Latest advances and clinical application prospects of resveratrol therapy for neurocognitive disorders.

Neurocognitive disorders, such as Alzheimer's disease, vascular dementia, and postoperative cognitive dysfunction, are non-psychiatric brain syndromes in which a significant decline in cognitive function causes great trauma to the mental status of the patient. The lack of effective treatments for neurocognitive disorders imposes a considerable burden on society, including a substantial economic impact. Over the past few decades, the identification of resveratrol, a natural plant compound, has provided researchers with an opportunity to formulate novel strategies for the treatment of neurocognitive disorders. This is because resveratrol effectively protects the brain of those with neurocognitive disorders by targeting some mechanisms such as inflammation and oxidative stress. This article reviews the status of recent research investigating the use of resveratrol for the treatment of different neurocognitive disorders. By examining the possible mechanisms of action of resveratrol and the shared mechanisms of different neurocognitive disorders, treatments for neurocognitive disorders may be further clarified.

A cutting-edge strategy for spinal cord injury treatment: resident cellular transdifferentiation.

Spinal cord injury causes varying degrees of motor and sensory function loss. However, there are no effective treatments for spinal cord repair following an injury. Moreover, significant preclinical advances in bioengineering and regenerative medicine have not yet been translated into effective clinical therapies. The spinal cord's poor regenerative capacity makes repairing damaged and lost neurons a critical treatment step. Reprogramming-based neuronal transdifferentiation has recently shown great potential in repair and plasticity, as it can convert mature somatic cells into functional neurons for spinal cord injury repair in vitro and in vivo, effectively halting the progression of spinal cord injury and promoting functional improvement. However, the mechanisms of the neuronal transdifferentiation and the induced neuronal subtypes are not yet well understood. This review analyzes the mechanisms of resident cellular transdifferentiation based on a review of the relevant recent literature, describes different molecular approaches to obtain different neuronal subtypes, discusses the current challenges and improvement methods, and provides new ideas for exploring therapeutic approaches for spinal cord injury.

One kind of challenging tetrapeptide biomimetic chromatographic resin for antibody separation.

Short peptide biomimetic chromatography technology as a developing protein separation technology has huge potential for antibody purification. In this study, four tetrapeptide ligands (Ac-FYKH, Ac-YEHF, Ac-YFLH and Ac-FYHI) with high potential binding ability to antibody were selected for the optimal ligand to antibody purification. The results showed that Ac-YEHF-4FF resin had higher binding capacity and selectivity for hIgG among the four resins. And at pH 7.0 and 0.3 ml/min, the highest Q10%-hIgG of Ac-YEHF-4FF resin was 26.2 mg/ml resin while its Q10%-BSA was just 2.2 mg/ml resin. Further, Ac-YEHF-4FF resin was used to purify protein mixtures. By binding at pH 7.0 and being eluted at pH 5.0 and pH 4.0, Ac-YEHF-4FF resin was well used to separate hIgG from BSA containing feedstock, HSA containing feedstock and human serum with the purity and yield both more than 95 %. And the screened resin could also separate mAb from CHO cell culture supernatant with purity 94.3 % and yield 97.5 %. The adsorption and separation results of Ac-YEHF-4FF resin indicated that the goal of getting the efficacy of critical residues from protein A to biomimetic its structure and function could be achieved, which had great significance to the establishment and improvement of tetrapeptide biomimetic chromatography, and also provided a new method for the field of antibody separation and purification.

A novel dextran-grafted tetrapeptide resin for antibody purification.

Short peptide biomimetic affinity chromatography as a novel antibody separation chromatography is a potential alternative to protein A chromatography. However, if directly attaching ligand to matrix, the adsorption capacity and mass transfer rate would be affected by pore blockage and steric effect. Grafting resin is an effective method to solve this problem by using polymer as a bridge between matrix and ligand. In this work, a novel resin was prepared by grafting a tetrapeptide to the dextran-grafted matrix. Then, the adsorption properties for human immunoglobin G and BSA were determined. The results showed the saturation adsorption capacity could reach to 133 mg/g resin at pH 8.9 with a significantly low dissociation constant (0.03 mg/mL). The influence of flow rates to dynamic binding capacity of this resin was less than that of the non-grafted resin. The separation performance of the resin showed monoclonal antibody could be well isolated from the Chinese hamster ovary culture supernatant at pH 9.0 with the purity of 93.0% and yield of 84.7% by one step. Overall, this resin could achieve higher binding capacity by the possible of gaining higher ligand density, indicating its potential significance for separation in larger scale systems.

A new tetrapeptide biomimetic chromatographic resin for antibody separation with high adsorption capacity and selectivity.

Biomimetic affinity chromatography with short peptide ligands is a developing technology, which has great potential for antibody separation and purification. In this study, a tetrapeptide library with critical residues of natural ligands to hIgG was constructed and a novel tetrapeptide ligand (Ac-FYHE) with high LibDock scores was selected by molecular docking. Then, Ac-FYHE ligand was linked to agarose bead to prepare a new chromatography resin. The properties of antibody adsorption were measured and evaluated by static/dynamic adsorption. It was found that the resin with ligand Ac-FYHE has high binding capacity and selectivity for hIgG. The results showed the Qm-hIgG of Ac-FYHE-4FF resin was 87.9 mg/g resin while the Qm-BSA of this resin was only 16.5 mg/g resin at pH 7.0. Moreover, at pH 7.0, Q10% of Ac-FYHE-4FF resin was 24.1 mg/mL for hIgG but just 2.1 mg/mL for BSA, which presented high selectivity of the screened resin at pH 7.0. Subsequently, the adsorption and separation properties of the Ac-FYHE-4FF resin were further investigated. As a result, with the addition of 0.5 M NaCl, Qm decreased by less than 20% but Qm decreased by 70% with the addition of 50% (v/v) ethylene glycol, which indicated that hydrophobic interaction would be the driving force for the binding between resin and hIgG. Besides, pH 7.5 and pH 4.5 could be the optimal loading and elution condition for hIgG, respectively. Finally, the Ac-FYHE-4FF resin was applied to separate mAb or/and hIgG from BSA containing feedstock, CHO cell culture supernatant and human serum, and the purity and recovery were both more than 90% with only one-step separation. The results indicate that the Ac-FYHE-4FF resin developed in this work would be promising for antibody separation and purification.

Review on biomimetic affinity chromatography with short peptide ligands and its application to protein purification.

Biomimetic affinity chromatography with short peptide ligands, as a promising bioseparation technique, has great potential to protein separation and purification, which is based on highly specific biological interactions between specially-designed ligands and target proteins. Generally, short peptide ligands with the chain length ranging from two to nine amino acids could be divided into two types, linear peptide ligands and cyclic peptide ligands. To obtain the desired short peptide ligands, rational design strategies could be applied by knowing the 3-dimensional (3D) information of the receptors or just knowing the surface cavities and the active site of the receptors. Subsequently, several technologies could be used to screen the optimal peptide ligands from the designed peptide ligands, such as combinatorial chemistry, phage display, mRNA display and computer-based screening technology. The screening efficiency is dependent on the different technology for individual target proteins. After screening, the chromatographic resin could be prepared by coupling the optimal short peptide ligand onto a matrix with some spacer arms. The suitable matrix and spacer arms are also important to enhance the ability of the peptide ligand for protein purification. With the advantages of high affinity, high adsorption capacity, structural stability, low immunogenicity and low cost, biomimetic affinity chromatography with short peptides as the functional ligands have shown an extensive development and application potentiality to protein purification. In this review, we focused on the strategies of rational designs and screening for short peptide ligands, and some items on the perpetration of new resins and their applications for protein purification would also be discussed.

Effect of Fetal Sex on Maternal and Obstetric Outcomes.

Fetal sex plays an important role in modifying the course and complications related to pregnancy and may also have an impact on maternal health and well-being both during and after pregnancy. The goal of this article is to review and summarize the findings from published research on physiologic and pathologic changes that may be affected by fetal sex and the effect of these changes on the maternal and obstetrical outcomes. This will help create awareness that fetal sex is not just a random chance event but an interactive process between the mother, the placenta, and the fetus. The reported effects of male sex on the course of pregnancy and delivery include higher incidence of preterm labor in singletons and twins, failure of progression in labor, true umbilical cord knots, cord prolapse, nuchal cord, higher cesarean section rate, higher heart rate variability with increased frequency, and duration of decelerations without acidemia and increased risk of gestational diabetes mellitus through the poor beta cells function. Similarly, female fetal sex has been reported to modify pregnancy and delivery outcomes including altered fetal cardiac hemodynamics, increased hypertensive diseases of pregnancy, higher vulnerability of developing type 2 DM after pregnancy possibly because of influences on increased maternal insulin resistance. Placental function is also influenced by fetal sex. Vitamin D metabolism in the placenta varies by fetal sex; and the placenta of a female fetus is more responsive to the relaxing action of magnesium sulfate. Male and female feto-placental units also vary in their responses to environmental toxin exposure. The association of fetal sex with stillbirths is controversial with many studies reporting higher risk of stillbirth in male fetuses; although some smaller and limited studies have reported more stillbirths with female fetus pregnancies. Maternal status such as BMI may in turn also affect the fetus and the placenta in a sex-specific manner. There is probably a sex-specific maternal-placental-fetal interaction that has significant biological implications of which the mechanisms may be genetic, epigenetic, or hormonal. Determination of fetal sex may therefore be an important consideration in management of pregnancy and childbirth.

Rates of intrauterine fetal demise and neonatal morbidity at term: determining optimal timing of delivery.

OBJECTIVE: To examine rates of unexplained intrauterine fetal demise (IUFD) and neonatal morbidity in uncomplicated term pregnancies to identify the optimal gestational age for delivery. METHODS: A retrospective case control study was performed with singleton pregnancies delivered between 37 0/7 weeks and 42 6/7 weeks. Exclusion criteria were "complicated pregnancies": emergency deliveries, maternal hypertension, diabetes, infection, fetal disease/malformations and placental abnormalities. RESULTS: Nineteen thousand two hundred and sixty-four maternal/infant pairs were examined. The overall rate of NICU admission was 2.7% and the rate of unexplained IUFD was 2.02 per 1000 births. The lowest rate of IUFD was found at 39 weeks (1.40 per 1000 births). Odds ratios adjusted for maternal smoking, ethnicity, age and mode of delivery showed 2.74 (95% CI 0.35-21.83) risk of IUFD at 42 versus 39 weeks, 2.09 (1.47-2.98) risk of NICU admission at 37 versus 38 weeks, 2.54 (1.62-3.97) risk of respiratory morbidity at 37 versus 38 weeks and 3.38 (1.84-6.18) risk of transient tachypnea of the newborn or respiratory distress syndrome at 37 versus 38 weeks. CONCLUSIONS: Neonatal respiratory morbidity was lowest for deliveries at 38-39 weeks. IUFD was 2.74 times more likely at 42 weeks versus 39 weeks. Our findings support current guidelines advising clinicians when to deliver term pregnancies.

Use of oral hypoglycemic and insulin agents in pregnant patients.

Although insulin remains the standard medication for the treatment of all types of patients with diabetes during pregnancy, oral hypoglycemics may be considered as alternative medications in the treatment of some types of diabetes in pregnancy.

Increased neonatal morbidity despite pulmonary maturity for deliveries occurring before 39 weeks.

OBJECTIVE: To compare neonatal outcomes following deliveries <39 weeks after confirmation of fetal lung maturity with scheduled deliveries ≥39 weeks. METHODS: A retrospective cohort study examining neonatal outcomes of women who were delivered following documented fetal pulmonary maturity at 36, 37, and 38 weeks compared to women undergoing a scheduled delivery at 39, 40, and 41 weeks. The χ(2)-test and Student's t-test were used to compare categorical and continuous data, respectively. RESULTS: Delivery prior to 39 weeks following fetal pulmonary maturity was associated with a 8.4% composite neonatal morbidity rate as compared to 3.3% for deliveries at 39 weeks or greater (relative risk [RR] 2.9; confidence interval [CI] 2.4-3.6). Neonatal respiratory morbidity was significantly higher (5.4%) for those delivering at less than 39 weeks with documented fetal pulmonary maturity as compared to 2.1% for those delivering at 39 weeks or greater (RR 3.0; CI 2.3-3.9). Increased neonatal morbidity persisted for those delivered prior to 39 weeks even after excluding all diabetics (p < 0.001). Significant increases in neonatal morbidity were noted for deliveries prior to 39 weeks regardless of the mode of delivery. CONCLUSION: Despite fetal pulmonary maturity, delivery before 39 weeks is associated with significantly increased neonatal morbidity when compared to scheduled deliveries at 39 weeks or greater.

[Optimization of culture conditions for production of extracellular polysaccharides by Morchella esculenta].

OBJECTIVE: To optimize the conditions for exopolysaccharides (EPS) production by Morchella esculenta GIM 5.69. METHODS: A Plackett-Burman design was used to evaluate the effects of variables factors. The optimal combined conditions for maximum polysaccharide production were further optimized by response surface methodology. RESULTS: The optimal fermentation conditions were determined as follows: glucose 30%, cultivation time 5.98 d, rotary speed 217.44 r/min. The average yield of polysaccharide validation experiments was 53.04%, the relative error was 1.64%. CONCLUSION: This research has the vital significance regarding the Morchella esculenta polysaccharide function of the product development and the application.

Isolation, partial characterisation and immunomodulatory activities of polysaccharide from Morchella esculenta.

BACKGROUND: Polysaccharides extracted from fungi or algae have shown a variety of medical activities, and the exploitation of polysaccharides for application in pharmacy has been very promising. In this study, the immunomodulatory properties of polysaccharides from Morchella esculenta were investigated to identify immunostimulatory activity and potentially contribute to the therapeutic potential of Morchella esculenta. RESULTS: A water-soluble polysaccharide, MEP, was obtained from the fermentation broth of Morchella esculenta. Two fractions of this polysaccharide (MEP-I and MEP-II) were extracted and purified. High-performance gel permeation chromatography analysis showed the average molecular weights of two polysaccharides. Structural properties and compositions of these two fractions were examined by Fourier transform infrared and a high-performance liquid chromatography with an evaporative light scattering detector. Active experiments suggested that the MEP had typical immunostimulatory activity. CONCLUSION: These bioactivity tests showed that the polysaccharides from Morchella esculenta presented significant immune modulating activity, and this finding may offer the basis for the popular use of polysaccharides in functional foods or medicine.

Primary sclerosing cholangitis in pregnancy refractory to ursodeoxycholic acid treatment: a case report.

BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease associated with fibrosis and inflammation of the bile ducts. Its complications include symptoms from pruritis and fatigue to dominant strictures, cholangiocarcinoma and liver failure necessitating liver transplant. Due to its predominance in young males, little is reported regarding PSC and pregnancy. CASE: We report a case of a pregnant woman with PSC whose symptoms were initially unresponsive to the traditional treatment of ursodeoxycholic acid (UDCA) early in her pregnancy but subsequently did well using high dose steroids for the duration of her pregnancy. CONCLUSION: With close management, successful pregnancy outcomes seem possible with patients with PSC, even when diagnosed multiple years prior to pregnancy, if not with UDCA, then possibly with steroid treatment.

Down syndrome screening in the United States in 2001 and 2007: a survey of maternal-fetal medicine specialists.

OBJECTIVE: The purpose of this study was to determine changes in screening and performance of invasive diagnostic procedures for Down syndrome between 2001 and 2007. STUDY DESIGN: The Society for Maternal-Fetal Medicine members completed a survey in 2007 regarding screening tests and diagnostic procedures for Down syndrome. With the use of descriptive statistics, the chi(2) test, and the Student t test, responses from 2007 were compared with responses from a similar 2001 survey. RESULTS: Performance of first-trimester screening more than doubled from 2001-2007 (43.1% in 2001, 97.3% in 2007; P < .0001). Between 2001 and 2007, the use of the quad screen increased 10-fold (8.5% in 2001, 85.6% in 2007; P < .0001). There was an estimated 20% decrease in invasive diagnostic procedures that were performed in risk-positive women (53.7% in 2001, 34.2% in 2007; P < .0001). In 2007, the average fetal loss rates that were quoted by maternal-fetal medicine specialists after chorionic villous sampling was 1:160 and after an amniocentesis was 1:493. CONCLUSION: Down syndrome screening evolved from 2001-2007, with an increasing emphasis on first-trimester screening. With more efficacious screening, the number of invasive procedures has declined.

A comparison of reasons for choosing obstetrician/gynecologist subspecialty training.

Recently, applications for subspecialty fellowship positions in obstetrics and gynecology have increased dramatically. A survey completed by fellows in Maternal-Fetal Medicine (MFM), Reproductive Endocrinology (REI), Gynecologic Oncology (Gyn Onc), and Urogynecology (Urogyn) training programs in the United States between January and March 2006 was aimed at determining why this trend was occuring. Of 449 fellows in 2006, 192 (42.8%) responded. The two most influential factors in all four subspecialties were interest and lifestyle (P < .001). Although these factors were similar throughout all subspecialties, variations exist in how fellows rated each factor by subspecialty. An overwhelming majority (99%) of fellows were either "very satisfied" or "satisfied" with their decisions to pursue fellowship training. The majority of fellows believe that when compared to a generalist Obstetrician/Gynecologist (OB/GYN) they will have a reduced workload, decreased liability, and a higher salary. The recent increase in the number of fellowship applicants is most likely due to a complex interplay of multiple factors.

Insulin glargine compared with Neutral Protamine Hagedorn insulin in the treatment of pregnant diabetics.

OBJECTIVE: To compare maternal and neonatal outcomes of pregestational and gestational diabetics treated with insulin glargine versus Neutral Protamine Hagedorn (NPH) insulin. METHODS: A retrospective cohort study examining outcomes from pregestational and gestational diabetics treated with either insulin regimen. Comparisons were made using the t-test for continuous data and the Chi-square or Fisher's exact test for categorical data. RESULTS: Fifty-two pregnant women treated with insulin glargine were compared with 60 pregnant women treated with NPH. No significant differences in rates of maternal complications were noted. No significant differences in neonatal outcomes for gestational diabetics were noted. Among pregestational diabetics treated with insulin glargine, significantly fewer macrosomic infants (relative risk [RR], 0.38; 95% confidence intervals (CI), 0.17-0.87; p = 0.04) and lower rates of neonatal hyperbilirubinemia (RR, 0.27; 95% CI, 0.07-0.98; p = 0.05) were noted when compared with those treated with NPH. There were no cases of neonatal hypoglycemia in pregestational diabetics treated with glargine; however, 25% of infants born to mothers treated with NPH experienced hypoglycemia (p = 0.01). No fetal anomalies or deaths were observed in either treatment group. CONCLUSION: Insulin glargine use during pregnancy is not associated with increased maternal or neonatal morbidity compared with NPH insulin. Among pregestational diabetics, insulin glargine use was associated with lower rates of macrosomia, neonatal hypoglycemia and neonatal hyperbilirubinemia.

Use of the genetic sonogram in the United States in 2001 and 2007.

OBJECTIVE: The purpose of this study was to determine whether there have been changes in the use of second-trimester genetic sonograms and in the second-trimester sonographic markers used to screen for fetal aneuploidy by maternal-fetal medicine specialists in the United States from 2001 to 2007. METHODS: A survey was mailed to Society for Maternal-Fetal Medicine members in the United States in April 2007 inquiring about their practice patterns regarding the genetic sonogram. Specific sonographic markers used for risk adjustment as part of the genetic sonogram were also assessed. The responses from 2007 were compared with responses from a similar survey administered in 2001 (Am J Obstet Gynecol 2002; 187:1230-1234) using descriptive statistics, the chi(2) test, and the Wilcoxon rank sum test. RESULTS: A total of 991 responses were analyzed: 543 of 1638 (32%) in 2001 and 448 of 1756 (26%) in 2007. Significant increases (P < .0001) were noted in the number of specialists who used the genetic sonogram as a screening tool for Down syndrome and for every single sonographic marker used to adjust a woman's risk for having a fetus with Down syndrome during a genetic sonogram, except for choroid plexus cyst, clinodactyly, sandal gap toes, and widened pelvic angle. CONCLUSIONS: Practitioners in the United States are using an increasing number of second-trimester sonographic markers to help identify aneuploid fetuses. The growing acceptance of sonography to screen for fetal aneuploidy and the recommendation by the American College of Obstetricians and Gynecologists for universal screening suggest that more resources may be necessary to meet the growing demand for second-trimester sonograms.