Chronically high stress hormone levels dysregulate sperm long noncoding RNAs and their embryonic microinjection alters development and affective behaviours.

Previous studies on paternal epigenetic inheritance have shown that sperm RNAs play a role in this type of inheritance. The microinjection of sperm small noncoding RNAs into fertilised mouse oocytes induces reprogramming of the early embryo, which is thought to be responsible for the differences observed in adult phenotype. While sperm long noncoding RNAs (lncRNAs) have also been investigated in a previous study, their microinjection into fertilised oocytes did not yield conclusive results regarding their role in modulating brain development and adult behavioural phenotypes. Therefore, in the current study we sought to investigate this further. We used our previously established paternal corticosterone (stress hormone) model to assess sperm lncRNA expression using CaptureSeq, a sequencing technique that is more sensitive than the ones used in other studies in the field. Paternal corticosterone exposure led to dysregulation of sperm long noncoding RNA expression, which encompassed lncRNAs, circular RNAs and transposable element transcripts. Although they have limited functional annotation, bioinformatic approaches indicated the potential of these lncRNAs in regulating brain development and function. We then separated and isolated the sperm lncRNAs and performed microinjections into fertilised oocytes, to generate embryos with modulated lncRNA populations. We observed that the resulting adult offspring had lower body weight and altered anxiety and affective behavioural responses, demonstrating roles for lncRNAs in modulating development and brain function. This study provides novel insights into the roles of lncRNAs in epigenetic inheritance, including impacts on brain development and behaviours of relevance to affective disorders.

Identification of susceptibility SNPs in CTLA-4 and PTPN22 for scleritis in Han Chinese.

The aim of this study was to determine the association between 13 single nucleotide polymorphisms (SNPs) in the cytotoxic T lymphocyte-associated antigen-4 (CTLA4) and protein tyrosine phosphatase non-receptor type 22 (PTPN22) genes with scleritis in a Chinese Han population. We recruited 432 scleritis patients and 710 healthy controls. Four tag SNPs of CTLA4 and nine tag SNPs of PTPN22 were selected using Haploview. Genotyping was performed with the Sequenom MassArray® iPLEX GOLD Assay. Genotype and allele frequency differences were analyzed by χ2 test and Bonferroni correction. Haplotype analysis was performed to further evaluate the association of these two genes with scleritis. In this study, CTLA4/rs3087243 G allele frequency and GG genotype frequency were significantly increased in scleritis patients compared to healthy controls [corrected P-value (Pc) = 0·02, odds ratio (OR) = 1·475, 95% confidence interval (CI) = 1·175-1·851; Pc = 0·04, OR = 1·546, 95% CI = 1·190-2·008, respectively]. None of the tested SNPs in the PTPN22 gene showed an association with scleritis. Haplotype analysis revealed a lower frequency of a CTLA4 TCAA haplotype (order of SNPs: rs733618, rs5742909, rs231775, rs3087243) (Pc = 4·26 × 10-3 , OR = 0·618, 95% CI = 0·540-0·858) and a higher frequency of a PTPN22 TTATACGCG haplotype (order of SNPs: rs3789604, rs150426536, rs1746853, rs1217403, rs1217406, rs3789609, rs1217414, rs3789612, rs2488457) (Pc = 2·83 × 10-4 , OR = 1·457, 95% CI = 1·210-1·754) in scleritis patients when compared to healthy controls. In conclusion, our findings indicate that CTLA4 and PTPN22 might confer genetic susceptibility to scleritis in a Chinese Han population.

A multicentre, UK, retrospective, observational study to assess the effectiveness of insulin glargine 300 units/ml in treating people with Type 1 diabetes mellitus in routine clinical practice (SPARTA).

AIM: To conduct an open-label study to provide UK real-world evidence regarding the use of insulin glargine 300 units/ml (U300) in people with Type 1 diabetes mellitus. METHODS: People with Type 1 diabetes who had been prescribed U300 ≥6 months before data collection and had HbA1c levels recorded within 3 months prior to U300 (baseline) were included. The primary endpoint was change in HbA1c from baseline to month 6 after U300 initiation. Other endpoints included number of documented hypoglycaemic and diabetic ketoacidosis episodes, and change in daily basal insulin dose. RESULTS: A total of 298 people with Type 1 diabetes were included [mean age 42.1 years, mean HbA1c 79 mmol/mol (9.4%)]. After U300 initiation, the mean reduction in HbA1c from baseline to month 6 was -4 mmol/mol (-0.4%; P<0.001; n=188). The total daily basal insulin dose at 6 months was 1.3 units higher than at the time of U300 initiation (P<0.001; n=275) but was not significantly different from the prior basal insulin dose. There was no clinically significant difference in weight between baseline and month 6 [mean difference +0.7 kg, 95% CI -0.1, 1.5; P=0.084; n=115). During the 6 months before and after U300 initiation, severe hypoglycaemic episodes were documented for 6/298 and 4/298 participants. Diabetic ketoacidosis episodes requiring Accident and Emergency department visits or hospitalization were documented for 4/298 and 6/298 participants, before and after U300 initiation, respectively. CONCLUSIONS: In people with Type 1 diabetes, a change in basal insulin to U300 was associated with clinically and statistically significant HbA1c improvements, without significant changes in basal insulin dose and weight. Documented severe hypoglycaemia episodes and diabetic ketoacidosis requiring Accident and Emergency department visits or hospitalization were low and similar before and after U300 initiation.

[Analysis of the effects and influencing factors of thymectomy for myasthenia gravis].

Objective: To explore the effects of surgical treatment for myasthenia gravis as well as its influencing factors. Methods: A total of 180 patients with myasthenia gravis who underwent thymectomy from August 2012 to September 2018 were enrolled. Clinical data such as age, gender, disease classification, preoperative AChR-Ab, preoperative course, operation time, intraoperative blood loss, and pathological type was retrospectively reviewed. Univariate analysis and Cox regression model were used to analyze possible influencing factors of surgical effects. Results: A total of 145 patients were finally enrolled and the follow-up period was from 4 to 78 months, with a median follow-up time of 34 months. Thirty-four patients (23.4%) achieved complete stable remission (CSR). The total clinical remission and effective rate reached 75.1% (109 cases) and 89.6% (130 cases), respectively. Correlation analysis showed that age below 45 years old, preoperative course within 12 months, positive AChR-Ab and thymic hyperplasia were clinical influencing factors for better surgical results (P=0.030, 0.048, 0.019 and 0.042, respectively). Conclusions: It is safe and effective to undergo thymectomy for myasthenia gravis. Age, preoperative course, AChR-Ab level and pathological type were the influencing factors of surgical effects.

[Clinical observation of continuous and intermittent application of lamivudine or entecavir resistance mutations in patients with chronic hepatitis B].

Objective: To observe continuous and intermittent application of lamivudine or entecavir resistance mutations in patients with chronic hepatitis B. Methods: Data of patients with active stage of chronic hepatitis B over the past 6 years were collected and analyzed retrospectively. The incidence of drug resistance mutation and related factors between patients taking LAM or ETV continuously and intermittently were compared with those taking LAM or ETV. Data comparison was performed using χ(2) test. Results: Patients with HBV DNA≥10(5) copies / ml at the time of initial treatment had higher resistance mutation rates than those with HBV DNA < 10(5) copies / ml at either continuous or intermittent treatment, and patients with intermittent treatment had higher resistance mutation rates than those with continuous treatment. Simultaneously, the incidence of drug resistance mutation in LAM and ETV in the first, second and third years were significantly higher in intermittent treatment than that of continuous treatment (P < 0.05). There was a positive correlation between the frequency of drug withdrawal and the rate of drug resistance mutation. There were no individual difference and drug difference between LAM and ETV. Conclusion: In the treatment of chronic hepatitis B with oral nucleoside analogues, drug resistance may occur in either continuous or intermittent treatment. When comparing continuous with intermittent treatment, it suggests that intermittent is more likely to cause viral resistance mutation.

LncRNA H19 contributes to Rh2-mediated MC3T3-E1cell proliferation by regulation of osteopontin.

20(R)-ginsenoside Rh2 (Rh2) is one of the most active components of red ginseng, possessing the beneficial effects in cancer prevention and metabolic diseases. However, the detailed mechanisms that contribute to Rh2-mediated bone formation remain largely unknown. In this study, we assessed the expression of 17 long non-coding RNAs (lncRNAs) in cultured MC3T3-E1 cells under Rh2 treatments. We found that lncRNA H19 was significantly increased in Rh2-treated MC3T3-E1 cells. Expression of lncRNA H19 was promoted in a dose- and time-dependent manner after Rh2 treatments. Increased expression of lncRNA H19 resulted in osteopontin (OPN) overexpression in Rh2-treated MC3T3-E1 cells. Furthermore, knockdown of lncRNA H19 by specific siRNAs significantly abolished the Rh2-mediated cell proliferation effects. Knockdown of lncRNA H19 also decreased both mRNA and protein levels of OPN in the Rh2-treated cells, which was accomplished by inhibiting histones H3 and H4 acetylation of OPN promoter. Importantly, OPN knockdown fully blocked Rh2 induced MC3T3-E1 cell proliferation. Our results suggest that lncRNA H19 is an important contributor to Rh2-mediated MC3T3-E1 proliferation by regulation of OPN.

A cultured endophyte community is associated with the plant Clerodendrum inerme and antifungal activity.

Fungal endophytes live in the inner tissues of Clerodendrum inerme and may be significant resources for new chemicals in drug discovery. A total of 242 endophytic fungi were recovered from 602 sample segments of C. inerme; 66 were purified. The 66 fungi belonging to 16 taxa and 11 genera (Alternaria, Nigrospora, Bartalinia, Pestalotiopsis, Fusarium, Mycoleptodiscus, Trichoderma, Phomopsis, Diaporthe, Lasiodiplodia, and Curvularia) were identified by morphological characteristics and fungal internal transcribed spacer sequences. The most abundant genera were Alternaria and Lasiodiplodia. Some of the endophytes exhibited tissue specificity. The colonization frequencies of endophytes in the stems were evidently higher than those in the roots and leaves. The crude ethyl acetate extracts were tested against 6 endophytes isolated from C. inerme. Three of 10 (33.3%) endophytes, which were identified as Phomopsis sp, Curvularia sp, and Mycoleptodiscus sp, displayed distinct antifungal activity against ≥3 tested fungi. To our knowledge, this is the first report of an endophytic community associated with C. inerme in China and its antifungal activity in vitro.

CD44 targets Na(+)/H(+) exchanger 1 to mediate MDA-MB-231 cells' metastasis via the regulation of ERK1/2.

BACKGROUND: CD44, a transmembrane glycoprotein expressed in a variety of cells and tissues, has been implicated in tumour metastasis. But the molecular mechanisms of CD44-mediated tumour cell metastasis remain to be elucidated. METHODS: The downregulation of CD44 was determined by immunofluorescence. Moreover, the motility of breast cancer cells was detected by wound-healing and transwell experiments. Then the spontaneous metastasis of CD44-silenced MDA-MB-231 cells was tested by histology with BALB/c nude mice. RESULTS: A positive correlation between CD44 and Na(+)/H(+) exchanger isoform 1 (NHE1) was found in two breast cancer cells. CD44 downregulation could inhibit the metastasis of MDA-MB-231 cells and the expressions of Na(+)/H(+) exchanger 1. Moreover, CD44 overexpression upregulated the metastasis of MCF-7 cells, but the elevated metastatic ability was then inhibited by Cariporide. Interestingly, during these processes only the p-ERK1/2 was suppressed by CD44 downregulation and the expression of matrix metalloproteinases and metastatic capacity of MDA-MB-231 cells were greatly inhibited by the MEK1 inhibitor PD98059, which even had a synergistic effect with Cariporide. Furthermore, CD44 downregulation inhibits breast tumour outgrowth and spontaneous lung metastasis. CONCLUSIONS: Taken together, this work indicates that CD44 regulates the metastasis of breast cancer cells through regulating NHE1 expression, which could be used as a novel strategy for breast cancer therapy.

WHO: retirement or reinvention?

WHO reform has become a perennial subject of debate that has seen familiar issues raised time and again by incumbent director-generals and member states. This paper begins by reflecting on the distinct nature of WHO reform debates since the 1990s and the global factors behind the pressures to change. It then argues for a shift in focus, from fixing a single UN organization, to the collective health needs of a rapidly globalizing world. The achievement of effective global health governance will require more fundamental changes, beginning with recognition of the shared responsibility for reform. The challenge in the twenty first century will require an even greater willingness to delegate authority and resources to a supranational entity. The compromise may be that the mandate and powers of a global health organization may need to be more carefully circumscribed, but more meaningful in terms of effectively delivering the essential functions needed to protect and promote health in a globalized world.

The Multi-domain Lifestyle Intervention for Cognitive Impairment in Community-Dwelling Older Adults in Hangzhou (The Heritage Study): Study Design and Protocol.

BACKGROUND: The globe has been working to promote a multi-domain lifestyle intervention for dementia prevention in older adults, referring to the Worldwide-FINGERS (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability) initiative. In China, the multi-domain lifestyle intervention has been implemented in rural communities (MIND-China), yet the adaptability of such intervention based on the urban communities in China has not been verified. OBJECTIVE: To examine the effectiveness and feasibility of the multi-domain lifestyle intervention on dementia prevention in at-risk community-dwelling older adults in China. DESIGN, SETTING, PARTICIPANTS: The multi-domain lifestyle intervention study is a community-based 2-year cluster randomized controlled trial (RCT). A total of 1200 participants aged 60-80 years old will be recruited from twelve communities in Hangzhou, Zhejiang. Inclusion criteria were the Montreal Cognitive Assessment 5 minutes protocol (5 min MoCA) score of 6-9 or the Ascertain Dementia 8 (AD 8) score of ≥2, and having modifiable lifestyle factors. INTERVENTION, MEASUREMENTS, RESULTS: Participating communities will be randomized into either the structured multi-domain intervention (SMI) arm or the self-guided intervention (SGI, general health education) arm. The SMI consists of cognitive training, physical exercise, and nutritional and dietary instruction for the first 12 months; and vascular risks monitoring and control for 24 months. The primary outcome is the global cognitive performance, measured by the comprehensive Neuropsychological Test Battery (NTB). The secondary outcomes include domain-specific cognitive performances, physical function, mental health, physiological and biochemical indices, adherence to healthy lifestyles, and neuroimaging metrics. The feasibility of intervention will be evaluated around the five dimensions of the RE-AIM framework and in conjunction with quantitative data, operational data and results of focus group discussions. CONCLUSIONS: Following the Worldwide-FINGERS, this cluster RCT will verify the adaptability of the multi-domain lifestyle intervention in the urban community settings in China. This study will add evidence for global dementia prevention and management among older adults.

Endothelial progenitor cells are influenced by serum of patients with systemic inflammatory response syndrome or multiple organ dysfunction.

BACKGROUND AND AIM: To investigate the effects of systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndromes (MODS) on human peripheral blood endothelial progenitor cells. PATIENTS AND METHODS: Twenty patients admitted to Changhai Hospital, Second Military Medical University, from February, 2011 to November, 2011 were recruited consecutively. The serum samples were collected from the twenty patients who were divided into four groups as following: normal group, post-traumatic group without SIRS, post-traumatic group with SIRS, and post-traumatic group with MODS. Endothelial progenitor cells (EPCs) were isolated from peripheral blood of healthy subjects by using density gradient centrifugation and the effect of the serum on EPCs was detected after stimulating by the serum samples for 0, 6, 12, 24, and 36 h. RESULTS: Compared with the normal group, the proliferation of EPCs was significantly increased in a time-independent manner in the other three groups, especially in the SIRS serum treated group. The expression of pro-inflammation cytokines was increased in the other three groups compared with the normal group, but the expression of IL-10 in the normal group was higher than the other groups. CONCLUSIONS: Oxidative stress balance was also broken as the disease progressed. Serum from patients with sepsis could influence proliferation and the inflammation and oxidative stress states of EPCs.

Can We Miniaturize CT Technology for a Successful Mobile Stroke Unit Roll-Out?

Mortality from stroke remains high in Australia, especially for patients located outside the metropolitan cities. This is because they have limited access to specialized stroke facilities for optimal stroke treatment. Mobile stroke units have the capability to take CT scanners out to the patient however current CT commercial scanner designs are large and heavy. As such, this paper aims to design and develop a lightweight CT scanner for use in a mobile stroke unit (either road-based or air-based ambulance) to bring healthcare solution to patients in the rural and remote areas. We used the engineering design optimization approach to redesign and reduce the weight of the existing CT scanner with without compromised it structural performance. We managed to reduce the weight the CT scanner by three-fold while reducing design costs by allowing numerous simulations to be performed using computer software to achieve our design goals. The results are not only useful to optimize CT scanner structure to retrofit on a mobile stroke unit, but also bring the medical device solution to the market and support scalable solution to the larger community. Such an advance will allow for improved equity in healthcare whereby patients can be treated irrespective of location.

What are the health benefits of physical activity in type 1 diabetes mellitus? A literature review.

Physical activity improves well-being and reduces the risk of heart disease, cancer and type 2 diabetes mellitus in the general population. In individuals with established type 2 diabetes, physical activity improves glucose and lipid levels, reduces weight and improves insulin resistance. In type 1 diabetes mellitus, however, the benefits of physical activity are less clear. There is poor evidence for a beneficial effect of physical activity on glycaemic control and microvascular complications, and significant risk of harm through hypoglycaemia. Here we review the literature relating to physical activity and health in type 1 diabetes. We examine its effect on a number of outcomes, including glycaemic control, lipids, blood pressure, diabetic complications, well-being and overall mortality. We conclude that whilst there is sufficient evidence to recommend physical activity in the management of type 1 diabetes, it is still unclear as to what form, duration and intensity should be recommended and whether there is benefit for many of the outcomes examined.

Is Online Video-Based Education an Effective Method to Teach Basic Surgical Skills to Students and Surgical Trainees? A Systematic Review and Meta-analysis.

BACKGROUND: Online education has been increasingly utilized over the past decades. The COVID-19 pandemic accelerated the transition of conventional face-to-face curricula to online platforms, with limited evidence for its teaching efficacy. This systematic review aims to assess the effectiveness of online video-based education compared with standard conventional education in teaching basic surgical skills to surgical trainees and students undergoing medical training. METHODS: We performed a literature search in Embase, Medline, Cochrane CENTRAL and Scopus from inception until February 2022. Studies included were randomised controlled trials (RCTs) and observational studies. We included randomised controlled trials only for meta-analysis. The primary outcome was surgical skill proficiency. The secondary outcomes were participant perception, confidence and satisfaction. Two authors independently assessed the search results for eligibility, extracted the data and assessed the risk of bias using the Cochrane Risk of Bias tool 2. Where appropriate, we performed random effects meta-analyses of the pooled study data to calculate a standardized mean difference. RESULTS: A total of 11 studies met the inclusion criteria totaling 715 participants; 603 were included in qualitative analysis and 380 in meta-analysis. All included studies were assessed as having a low risk of bias. The majority of studies found no significant difference between conventional and video-based education in teaching basic surgical skills, three studies found video-based education was superior and one study found conventional education was superior. There was no statistically significant difference in skill proficiency between the two groups (standardized mean difference of -0.02 (95% CI: -0.34, 0.30); p=0.90). Video-based education results in an equivalent improvement in confidence and satisfaction rates. Additional benefits of video-based education include convenience, accessibility and efficiency. CONCLUSIONS: Basic surgical skills can be taught as effectively through online video-based education as conventional teaching methods. Online education should be utilized as an adjunct to medical curricula beyond the COVID-19 era.

Wheel running and environmental enrichment differentially modify exon-specific BDNF expression in the hippocampus of wild-type and pre-motor symptomatic male and female Huntington's disease mice.

Brain-derived neurotrophic factor (BDNF) is an essential neurotrophin and regulation of its expression is complex due to multiple 5' untranslated exons which are separately spliced to a common coding exon to form unique mRNA transcripts. Disruption of BDNF gene expression is a key to the development of symptoms in Huntington's disease (HD), a fatal neurodegenerative condition. Abnormal epigenetic modifications are associated with reduced gene expression in late-stage HD but such regulation of BDNF gene expression has yet to be investigated. We hypothesized that BDNF gene expression is altered in the HD hippocampus of pre-motor symptomatic R6/1 transgenic HD mice, correlating with a change in the DNA methylation profile. The effects of wheel-running and environmental enrichment on wild-type mice, in association with a proposed environment-mediated correction of BDNF gene expression deficits in HD mice, were also investigated. Using real-time PCR, levels of total BDNF mRNA were found to be reduced in the hippocampus of both male and female HD mice. Wheel-running significantly increased total BDNF gene expression in all groups of mice except male HD mice. In contrast, environmental enrichment significantly increased expression only in male wild-type animals. Further quantification of BDNF exon-specific transcripts revealed sex-specific changes in relation to the effect of the HD mutation and differential effects on gene expression by wheel-running and environmental enrichment. The HD-associated reduction of BDNF gene expression was not due to increased methylation of the gene sequence. Furthermore, environment-induced changes in BDNF gene expression in the wild-type hippocampus were independent of the extent of DNA methylation. Overall, the results of this study provide new insight into the role of BDNF in HD pathogenesis in addition to the mechanisms regulating normal BDNF gene expression.

Regulation of the T-cell response to ectromelia virus infection. I. Feedback suppression by effector T cells.

Spleen cells and serum from mice immunized with ectromelia virus suppressed the immune response to infectious virus when transferred intravenously into recipient mice given an immunizing virus dose. The suppression was reflected in decreased cytotoxic T-cell activity directed against H-2 compatible virus-infected target cells in the spleens of recipients. Suppression was observed when immune cells or serum were transferred 1-2 h or 1 day after immunization of recipients, but not 2 days after, and was maximal when 6-day immune spleen cells were used as suppressor cells. H-2 compatibility between donor and recipient mice was necessary for suppression to be expressed. Use of recombinant mice showed that I-region compatibility was neither sufficient nor necessary, and that D-region compatibility was sufficient. Specificity of suppression was suggested by the finding that cells and serum from mice immunized with Listeria monocytogenes, a bacterium, had no suppressive activity on the antiviral response. Anti-theta treatment eliminated the ability of immune cells to suppress, and the suppressive effect was not markedly dose-dependent with respect to both cell dose and virus dose under the conditions employed. Virus levels in the spleens of recipients were significantly reduced after injection of immune cells. Adult thymectomy had no effect on the primary immune response to ectromelia virus infection, thus indicating no role for T1 cells in the suppressive mechanism. The results obtained therefore suggested that suppression in this system was due to effector T cells which triggered clearance of virus (and thus, of virus-induced antigens) necessary for the induction of precursors of effector T cells, and that this simple feed-back mechanism normally plays an important role in the regulation of the primary immune response to ectromelia infection at the level of precursor induction. The existence of other postinduction regulatory mechanisms, however, is unknown and under investigation.

Propofol suppresses migration, invasion, and epithelial-mesenchymal transition in papillary thyroid carcinoma cells by regulating miR-122 expression.

OBJECTIVE: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer and PTC patients with invasion and metastases features have a poor prognosis. Propofol is an intravenous anesthetic which has been reported to be involved in cancer progression. However, the roles of propofol and the exact molecular mechanisms in PTC remain largely unknown. MATERIALS AND METHODS: Cells viability was detected using the CCK-8 (Cell Counting Kit-8) assay. The expressions of microRNA-122 (miR-122) were measured by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Cells migration and invasion abilities were investigated by transwell. Western blot was used to demonstrate the expression of metastasis-and EMT-related proteins. RESULTS: We found a significant inhibition of cells viability in TPC-1 and IHH-4 cells compared to Nthy-ori 3-1 cell line after exposed to propofol. The functional experiment showed propofol could suppress cells migration, invasion, and EMT in PTC. Subsequently, a decreased expression of miR-122 was detected in TPC-1 and IHH-4 cells, while a promotion of propofol on miR-122 expression was identified. Furthermore, we found miR-122 could inhibit cells migration, invasion, and EMT in PTC. Next, the rescue study indicated that miR-122 inhibitor transfection could attenuate propofol-induced suppression on TPC-1 and IHH-4 cells metastasis. CONCLUSIONS: Propofol suppresses migration, invasion, and EMT in papillary thyroid carcinoma cells by regulating miR-122 expression. The findings may indicate significant clinical implications for anesthetic agents to prevent metastasis and improve outcomes in papillary thyroid carcinoma.

Limitations to intergenerational inheritance: subchronic paternal stress preconception does not influence offspring anxiety.

Independent studies have observed that a paternal history of stress or trauma is associated with his children having a greater likelihood of developing psychopathologies such as anxiety disorders. This father-to-child effect is reproduced in several mouse models of stress, which have been crucial in developing a greater understanding of intergenerational epigenetic inheritance. We previously reported that treatment of C57Bl/6J male breeders with low-dose corticosterone (CORT) for 28 days prior to mating yielded increased anxiety-related behaviours in their male F1 offspring. The present study aimed to determine whether subchronic 7-day CORT treatment of male mice just prior to mating would be sufficient to induce intergenerational modifications of anxiety-related behaviours in offspring. We report that subchronic CORT treatment of male breeders reduced their week-on-week body weight gain and altered NR3C1 and CRH gene expression in the hypothalamus. There were no effects on sperm count and glucocorticoid receptor protein levels within the epididymal tissue of male breeders. Regarding the F1 offspring, screening for anxiety-related behaviours using the elevated-plus maze, light-dark box, and novelty-suppressed feeding test revealed no differences between the offspring of CORT-treated breeders compared to controls. Thus, it is crucial that future studies take into consideration the duration of exposure when assessing the intergenerational impacts of paternal health.

Sevoflurane inhibits the progression of PTC by downregulating miR-155.

OBJECTIVE: Surgery resection is the primary treatment for papillary thyroid carcinoma (PTC) patients with the risk of tumor cell invasion and distant metastasis. Sevoflurane is a volatile anesthetic agent widely used in clinical applications. However, the effect of sevoflurane on PTC cells and its precise mechanism remain largely unknown. MATERIALS AND METHODS: Cell viability was assessed by MTT assay. The migrative and invasive abilities of the cells were measured by transwell assay. The protein expression level of Bax, Bcl-2, MMP 9, and MMP 2 were detected by Western blot. Cell apoptosis was analyzed by flow cytometry. The qRT-PCR analysis was used to determine miR-155 expressions. RESULTS: Sevoflurane greatly decreased the viability of PTC cells in a dose-dependent manner. Moreover, sevoflurane significantly inhibited migration and invasion, but increased the apoptosis in PTC cells, which could be reversed by the addition of miR-155. Besides, sevoflurane evidently increased the Bax protein level and inhibited the protein level of Bcl-2, MMP9, and MPP2 in PTC cells. In addition, miR-155 was upregulated in PTC cells; however, the amount of miR-155 would be decreased in PTC cells treated with sevoflurane. Furthermore, abrogation of miR-155 promoted cell apoptosis and inhibited cell migration and invasion in PTC cells. CONCLUSIONS: Sevoflurane inhibited migration and invasion, while enhanced cell apoptosis by downregulating miR-155 in PTC cells, suggesting important clinical implications for anesthetic agents to prevent the metastasis in PTC.