Magnolol, a natural aldehyde dehydrogenase-2 agonist, inhibits the proliferation and collagen synthesis of cardiac fibroblasts.

Inhibiting myocardial fibrosis can help prevent cardiovascular diseases, including heart failure. Magnolol (Mag), a natural component of Magnoliae officinalis, has been reported to inhibit fibrosis. However, the mechanism of Mag activity and its effects on myocardial fibrosis remain unclear. Here, we investigated the involvement of ALDH2, an endogenous protective agent against myocardial fibrosis, in the Mag-mediated inhibition of cardiac fibroblast proliferation and collagen synthesis. We found that Mag significantly inhibited cardiac fibroblast proliferation and collagen synthesis, based on the results of MTT, EdU and western blot assays. Moreover, molecular docking, molecular dynamics simulation and surface plasmon resonance (SPR) assays showed that Mag could bind directly and stably to ALDH2. Further analysis of the mechanism of these effects indicated that treatment with Mag dose-dependently enhanced ALDH2 activity without altering protein expression. Mag could enhance the activity of recombinant human ALDH2 proteins with a half-maximal effective concentration of 5.79 × 10-5 M. In addition, ALDH2 activation via Alda-1 inhibited cardiac fibroblast proliferation and collagen synthesis, while ALDH2 inhibition via daidzin partially blocked the suppressive effects of Mag. In summary, Mag may act as a natural ALDH2 agonist and inhibit cardiac fibroblast proliferation and collagen synthesis.

[Placental PHLDA2 gene imprinting in patients with pre-eclampsia].

OBJECTIVE: To observe the imprinting status of maternally expressed gene pleckstrin homology-like domain, family A, member 2 (PHLDA2) in placental tissues from patients with pre-eclampsia. METHODS: Samples of placental tissues were collected from women with normal pregnancy (n=21) and pre-eclampsia (n=19). We examined two single nucleotide polymorphism (SNPs) which are prone to variation in PHLDA2: the C/T polymorphism in exon 1 and the G/A polymorphism in exon 2, corresponding to rs13390 (PHLDA2-1) and rs1056819 (PHLDA2-2), respectively. DNA PCR-direct sequencing and cDNA RT-PCR-direct sequencing were applied to detect the special-allelic imprinting status of PHLDA2. RESULTS: No heterozygote was found in placental tissues in relation to C/T polymorphism in PHLDA2 exon 1. Differences in heterozygote in relation to G/A polymorphism in PHLDA2 exon 2 were found between pre-eclampsia (4/19) and normal pregnancy(5/21), but without statistical significance. PHLDA2 cDNA from heterozygotes (PHLDA2-2) were all exclusively monoallelically expressed. CONCLUSION: Similargene polymorphism of PHLDA2 (PHLDA2-1 and PHLDA2-2) in placental tissues was found between pre-eclampsia and normal pregnancies. No loss of imprinting (LOI) of PHLDA2 was found in this study.

Hyaluronidase for reducing perineal trauma.

BACKGROUND: Perineal hyaluronidase (HAase) injection was widely used to reduce the occurrence of perineal trauma, pain and need for episiotomy in the 1950s to 1960s. Reports suggested that the administration of HAase was a simple, low risk, low cost and effective way to decrease perineal trauma without adverse effects. OBJECTIVES: The objective of this review was to assess the effectiveness and safety of perineal HAase injection for reducing spontaneous perineal trauma, episiotomy and perineal pain in vaginal deliveries. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2013), the International Clinical Trials Registry Platform (ICTRP) and the Networked Digital Library of Theses and Dissertations (both on 1 April 2013), and reference lists of retrieved studies. We also contacted relevant organisations. SELECTION CRITERIA: Published and unpublished randomised and quasi-randomised controlled trials comparing perineal HAase injection with placebo injection or no intervention in vaginal deliveries. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion, extracted data and evaluated methodological quality. Data were checked for accuracy. MAIN RESULTS: The search strategy identified six potentially eligible studies. Two studies were excluded. We included four randomised controlled trials that randomised a total of 599 women (data were available for 595 women).Two trials (283 women) compared the effects of perineal HAase injection during the second stage of labour with placebo injection and were at low risk of bias. Three trials (one three-armed trial was analysed twice) (373 women) compared the effects of perineal HAase injection during second stage of labour with no intervention and two out of the three trials were at high risk of bias. Data from four trials involving 599 women suggested that perineal HAase injection during second stage of labour had a lower incidence of perineal trauma (average risk ratio (RR) 0.69, 95% confidence interval (CI) 0.50 to 0.95,Tau² = 0.08, I² = 82% compared with women in the control group, but there was no clear evidence of a reduction in the incidence of episiotomy (average RR 0.74, 95% CI 0.43 to 1.29, Tau² = 0.17, I² = 66%), first and second degree perineal lacerations (average RR 0.54, 95% CI 0.38 to 1.33, Tau² = 0.30 , I² = 85%) and third and fourth degree perineal lacerations (RR 0.12, 95% CI 0.01 to 2.13). Data from two trials involving 283 women indicated that there was no clear evidence of a reduction in the incidence of perineal trauma (RR 0.90, 95% CI 0.77 to 1.06, Tau²=1.07, I² = 7%), episiotomy (RR 0.77, 95% CI 0.32 to 1.89, Tau² = 0.27, I² = 54%), first and second degree perineal lacerations (RR 1.08, 95% CI 0.83 to 1.40, Tau² = 1.11, I² = 10%) and third and fourth degree perineal lacerations (RR 0.12, 95% CI 0.01 to 2.13) with perineal HAase injection. Data from three trials involving 373 women suggested that perineal HAase injection during second stage of labour had a lower incidence of perineal trauma (RR 0.61, 95% CI 0.42 to 0.88, Tau² = 0.08, I² = 78%) compared with no intervention, but had no clear effect on in the incidence of episiotomy (RR 0.79, 95% CI 0.44 to 1.42, Tau² = 0.16, I² = 70%) and first and second degree perineal lacerations (RR 0.58, 95% CI 0.31 to 1.10, Tau² = 0.18, I² = 59%). No side effects were reported in the included trials.No included trials reported on perineal pain and other pre-specified secondary outcomes: perineal trauma requiring suturing; blood loss; dyspareunia; urinary incontinence; faecal incontinence; assisted delivery rate; women's satisfaction; Apgar score less than seven at five minutes and need for admission to special care baby unit. AUTHORS' CONCLUSIONS: Perineal HAase injection during second stage of labour had a lower incidence of perineal trauma compared with control or no intervention, but there was no clear evidence of benefit compared with placebo injection. The difference in incidence of perineal trauma may probably be due to bias and confounding in the non-placebo controlled comparison, this result should be interpreted cautiously. The potential use of perineal HAase injection as a method to reduce perineal trauma were yet to be determined as there was no appropriate established dose for HAase, no evidence of follow up, and the number of high-quality trials and outcomes reported were too limited to draw conclusions on its effectiveness and safety. Further rigorous randomised controlled trials are required to evaluate the role of perineal HAase injection in vaginal deliveries.

Corrigendum to "Ginsenoside Ro, an oleanolic saponin of Panax ginseng, exerts anti-inflammatory effect by direct inhibiting toll like receptor 4 signaling pathway" [J Ginseng Res 46 (2022) 156-166].

[This corrects the article DOI: 10.1016/j.jgr.2021.05.011.].

Ginsenoside Ro, an oleanolic saponin of Panax ginseng, exerts anti-inflammatory effect by direct inhibiting toll like receptor 4 signaling pathway.

BACKGROUND: Panax ginseng Meyer (P. ginseng), a herb distributed in Korea, China and Japan, exerts benefits on diverse inflammatory conditions. However, the underlying mechanism and active ingredients remains largely unclear. Herein, we aimed to explore the active ingredients of P. ginseng against inflammation and elucidate underlying mechanisms. METHODS: Inflammation model was constructed by lipopolysaccharide (LPS) in C57BL/6 mice and RAW264.7 macrophages. Molecular docking, molecular dynamics, surface plasmon resonance imaging (SPRi) and immunofluorescence were utilized to predict active component. RESULTS: P. ginseng significantly inhibited LPS-induced lung injury and the expression of pro-inflammatory factors, including TNF-α, IL-6 and IL-1ß. Additionally, P. ginseng blocked fluorescence-labeled LPS (LPS488) binding to the membranes of RAW264.7 macrophages, the phosphorylation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs). Furthermore, molecular docking demonstrated that ginsenoside Ro (GRo) docked into the LPS binding site of toll like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD2) complex. Molecular dynamic simulations showed that the MD2-GRo binding conformation was stable. SPRi demonstrated an excellent interaction between TLR4/MD2 complex and GRo (KD value of 1.16 × 10-9 M). GRo significantly inhibited LPS488 binding to cell membranes. Further studies showed that GRo markedly suppressed LPS-triggered lung injury, the transcription and secretion levels of TNF-α, IL-6 and IL-1ß. Moreover, the phosphorylation of NF-κB and MAPKs as well as the p65 subunit nuclear translocation were inhibited by GRo dose-dependently. CONCLUSION: Our results suggest that GRo exerts anti-inflammation actions by direct inhibition of TLR4 signaling pathway.

[Influence of Qingxiang San on substance P, somatostatin in rats model with the spleen and stomach wet heat syndrome].

OBJECTIVE: To observe the influence of Qingxiang San (QS) on substance P (SP), somatostatin (SS) in rats model of spleen and stomach wet heat syndrome. METHODS: 24 rats were divided into 3 groups (each group 8 rats) randomly: the normal control group (NCG), wet heat group (WHG), QS group (QSG). We set up the spleen and stomach wet heat syndrome of rats model by the composite factors such as greasy and sweet food, wet and hot environment, pathogen and so on. Then the contents of SP, SS were detected by radioimmuno assay. RESULTS: The content of SP, SS in WHG were obviously lower than NCG (P<0.01); QSG compared with WHG, the content of SP, SS increased (P<0.01); The content of SP obviously increased when QSG compared with NCG (P<0.01); About the content of SS, there was no significant difference between QSG and NCG (P>0.05), illustrating that QS can increase the content of SP, SS which had decreased. CONCLUSION: QS can regulate the content of SP and SS and increase them which had decreased.

Low-Dose Aspirin for Preventing Preeclampsia and Its Complications: A Meta-Analysis.

Low-dose aspirin (LDA) is thought to prevent preeclampsia in high-risk pregnancy, but it is not universally used out of concern for its efficacy and safety. The authors meta-analyzed 29 randomized controlled trials (RCTs) to evaluate LDA for preventing preeclampsia and its complications. LDA can reduce the incidence of preeclampsia (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.57-0.87), severe preeclampsia (OR, 0.37; 95% CI, 0.23-0.61), preterm birth (OR, 0.81; 95% CI, 0.75-0.88), and intrauterine growth restriction (IUGR) (OR, 0.80; 95% CI, 0.71-0.90). LDA is more effective in reducing incidence of preeclampsia or IUGR if used before 16 gestational weeks than if used later. LDA increases the incidence of placental abruption (OR, 1.35; 95% CI, 1.05-1.73) but not other major complications. The available evidence suggests that LDA is effective in preventing preeclampsia, preterm birth, and IUGR in high-risk pregnancies without posing a major safety risk to mothers or fetuses.