated using the advanced gene‐editing technique, CRISPR/Cas9. Contemporary research is exploiting different in silico and modern molecular biology techniques to utilize PIs in controlling insect pests efficiently. This review is structured to update recent advancements in this field, along with its chronological background. [ABSTRACT FROM AUTHOR]

Microbial infection and oxidative damage of the fibroblast often results in prolonged and incomplete wound healing. Therefore, there is an increasing demand for a scaffold being effective to prevent any possible infection and neutralize excessively released free radicals. Herein, we designed a PCL-based nanofiber loaded with ciprofloxacin hydrochloride (CHL) and quercetin. Developed nanofiber showed the formation of smooth and continuous nanofiber with 101.59 ± 29.18 nm average diameter and entrapping the drugs in amorphous form without any possible physico-chemical interaction between drugs and excipient. High entrapment efficiency (CHL: 92.04% and Que: 94.32%) and prolonged in-vitro release (for 7 days) demonstrated the capability of scaffold to suppress any probable infection and oxidative damage, which was further confirmed by in-vitro antibacterial and antioxidant activity. The biocompatibility of scaffold for direct application to wound site was evaluated through hemocompatibility and cytocompatibility assay. The wound healing efficacies of nanofiber were assessed using full thickness wound model in rats, which displayed accelerated wound healing with complete re-epithelialization and improved collagen deposition within 16 days. In-vivo wound healing finding was further corroborated by SOD, catalase, and hydroxyproline assay. The current study validates the application of ciprofloxacin HCl and quercetin functionalized nanofiber as a potential wound dressing material. [ABSTRACT FROM AUTHOR]

In at least one case without a third-trimester test, the patient was confirmed as having HIV and the newborn was found to have HIV at birth. In another 31 cases (24%), testing was done in addition to first- and third-trimester screening, often in the absence of acute HIV symptoms or ongoing HIV risk factors. The provision of rapid HIV testing for women who present to the labor and delivery unit with inadequate prenatal HIV testing has been a critical public health intervention. [Extracted from the article]

Objective: We aimed to determine the differences in the pattern and magnitude of thrombin generation between patients with preeclampsia (PE) and those with a small-for-gestational-age (SGA) fetus.Methods: This cross-sectional study included women in the following groups: (1) normal pregnancy (NP) (n = 49); (2) PE (n = 56); and (3) SGA (n = 28). Maternal plasma thrombin generation (TGA) was measured, calculating: (a) lag time (LT); (b) velocity index (VI); (c) peak thrombin concentration (PTC); (d) time-to-peak thrombin concentration (TPTC); and (e) endogenous thrombin potential (ETP).Results: (1) The median TPTC, VI, and ETP differed among the groups (p = .001, p = .006, p < .0001); 2) the median ETP was higher in the PE than in the NP (p < .0001) and SGA (p = .02) groups; 3) patients with SGA had a shorter median TPTC and a higher median VI than the NP (p = .002, p = .012) and PE (p < .0001, p = .006) groups.Conclusions: (1) Patients with PE had higher in vivo thrombin generation than women with NP and those with an SGA fetus; (2) the difference in TGA patterns between PE and SGA suggests that the latter group had faster TGA, while patients with PE had a longer reaction, generating more thrombin. This observation is important for the identification of a subset of patients who might benefit from low molecular-weight heparin. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to determine whether the activity of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in the plasma of women with preeclampsia (PE) and small for gestational age (SGA) neonate differ from that of normal pregnant women and whether they are related to specific placental lesions.Methods: This cross-sectional study included the following groups: (1) normal pregnancy (n = 68); (2) PE (n= 128); and (3) SGA (n = 56). Maternal plasma TF and TFPI activity was determined with chromogenic assays.Results: (1) The median maternal plasma TF activity, but not TFPI activity, differed among the study groups (p < .0001 and p = .4, respectively); (2) patients with PE had a higher median maternal plasma TF activity than women with normal pregnancies (p < .0001) and mothers with SGA fetuses (p = .002); (3) among patients with PE, those with distal villous hypoplasia had a higher median maternal TF activity than those without these placental lesions (p = .018); and (4) following adjustment for confounding variables, maternal plasma TF and TFPI activity were not associated with an SGA neonate.Conclusions: Plasma TF activity is higher in women with PE than in those with SGA or normal pregnancies. We propose that these changes may be responsible, at least in part, for the increased in-vivo thrombin generation observed in this obstetrical syndrome. [ABSTRACT FROM AUTHOR]

Citation Xu Y, Tarquini F, Romero R, Kim CJ, Tarca AL, Bhatti G, Lee J, Sundell IB, Mittal P, Kusanovic JP, Hassan SS, Kim J-S. Peripheral CD300a+CD8+ T lymphocytes with a distinct cytotoxic molecular signature increase in pregnant women with chronic chorioamnionitis. Am J Reprod Immunol 2012; 67: 184-197 Problem CD300a is an immunomodulatory molecule of the immunoglobulin receptor superfamily expressed in the leukocytes of myeloid and lymphoid lineages. However, its biological function on CD8+ T lymphocytes remains largely unknown. This study was conducted to assess the biological significance of CD300a expression in T lymphocytes and to determine whether its expression in peripheral T lymphocytes changes in pregnant women presenting with antifetal rejection. Methods of Study Microarray analysis was performed using total RNA isolated from peripheral CD300a+ and CD300a− T lymphocytes. Flow cytometric analysis of the peripheral blood samples of pregnant women and pathologic examination of the placentas were conducted. Results A large number of genes ( N = 1245) were differentially expressed between CD300a− and CD300a+ subsets of CD8+ T lymphocytes, which included CCR7, CD244, CX3CR1, GLNY, GZMB, GZMK, IL15, ITGB1, KLRG1, PRF1, and SLAMF7. Gene ontology analysis of differentially expressed genes demonstrated enrichment of biological processes such as immune response, cell death, and signal transduction. CD300a expression in CD8+ T lymphocytes was coupled to a more cytotoxic molecular signature. Of note, the proportion of CD300a+CD8+ T lymphocytes increased in pregnant women with chronic chorioamnionitis (antifetal rejection of the chorioamniotic membranes; P < 0.05). Conclusion The findings of this study strongly suggest an increase in systemic T-lymphocyte-mediated cytotoxicity in pregnant women with chronic chorioamnionitis as a manifestation of maternal antifetal rejection. [ABSTRACT FROM AUTHOR]

Lee J, Romero R, Dong Z, Xu Y, Qureshi F, Jacques S, Yoo W, Chaiworapongsa T, Mittal P, Hassan S S & Kim C J (2011) Histopathology 59, 928-938 Unexplained fetal death has a biological signature of maternal anti-fetal rejection: chronic chorioamnionitis and alloimmune anti-human leucocyte antigen antibodies Aims: Chronic chorioamnionitis is a histological manifestation of maternal anti-fetal cellular rejection. As failure of graft survival is the most catastrophic event in organ transplantation, we hypothesized that fetal death could be a consequence of maternal rejection. The aim of this study was to assess whether there is evidence of cellular and antibody-mediated rejection in fetal death. Methods and results: Placental histology was reviewed for the presence of chronic chorioamnionitis in unexplained preterm fetal death ( n = 30) and preterm live birth ( n = 103). Amniotic fluid CXCL10 concentrations were measured with a specific immunoassay. Chronic chorioamnionitis was more frequent in fetal death than in live birth (60.0% versus 37.9%; P < 0.05) and fetal death had a higher median amniotic fluid CXCL10 concentration than live birth (2.0 versus 1.8 ng/ml, P < 0.05), after adjusting for gestational age at amniocentesis. Maternal anti-human leucocyte antigen class II panel-reactive seropositivity determined by flow cytometry was higher in fetal death compared to live birth (35.7% versus 10.9%; P < 0.05). Conclusions: Chronic chorioamnionitis is a common pathologic feature in unexplained preterm fetal death. This novel finding suggests that cellular and antibody-mediated anti-fetal rejection of the mother is associated with fetal death (graft failure) in human pregnancy. [ABSTRACT FROM AUTHOR]

Objective. Women with a fetal death at the time of diagnosis have higher maternal plasma concentrations of the anti-angiogenic factor, soluble vascular endothelial growth factor receptor (sVEGFR)-1, than women with a normal pregnancy. An important question is whether these changes are the cause or consequence of fetal death. To address this issue, we conducted a longitudinal study and measured the maternal plasma concentrations of selective angiogenic and anti-angiogenic factors before the diagnosis of a fetal death. The anti-angiogenic factors studied were sVEGFR-1 and soluble endoglin (sEng), and the angiogenic factor, placental growth factor (PlGF). Methods. This retrospective longitudinal nested case-control study included 143 singleton pregnancies in the following groups: (1) patients with uncomplicated pregnancies who delivered a term infant with an appropriate weight for gestational age ( n = 124); and (2) patients who had a fetal death ( n = 19). Blood samples were collected at each prenatal visit, scheduled at 4-week intervals from the first trimester until delivery. Plasma concentrations of sVEGFR-1, sEng, and PlGF were determined by specific and sensitive ELISA. A linear mixed-effects model was used for analysis. Results. (1) The average profiles of analyte concentrations as a function of gestational age for sVEGFR-1, sEng and PlGF were different between women destined to have a fetal death and those with a normal pregnancy after adjusting for covariates ( p < 0.05); (2) Plasma sVEGFR-1 concentrations in patients destined to have a fetal death were significantly lower between 7 and 11 weeks of gestation and became significantly higher than those of women with a normal pregnancy between 20 and 37 weeks of gestation ( p < 0.05); (3) Similarly, plasma sEng concentrations of women destined to have a fetal death were lower at 7 weeks of gestation ( p = 0.04) and became higher than those of controls between 20 and 40 weeks of gestation ( p < 0.05); (4) In contrast, plasma PlGF concentrations were higher among patients destined to develop a fetal death between 7 and 14 weeks of gestation and became significantly lower than those in the control group between 22 and 39 weeks of gestation ( p < 0.05); (5) The ratio of PlGF/(sVEGFR-1 × sEng) was significantly higher in women destined to have a fetal death between 7 and 13 weeks of gestation (94-781%) and significantly lower (44-75%) than those in normal pregnant women between 20 and 40 weeks of gestation ( p < 0.05); (6) Similar results were obtained when patients with a fetal death were stratified into those who were diagnosed before or after 37 weeks of gestation. Conclusions. Fetal death is characterised by higher maternal plasma concentrations of PlGF during the first trimester compared to normal pregnancy. This profile changes into an anti-angiogenic one during the second and third trimesters. [ABSTRACT FROM AUTHOR]

Objective. Pyelonephritis during pregnancy is associated with a more severe course than in the non-pregnant state. This has been attributed to an increased susceptibility of pregnant women to microbial products. The complement system is part of innate immunity and its alternative pathway is activated mainly by microorganisms. The purpose of this study was to determine if activation of the alternative pathway of the complement system (determined by maternal fragment Bb concentrations) occurs in pregnant women with acute pyelonephritis. Methods. This cross-sectional study included the following groups: (1) normal pregnant women ( n = 62) and (2) pregnant women with pyelonephritis ( n = 38). Maternal plasma fragment Bb concentrations were determined by ELISA. Non-parametric statistics were used for analyses. Results. (1) Pregnant women with pyelonephritis had a higher median plasma concentration of fragment Bb than those with a normal pregnancy (1.3 μg/ml, IQR: 1.1–1.9 vs. 0.8 μg/ml, IQR: 0.7–0.9; p < 0.001); (2) No significant differences were observed in the median maternal plasma concentration of fragment Bb between pregnant women with pyelonephritis who had a positive blood culture and those with a negative blood culture (1.4 μg/ml, IQR: 1.1–3.5 vs. 1.3 μg/ml, IQR: 1.1–1.9; p = 0.2). Conclusions. Pregnant women with acute pyelonephritis have evidence of activation of the alternative pathway of the complement system, regardless of the presence or absence of a positive blood culture. [ABSTRACT FROM AUTHOR]

Objective. Pentraxin 3 (PTX3) is an acute-phase protein that has an important role in the regulation of the innate immune response. The aim of this study was to determine if maternal plasma PTX3 concentration changes in the presence of intra-amniotic infection and/or inflammation (IAI) in women with preterm labor (PTL) and intact membranes, as well as those with preterm prelabor rupture of membranes (preterm PROM). Study design. This cross-sectional study included women in the following groups: (1) nonpregnant ( n = 40); (2) uncomplicated pregnancies in the first ( n = 22), second ( n = 22) or third trimester ( n = 71, including 50 women at term not in labor); (3) uncomplicated pregnancies at term with spontaneous labor ( n = 49); (4) PTL and intact membranes who delivered at term ( n = 49); (5) PTL without IAI who delivered preterm ( n = 26); (6) PTL with IAI ( n = 65); (7) preterm PROM without IAI ( n = 25); and (8) preterm PROM with IAI ( n = 77). Maternal plasma PTX3 concentrations were determined by ELISA. Results. (1) Maternal plasma PTX3 concentrations increased with advancing gestational age ( r = 0.62, p < 0.001); (2) women at term with spontaneous labor had a higher median plasma PTX3 concentration than those at term not in labor (8.29 ng/ml vs. 5.98 ng/ml, p = 0.013); (3) patients with an episode of PTL, regardless of the presence or absence of IAI and whether these patients delivered preterm or at term had a higher median plasma PTX3 concentration than normal pregnant women ( p < 0.001 for all comparisons); (4) similarly, patients with preterm PROM, with or without IAI had a higher median plasma PTX3 concentration than normal pregnant women ( p < 0.001 for both comparisons); and (5) among patients with PTL and those with preterm PROM, IAI was not associated with significant changes in the median maternal plasma PTX3 concentrations. Conclusions. The maternal plasma PTX3 concentration increases with advancing gestational age and is significantly elevated during labor at term and in the presence of spontaneous preterm labor or preterm PROM. These findings could not be explained by the presence of IAI, suggesting that the increased PTX3 concentration is part of the physiologic or pathologic activation of the pro-inflammatory response in the maternal circulation during the process of labor at term or preterm. [ABSTRACT FROM AUTHOR]

Objective. Maternal circulating visfatin concentrations are higher in patients with a small-for-gestational-age (SGA) neonate than in those who delivered an appropriate-for-gestational age (AGA) neonate or in those with pre-eclampsia. It has been proposed that enhanced transfer of visfatin from the foetal to maternal circulation may account for the high concentrations of maternal visfatin observed in patients with an SGA neonate. The aims of this study were: (1) to determine whether cord blood visfatin concentrations differ between normal neonates, SGA neonates and newborns of pre-eclamptic mothers; and (2) to assess the relationship between maternal and foetal circulating visfatin concentrations in patients with an SGA neonate and those with pre-eclampsia. Study design. This cross-sectional study included 88 pregnant women and their neonates, as well as 22 preterm neonates in the following groups: (1) 44 normal pregnant women at term and their AGA neonates; (2) 22 normotensive pregnant women and their SGA neonates; (3) 22 women with pre-eclampsia and their neonates; and (4) 22 preterm neonates delivered following spontaneous preterm labour without funisitis or histologic chorioamnionitis, matched for gestational age with infants of pre-eclamptic mothers. Maternal plasma and cord blood visfatin concentrations were determined by ELISA. Non-parametric statistics were used for analyses. Results. (1) The median visfatin concentration was lower in umbilical cord blood than in maternal circulation, in normal pregnancy, SGA and pre-eclampsia groups ( p < 0.001 for all comparisons); (2) the median cord blood visfatin concentrations did not differ significantly between term AGA or SGA neonates, infants of mothers with pre-eclampsia and their gestational-age-matched preterm AGA neonates; (3) maternal and cord blood visfatin concentrations correlated only in the normal term group ( r = 0.48, p = 0.04). Conclusion. Circulating visfatin concentrations are lower in the foetal than in the maternal circulation and did not significantly differ between the study groups. Thus, it is unlikely that the foetal circulation is the source of the high maternal visfatin concentrations reported in patients with an SGA neonate. [ABSTRACT FROM AUTHOR]

Objective. An anti-angiogenic state has been implicated in the pathophysiology of preeclampsia, fetal growth restriction and fetal death. Vascular endothelial growth factor (VEGF), an indispensible angiogenic factor for embryonic and placental development exerts its angiogenic properties through the VEGF receptor (VEGFR)-2. A soluble form of this protein (sVEGFR-2) has been recently detected in maternal blood. The aim of this study was to determine if fetal death was associated with changes in the concentrations of sVEGFR-2 in maternal plasma and amniotic fluid. Study Design. Maternal plasma was obtained from patients with fetal death ( n = 59) and normal pregnant women ( n = 134). Amniotic fluid was collected from 36 patients with fetal death and the control group consisting of patients who had an amniocentesis and delivered at term ( n = 160). Patients with fetal death were classified according to the clinical circumstances into the following groups: (1) unexplained; (2) preeclampsia and/or placental abruption; (3) chromosomal and/or congenital anomalies. Plasma and amniotic fluid concentrations of sVEGFR-2 were determined by ELISA. Non-parametric statistics and logistic regression analysis were applied. Results. (1) Patients with a fetal death had a significantly lower median plasma concentration of sVEGFR-2 than normal pregnant women ( p < 0.001). The median plasma concentration of sVEGFR-2 in patients with unexplained fetal death and in those with preeclampsia/abruption, but not that of those with congenital anomalies, was lower than that of normal pregnant women ( p = 0.006, p < 0.001 and p = 0.2, respectively); (2) the association between plasma sVEGFR-2 concentrations and preterm unexplained fetal death remained significant after adjusting for potential confounders (OR: 3.2; 95% CI: 1.4–7.3 per each quartile decrease in plasma sVEGFR-2 concentrations); (3) each subgroup of fetal death had a higher median amniotic fluid concentration of sVEGFR-2 than the control group ( p < 0.001 for each); (4) the association between amniotic fluid sVEGFR-2 concentrations and preterm unexplained fetal death remained significant after adjusting for potential confounders (OR: 15.6; 95% CI: 1.5–164.2 per each quartile increase in amniotic fluid sVEGFR-2 concentrations); (5) among women with fetal death, there was no relationship between maternal plasma and amniotic fluid concentrations of sVEGFR-2 (Spearman Rho: 0.02; p = 0.9). Conclusion. Pregnancies with a fetal death, at the time of diagnosis, are characterized by a decrease in the maternal plasma concentration of sVEGFR-2, but an increase in the amniotic fluid concentration of this protein. Although a decrease in sVEGFR-2 concentration in maternal circulation depends upon the clinical circumstances of fetal death, an increase in sVEGFR-2 concentration in amniotic fluid seems to be a common feature of fetal death. It remains to be determined if the perturbation in sVEGFR-2 concentrations in maternal and fetal compartments observed herein preceded the death of a fetus. [ABSTRACT FROM AUTHOR]

Objective: Infection has been implicated in the pathogenesis of preeclampsia, yet the association between microbial invasion of the amniotic cavity (MIAC) and preeclampsia has not been determined. The aim of this study was to determine the prevalence, and microbial diversity associated with MIAC, as well as the nature of the host response to MIAC in patients with preeclampsia. Method of study: Amniotic fluid (AF) from 62 subjects with preeclampsia, not in labor, was analyzed with both cultivation and molecular methods. Broad-range and group-specific PCR assays targeting small subunit ribosomal DNA, or other gene sequences, from bacteria, fungi and archaea were used. Results were correlated with measurements of host inflammatory response, including AF white blood cell count and AF concentrations of glucose, interleukin-6 (IL-6) and MMP-8. Results: 1) The rate of MIAC in preeclampsia was 1.6% (1/62) based on cultivation techniques, 8% (5/62) based on PCR, and 9.6% (6/62) based on the combined results of both methods; 2) among the six patients diagnosed with MIAC, three had a positive PCR for Sneathia/Leptotrichia spp.; and 3) patients with MIAC were more likely to have evidence of an inflammatory response in the amniotic cavity than those without MIAC, as determined by a higher median AF IL-6 [1.65 ng/mL interquartile range (IQR): 0.35–4.62 vs. 0.22 ng/mL IQR: 0.12–0.51; P=0.002). Conclusion: The prevalence of MIAC in preeclampsia is low, suggesting that intra-amniotic infection plays only a limited role in preeclampsia. However, the unexpectedly high number of positive AF specimens for Sneathia/Leptotrichia warrants further investigation. [ABSTRACT FROM AUTHOR]

Objective: Microbial invasion of the amniotic cavity (MIAC) has been detected in women with preterm labor, preterm prelabor rupture of membranes (PROM), and in patients at term with PROM or in spontaneous labor. Intrauterine infection is recognized as a potential cause of fetal growth restriction; yet, the frequency of MIAC in pregnancies with small-for-gestational-age (SGA) fetuses is unknown. The aim of this study was to determine the frequency, diversity and relative abundance of microbes in amniotic fluid (AF) of women with an SGA neonate using a combination of culture and molecular methods. Method: AF from 52 subjects with an SGA neonate was analyzed with both cultivation and molecular methods in a retrospective cohort study. Broad-range and group-specific PCR assays targeted small subunit rDNA, or other gene sequences, from bacteria, fungi and archaea. Results of microbiologic studies were correlated with indices of the host inflammatory response. Results: 1) All AF samples (n=52) were negative for microorganisms based on cultivation techniques, whereas 6% (3/52) were positive based on PCR; and 2) intra-amniotic inflammation was detected in one of the three patients with a positive PCR result, as compared with three patients (6.1%) of the 49 with both a negative culture and a negative PCR (P=0.2). Conclusion: MIAC is detected by PCR in some patients with an SGA fetus who were not in labor at the time of AF collection. [ABSTRACT FROM AUTHOR]

Objective. Women with preeclampsia and those who delivered a small-for-gestational-age (SGA) neonate share several mechanisms of disease, including chronic uteroplacental ischemia and failure of physiologic transformation of the spiral arteries. However, the clinical manifestation of these obstetrical syndromes is remarkably different. It has been proposed that an altered maternal metabolic state, as well as a unique circulating cytokines milieu, predispose women to develop either preeclampsia or SGA. Compelling evidence suggests that adipose tissue orchestrates both metabolic pathways and immunological responses via the production of adipokines. Visfatin is a novel adipocytokine with metabolic and immunomodulating properties. The objective of this study was to determine whether preeclampsia and SGA are associated with alterations in maternal circulating visfatin concentrations. Methods. This cross-sectional study included pregnant women in the following groups: (1) normal pregnancy ( n = 158); (2) patients with preeclampsia ( n = 43) of which 32 had an AGA and 11 had an SGA neonate; (3) patients without preeclampsia who delivered an SGA neonate ( n = 55). Maternal plasma visfatin concentrations were measured by ELISA. Nonparametric tests and multiple linear regression analysis were used. Results. (1) Women who delivered an SGA neonate had a higher median maternal plasma visfatin concentration than those with a normal pregnancy (20.0 ng/ml, interquartile range: 17.2–24.6 vs. 15.2 ng/ml, 12.1–19.2, respectively; P < 0.001) and than those with preeclampsia (14.5 ng/ml, 12.5–18.7; P < 0.001); (2) the median maternal plasma visfatin concentration did not differ significantly between patients with preeclampsia and those with a normal pregnancy ( P = 0.8); (3) among patients with preeclampsia, there was no significant difference in the median maternal plasma visfatin concentration between those with or without an SGA neonate ( P = 0.5); (4) in a linear regression model, delivery of an SGA neonate and pregestational body mass index were independently associated with increased visfatin concentration after adjustment for confounding factors (maternal age, smoking, gestational age at blood collection and the presence of preeclampsia or SGA). Conclusion. (1) Patients with SGA, but not those with preeclampsia, had a higher maternal plasma visfatin concentration than those with a normal pregnancy; (2) this finding suggests differential involvement of visfatin in SGA and preeclampsia; (3) we propose that changes in circulating maternal visfatin concentration may be implicated in the phenotypic definitions and distinction of preeclampsia and SGA. [ABSTRACT FROM AUTHOR]

Objective. Angiogenesis is critical for successful pregnancy. An anti-angiogenic state has been implicated in preeclampsia, fetal growth restriction and fetal death. Increased maternal plasma concentrations of the anti-angiogenic factor, soluble vascular endothelial growth factor receptor (sVEGFR)-1, have been reported in women with preeclampsia and in those with fetal death. Recent observations indicate that an excess of sVEGFR-1 and soluble endoglin (sEng) is also present in the amniotic fluid of patients with preeclampsia. The aim of this study was to determine whether fetal death is associated with changes in amniotic fluid concentrations of sVEGFR-1 and sEng, two powerful anti-angiogenic factors. Study design. This cross-sectional study included patients with fetal death ( n = 35) and controls ( n = 129). Fetal death was subdivided according to clinical circumstances into: (1) unexplained ( n = 25); (2) preeclampsia and/or placental abruption ( n = 5); and (3) chromosomal/congenital anomalies ( n = 5). The control group consisted of patients with preterm labor (PTL) who delivered at term ( n = 92) and women at term not in labor ( n = 37). AF concentrations of sVEGFR-1 and sEng were determined by ELISA. Non-parametric statistics and logistic regression analysis were applied. Results. (1) Patients with a fetal death had higher median amniotic fluid concentrations of sVEGFR-1 and sEng than women in the control group ( p < 0.001 for each); (2) these results remained significant among different subgroups of stillbirth ( p < 0.05 for each); and (3) amniotic fluid concentrations of sVEGFR-1 and those of sEng above the third quartile were associated with a significant risk of unexplained preterm fetal death (adjusted OR = 10.8; 95%CI 1.3–89.2 and adjusted OR 87; 95% CI 2.3–3323, respectively). Conclusion. Patients with an unexplained fetal death at diagnosis are characterized by an increase in the amniotic fluid concentrations of sVEGFR-1 and sEng. These observations indicate that an excess of anti-angiogenic factors in the amniotic cavity is associated with unexplained fetal death especially in preterm gestations. [ABSTRACT FROM AUTHOR]

Objective. The importance of an anti-angiogenic state as a mechanism of disease in preeclampsia is now recognized. Assays for the determination of concentrations of soluble vascular endothelial growth factor receptor (sVEGFR)-1, sVEGFR-2, placental growth factor (PlGF) and soluble endoglin (sEng) have been developed for research and clinical laboratories. A key question is whether these factors should be measured in plasma or serum. The purpose of this study was to determine if there are differences in the concentrations of these analytes between plasma and serum in normal pregnancy and in preeclampsia. Methods. Samples of maternal blood were obtained by venipuncture and collected in EDTA (lavender top) and serum collection tubes (red top). A standard laboratory procedure was implemented for the centrifugation, aliquoting and storage of samples. Plasma and serum from 70 women with normal pregnancies and 34 patients with preeclampsia were assayed for sVEGFR-1, sVEGFR-2, PlGF and sEng by ELISA. Nonparametric paired tests were used for analyses. Results. A significant difference between plasma and serum concentration was observed for sVEGFR-1 and sVEGFR-2 in normal pregnancy, and for sVEGFR-1, sVEGFR-2, PlGF and sEng in women with preeclampsia. Conclusion. The concentrations of sVEGFR-1, sVEGFR-2, PlGF and sEng when measured in maternal plasma and in serum are different. Therefore, the matrix used for the assay (serum versus plasma) needs to be considered when selecting thresholds for predictive studies and interpreting the growing body of literature on this subject. [ABSTRACT FROM AUTHOR]

Objective. Vaginal bleeding, placental abruption, and defective placentation are frequently observed in patients with preterm prelabor rupture of membranes (PROM). Recently, a role of vascular endothelial growth factor (VEGF) and its receptor, VEGF receptor (VEGFR)- 1 has been implicated in the mechanisms of membrane rupture. The purpose of this study was to determine whether the soluble form of VEGFR-1 and -2 concentrations in amniotic fluid (AF) change with preterm PROM, intra-amniotic infection/inflammation (IAI), or parturition. Study design. This cross-sectional study included 544 patients in the following groups: (1) midtrimester (MT) ( n = 48); (2) preterm labor (PTL) leading to term delivery ( n = 143); (3) PTL resulting in preterm delivery with ( n = 72) and without IAI ( n = 100); (4) preterm PROM with ( n = 46) and without IAI ( n = 42); (5) term in labor ( n = 48); and (6) term not in labor ( n = 45). The concentrations of sVEGFR-1 and sVEGFR-2 were determined by ELISA. Non-parametric statistics and logistic regression analysis were applied. Results. (1) Preterm PROM (with and without IAI) had a lower median AF concentration of sVEGFR-1 than patients with PTL who delivered at term ( p < 0.001 for each comparison); (2) A decrease in AFsVEGFR-1 concentrations per each quartile was associated with PROM after adjusting for confounders (OR 1.8; 95%CI 1.4–2.3); (3) IAI, regardless of the membrane status, was not associated with a change in the median AF concentrations of sVEGFR-1 and sVEGFR-2 ( p > 0.05 for each comparison); and (4) Spontaneous term and PTL did not change the median sVEGFR-1 and sVEGFR-2 concentrations ( p > 0.05 for each comparison). Conclusion. (1) This is the first evidence that preterm PROM is associated with a lower AF concentration of sVEGFR-1 than patients with PTL intact membranes. These findings cannot be attributed to gestational age, labor, or IAI; and (2) AF concentrations of sVEGFR-2 did not change with preterm PROM, IAI, or labor at term and preterm. [ABSTRACT FROM AUTHOR]

Citation Xu Y, Madsen-Bouterse SA, Romero R, Hassan S, Mittal P, Elfline M, Zhu A, Petty HR. Leukocyte pyruvate kinase expression is reduced in normal human pregnancy but not in pre-eclampsia. Am J Reprod Immunol 2010; 64: 137–151 Problem Emerging evidence suggests that metabolism influences immune cell signaling and immunoregulation. To examine the immunoregulatory role of glycolysis in pregnancy, we evaluated the properties of pyruvate kinase in leukocytes from non-pregnant women and those with normal pregnancy and pre-eclampsia. Method of study We evaluated pyruvate kinase expression in lymphocytes and neutrophils from non-pregnant, pregnant, and pre-eclampsia patients using fluorescence microscopy and flow cytometry. Leukocyte pyruvate kinase activity and pyruvate concentrations were also evaluated. To study pyruvate’s effect on signaling, we labeled Jurkat T cells with Ca2+ dyes and measured cell responses in the presence of agents influencing intracellular pyruvate. Results The expression of pyruvate kinase is reduced in lymphocytes and neutrophils from normal pregnant women in comparison with those of non-pregnant women and pre-eclampsia patients. Similarly, the activity of pyruvate kinase and the intracellular pyruvate concentration are reduced in leukocytes of normal pregnant women in comparison with non-pregnant women and women with pre-eclampsia. Using Jurkat cells as a model of leukocyte signaling, we have shown that perturbations of intracellular pyruvate influence Ca2+ signals. Conclusion Normal pregnancy is characterized by reduced pyruvate kinase expression within lymphocytes and neutrophils. We speculate that reduced pyruvate kinase expression modifies immune cell responses due to reduced pyruvate concentrations. [ABSTRACT FROM AUTHOR]

Objective. Preeclampsia and pregnancies complicated by small-for-gestational age (SGA) neonates share several underlying mechanisms of disease. However, while an exaggerated systemic maternal inflammatory response is regarded as one of the hallmarks of the pathogenesis of preeclampsia, the presence of a similar systemic intra-vascular inflammation in mothers of SGA neonates without hypertension is controversial. The aim of this study was to determine phenotypic and metabolic changes in granulocytes and monocytes of women who develop preeclampsia and those who deliver an SGA neonate, compared to normal pregnant women. Methods. This cross-sectional study included patients with a normal pregnancy ( n = 33), preeclampsia ( n = 33), and an SGA without preeclampsia ( n = 33), matched for gestational age at blood sample collection. Granulocyte and monocyte phenotypes were determined by flow cytometry, using monoclonal antibodies against selective cluster of differentiation (CD) antigens. The panel of antibodies included the following: CD11b, CD14, CD16, CD18, CD49d, CD62L, CD64, CD66b, and HLA-DR. Intracellular reactive oxygen species (iROS) were assessed at the basal state and after stimulation (oxidative burst). Results were reported as mean channel brightness (MCB) or intensity of detected fluorescence. Analysis was conducted with non-parametric statistics. A p-value < 0.01 was considered statistically significant. Results. (1) Women who delivered an SGA neonate had a higher MCB of CD11b in granulocytes and monocytes than those with a normal pregnancy ( p < 0.001 for both); (2) patients with preeclampsia had a lower median MCB of CD62L in granulocytes ( p = 0.006) and a higher median basal iROS and oxidative burst in monocytes than women with an SGA neonate ( p = 0.003 and p = 0.002, respectively). Conclusion. Pregnancies complicated by the delivery of an SGA neonate are characterized by a higher activation of maternal peripheral leukocytes than in normal pregnancies, but lower than in pregnancies complicated by preeclampsia. [ABSTRACT FROM AUTHOR]

Objective: Visfatin, a novel adipokine with metabolic and immunoregulatory properties, has been implicated in the regulation of fetal growth, as well as in preterm labor. A gap in knowledge is whether spontaneous labor at term is associated with changes in the maternal and fetal concentrations of visfatin. The aim of this study was to determine if the presence of labor at term is associated with alterations in maternal and neonatal plasma visfatin concentrations. Study design: This cross-sectional study included 50 normal pregnant women at term and their appropriate-for-gestational age (AGA) neonates in the following groups: 1) 25 mother-neonate pairs delivered by elective cesarean section without spontaneous labor, and 2) 25 mother-neonate pairs who delivered vaginally following spontaneous labor. Maternal plasma and cord blood visfatin concentrations were determined by ELISA. Non-parametric statistics were used for analyses. Results: 1) The median visfatin concentration was higher in umbilical cord plasma of neonates born following a spontaneous labor at term than that of those who were born by an elective cesarean section (P=0.02); 2) in contrast, the median maternal plasma visfatin concentration did not differ significantly between patients with and without labor (P=0.44); and 3) there was a significant correlation between umbilical cord plasma concentration of visfatin and both maternal visfatin concentration (r=0.54, P=0.005) and gestational age (GA) at delivery (r=0.58; P=0.002) only in the absence of labor. Conclusion: Term labor is associated with increased fetal, but not maternal, circulating visfatin concentrations. Previous reports indicate that preterm labor leading to preterm delivery is characterized by an increase in maternal plasma concentrations of visfatin. The observations reported herein support the view that there are fundamental differences in the endocrine and metabolic adaptations in normal labor at term and preterm labor. [ABSTRACT FROM AUTHOR]

Objective: Idiopathic vaginal bleeding, a common complication of pregnancy, increases the risk of small-for-gestational age (SGA) neonate, preeclampsia and preterm delivery and can be the only clinical manifestation of intra-amniotic infection and/or inflammation (IAI). Placenta previa is thought to be protective against ascending intrauterine infection, yet an excess of histologic chorioamnionitis has been reported in this condition. The aim of this study was to determine the frequency and clinical significance of IAI in women with placenta previa and vaginal bleeding in the absence of preterm labor. Study design: A retrospective cohort study including 35 women with placenta previa and vaginal bleeding <37 weeks of gestation who underwent amniocentesis was undertaken. Patients with multiple gestations were excluded. Intra-amniotic infection was defined as a positive culture for microorganisms, and intra-amniotic inflammation as an elevated amniotic fluid interleukin (IL)-6 concentration. IL-6 concentrations were determined by ELISA in 28 amniotic fluid samples available. Non-parametric statistics were used for analysis. Results: 1) The prevalence of intra-amniotic infection was 5.7% (2/35), and that of IAI was 17.9% (5/28); 2) the gestational age at delivery was lower in patients with IAI than in those without IAI [29.4 weeks, interquartile range (IQR): 23.1–34.7 vs. 35.4 weeks, IQR: 33.9–36.9; P=0.028]; and 3) patients with placenta previa and IAI had a higher rate of delivery within 48 h (80% (4/5) vs. 19% (4/21); P=0.008) than those without IAI. Conclusions: Patients with placenta previa presenting with vaginal bleeding have intra-amniotic infection in 5.7% of the cases, and IAI in 17.9%. IAI in patients with placenta previa and vaginal bleeding is a risk factor for preterm delivery within 48 h. [ABSTRACT FROM AUTHOR]

Objective. White blood cells are not traditionally considered to be normally present in amniotic fluid. This study was conducted after the observation that a patient with preterm labor and intact membranes had eosinophils as a predominant cell in the amniotic fluid, and had an episode of asthma during the index pregnancy. The goal of this study was to determine whether women presenting with preterm labor with eosinophils in the amniotic fluid had a different outcome than those without eosinophils as the predominant white blood cell in the amniotic cavity. Methods. This retrospective case–control study included women who presented with preterm labor and intact membranes between 24 and 34 weeks of gestation. Patients underwent an amniocentesis shortly after admission for the assessment of the microbiologic status of the amniotic cavity and/or fetal lung maturity. Amniotic fluid was cultured for aerobic and anaerobic bacteria as well as genital mycoplasmas. Cytologic studies included amniotic fluid white blood cell count and differential, which was performed on cytocentrifuged specimens. Patients with microbial invasion of the amniotic cavity and/or an amniotic fluid white blood cell count >20 cells/mm3 were excluded from the study. Cases were defined as women in whom the differential contained >20% of eosinophils. Controls were selected among women with an amniotic fluid eosinophil count ≤20% and matched for gestational age at amniocentesis. The analysis was conducted with non-parametric statistics. Results. The study population consisted of 10 cases and 50 controls. Gestational age and cervical dilatation at admission were similar in both groups. Cases had a lower gestational age at delivery than controls [34.6 weeks, inter-quartile range (IQR) 32–37.3 weeks vs. 38.0 weeks, IQR 35–40 weeks, respectively; p = 0.018]. The prevalence of preterm delivery ≤35 weeks was higher among patients who had >20% eosinophils than in the control group [50% (5/10) vs. 18% (9/50), respectively; p = 0.029]. Similar results were observed for delivery at <37 weeks [cases: 70% (7/10) vs. controls: 36% (18/50); p = 0.046]. Conclusions. Women with preterm labor and intact membranes who have a large proportion of eosinophils in the amniotic fluid are at an increased risk for spontaneous preterm delivery. These patients may have had an episode of preterm labor related to a type I hypersensitivity reaction. [ABSTRACT FROM AUTHOR]

Citation Mazaki-Tovi S, Vaisbuch E, Romero R, Kusanovic JP, Chaiworapongsa T, Kim SK, Nhan-Chang C-L, Gomez R, Yoon BH, Yeo L, Mittal P, Ogge G, Gonzalez JM, Hassan SS. Maternal plasma concentration of the pro-inflammatory adipokine pre-B-cell-enhancing factor (PBEF)/visfatin is elevated in pregnant patients with acute pyelonephritis. Am J Reprod Immunol 2010; 63: 252–262 Problem Visfatin/pre-B-cell-enhancing factor (PBEF) has been implicated in the regulation of the innate immune system, as well as in glucose metabolism. Specifically, visfatin plays a requisite role in delayed neutrophil apoptosis in patients with sepsis. The aim of this study was to determine whether pyelonephritis during pregnancy is associated with changes in maternal plasma visfatin concentration in normal weight and overweight/obese patients. Method of study This cross-sectional study included the following groups: (1) normal pregnant women ( n = 200) and (2) pregnant women with pyelonephritis ( n = 40). Maternal plasma visfatin concentrations were determined by ELISA. Non-parametric statistics was used for analyses. Results (1) The median maternal plasma visfatin concentration was significantly higher in patients with pyelonephritis than in those with a normal pregnancy; (2) among overweight/obese pregnant women, those with pyelonephritis had a significantly higher median plasma visfatin concentration than women with a normal pregnancy; and (3) pyelonephritis was independently associated with higher maternal plasma visfatin concentrations after adjustment for maternal age, pre-gestational body mass index, smoking status, gestational age at sampling, and birthweight. Conclusion Acute pyelonephritis during pregnancy is associated with a high circulating maternal visfatin concentration. These findings suggest that visfatin/PBEF may play a role in the regulation of the complex and dynamic crosstalk between inflammation and metabolism during pregnancy. [ABSTRACT FROM AUTHOR]

Objective: Pentraxin 3 (PTX3) is a soluble pattern recognition receptor (PRR) that has an important role in immunoregulation and vascular integrity. The aim of this study was to determine if PTX3 is present in amniotic fluid (AF) and whether its concentration changes with gestational age (GA), in the presence of preterm or term labor, and in cases of intra-amniotic infection/inflammation (IAI) associated with spontaneous preterm labor (PTL) or preterm prelabor rupture of membranes (PROM). Study design: This cross-sectional study included the following groups: 1) mid-trimester (n=45); 2) uncomplicated pregnancies at term with (n=48) and without (n=40) spontaneous labor; 3) women with PTL and intact membranes who: a) delivered at term (n=44); b) delivered preterm without IAI (n=40); or c) delivered preterm with IAI (n=62); 4) women with preterm PROM with (n=63) and without (n=36) IAI. PTX3 concentration in AF was determined by ELISA. Non-parametric statistics were used for analyses. Results: 1) Among women with PTL and intact membranes, the median AF PTX3 concentration was significantly higher in women with IAI than in those without IAI (7.95 ng/mL vs. 0.38 ng/mL; P<0.001) and than in those who delivered at term (0.55 ng/mL; P<0.001); 2) women with preterm PROM and IAI had a higher median AF PTX3 concentration than those without IAI (9.12 ng/mL vs. 0.76 ng/mL; P<0.001); 3) the median AF PTX3 concentration did not change with GA (mid-trimester: 0.79 ng/mL vs. term not in labor: 0.58 ng/mL; P=0.09); and 4) labor at term was not associated with a significant change of AF PTX 3 concentration (in labor: 0.54 ng/mL vs. not in labor: 0.58 ng/mL, P=0.9). Conclusions: PTX3 is a physiologic constituent of the AF, and its median concentration is elevated in the presence of IAI, suggesting that PTX3 may play a role in the innate immune response against IAI. [ABSTRACT FROM AUTHOR]

Objective: Adipokines (cytokines produced by adipose tissue) play a major role in the control of body weight and energy distribution. Retinol-binding protein 4 (RBP4), only recently recognized as an adipokine, has been proposed to modulate systemic insulin sensitivity. The goal of this study was to determine whether there is an association between maternal plasma RBP4 concentration and the birth of a large-for-gestational-age (LGA) newborn in women with and without gestational diabetes mellitus (GDM). Study design: This cross-sectional study included pregnant women at term in the following groups: 1) normal pregnancy with an appropriate-for-gestational-age (AGA) neonate (n=64); 2) normal pregnancy with an LGA neonate (n=44); 3) GDM with an AGA neonate (n=55); and 4) GDM with an LGA neonate (n=42). Maternal plasma RBP4 concentration was determined by ELISA. Parametric and non-parametric statistics were used for analyses. Results: 1) Patients with GDM, either with AGA or LGA neonates, had a higher median plasma concentration of RBP4 than normal pregnant women who delivered an AGA neonate (P=0.01 and P=0.008, respectively); 2) mothers without GDM but with LGA neonates had a higher median plasma concentration of RBP4 than those with normal pregnancy and AGA newborns (P=0.001); 3) these findings remained significant after adjusting for maternal age, body mass index and gestational age at blood sampling. Conclusion: GDM is characterized by alterations in maternal circulating RBP4 concentrations akin to those of Type 2 diabetes mellitus. RBP4 concentrations in maternal plasma may play a role in accelerated fetal growth in the absence of overt carbohydrate intolerance. [ABSTRACT FROM AUTHOR]