Clinical and genetic characterization of a Chinese family with pontocerebellar hypoplasia type 7.

We report compound heterozygous variants in TOE1 in siblings of Chinese origin who presented with dyskinesia and intellectual disabilities. Our report provides further information regarding the etiology and pathogenesis of pontocerebellar hypoplasia type 7 syndrome (PCH7). Clinical manifestations were obtained, and genomic DNA was collected from family members. Whole-exome and Sanger sequencing were performed to identify associated genetic variants. Bioinformatics analysis was conducted to identify and characterize the pathogenicity of the heterozygous variants. Following long-term rehabilitation, both siblings showed minimal improvement, and their condition tended to progress. Whole-exome sequencing revealed two unreported heterozygous variants, NM_025077: c.C553T (p.R185W) and NM_025077: c.G562T (p.V188L), in the TOE1 gene mapped to 1p34.1. Sanger sequencing confirmed that the two variants in the proband and her brother were inherited from their parents. The NM_025077: c.C553T (p.R185W) variant was inherited from the father, and the NM_025077: c.G562T (p.V188L) variant was inherited from the mother. Although the two variants in the TOE1 gene have not been reported previously, they were associated with PCH7 based on integrated analysis. Thus, our report contributes to our knowledge regarding the etiology and phenotype of PCH 7.

Preparation, characterization, and pharmacokinetics of oridonin-loaded liposomes.

The aim of this study was to prepare oridonin liposomes and evaluate the physicochemical characteristics and pharmacokinetics in rats. A three-level, three-factor Box-Behnken design was used to optimize the preparation of oridonin liposomes. A highly sensitive high-performance liquid chromatographic quantification method using ultraviolet detection was established and validated for the determination of oridonin in rat plasma. Twelve Sprague-Dawley rats were randomly assigned and injected with 15 mg/kg of oridonin or oridonin liposomes via the tail vein. Pharmacokinetic parameters were estimated using a compartmental modeling approach using PKsolver software. The optimum conditions were as follows: soybean phospholipids/cholesterol ratio, 3.9:1; soybean phospholipids/drug ratio, 8.5:1; and soybean phospholipid concentration, 1.1%. Under these conditions, the mean particle size, polydispersity index, zeta potential, and encapsulation efficiency of oridonin liposomes were 170.5 nm, 0.246, -30.3 mV, and 76.15%, respectively. The pharmacokinetic results showed that liposomes could significantly prolong the elimination half-life (from 2.88 ± 0.55 to 13.67 ± 3.52 h), increase the area under the concentration-time curve (from 1.65 ± 0.17 to 6.22 ± 0.83 µg h/ml), and decrease the clearance (from 6.62 ± 1.38 to 1.96 ± 0.24 L/kg h). The oridonin liposomes increased the elimination half-life and area under the concentration-time curve and provided a reference for the development of drugs with a short half-life.

Versatile Application of TiO2@PDA Modified Filter Paper for Oily Wastewater Treatment.

Although membrane separation technology has been widely used in the treatment of oily wastewater, the complexity and high cost of the membrane preparation, as well as its poor stability, limit its further development. In this study, via the vacuum-assisted suction filtration method, polydopamine (PDA)-coated TiO2 nanoparticles were tightly attached and embedded on both sides of laboratory filter paper (FP). The resultant FP possessed the typical wettability of high hydrophilicity in the air with the water contact angle (WCA) of 28°, superoleophilicity with the oil contact angle (OCA) close to 0°, underwater superoleophobicity with the underwater OCA greater than 150°, and superhydrophobicity under the water with the underoil WCA over 150° for five kinds of organic solvents (carbon tetrachloride, toluene, n-hexane, n-octane, and iso-octane). The separation efficiency of immiscible oil/water, oil-in-water, and water-in-oil emulsions using the modified FP is higher than 99%. After 17 cycles of emulsion separation, a high separation efficiency of 99% was still maintained for the FP, along with good chemical and mechanical stability. In addition, successful separation and purification were also realized for the oil-in-water emulsion that contained the methylene blue (MB) dye, along with the complete degradation of MB in an aqueous solution under UV irradiation.

Clinical Analysis of Intranasal Dexmedetomidine Combined With Midazolam in Pediatric Cranial Magnetic Resonance Examinations.

PURPOSE: To observe the efficacy and safety of intranasal dexmedetomidine combined with midazolam in cranial magnetic resonance imaging of children. DESIGN: A prospective, observational, single-arm, one-center study. METHODS: A total of 474 children were scheduled for cranial 3.0 T MRI at the first time. All patients were initially given 3 mcg/kg dexmedetomidine combined with 0.15 mg/kg midazolam. The one-time success rate, vital signs before and after treatment, onset time, recovery time, and incidence of adverse reactions were recorded. FINDINGS: The one-time success rate was 78.1%. There were significant differences in respiration, heart rate, and blood oxygen saturation before and after treatment (P < .001). The onset time was 10 (8-15) minutes. The average recovery time was 2.58 ± 1.10 hours. Only 1.27% (6 cases) of adverse reactions were observed, including bradycardia (3 cases, 0.6%), tachycardia (1 case, 0.2%), and startle (2 cases, 0.4%). No special treatment was needed. The success of the examination was significantly correlated with age (OR 1.320, 95% CI 1.019-1.710, P = .035) and onset time (OR 0.959, 95% CI 0.921-0.998, P = .038). CONCLUSION: Dexmedetomidine 3 mcg/kg combined with midazolam 0.15 mg/kg intranasally has a good sedative effect in pediatric cranial magnetic resonance examinations, little impact on breathing and circulation, and few adverse reactions. Age and onset time are related factors affecting the one-time success rate.

Robust Superhydrophobic Brass Mesh with Electrodeposited Hydroxyapatite Coating for Versatile Applications.

A robust superhydrophobic brass mesh was fabricated based on a low-energy surface and a roughness on the nano/micro-meter scale. It was carried out by the forming of hydroxyapatite (HP) coatings on its surface through a constant current electro-deposition process, followed by immersion in fluoroalkylsilane solution. Surface morphology, composition and wetting behavior were investigated by field-emission scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), high speed camera, and contact angle goniometer. Under optimal conditions, the resulting brass mesh exhibited superhydrophobicity, excellent anti-corrosion (η = 91.2%), and anti-scaling properties. While the surfactant liquid droplets of tetradecyl trimethyl ammonium bromide (TTAB) with different concentration were dropped on the superhydrophobic surface, maximum droplet rebounding heights and different contact angles (CAs) were observed and measured from side-view imaging. The plots of surfactant-concentration-maximum bounding height/CA were constructed to determine its critical-micelle-concentration (CMC) value. Close CMC results of 1.91 and 2.32 mM based on the determination of maximum rebounding height and CAs were obtained. Compared with its theoretical value of 2.1 mM, the relative errors are 9% and 10%, respectively. This indicated that the novel application based on the maximum rebounding height could be an alternative approach for the CMC determination of other surfactants.

Characterization of autoantibodies and cytokines related to cutaneous lupus erythematosus.

OBJECTIVE: To investigate the profiles of anti-RPLP0, anti-galectin3 antibodies, interferon-α (IFN-α), interferon-λ1(IFN-λ1) and interleukin-17A/F(IL-17A/F) in the subtypes of cutaneous lupus erythematosus (CLE) including acute CLE (ACLE), subacute CLE (SCLE) and discoid lupus erythematosus (DLE). METHODS: Serum levels of autoantibodies and cytokines were determined by enzyme-linked immunoabsorbent assay (ELISA). Lupus lesions were evaluated by cutaneous lupus erythematosus disease area and severity index (CLASI). RESULTS: Serum anti-RPLP0, anti-galectin3 antibodies and IFN-λ1 were higher in systemic lupus erythematosus (SLE) patients with skin lesions than those without skin lesions, compared to healthy controls. IFN-α, IL-17A and IL-17F was elevated in all patients regardless of skin lesions. The two antibodies, IFN-α and IL-17A were positively correlated with the CLASI score in all patients with CLE. In addition, serum IL-17A was positively correlated to the CLASI score of ACLE, SCLE and DLE, while anti-RPLP0 and anti-galectin3 antibodies were only correlated to the score of SCLE and IL-17F to DLE. CONCLUSION: Serum anti-RPLP0, anti-galectin3 antibodies, IFN-α, IFN-λ1 and IL-17A/F are associated with the occurrence of lupus skin lesions regardless of the systemic complications, whereas the profiles of these inflammatory mediators vary with the subtypes of lupus skin lesions.

Do-not-resuscitate decision making for terminally ill older patients in the emergency department: An explorative, descriptive inquiry of Chinese family members.

Many terminally ill older adults depend on family members to make medical decisions in China. Many family members find it difficult to make do-not-resuscitate (DNR) decisions in emergency departments (ED). Currently, factors that affect DNR decision making by family members for older adults needing emergency care have not been well studied. This qualitative inquiry explores factors influencing DNR decision-making among family members of terminally ill older adults in ED. Semi-structured in-depth interviews were conducted for a 12-family member of terminally ill older adults at ED in China. Results of the conventional content analysis showed that family members made DNR decisions based on a wide of reasons: (a) subjective perception of family members, (b) conditions of the terminally ill older adults, (c) external environmental factors, and (d) internal family factors. The findings of this study expand our knowledge and understanding of factors influencing DNR decision-making by family members of terminally ill older adults in ED.

[Interpretation of the international expert recommendations of clinical features to prompt referral for diagnostic assessment of cerebral palsy].

Under the guidance and support of national policies in recent years, the community medical system has been developed rapidly, among which primary child healthcare is carried out routinely in community hospitals, greatly alleviating the pressure of specialized pediatric hospitals and departments of pediatrics in secondary and tertiary general hospitals. However, due to the lack of professional training for primary child healthcare personnel in community medical institutions, early symptoms of children with cerebral palsy cannot be identified and so children with cerebral palsy are often unable to receive early diagnosis and intervention, which may affect their prognosis. An article about international expert consensus and recommendations on early identification and referral of cerebral palsy in community medical institutions was published in Development Medicine and Child Neurology in 2020. It proposed six clinical features that should prompt referral and two warning signs that warrant enhanced monitoring, as well as five recommendations for referral to medical experts and other healthcare professionals for the diagnosis of cerebral palsy. The recommendations may help primary child healthcare personnel in community medical institutions to early identify the children at high risk of cerebral palsy, thus reducing the delay of referral and intervention. This article gives an interpretation of the recommendations based on the actual situation in China, in order to improve the ability of primary child healthcare personnel in community medical institutions to early identify high-risk signals of cerebral palsy and conduct reasonable referral. This will help to achieve the early identification, early diagnosis, and early intervention to improve the prognosis of children with cerebral palsy.

Blockade of angiotensin-converting enzyme or tumor necrosis factor-α reverses maternal high-fat diet-induced sensitization of angiotensin II hypertension in male rat offspring.

Maternal high-fat diet (HFD) is associated with metabolic syndrome and cardiovascular diseases in adult offspring. Our previous study demonstrated that maternal HFD enhances pressor responses to ANG II or a proinflammatory cytokine (PIC), which is associated with increased expression of brain renin-angiotensin system (RAS) components and PICs in adult offspring. The present study further investigated whether inhibition of angiotensin-converting enzyme (ACE) or tumor necrosis factor-α (TNF-α) blocks sensitization of ANG II hypertension in offspring of HFD dams. All offspring were bred from dams with normal fat diet (NFD) or HFD starting two weeks before mating and maintained until weaning of the offspring. Then the weaned offspring were treated with an ACE inhibitor (captopril) or a TNF-α inhibitor (pentoxifylline) in the drinking water through the end of testing with a slow-pressor dose of ANG II. RT-PCR analyses of the lamina terminalis and paraventricular nucleus revealed upregulation of mRNA expression of several RAS components and PICs in male offspring of HFD dams when compared with age-matched offspring of NFD dams. The enhanced gene expression was attenuated by blockade of either RAS or PICs. Likewise, ANG II administration produced an augmented pressor response in offspring of HFD dams. This was abolished by either ACE or TNF-α inhibitor. Taken together, this study provides mechanistic evidence and a therapeutic strategy that systemic inhibition of the RAS and PICs can block maternal HFD-induced sensitization of ANG II hypertension, which is associated with attenuation of brain RAS and PIC expression in offspring.

Comparable survival outcome between transplantation from haploidentical donor and matched related donor or unrelated donor for severe aplastic anemia patients aged 40 years and older: A retrospective multicenter cohort study.

This retrospective multicenter cohort study aimed to compare the outcome of haploidentical hematopoietic stem cell transplantation (HID-HSCT) with matched sibling donor (MSD) and unrelated donor (URD) transplantation in severe aplastic anemia (SAA) patients 40 years of age and older. With a median follow-up time of 17.6 months, 85 consecutive patients were enrolled in the study, and the median patient age was 45 years (40, 58). The cumulative engraftment rates of neutrophil and platelet were 98.8 ± 0.0% and 92.9 ± 0.1%. The cumulative incidences of Grade 2-4 acute graft-versus-host disease (aGvHD) and chronic graft-versus-host disease (cGvHD) at 3 years were 14.1 ± 0.1% and 17.3 ± 0.2%. The 3-year estimated overall survival (OS) and failure-free survival (FFS) were 91.2 ± 3.2% and 89.7 ± 3.5%. In multivariate analysis, the only factor associated with inferior survival was an ECOG score ≥2. HID-HSCT was associated with a higher incidence of GvHD, but the difference of 3-year estimated OS between HID group and the other two cohorts was not significant (86.7 ± 6.4% for HID vs 92.1% ± 4.4% for MSD and 100% for URD, P = .481). HID-HSCT might be a feasible alternative option for selected SAA patients aged 40 years and older without a matched donor.

Observation of the Sedative Effect of Dexmedetomidine Combined With Midazolam Nasal Drops Before a Pediatric Craniocerebral MRI.

OBJECTIVE: This study aimed to investigate the sedative effect of dexmedetomidine combined with midazolam nasal drops before a pediatric craniocerebral magnetic resonance imaging (MRI). METHODS: Eighty children who needed an MRI examination were enrolled in the present study and randomly divided into 2 groups: the observation group (dexmedetomidine combined with midazolam nasal drops) and the control group. After the children were given the medication, their heart rate, blood oxygen saturation (SpO2), and respiratory rate were continuously monitored and the adverse reactions such as nausea and vomiting, cough, restlessness, heart rate slowdown, and respiratory depression were observed. RESULTS: The difference in the onset time between the 2 groups was not statistically significant (P > 0.05), but the duration was significantly longer in the observation group than in the control group (P < 0.01) and the examination success rate were significantly higher in the observation group than in the control group (P < 0.05). CONCLUSION: The protocol of 3 µg/kg of a dexmedetomidine injection combined with 0.3 mg/kg of midazolam nasal drops is safe, easy to operate, and has a high success rate, which is worthy of clinical promotion.

[Clinical effect of functional chewing training in treatment of oral motor dysfunction in children with cerebral palsy: a prospective randomized controlled clinical trial].

OBJECTIVE: To study the effect of functional chewing training (FuCT) on masticatory function, the severity of tongue thrust, and the severity and frequency of drooling in children with cerebral palsy. METHODS: A prospective study was performed for 48 children who were diagnosed with oral motor dysfunction from January 2019 to January 2020, and they were randomly divided into an FuCT group and an oral motor training group, with 24 children in each group. Both groups received FuCT or oral motor training for 12 weeks, and then they were evaluated in terms of the changes in the masticatory function, the severity of tongue thrust, and the severity and frequency of drooling. RESULTS: There were no significant differences between the two groups in the masticatory function, the severity of tongue thrust, and the severity and frequency of drooling before treatment (P>0.05). After the 12-week training, the FuCT group showed significant improvements in the masticatory function and the severity of tongue thrust and drooling (P<0.05), but with no improvement in the frequency of drooling (P>0.05), while the oral motor training group had no improvements in the masticatory function, the severity of tongue thrust, and the severity and frequency of drooling (P>0.05). After the 12-week training, the FuCT group had more significantly improvements in the severity of tongue thrust and the severity and frequency of drooling than the oral motor training group (P<0.05). CONCLUSIONS: FuCT can effectively improve the masticatory function, the severity of tongue thrust, and the severity and frequency of drooling in children with cerebral palsy.

Downregulated microRNA-135a ameliorates rheumatoid arthritis by inactivation of the phosphatidylinositol 3-kinase/AKT signaling pathway via phosphatidylinositol 3-kinase regulatory subunit 2.

Synovial fibroblasts (SFs) of rheumatoid arthritis (RA) are phenotypically aggressive, typically progressing into arthritic cartilage degradation. Throughout our study, we made explorations into the effects of microRNA-135a (miR-135a) on the SFs involved in RA by mediating the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway via regulation of phosphatidylinositol 3-kinase regulatory subunit 2 (PIK3R2). The expression of PI3K was higher, the expression of PIK3R2 was lower, and AKT was phosphorylated in the RA synovial tissues, relative to the levels found in the normal synovial tissues. We predicted miR-135a to be a candidate miR targeting PIK3R2 using an online website, microRNA.org, which was verified with a dual-luciferase reporter gene assay. Subsequently, high miR-135a expression was observed in RA synovial tissues. To study the effect of the interaction between miR-135a and PIK3R2 in RA, the SFs isolated from RA samples were cultured and transfected with mimic, inhibitor, and small interfering RNA. The proliferation, invasion, and apoptosis of the SFs were detected after the transfection. The cells transfected with miR-135a inhibitor showed inhibited cell proliferation, migration, and invasion, while also displaying promoted cell apoptosis, G0/G1 cell ratio, and decreased S cell ratio, through upregulation of PIK3R2 and inactivation of the PI3K/AKT signaling pathway. These findings provided evidence that downregulation of miR-135a inhibits proliferation, migration, and invasion and promotes apoptosis of SFs in RA by upregulating the PIK3R2 coupled with inactivating the PI3K/AKT signaling pathway. The downregulation of miR-135a might be a potential target in the treatment of RA.

Benchmark study of popular density functionals for calculating binding energies of three-center two-electron bonds.

Density functional theory (DFT) can be used to study the three-center two-electron (3c2e) bonding mode, which is universal in catalysts containing alkaline-earth (Ae) and boron-group (Bg) elements. However, because of the delocalization pattern of the 3c2e bond, the wavefunction cannot be accurately described by DFT methods. The calculated energies of Ae and Bg catalysts therefore fluctuate greatly when different functionals are used, largely because of inconsistent DFT-calculated binding energies of 3c2e bonds. Nevertheless, with the development of supercomputers and theoretical calculation software, the DFT method is becoming increasingly popular for studying Ae and Bg catalysts. In this study, we compared the performances of 21 functionals with the high-level composite G3B3 method in calculations for the binding energies of 3c2e bonds. Several frequently used post-Hartree-Fock methods were also tested. The calculation results indicate that the M06-2X, MN12-L, and MN15 functionals give consistent and reliable binding energies for common 3c2e bonds. © 2018 Wiley Periodicals, Inc.

Blockade of Stellate Ganglion Remediates Hemorrhagic Shock-Induced Intestinal Barrier Dysfunction.

BACKGROUND: Acute hemorrhage-induced excessive excitation of sympathetic-adrenal-medullary system (SAS) leads to gut hypoperfusion and barrier dysfunction, which is a critical event during hemorrhagic shock-induced multiple organ injury. Stellate ganglion blockade (SGB) has been widely used for suppression of sympathetic-adrenal-medullary system in the clinical practice. However, whether SGB improves intestinal barrier function after hemorrhagic shock remains unclear. Here, we hypothesized that the implementation of SGB restores intestinal barrier function and reduces gut injury. MATERIALS AND METHODS: Male rats received the SGB pretreatment and underwent hemorrhagic shock followed by resuscitation. The 96-h survival rate, intestinal permeability and morphology, D-lactic acid concentration and diamine oxidase activity in plasma, and expressions of F-actin, Claudin-1, and E-cadherin in intestinal tissues were observed. RESULTS: Pretreatment with SGB significantly enhances the 96-h survival rate in rats subjected to hemorrhagic shock (from 8.3% to 66.7%). Hemorrhagic shock reduced the coverage scale of intestinal mucus and intestinal villus width and height, enhanced the intestinal permeability to fluorescein isothiocyanate-dextran 4 and D-lactic acid concentration in plasma, and decreased the expressions of F-actin, Claudin-1, and E-Cadherin in intestinal tissue. These hemorrhagic shock-induced adverse effects were abolished by SGB treatment. CONCLUSIONS: SGB treatment has a beneficial effect during hemorrhagic shock, which is associated with the improvement of intestine barrier function. SGB may be considered as a new therapeutic strategy for treatment of hemorrhagic shock.

Simultaneous determination of six components in commercial Roukou Wuwei pills using ultra-high-performance liquid chromatography with diode-array detector.

An efficient ultra-performance liquid chromatography with diode-array detector method was established for simultaneous determination of six active components in Roukou Wuwei pills, namely gallic acid, piperine, costundide, dehydrocostus lactone, isoalantolactone and alantolactone. Chromatographic separation of six components was successfully achieved on an Waters BEH C18 column (50 × 2.1 mm, 1.7 µm) with a mobile phase composed of acetonitrile and water using a gradient elution. Gallic acid and piperine were detected at 270 nm and 343 nm, respectively; while costundide, dehydrocostus lactone, isoalantolactone and alantolactone were simultaneously measured at 225 nm. All six calibration curves showed good linearity (R2 ≥ 0.9994) between the peak area of each component and corresponding concentration. Relative standard deviations for inter- and intra-day precisions were <0.45 and 0.77%, respectively. The mean recovery rates ranged from 96.72 to 102.2% with relative standard deviations <2.07%. The developed method was validated in terms of linearity, precision and accuracy and then successfully applied for the quality control of commercial Roukou Wuwei samples.

Preparation, characterization and antimicrobial activity of inclusion complexes of Myristica fragrans Hott. essential oil in ß-cyclodextrins.

Inclusion complexes of essential oils with cyclodextrins are an effective way to improve stability and solubility, and turn liquid materials into easy to handle powders. In this work, an essential oil of Myristica fragrans Hott. (MFEO), already used in the food and cosmetics industries, was formulated with beta-cyclodextrins (ß-CD) using a co-precipitation method. The orthogonal array scheme was adapted for the optimization of preparation process. DSC and FT-IR spectroscopy analysis indicated the successful formation of MFEO/ß-CD inclusion complexes, which improved the thermal stability of MFEO. Furthermore, comparing the antimicrobial activity of MFEO/ß-CD inclusion complexes and free essential oil against Staphyloccocus aureus, Staphyloccocus epidermidis, Escherichia coli, Klebsiella pneumoniae, yeast Saccharomyces cerevisiae and Bacillus subtilis, it was found that the antimicrobial effect was enhanced after the formation of inclusion complexes. This study demonstrates the potential for the use of MFEO/ß-CD inclusion complexes in the treatment of bacterial infection.

[Infection factors associated with neurodysplasia in early and moderately preterm infants].

OBJECTIVE: To investigate the infection factors associated with neurodysplasia in early and moderately preterm infants at a corrected age of 18 months. METHODS: The preterm infants with a gestational age of 28 weeks to <34 weeks who were admitted to the neonatal intensive care unit and followed up at the outpatient service for high-risk preterm infants from June 2015 to December 2018 were enrolled as subjects. At a corrected age of 18 months, the revised Bayley Scales of Infant Development was used to evaluate neurodevelopment. Univariate and multivariate logistic regression analyses were used to investigate the infection factors affecting neurodevelopment. RESULTS: A total of 138 early or moderately preterm infants were enrolled, among whom 59 had neurodysplasia at a corrected age of 18 months. The univariate logistic regression analysis showed that neurodysplasia was associated with late-onset infection, positive blood culture, and other systemic infections (P<0.05). The multivariate logistic regression analysis showed that late-onset infection was an independent risk factor for neurodysplasia (OR=1.510, 95%CI: 1.133-3.600, P<0.05). CONCLUSIONS: Late-onset infection can increase the risk of neurodysplasia in early and moderately preterm infants.

Maternal high-fat diet acts on the brain to induce baroreflex dysfunction and sensitization of angiotensin II-induced hypertension in adult offspring.

Accumulating evidence indicates that maternal high-fat diet (HFD) is associated with metabolic syndrome and cardiovascular disease in adult offspring. The present study tested the hypothesis that maternal HFD modulates the brain renin-angiotensin system (RAS), oxidative stress, and proinflammatory cytokines that alter angiotensin II (ANG II) and TNF-α actions and sensitize the ANG II-elicited hypertensive response in adult offspring. All offspring were cross fostered by dams on the same or opposite diet to yield the following four groups: offspring from normal-fat control diet-fed dams suckled by control diet-fed dams (OCC group) or by HFD-fed dams (OCH group) and offspring from HFD-fed dams fed a HFD suckled by control diet-fed dams (OHC group) or by HFD-fed dams (OHH group). RT-PCR analyses of the lamina terminalis and paraventricular nucleus indicated upregulation of mRNA expression of several RAS components, NADPH oxidase, and proinflammatory cytokines in 10-wk-old male offspring of dams fed a HFD during either pregnancy, lactation, or both (OHC, OCH, and OHH groups). These offspring also showed decreased cardiac baroreflex sensitivity and increased pressor responses to intracerebroventricular microinjection of either ANG II or TNF-α. Furthermore, chronic systemic infusion of ANG II resulted in enhanced upregulation of mRNA expression of RAS components, NADPH oxidase, and proinflammatory cytokines in the lamina terminalis and paraventricular nucleus and an augmented hypertensive response in the OHC, OCH, and OHH groups compared with the OCC group. The results suggest that maternal HFD blunts cardiac baroreflex function and enhances pressor responses to ANG II or proinflammatory cytokines through upregulation of the brain RAS, oxidative stress, and inflammation. NEW & NOTEWORTHY The results of our study indicate that a maternal high-fat diet during either pregnancy or lactation is sufficient for perinatal programming of sensitization for hypertension, which is associated with hyperreactivity of central cardiovascular nuclei that, in all likelihood, involves elevated expression of the renin-angiotensin system, NADPH oxidase, and proinflammatory cytokines. The present study demonstrates, for the first time, the central mechanism underlying maternal high-fat diet sensitization of the hypertensive response in adult offspring.

Decrease of galectin-3 in keratinocytes: A potential diagnostic marker and a critical contributor to the pathogenesis of psoriasis.

Psoriasis-specific proteins dysregulated in keratinocytes and involved in the pathophysiological process of psoriasis remains elusive. We report here that epidermal galectin-3 expression is significantly downregulated in lesional skin, but not in non-lesional skin in psoriasis patients, nor in a group of diseases known as psoriasiform dermatitis clinically and histologically similar to psoriasis. The deficiency of epidermal galectin-3 is sufficient to promote development of psoriatic lesions, as evidenced by more severe skin inflammation in galectin-3 knockout (gal3-/-) mice, compared to wild-type mice, after imiquimod treatment, and in skin from gal3-/- mice grafted onto wildtype mice. The development of psoriatic-like lesions is attributable to 1) the spontaneously tuning up of psoriasis signatures in keratinocytes through JNK pathway; and 2) neutrophil accumulation caused by the enhanced leukocyte-recruiting capacity associated with overexpression of S100A7-9 and CXCL-1, 8 in keratinocytes with impaired galectin-3 expression. Psoriasis-like skin inflammation is significantly improved in gal-3-/- mice both by inhibition of neutrophils accumulation with a selective CXCR2 antagonist of SB225002, and by intracutaneous injection of recombinant galectin-3. Overall, these findings offer promising galectin-3-related diagnostic and therapeutic resolutions of psoriasis.