Effect of Prenatal Omega-3 Polyunsaturated Fatty Acid Supplementation on Childhood Eczema: A Systematic Review and Meta-Analysis.

It is uncertain about the effect of omega-3 polyunsaturated fatty acid (ω-3 PUFA) supplementation during pregnancy on the incidence of eczema among children. The aim of this review was to test if there is an effect of ω-3 PUFA supplementation during pregnancy on the risk of eczema among children of different ages. Two authors independently carried out the selection of published works, data extraction, and evaluation of the likelihood of bias. The PubMed, Medline, the Cochrane Library, Web of Science, and Embase databases updated to the date of March 2021 have been researched thoroughly for literature review. Quality Assessment of studies was evaluated using the updated tool (Rob2) provided by the Cochrane collaboration group. Six unique randomized controlled trials from 7 studies including 1,646 mother-infant pairs were contained in this review. Pooled data showed no pronounced decline in the incidence of eczema (RR = 1.09, 95% CI = 0.82~1.46, p = 0.54) or IgE-associated eczema (RR = 0.67; 95% CI = 0.29~1.57; p = 0.34). However, the subgroup analyses on "IgE-associated eczema" showed a significant decrease among the "≤3-year-old children" (RR = 0.70; 95% CI = 0.50~0.96; p = 0.03) in the ω-3 PUFAs group compared with the placebo. Supplementing the maternal diet with ω-3 PUFAs during pregnancy cannot reduce the danger of eczema or IgE-associated eczema among all children; however, there may be a subgroup-specific effect on 3-year-old or even younger children in reducing the incidence of IgE-associated eczema.

A dose-response meta-analysis of the association between the maternal omega-3 long-chain polyunsaturated fatty acids supplement and risk of asthma/wheeze in offspring.

BACKGROUND: Prenatal exposure to omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) in oily fish may prevent asthma or wheeze in childhood. OBJECTIVE: By limiting n-3 LC-PUFA capsules interventions commenced in pregnancy, this systematic review aimed to find more clear evidence on the relationship between the supplement with n-3 LC-PUFA during pregnancy and the risk of asthma/wheeze in offspring and to improve the life satisfaction of children with asthma. METHODS: The Cochrane library, Embase, Medline, Web of Science, and PubMed were searched from origin to March 2021 in the above-mentioned databases. Studies selection, data of characteristics extraction, and risk of bias assessment were conducted by two authors, independently. A total of 3037 mother-infant pairs from eight randomized controlled trials were ultimately analyzed. The primary outcome was the risk of "asthma and/or wheeze", and the secondary outcome was "Allergic asthma" in this dose-response meta-analysis. Sensitivity analysis and subgroup analysis were conducted. The robust-error meta-regression model was used for dose-response analysis. RESULTS: This meta-analysis showed that n-3 LC-PUFA during pregnancy did not obviously reduce the risk of asthma/wheeze (RR 0.93; 95% CI 0.82 to 1.04, p = 0.21) and allergic asthma (RR 0.66, 95% CI 0.24 to 1.86, p = 0.44). The risk of asthma/wheeze in offspring was significantly decreased in the subgroup analysis when:: (1) studies conducted in Europe (RR 0.69; 95% CI 0.53 to 0.89); (2) daily supplementary dose of n-3 LC-PUFA was at least 1200 mg (RR 0.69; 95% CI 0.55 to 0.88); (3) supplementation lasts from pregnancy to lactation period (RR 0.69; 95% CI 0.51 to 0.95). Furthermore, the risk of asthma/wheeze reduce 2% when daily supplemental dose of n-3 LC-PUFA was increased by 100 mg in the linear dose-response analysis model. CONCLUSIONS: Perinatal supplementation with n-3 LC-PUFA can reduce the incidence of asthma/wheeze and allergic asthma in children under certain conditions, and higher doses indicate better protective effects. Further studies are required to confirm the hypothesis of an association between n-3 LC-PUFA intake and childhood asthma/wheeze prevention.

Targeted Delivery of Curcumin Rescues Endoplasmic Reticulum-Retained Mutant NOX2 Protein and Avoids Leukocyte Apoptosis.

Chronic granulomatous disease (CGD) is a primary immunodeficiency disease caused by defects in the leukocyte NADP oxidase. We previously reported that sarcoplasmic/endoplasmic reticulum calcium pump (SERCA) inhibitors could be used to rescue mutant H338Y-gp91phox protein of a particular type of CGD with a CybbC1024T mutation, leading to endoplasmic reticulum (ER) retention of the mutant protein. In this study, we developed a novel mouse model with the CybbC1024T mutation on a Cybb knockout background and investigated the therapeutic effects of ER-targeted delivery of the SERCA inhibitor, curcumin, with poly(lactic-coglycolic acid) (PLGA) nanoparticles (NPs). We found that PLGA encapsulation improved the efficacy of curcumin as a SERCA inhibitor to induce ER calcium release. ER-targeting curcumin-loaded PLGA NPs reduced and delayed extracellular calcium entry and protected the cells from mitochondrial damage and apoptosis. In vivo studies showed that ER-targeting curcumin-loaded PLGA NPs treatment enhanced neutrophil gp91phox expression, ROS production and peritoneal bacterial clearance ability of the CybbC1024T transgenic Cybb -/- mice. Our findings indicate that ER-targeted delivery of curcumin not only rescues ER-retained H338Y-gp91phox protein, and hence leukocyte function, but also enhances the bioavailability and reduces cytotoxicity. Modulation of ER function by using organelle-targeted NPs may be a promising strategy to improve the therapeutic potential of curcumin as a treatment for CGD.

Molecular Mechanisms of Anticancer Effects of Phytoestrogens in Breast Cancer.

Phytoestrogens derived from plants exert estrogenic as well as antiestrogenic effects and multiple actions within breast cancer cells. Chemopreventive properties of phytoestrogens have emerged from epidemiological observations. In recent clinical research studies, phytoestrogens are safe and may even protect against breast cancer. In this brief review, the molecular mechanisms of phytoestrogens on regulation of cell cycle, apoptosis, estrogen receptors, cell signaling pathways, and epigenetic modulations in relation to breast cancer are discussed. Phytoestrogens have a preferential affinity for estrogen receptor (ER)-ß, which appears to be associated with antiproliferative and anticarcinogenic effects. Moreover, while phytoestrogens not only inhibit ER-positive but also ER-negative breast cancer cells, the possibility of epigenetic modulation playing an important role is also discussed. In conclusion, as there are multiple targets and actions of phytoestrogens, extensive research is still necessary. However, due to low toxicity, low cost, and easy availability, their potent chemoprevention effects deserve further study.

Yoga for asthma.

BACKGROUND: Asthma is a common chronic inflammatory disorder affecting about 300 million people worldwide. As a holistic therapy, yoga has the potential to relieve both the physical and psychological suffering of people with asthma, and its popularity has expanded globally. A number of clinical trials have been carried out to evaluate the effects of yoga practice, with inconsistent results. OBJECTIVES: To assess the effects of yoga in people with asthma. SEARCH METHODS: We systematically searched the Cochrane Airways Group Register of Trials, which is derived from systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, AMED, and PsycINFO, and handsearching of respiratory journals and meeting abstracts. We also searched PEDro. We searched ClinicalTrials.gov and the WHO ICTRP search portal. We searched all databases from their inception to 22 July 2015, and used no restriction on language of publication. We checked the reference lists of eligible studies and relevant review articles for additional studies. We attempted to contact investigators of eligible studies and experts in the field to learn of other published and unpublished studies. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared yoga with usual care (or no intervention) or sham intervention in people with asthma and reported at least one of the following outcomes: quality of life, asthma symptom score, asthma control, lung function measures, asthma medication usage, and adverse events. DATA COLLECTION AND ANALYSIS: We extracted bibliographic information, characteristics of participants, characteristics of interventions and controls, characteristics of methodology, and results for the outcomes of our interest from eligible studies. For continuous outcomes, we used mean difference (MD) with 95% confidence interval (CI) to denote the treatment effects, if the outcomes were measured by the same scale across studies. Alternatively, if the outcomes were measured by different scales across studies, we used standardized mean difference (SMD) with 95% CI. For dichotomous outcomes, we used risk ratio (RR) with 95% CI to measure the treatment effects. We performed meta-analysis with Review Manager 5.3. We used the fixed-effect model to pool the data, unless there was substantial heterogeneity among studies, in which case we used the random-effects model instead. For outcomes inappropriate or impossible to pool quantitatively, we conducted a descriptive analysis and summarized the findings narratively. MAIN RESULTS: We included 15 RCTs with a total of 1048 participants. Most of the trials were conducted in India, followed by Europe and the United States. The majority of participants were adults of both sexes with mild to moderate asthma for six months to more than 23 years. Five studies included yoga breathing alone, while the other studies assessed yoga interventions that included breathing, posture, and meditation. Interventions lasted from two weeks to 54 months, for no more than six months in the majority of studies. The risk of bias was low across all domains in one study and unclear or high in at least one domain for the remainder.There was some evidence that yoga may improve quality of life (MD in Asthma Quality of Life Questionnaire (AQLQ) score per item 0.57 units on a 7-point scale, 95% CI 0.37 to 0.77; 5 studies; 375 participants), improve symptoms (SMD 0.37, 95% CI 0.09 to 0.65; 3 studies; 243 participants), and reduce medication usage (RR 5.35, 95% CI 1.29 to 22.11; 2 studies) in people with asthma. The MD for AQLQ score exceeded the minimal clinically important difference (MCID) of 0.5, but whether the mean changes exceeded the MCID for asthma symptoms is uncertain due to the lack of an established MCID in the severity scores used in the included studies. The effects of yoga on change from baseline forced expiratory volume in one second (MD 0.04 liters, 95% CI -0.10 to 0.19; 7 studies; 340 participants; I2 = 68%) were not statistically significant. Two studies indicated improved asthma control, but due to very significant heterogeneity (I2 = 98%) we did not pool data. No serious adverse events associated with yoga were reported, but the data on this outcome was limited. AUTHORS CONCLUSIONS: We found moderate-quality evidence that yoga probably leads to small improvements in quality of life and symptoms in people with asthma. There is more uncertainty about potential adverse effects of yoga and its impact on lung function and medication usage. RCTs with a large sample size and high methodological and reporting quality are needed to confirm the effects of yoga for asthma.

Yoga for asthma.

BACKGROUND: Asthma is a common chronic inflammatory disorder affecting about 300 million people worldwide. As a holistic therapy, yoga has the potential to relieve both the physical and psychological suffering of people with asthma, and its popularity has expanded globally. A number of clinical trials have been carried out to evaluate the effects of yoga practice, with inconsistent results. OBJECTIVES: To assess the effects of yoga in people with asthma. SEARCH METHODS: We systematically searched the Cochrane Airways Group Register of Trials, which is derived from systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, AMED, and PsycINFO, and handsearching of respiratory journals and meeting abstracts. We also searched PEDro. We searched ClinicalTrials.gov and the WHO ICTRP search portal. We searched all databases from their inception to 22 July 2015, and used no restriction on language of publication. We checked the reference lists of eligible studies and relevant review articles for additional studies. We attempted to contact investigators of eligible studies and experts in the field to learn of other published and unpublished studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared yoga with usual care (or no intervention) or sham intervention in people with asthma and reported at least one of the following outcomes: quality of life, asthma symptom score, asthma control, lung function measures, asthma medication usage, and adverse events. DATA COLLECTION AND ANALYSIS: We extracted bibliographic information, characteristics of participants, characteristics of interventions and controls, characteristics of methodology, and results for the outcomes of our interest from eligible studies. For continuous outcomes, we used mean difference (MD) with 95% confidence interval (CI) to denote the treatment effects, if the outcomes were measured by the same scale across studies. Alternatively, if the outcomes were measured by different scales across studies, we used standardised mean difference (SMD) with 95% CI. For dichotomous outcomes, we used risk ratio (RR) with 95% CI to measure the treatment effects. We performed meta-analysis with Review Manager 5.3. We used the fixed-effect model to pool the data, unless there was substantial heterogeneity among studies, in which case we used the random-effects model instead. For outcomes inappropriate or impossible to pool quantitatively, we conducted a descriptive analysis and summarised the findings narratively. MAIN RESULTS: We included 15 RCTs with a total of 1048 participants. Most of the trials were conducted in India, followed by Europe and the United States. The majority of participants were adults of both sexes with mild to moderate asthma for six months to more than 23 years. Five studies included yoga breathing alone, while the other studies assessed yoga interventions that included breathing, posture, and meditation. Interventions lasted from two weeks to 54 months, for no more than six months in the majority of studies. The risk of bias was low across all domains in one study and unclear or high in at least one domain for the remainder.There was some evidence that yoga may improve quality of life (MD in Asthma Quality of Life Questionnaire (AQLQ) score per item 0.57 units on a 7-point scale, 95% CI 0.37 to 0.77; 5 studies; 375 participants), improve symptoms (SMD 0.37, 95% CI 0.09 to 0.65; 3 studies; 243 participants), and reduce medication usage (RR 5.35, 95% CI 1.29 to 22.11; 2 studies) in people with asthma. The MD for AQLQ score exceeded the minimal clinically important difference (MCID) of 0.5, but whether the mean changes exceeded the MCID for asthma symptoms is uncertain due to the lack of an established MCID in the severity scores used in the included studies. The effects of yoga on change from baseline forced expiratory volume in one second (MD 0.04 litres, 95% CI -0.10 to 0.19; 7 studies; 340 participants; I(2) = 68%) were not statistically significant. Two studies indicated improved asthma control, but due to very significant heterogeneity (I(2) = 98%) we did not pool data. No serious adverse events associated with yoga were reported, but the data on this outcome was limited. AUTHORS' CONCLUSIONS: We found moderate-quality evidence that yoga probably leads to small improvements in quality of life and symptoms in people with asthma. There is more uncertainty about potential adverse effects of yoga and its impact on lung function and medication usage. RCTs with a large sample size and high methodological and reporting quality are needed to confirm the effects of yoga for asthma.

Tong-xin-luo capsule for patients with coronary heart disease after percutaneous coronary intervention.

BACKGROUND: Percutaneous coronary intervention (PCI) is a standard treatment for coronary heart disease (CHD). Restenosis, defined as a 50% reduction in luminal diameter at six months after PCI, indicates a need for revascularisation. Restenosis has proven to be a major drawback to PCI. Tong-xin-luo is one of the prophylactic strategies for cardiovascular events in patients after PCI that is widely used in China, but its efficacy and safety have not been systematically evaluated. OBJECTIVES: To systematically assess the efficacy and safety of Tong-xin-luo capsules in preventing cardiovascular events after PCI in patients with CHD. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE (OVID), EMBASE (OVID), WanFang, Chinese Biomedical Database, Chinese Medical Current Contents, and China National Knowledge Infrastructure from their inception to June 2014. We also searched other resources, including ongoing trials and research registries. We applied no language restrictions. SELECTION CRITERIA: Randomised controlled trials of participants with CHD after PCI were included. Participants in the intervention group received Tong-xin-luo capsules for at least three months. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed the risk of bias. Any disagreements were resolved by discussion with a third review author. The primary outcomes included occurrence of angiographic restenosis and adverse events; the secondary outcomes included myocardial infarction, heart failure, angina, all cause mortality, mortality due to any cardiovascular event, use of revascularisation, patient acceptability, quality of life and cost-effectiveness. Dichotomous data were measured with risk ratios (RRs) with 95% confidence intervals (CIs). MAIN RESULTS: Sixteen studies involving 1063 participants were identified. The risk of bias for fifteen studies was high and along with imprecision and possible publication bias, this lowered our confidence in the results. There was low quality evidence that Tong-xi-luo reduced the rates of angiographic restenosis (RR 0.16, 95% CI 0.07 to 0.34), myocardial infarction (RR 0.32, 95% CI 0.16 to 0.66), heart failure (RR 0.26, 95% CI 0.11 to 0.62), and use of revascularisation (RR 0.26, 95% CI 0.15 to 0.45). There was very low quality evidence for the effect of Tong-xin-luo on all-cause mortality (RR 0.38, 95% CI 0.06 to 2.56), angina (RR 0.24, 95% CI 0.17 to 0.34) and death due to any cardiovascular event (RR 0.31, 95% CI 0.08 to 1.12). Adverse events were seldom reported, and included gastrointestinal reactions and nausea. AUTHORS' CONCLUSIONS: The addition of Tong-xin-luo to conventional Western medicine may possibly prevent restenosis and recurrence of cardiovascular events in patients with CHD after PCI. However, the data are limited by publication bias and high risk of bias for included studies. Further high-quality trials are required to evaluate the potential effects of this intervention.

Redox Regulation of Pro-IL-1ß Processing May Contribute to the Increased Severity of Serum-Induced Arthritis in NOX2-Deficient Mice.

AIMS: To elucidate the role of reactive oxygen species (ROS) in arthritis and to identify targets of arthritis treatment in conditions with different levels of oxidant stress. RESULTS: Through establishing an arthritis model by injecting arthritogenic serum into wild-type and NADPH oxidase 2 (NOX2)-deficient mice, we found that arthritis had a neutrophilic infiltrate and was more severe in Ncf1(-/-) mice, a mouse strain lacking the expression of the NCF1/p47(phox) component of NOX2. The levels of interleukin-1ß (IL-1ß) and IL-6 in inflamed joints were higher in Ncf1(-/-) than in controls. Antagonists of tumor necrosis factor-α (TNFα) and IL-1ß were equally effective in suppressing arthritis in wild-type mice, while IL-1ß blockade was more effective than TNFα blockade in Ncf1(-/-) mice. A treatment of caspase inhibitor and the combination treatment of a caspase inhibitor and a cathepsin inhibitor, but not a cathepsin inhibitor alone, suppressed arthritic severity in the wild-type mice, while a treatment of cathepsin inhibitor and the combination treatment of a caspase inhibitor and a cathepsin inhibitor, but not a caspase inhibitor alone, were effective in treating Ncf1(-/-) mice. Consistently, cathepsin B was found to proteolytically process pro-IL-1ß to its active form and this activity was suppressed by ROS. INNOVATION: This novel mechanism of a redox-mediated immune regulation of arthritis through leukocyte-produced ROS is important for devising an optimal treatment for patients with different levels of tissue ROS. CONCLUSION: Our results suggest that ROS act as a negative feedback to constrain IL-1ß-mediated inflammation, accounting for the more severe arthritis in the absence of NOX2.

Wedelolactone inhibits breast cancer-induced osteoclastogenesis by decreasing Akt/mTOR signaling.

The bone is the most common metastatic site of breast cancer. Bone metastasis causes pain, pathologic fractures, and severely reduces the quality of life. Breast cancer causes osteolytic bone metastasis, which is dependent on osteoclast-mediated bone resorption. While current treatments rely on palliative anti-resorptive agents, there is a need to develop a drug based on potential alternative therapies. This study is the first to determine that wedelolactone (WDL), a natural coumarin isolated from plants, can inhibit breast cancer-mediated osteoclastogenesis. Osteoclasts were generated from human CD14(+) monocytes cultured with M-CSF/RANKL and WDL suppressed human osteoclast differentiation and activity in vitro in a dose-dependent manner. Moreover, WDL inhibited the upregulation of osteoclasts stimulated by MDA­MB­231 breast cancer cells. The activity of WDL on osteoclasts and breast cancer-mediated osteoclastogenesis was associated with the inhibition of Akt/mammalian target of the rapamycin signaling pathway (mTOR). Blocking Akt and mTOR by specific inhibitors significantly decreased osteoclast differentiation and bone resorption. Furthermore, WDL regulated breast cancer-enhanced interaction of osteoblasts and osteoclasts by decreasing M-CSF expression in MDA­MB­231-stimulated osteoblasts. Thus, this study suggests that WDL may be a potential natural agent for preventing and treating bone destruction in patients with bone metastasis due to breast cancer.

Arctigenin, a dietary phytoestrogen, induces apoptosis of estrogen receptor-negative breast cancer cells through the ROS/p38 MAPK pathway and epigenetic regulation.

This study investigates the anticancer effect of arctigenin (ATG), a natural lignan product of Arctium lappa L., in human breast cancer MDA-MB-231 cells. Results indicate that ATG inhibits MDA-MB-231 cell growth by inducing apoptosis in vitro and in vivo. ATG triggers the mitochondrial caspase-independent pathways, as indicated by changes in Bax/Bcl-2 ratio, resulting in AIF and EndoG nuclear translocation. ATG increased cellular reactive oxygen species (ROS) production by increasing p22(phox)/NADPH oxidase 1 interaction and decreasing glutathione level. ATG clearly increases the activation of p38 MAPK, but not JNK and ERK1/2. Antioxidant EUK-8, a synthetic catalytic superoxide and hydrogen peroxide scavenger, significantly decreases ATG-mediated p38 activation and apoptosis. Blocking p38 with a specific inhibitor suppresses ATG-mediated Bcl-2 downregulation and apoptosis. Moreover, ATG activates ATF-2, a transcription factor activated by p38, and then upregulates histone H3K9 trimethylation in the Bcl-2 gene promoter region, resulting in Bcl-2 downregulation. Taken together, the results demonstrate that ATG induces apoptosis of MDA-MB-231 cells via the ROS/p38 MAPK pathway and epigenetic regulation of Bcl-2 by upregulation of histone H3K9 trimethylation.

Induction of apoptosis in human Hep3B hepatoma cells by norcantharidin through a p53 independent pathway via TRAIL/DR5 signal transduction.

OBJECTIVE: To investigate the inhibitory activities of norcantharidin (NCTD), a demethylated analogue of cantharidin, on Hep3B cells (a human hepatoma cell line) with deficiency of p53. METHODS: The survival rate of the Hep3B cells after treating with NCTD was measured by MTT assay. Cell cycle of treated cells was analyzed by flow cytometry, and DNA fragmentation was observed by electrophoresis. The influence of inhibitors for various caspases and anti-death receptors antibodies on the NCTD-induced apoptosis in the cells was determined. RESULTS: NCTD treatment resulted in growth inhibition of Hep3B cells in a dose- and time-dependent manner. Cell cycle analysis of the cells after treatment with NCTD for 48 h shows that NCTD induced G(2)M phase arrest occurs at low concentration ([Symbol: see text] 25 µmol/L) but G(0)G(1) phase arrest at high concentration (50 µmol/L). The addition of both caspase-3 and caspase-10 inhibitors completely inhibited DNA fragmentation. Addition of anti-TRAIL/DR5 antibody significantly inhibited DNA fragmentation. CONCLUSION: NCTD may inhibit the proliferation of Hep3B cells by arresting cell cycle at G(2)M or G(0)G(1) phase, and induce cells apoptosis via TRAIL/DR5 signal transduction through activation of caspase-3 and caspase-10 by a p53-independent pathway.