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Sleep deprivation is a common problem during pregnancy, but its impact on the fetus remains unclear. We aimed to investigate the effect of sleep deprivation during pregnancy on fetal outcomes and its mechanism in Sprague–Dawley rats. Sleep deprivation was performed from gestational day(GD) 1–19 using a multiplatform method for 18 h/day. Rats were sacrificed on GD20, and their blood and placentas were collected. Fetal and placental parameters were ascertained. Melatonin, adrenocorticotropic hormone (ACTH) and corticosterone were also measured in serum. The levels of arylalkylamine N-acetyltransferase (AANAT) and two melatonin receptors MT1 and MT2, in placental tissues were detected by western blotting. The inflammatory status and oxidative stress in serum and placentas were investigated. Miscarriage and intrauterine growth restriction were observed in the sleep deprivation group. Sleep deprivation resulted in an increased fetal absorption rate, while fetal weight, crown-rump length and placental weight were reduced. Placental histopathology showed that the labyrinth ratio in the sleep deprivation group was significantly reduced, with hypoplastic villi and obviously decreased blood vessels. Sleep deprivation decreased melatonin in serum and the expression of AANAT, MT1 and MT2 in placental tissues, elevated the oxidative stress products 8-hydroxy-deoxyguanosine (8-OHdG) and malondialdehyde(MDA) in serum and 4-hydroxynonenal (4HNE) in the placenta, and decreased the antioxidants superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) in serum. Serum proinflammatory cytokines including interleukin-1-beta (IL-1β), interleukin-6 (IL-6), necrotizing factor-alpha (TNF-α), and interleukin-8(IL-8), were all elevated by sleep deprivation, and the inflammatory regulatory factor nuclear factor-κB p65 (NF-κB p65) in the placenta was enhanced when examined by immunohistochemistry. Corticosterone levels were comparable between the two groups, although ACTH levels were elevated significantly in the sleep deprivation group. Our study revealed that sleep deprivation during pregnancy can adversely impact fetal outcomes. Melatonin may play an important role in this pathology through the oxido-inflammatory process. • Sleep deprivation during pregnancy leaded to poor fetal outcomes, including miscarriage and intrauterine growth restriction. • Sleep deprivation inhibited the synthesis of melatonin and the expression of melatonin receptors in placental tissue. • Decreased melatonin production, accompanied by excessive oxidative stress and inflammation may be the underlying mechanism. [ABSTRACT FROM AUTHOR]

Aims and Objective: To summarize evidence from systematic reviews (SRs)/meta‐analyses (MAs) regarding the impact of dyadic interventions delivered to both members of a cancer dyad, including a cancer patient and caregiver (e.g. family caregiver, intimate partner). Design: This overview of SRs was conducted in accordance with the preferred reporting items for overviews of reviews statement. Methods: A comprehensive search of multiple databases, including PubMed, Cochrane Library, Embase, CINAHL, Web of Science, China National Knowledge Infrastructure and Wan Fang. The methodological and reporting quality of SRs and MAs was assessed using the Assessing the Methodological Quality of Systematic Reviews 2. The quality of the included SRs/MAs was evaluated using the Grades of Recommendations, Assessment, Development and Evaluation approach. Results: Eighteen SRs/MAs undertook quantitative synthesis to assess the impact of dyadic interventions on cancer dyads. Both the credibility of the SRs/MAs and the evidence quality of the outcome measures were below satisfactory standards. Prior SRs/MAs revealed several limitations such as lack of pre‐published protocols or research objectives, failure to report excluded studies and insufficient details on funding sources for individual studies. Conclusions: Dyadic interventions may prove advantageous for the physical health and dyadic adjustment of cancer dyads. Nevertheless, the reported results of dyadic interventions on the psychological health of patient–caregiver dyads affected by cancer are inconsistent. Thus, rigorous and comprehensive studies are requisite to establish reliable evidence for conclusive determinations. Relevance to Clinical Practice: The findings of this overview can guide healthcare practitioners when considering the use of dyadic interventions for cancer dyads. Moreover, these findings have the potential to enhance the integration of these approaches into clinical practice. Patient or Public Contribution: Our paper presents an overview of systematic reviews, and therefore, such specific details may not be relevant to our study. [ABSTRACT FROM AUTHOR]

Previous evidence has indicated a beneficial role for aldehyde dehydrogenase 2 (ALDH2) in suppressing atherosclerotic plaque progression and instability. However, the underlying mechanism remains somewhat elusive. This study was designed to examine the effect of ALDH2 deficiency on high-cholesterol diet-induced atherosclerotic plaque progression and plaque vulnerability in atherosclerosis-prone ApoE knockout (ApoE−/−) mice with a focus on foam cell formation in macrophages and senescence of vascular smooth muscle cells (VSMCs). Serum lipid profile, plaque progression, and plaque vulnerability were examined in ApoE−/− and ALDH2/ApoE double knockout (ALDH2−/−ApoE−/−) mice after high-cholesterol diet intake for 8 weeks. ALDH2 deficiency increased the serum levels of triglycerides while it decreased levels of total cholesterol and high-density lipoprotein cholesterol. Unexpectedly, ALDH2 deficiency reduced the plaque area by 58.9% and 37.5% in aorta and aortic sinus, respectively. Plaque instability was aggravated by ALDH2 deficiency along with the increased necrotic core size, decreased collagen content, thinner fibrous cap area, decreased VSMC content, and increased macrophage content. In atherosclerotic lesions, ALDH2 protein was located in both macrophages and VSMCs. Further results revealed downregulated ALDH2 expression in aorta of aged ApoE−/− mice compared with young mice. However, in vitro study suggested that ALDH2 expression was upregulated in bone marrow-derived macrophages (BMDMs) with an opposite effect in VSMCs following 80 μg/ml oxidized low-density lipoprotein (oxLDL) treatment. Interestingly, ALDH2 deficiency displayed little effect in oxLDL-induced foam cell formation from BMDMs, while ALDH2 knockdown by siRNA and ALDH2 overexpression by lentivirus infection promoted and retarded oxLDL-induced VSMC senescence, respectively. Mechanistically, ALDH2 mitigated oxLDL-induced overproduction of mitochondrial reactive oxygen species (mROS) and activation of downstream p53/p21/p16 pathway. Clearance of mROS by mitoTEMPO significantly reversed the promotive effect of ALDH2 knockdown on VSMC senescence. Taken together, our data revealed that ALDH2 deficiency suppressed atherosclerotic plaque area while facilitating plaque instability possibly through accelerating mROS-mediated VSMC senescence. This article is part of a Special Issue entitled: Genetic and epigenetic regulation of aging and longevity edited by Jun Ren & Megan Yingmei Zhang. • Although ALDH2 deficiency reduced the atherosclerotic plaque area, plaque instability was aggravated by ALDH2 deficiency. • ALDH2 knockdown and ALDH2 overexpression promoted and retarded oxLDL-induced VSMC senescence, respectively. • ALDH2 mitigated oxLDL-induced mROS overproduction and activation of downstream p53/p21/p16 pathway. • Clearance of mROS by mitoTEMPO reversed the aggra effect of ALDH2 knockdown on VSMC senescence. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) persistent infection is associated with ineffective immune response for the clearance of virus. Immunomodulators represent an important class of therapeutics, which potentially could be beneficial for the treatment of HBV infection. The particulate yeast-derived glucan (PYDG) has been shown to enhance the innate and adaptive immune responses. We therefore, assessed the efficacy of PYDG in enhancing HBV specific immune responses by employing the hydrodynamic injection-based (HDI) HBV transfection mouse model. Mice were intragatric administered PYDG daily for 9 weeks post pAAV/HBV1.2 hydrodynamic injection. PYDG treatment significantly promoted HBV DNA clearance and production of HBsAb compared to control mice. PYDG treatment resulted in recruitment of macrophages, dendritic cells (DCs) and effector T cells to the liver microenvironment, accompanied by a significantly augmented DCs maturation and HBV-specific IFN-γ and TNF-α production by T cell. In addition, enhanced production of Th1 cytokines in liver tissue interstitial fluid (TIF) was associated with PYDG administration. Live imaging showed the accumulation of PYDG in the mouse liver. Our results demonstrate that PYDG treatment significantly enhances HBV-specific Th1 immune responses, accompanied by clearance of HBV DNA, and therefore holds promise for further development of therapeutics against chronic hepatitis B. [ABSTRACT FROM AUTHOR]

The hepatitis B virus (HBV) is a DNA virus that can cause chronic hepatitis B (CHB) in humans. Current therapies for CHB infection are limited in efficacy and do not target the pre-existing viral genomic DNA, which are present in the nucleus as a covalently closed circular DNA (cccDNA) form. The transcription activator-like (TAL) effector nucleases (TALENs) are newly developed enzymes that can cleave sequence-specific DNA targets. Here, TALENs targeting the conserved regions of the viral genomic DNA among different HBV genotypes were constructed. The expression of TALENs in Huh7 cells transfected with monomeric linear full-length HBV DNA significantly reduced the viral production of HBeAg, HBsAg, HBcAg, and pgRNA, resulted in a decreased cccDNA level and misrepaired cccDNAs without apparent cytotoxic effects. The anti-HBV effect of TALENs was further demonstrated in a hydrodynamic injection-based mouse model. In addition, an enhanced antiviral effect with combinations of TALENs and interferon-α (IFN-α) treatment was observed and expression of TALENs restored HBV suppressed IFN-stimulated response element-directed transcription. Taken together, these data indicate that TALENs can specifically target and successfully inactivate the HBV genome and are potently synergistic with IFN-α, thus providing a potential therapeutic strategy for treating CHB infection. [ABSTRACT FROM AUTHOR]

• 919 syrup (919 T J) can inhibit liver inflammation to provide hepatoprotection. • 919 T J can reduce weight and food intake in a NAFLD model. • 919 T J improves lipid metabolism and liver function abnormalities in a NAFLD model. • 919 T J increases PPARγ expression and inhibits IL-1β, TNF-α, and CXCL6 expression. • 919 T J downregulates the expression of NF-κB-related pro-inflammatory signaling. In many countries, nonalcoholic fatty liver disease (NAFLD) has risen to be the leading cause of liver disease, seriously threatening public health, while effective medical treatments are currently limited. 919 syrup (919 T J) is a Chinese herbal medicine, and both clinical and experimental studies have revealed that it can improve liver function. To study whether 919 T J shows a protective effect in a NAFLD rat model and explore its underlying mechanism, with a focus on the NF-κB pathway. Rats were randomly divided into three groups, including a control group, NAFLD group, and 919 T J group (n = 10 each). The control group received a standard diet, and the other two groups were fed a high-fat diet to establish the NAFLD model. From week 10, rats in the 919 T J group were intragastrically administered 919 T J for 4 weeks, and the NAFLD group was administered the same amount of saline. All rats were anesthetized at the beginning of week 14 to collect blood and liver specimens. Serum lipid levels, serum biochemical markers of liver function, and the gene expression levels of IL-1β, TNF-α, CXCL6, CXCR1, SREBP-1c, PPARγ, and NF-κB in the liver were measured. Oil Red O and hematoxylin and eosin staining of the liver was performed to observe pathological changes in the liver. Significant abnormalities in serum lipid levels and serum biochemical markers of liver function were found in the NAFLD group relative to those in the control group. In addition, serious abnormalities were noted in the expression levels of liver inflammatory factors and lipid metabolism-related genes. Treatment of NAFLD rats with 919 T J reduced body weight and food intake and ameliorated the abnormal blood lipid levels and liver function markers. By regulating the NF-κB pathway, 919 T J downregulated the NF-κB-related proinflammatory signals, ameliorating the expression of inflammatory (IL-1β, TNF-α, CXCL6, and CXCR1) and lipid metabolism-related (SREBP-1c) factors in the liver and improving the NAFLD-induced pathological changes in the liver. 919 T J reduces the liver injury, steatosis, and inflammation caused by NAFLD, thus reversing the disease process. [ABSTRACT FROM AUTHOR]