Female Liver Research Articles

Genome-wide association study for stayability at different calvings in Nellore beef cattle

BackgroundingStayability, which may be defined as the probability of a cow remaining in the herd until a reference age or at a specific number of calvings, is usually measured late in the animal’s life. Thus, if used as selection criteria, it will increase the generation interval and consequently might decrease the annual genetic gain. Measuring stayability at an earlier age could be a reasonable strategy to avoid this problem. In this sense, a better understanding of the genetic architecture of this trait at different ages and/or at different calvings is important. This study was conducted to identify possible regions with major effects on stayability measured considering different numbers of calvings in Nellore cattle as well as pathways that can be involved in its expression throughout the female’s productive life.ResultsThe top 10 most important SNP windows explained, on average, 17.60% of the genetic additive variance for stayability, varying between 13.70% (at the eighth calving) and 21% (at the fifth calving). These SNP windows were located on 17 chromosomes (1, 2, 4, 6, 7, 8, 9, 10, 11, 12, 13, 14, 18, 19, 20, 27, and 28), and they harbored a total of 176 annotated genes. The functional analyses of these genes, in general, indicate that the expression of stayability from the second to the sixth calving is mainly affected by genetic factors related to reproductive performance, and nervous and immune systems. At the seventh and eighth calvings, genes and pathways related to animal health, such as density bone and cancer, might be more relevant.ConclusionOur results indicate that part of the target genomic regions in selecting for stayability at earlier ages (from the 2th to the 6th calving) would be different than selecting for this trait at later ages (7th and 8th calvings). While the expression of stayability at earlier ages appeared to be more influenced by genetic factors linked to reproductive performance together with an overall health/immunity, at later ages genetic factors related to an overall animal health gain relevance. These results support that selecting for stayability at earlier ages (perhaps at the second calving) could be applied, having practical implications in breeding programs since it could drastically reduce the generation interval, accelerating the genetic progress.

Sexual Dimorphism in Substrate Metabolism During Exercise.

During aerobic exercise, women oxidize significantly more lipids and less carbohydrates than men. This sexual dimorphism in substrate metabolism has been attributed, in part, to the observed differences in epinephrine and glucagon levels between men and women during exercise. To identify the underpinning candidate physiological mechanisms for these sex differences, we developed a sex-specific multi-scale mathematical model that relates cellular metabolism in the organs to whole-body responses during exercise. We conducted simulations to test the hypothesis that sex differences in the exercise-induced changes to epinephrine and glucagon would result in the sexual dimorphism of hepatic metabolic flux rates via the glucagon-to-insulin ratio (GIR). Indeed, model simulations indicate that the shift towards lipid metabolism in the female model is primarily driven by the liver. The female model liver exhibits resistance to GIR-mediated glycogenolysis, which helps maintain hepatic glycogen levels. This decreases arterial glucose levels and promotes the oxidation of free fatty acids. Furthermore, in the female model, skeletal muscle relies on plasma free fatty acids as the primary fuel source, rather than intramyocellular lipids, whereas the opposite holds true for the male model.

'The Year of Living Dangerously': Successful Rhodococcus Equi Therapy in an Immunosuppressed Patient with Minimal Toxicity by One Year of Continuous Intravenous Vancomycin Therapy Combined with Oral Levofloxacin And Rifampicin.

Rhodococcus equi is a Gram-positive microorganism that causes infections, particularly in immunocompromised patients. Treatment duration can be prolonged. While vancomycin is an effective drug in this scenario, its use may lead to renal damage. Studies have shown that continuous vancomycin infusion appears to be a safe strategy in terms of adverse effects compared to bolus administration. We present the case of a 71-year-old female liver transplant recipient. After being diagnosed with a mediastinal infection caused by Rhodococcus equi with poor response to initial therapy, she required 12 months of continuous intravenous domiciliary infusion of vancomycin combined with oral levofloxacin and rifampicin. There was no drug-related complication throughout the follow-up. The use of continuous vancomycin infusion has emerged as a safer, more efficient, and cost-effective alternative to intermittent administration. We want to emphasise the uniqueness of this case, where despite the unprecedented treatment duration, no adverse effects occurred. Vancomycin therapy based on continuous infusion represents a safer and cheaper strategy than classic intermittent administration.The use of continuous infusion facilitates the management of complex infections with outpatient antimicrobial therapy.

Ontogenetic instars of Ciprusenia troglobionta sp. nov. (Acari: Astigmata: Canestriniidae) from a cave of Zagros Mountains, Iran

A new species of canestriniid mite belonging to the genus Ciprusenia Haitlinger, 2022 is described based on the morphological characteristics of male, female, tritonymph, protonymph and larva life stages. It is the sixth species of this genus and was collected from Blaps bushirensis Kaszab, 1959 (Coleoptera: Tenebrionidae) on the surface soil of Sahlak Cave (Fars, Iran). The genus Ciprusenia is a new record for the Astigmata fauna of Iran and the host species is a new host record for the family Canestriniidae. In this study, descriptions are carried out in detailed line drawings and scanning electron microscopic images. The identification key to the world-known species of the genus is also provided.

Efficacy and safety of traditional Chinese medicine in the treatment of menopause-like syndrome for breast cancer survivors: a systematic review and meta-analysis

BackgroundIn recent years, breast cancer (BC) incidence and mortality have been the highest in females. Menopause-like syndrome (MLS), arising from hypoestrogenism caused by endocrine therapy, significantly affects the quality of life for females. Traditional Chinese Medicine (TCM) has advantages in ameliorating MLS, but the efficacy of TCM in patients with BC has not been systematically evaluated.MethodsA comprehensive search was performed on PubMed, Web of Science, Embase, Ovid, Cochrane Library, China National Knowledge Infrastructure, Wanfang database, Chinese Scientific Journals Database, and Clinical Trial Registry from inception to September 4, 2023. The Cochrane Risk of Bias assessment tool was used for the quality evaluation of the randomized controlled trials (RCTs). Review Manager 5.4 software was used for statistical analysis, and the Grading of Recommendations Assessment, Development, and Evaluation was used for quality evaluation of the synthesized evidence.ResultsThis review included 42 studies involving 3112 female patients with BC. The results showed that the TCM group was better at decreasing the Kupperman Menopausal Index (KMI) scores (standardized MD, SMD = − 1.84, 95% confidence interval, CI [− 2.21–-1.46], Z = 9.63, P < 0.00001). Regarding the main symptoms of MLS, the TCM groups could significantly decrease the scores of hot flashes and night sweats (SMD = − 0.68, 95% CI [− 1.1–-0.27], Z = 3.24, P = 0.001), paraesthesia (SMD = − 0.48, 95% CI [− 0.74–-0.21], Z = 3.53, P = 0.0004), osteoarthralgia (SMD = − 0.41, 95% CI [− 0.6–0.21], Z = 4.09, P < 0.0001), anxiety (MD = − 0.85, 95% CI [− 1.13, − 0.58], Z = 6.08, P < 0.00001) and insomnia (MD = − 0.61, 95% CI [− 0.8, − 0.43], Z = 6.51, P < 0.00001). TCM can effectively improve the symptoms of MLS in patients with BC. Moreover, TCM could improve the objective response rate (ORR) by 50% (RR = 1.5, 95% CI [1.37–1.64], Z = 9.01, P < 0.00001). Follicle-stimulating hormone (FSH) and oestradiol (E2) had no significant difference compared with the control group (p = 0.81 and p = 0.87), and luteinizing hormone (LH) in the TCM group decreased significantly (MD = − 0.99, 95% CI [− 1.38, − 0.5], Z = 5.01, P < 0.00001). This means that the use of TCM does not negatively affect endocrine therapy and may even have a synergistic effect. The incidence of adverse events (AEs) was lower in the TCM groups than in the control groups.ConclusionsThe meta-analysis stated that TCM could better improve the MLS of patients, alleviate related symptoms, and did not increase adverse drug reactions in BC survivors. This review brings more attention to MLS, and the present findings shed light on the potential applications of TCM in the treatment of MLS in BC survivors.

Hit by the wave: The experiences of adult males living with lymphoedema.

Lymphoedema arises when the lymphatic system has been damaged and may occur secondary to cancer treatment. While much of the extant literature focuses on quality of life in females with breast cancer- related lymphoedema, this study explores the impact of living with lymphoedema secondary to cancer treatment in males. Semi-structured interviews were conducted with 13 male participants, aged between 50 to 85 years. Data collected were analysed using interpretative phenomenological analysis. The super-ordinate theme 'Hit by a wave' encompasses the profound impact of lymphoedema on the participants' quality of life. The males expressed body image concerns and struggled with feelings of frustration, anger, anxiety and depression. Physical changes such as weight increase, disrupted sleep, pain, swollen genitals and urinary difficulties were experienced. Changes in lifestyle were also expressed, such as an increased dependence on carers; work-related and role changes. Nevertheless, many participants endorsed the need to focus on the present moment and expressed a heightened appreciation of authenticity in life. By understanding the unique narratives of males with lymphoedema, health care practitioners together with patients can formulate care plans that truly resonate with the needs, concerns, and experiences of males living with lymphoedema.

Traumatic brain injury-induced peripheral damage: The dynamics of the inflammatory and autophagy pathway from acute to chronic stages.

Traumatic brain injury (TBI) is one of the major causes of death and disability worldwide, and brings a huge burden on the quality of life of patients with TBI and the country's healthcare system. Peripheral organs, especially the kidney, and liver, may be affected by the onset of molecular responses following brain tissue damage. While secondary injury responses post TBI has been well studied in the brain, the effect/consequences of these responses in the peripheral organs have not yet been fully elucidated. Thus, our study aimed to investigate the immunoreactivity of these responses, particularly via proinflammatory cytokines and autophagy markers in the kidney and liver post-acute and chronic TBI. Mild TBI (mTBI) and repetitive mTBI (r-mTBI) were induced in male and female 2-month-old Balb/c mice via the Marmarou weight-drop model. Liver and kidney tissues were sampled at 24 hours (acute) and 30 days (chronic) post TBI and subjected to histopathological and immunoreactivity analysis. Interleukin (IL)-6 levels were significantly increased in the male liver and kidney tissues in both TBI groups compared to the control group but were seen to be decreased in the female r-mTBI chronic liver and r-mTBI acute kidney. Tumor necrosis factor a (TNF-a) levels were found to increase only in the female r-mTBI chronic kidney tissue and mTBI chronic liver tissue. IL-1b levels were increased in the male and female r-mTBI liver tissues but decreased in the female mTBI kidney tissue. Inducible nitric oxide synthase (iNOS) levels were found to be significantly increased in the female mTBI acute and r-mTBI chronic kidney tissue and mTBI liver tissue, but decreased in the r-mTBI acute kidney and r-mTBI liver tissues. Beclin-1 levels were increased in male mTBI chronic and r-mTBI acute liver tissue but decreased in the r-mTBI chronic group. LC3A/B and P62/SQSTM1 levels were significantly increased in the female mTBI chronic and male r-mTBI chronic liver tissues but decreased in the male r-mTBI and female r-mTBI acute kidney tissues. Significant histopathological changes were also observed in the liver and kidney tissue which were dependent on the TBI severity, gender, and time post TBI. The results showed that TBI may elicit peripheral molecular responses, particularly in terms of alteration in the levels of inflammatory cytokines and autophagy markers, which were gender- and time-dependent. This suggests that TBI may have a significant role in the cellular damage of the kidney and liver in both the acute and chronic phases post TBI, thus ensuring that the effects of TBI may not be confined to the brain.

Sexual Dimorphism in Decompensated Non Ethanol-related Chronic Liver Disease: A Retrospective Cohort Study

Introduction: Women exhibit a distinct natural history of chronic liver disease compared to men, particularly regarding progression and outcomes. Although liver disease prevalence is generally higher in men, the incidence of non ethanol-related liver disease is increasing among females. Metabolic syndromes and their consequences are less recognised in the female population until they develop end-stage cirrhosis. Limited studies have explored the differences between male and female cirrhosis. The present study aimed to address the knowledge gap in female Decompensated Chronic Liver Disease (DCLD). Aim: To identify the differences in presentation and outcomes between females and males with non ethanol-related cirrhosis. Materials and Methods: The present retrospective cohort study was conducted in the Department of Medical Gastroenterology and Hepatology,Tirunelveli Medical College, Tirunelveli, Tamil Nadu, India, involving 27 males and 33 females with non ethanol-related decompensated cirrhosis. A comparison was made between the aetiologies, presenting symptoms, complications, laboratory values, Model for End-stage Liver Disease (MELD) score, and in-hospital mortality during the first decompensation. Data analysis was performed using Statistical Packages for Social Sciences (SPSS) version 24.0 Quantitative variables were expressed as mean and Standard Deviation, while qualitative variables were expressed as frequency and percentage. The association between categorical variables was analysed using the Chi-square test, and the comparison of continuous variables between the two groups was analysed using independent sample t-test. A p-value of &lt;0.05 was considered statistically significant. Results: The mean age of decompensation was 56.5 years for men and 50.9 years for women. The most common aetiology in men was Non Alcoholic Fatty Liver Disease (NAFLD) (63%), while in females, it was NAFLD (45%) and cryptogenic cirrhosis (45%) (p=0.020). Diabetes Mellitus (DM) was more prevalent in males (55.6% versus 33.3%). Variceal bleed was more common in females (66.7% versus 48.1%). Jaundice was more frequently observed in males (44.4% versus 21.2%) (p=0.05). Ascites was more prominent in males (70.4% versus 45.5%) (p=0.05). Hepatic Encephalopathy (HE) was more prevalent in males (22.2% versus 15.2%). Females had a lower MELD scores compared to males (12.4±6.1 versus 15.2±6.4). Mortality was higher in males (22.2% versus 12.1%). Conclusion: Women with Decompensated Chronic Liver Disease tend to decompensate at a younger age compared to males and have a higher risk of Upper Gastrointestinal (UGI) bleeding. NAFLD was the most common aetiology in both groups. Ascites and HE were more commonly observed in men. Females had lower MELD scores, resulting in a longer waiting period on the transplant list compared to males. Mortality was higher in males.

Stripping the Veil: Convent Reform, Protestant Nuns, and Female Devotional Life in Sixteenth-Century Germany. Marjorie Elizabeth Plummer. Oxford: Oxford University Press, 2022. xxii + 349 + b/w pls. $100.

Stripping the Veil: Convent Reform, Protestant Nuns, and Female Devotional Life in Sixteenth-Century Germany. Marjorie Elizabeth Plummer. Oxford: Oxford University Press, 2022. xxii + 349 + b/w pls. $100.

Physiological changes in the mammary glands during a female's life.

The intricate development and physiological dynamics of the mammary glands, orchestrated by a delicate interplay of hormones, are crucial for reproductive function and lactation. Beginning with intrauterine clusters evolving into mature glands, hormonal fluctuations throughout puberty and the menstrual cycle finely tune mammary tissue growth. Oestrogens stimulate the proliferation of epithelial cells, while progesterone orchestrates the formation of lactiferous glands. During pregnancy, oestrogen and progesterone induces hyperplasia of lobules and ducts, preparing the breast for lactation. Prolactin is vital for lactation and stimulates milk production during pregnancy and postpartum. As shown by ultrasonography, physiological changes during lactation reflect glandular tissue transformation for milk secretion. Clinical and physiological changes, including increased blood flow, contribute to mammary growth and firmness, complicating clinical examination. Ultrasonographic findings reveal variability in women's glandular and fat tissue distribution, suggesting that milk production is not solely determined by anatomical factors. Though not directly linked to milk production, blood flow dynamics hint at a threshold for optimal lactation. Understanding these complex hormonal and physiological mechanisms is crucial for comprehending mammary development, function, and clinical assessment.

Associations between physical activity and risk of liver cancer: results from a population-based cohort study in Chinese women

Aims : Epidemiological evidence has revealed varying degrees of relationship between physical activity and risk of most cancers, but the association between physical activity and risk for primary liver cancer in Chinese has seldom been reported. This study aims to characterize the associations between different physical activity types and liver cancer risk in Chinese women. Methods: We collected physical activity information through the physical activity questionnaire (PAQ) and assigned a corresponding metabolic equivalent value according to the physical activity compendium. Multivariable-adjusted Cox regression models were utilized to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the relationships between physical activity and liver cancer. Results : A total of 72,674 females were enrolled in the cohort, with a median follow-up time of 18.12 years. By the end of 2016, 255 females were identified as incident cases of liver cancer. In Multivariable-adjusted Cox regression analysis, total physical activity (TPA), daily living physical activity (DPA) and leisure-time physical activity (LTPA) were not associated with the liver cancer risk in women. The highest tertile vs . none of HRs (95%CIs) were 0.82 (0.58, 1.17) for TPA, 0.80 (0.56, 1.15) for DPA, and 1.15 (0.82, 1.61) for adult LTPA in terms of measures as the METs-hour/week. For each activity, we found that the HRs (95%CIs) were 0.77 (0.55, 1.08) for stair climbing and 0.78 (0.53, 1.15) for participation in housework after further adjusting for body mass index and type 2 diabetes. Conclusion : Null significant results were found in the association between physical activity and female liver cancer risk in China.

A diet-wide association study for liver cancer risk: findings from a prospective cohort study in Chinese women

Abstract Although dietary factors have been examined as potential risk factors for liver cancer, the evidence is still inconclusive. Using a diet-wide association analysis, our research evaluated the associations of 126 foods and nutrients on the risk of liver cancer in a Chinese population. We obtained the diet consumption of 72,680 women in the Shanghai Women’s Health Study using baseline dietary questionnaires. The association between each food and nutrient and liver cancer risk was quantified by Cox regression model. A false discovery rate of 0.05 was used to determine the foods and nutrients which need to be verified. Totally 256 incident liver cancer cases were identified in 1,267,391 person-years during the follow-up duration. At the statistical significance level (P ≤ 0.05), higher intakes of cooked wheaten foods, pear, grape and copper were inversely associated with liver cancer risk, while spinach, leafy vegetables, eggplant and carrots showed the positive associations. After considering multiple comparisons, no dietary variable was associated with liver cancer risk. Similar findings were seen in the stratification, secondary and sensitivity analyses. Our findings observed no significant association between dietary factors and liver cancer risk after considering multiple comparisons in Chinese women. More evidence is needed to explore the associations between diet and female liver cancer occurrence.

Research Across the Female Life Cycle: Reframing the Narrative for Health and Performance in Athletic Females and Showcasing Solutions to Drive Advancements in Research and Translation

Over the last few decades, there has been an unprecedented growth in the number of females in sport and exercise, including an exponential rise in female participation, alongside an increased interest and investment in female sport. This success in many aspects underscores the demand for and importance of female-specific research to optimize health, participation, and performance of athletic females. It has also brought awareness to the numerous inequities that exist between females and males. Indeed, the prevailing narrative within sport and exercise science focuses on the disparity of research in females compared with males, which has led to a lack of a critical mass of high-quality data on athletic females. While acknowledging the current gap and the need for further higher quality data, there is still a body of knowledge pertaining to athletic females spanning over a century. This existing literature, amid its criticisms, offers a valuable foundation to build upon for current translation and to inform future research. Thus, it is essential to acknowledge, interpret, and apply prior learnings from previous work, while also considering any limitations. This commentary proposes a reframing of the current narrative that there is an absence of useful data in athletic females, to one that recognizes both the strides made and how past findings can be integrated into practice today as well as inform future research directions. It also addresses the opportunities that remain, and how a more comprehensive and pragmatic body of knowledge can be developed and translated to better serve athletic females in the future.

Double-Gap Model for life expectancy for Argentina

In this work, a probabilistic method is implemented to estimate the life expectancy of men and women by age; the Double GAP or Double Gap method. The application to the case of Argentina attempts to provide information on the phenomenon of population aging and its relationship with the pension system. Present estimates and projections of the life expectancy of men and women by age obtained through a probabilistic method that considers the differential by sex. The Double GAP or Double Gap method is estimated, and then the life expectancies at 60 and 65 years are selected (for women and men respectively), given that these are the retirement ages in Argentina and are present the forecasts and their corresponding confidence intervals. The forecasts of the Double Gap model indicate that life expectancy in Argentina at both 60 and 65 years of age will grow slightly until 2025. For women it increases by half a year, while for men the growth in hope is slightly higher. The latter also shows a slow trend towards a convergence between male and female life expectancies. It is evident that Argentina is far from registering a record in life expectancy worldwide for these ages, because the life expectancy forecasts generated by the Double Gap model for the country are very far from the trend of good practices (series of maximums in life expectancy).

Breastfeeding vs. Formula Feeding and Maternal Sexuality among Polish Women: A Preliminary Report.

Although postpartum sexual problems are common, there is a poor understanding of the underlying influencing factors and the impact of the infant feeding method on the mother's sexual life. A cross-sectional control study was conducted with a group of 253 women during their postpartum period. This study aimed to investigate the effects of different infant feeding methods on female sexual life after childbirth. The study followed the STROBE guidelines for cross-sectional control analysis. The study design included a questionnaire characterizing sociodemographic, obstetric and breastfeeding variables and the PL-FSFI (Female Sexual Function Index). The authors collected the data in compliance with the CAWI (Computer-Assisted Web Interview) research methodology-an interview conducted via an Internet channel. Each respondent received and completed the survey provided to them via the same online link. This study included women in the postpartum period: 170 breastfeeding women (study group) and 83 formula-feeding women (control group). There were statistically significant difference between the groups that practiced different types of breastfeeding. Out of all the PL-FSFI-assessing domains, the highest average score for the whole group correlated with satisfaction and the lowest score correlated with lubrication use. Our findings indicate that women practicing only breastfeeding are more likely to develop sexual problems. In order to maintain sexual health and promote long-term breastfeeding, extensive and professional counseling is needed for couples about postpartum sexuality and the factors that affect it, such as breastfeeding.

Dhr96[1] mutation and maternal tudor[1] mutation increase life span and reduce the beneficial effects of mifepristone in mated female Drosophila.

Mating and receipt of male Sex Peptide hormone cause increased egg laying, increased midgut size and decreased life span in female Drosophila. Feeding mated females with the synthetic steroid mifepristone decreases egg production, reduces midgut size, and increases life span. Here, several gene mutations were assayed to investigate possible mechanisms for mifepristone action. Drosophila Dhr96 is a hormone receptor, and a key positive regulator of midgut lipid uptake and metabolism. Dhr96[1] null mutation increased female life span, and reduced the effects of mifepristone on life span, suggesting that Dhr96[1] mutation and mifepristone may act in part through the same mechanism. Consistent with this idea, lipidomics analysis revealed that mating increases whole-body levels of triglycerides and fatty-acids in triglycerides, and these changes are reversed by mifepristone. Maternal tudor[1] mutation results in females that lack the germ-line and produce no eggs. Maternal tudor[1] mutation increased mated female life span, and reduced but did not eliminate the effects of mating and mifepristone on life span. This indicates that decreased egg production may be related to the life span benefits of mifepristone, but is not essential. Mifepristone increases life span in w[1118] mutant mated females, but did not increase life span in w[1118] mutant virgin females. Mifepristone decreased egg production in w[1118] mutant virgin females, indicating that decreased egg production is not sufficient for mifepristone to increase life span. Mifepristone increases life span in virgin females of some, but not all, white[+] and mini-white[+] strains. Backcrossing of mini-white[+] transgenes into the w[1118] background was not sufficient to confer a life span response to mifepristone in virgin females. Taken together, the data support the hypothesis that mechanisms for mifepristone life span increase involve reduced lipid uptake and/or metabolism, and suggest that mifepristone may increase life span in mated females and virgin females through partly different mechanisms.

The Mechanism of Blood Coagulation Induced by Sodium Dehydroacetate via the Regulation of the mTOR/ERK Pathway in Rats

Dehydroacetic acid (DHA-S), a potent antifungal and antibacterial agent, is widely used in food, feed and cosmetics. However, recent studies have shown that DHA-S could pose a risk for human and animal health. We had previously reported that DHA-S could cause coagulation disorders in rats and chicken. In the present study, we further confirmed that DHA-S induced blood coagulation via VKORC1 and VKORC1L1 in rats, and elucidated the role played by mTOR/ERK signaling. The in vivo studies demonstrated that PT, APTT, and DHA-S content and relative protein expressions in tissues rebounded after drug withdrawal. In BRL-3A cells, 1.0mM DHA-S increased the expression levels of mTOR, p-mTOR and p-ERK and decreased the levels of VKORC1, VKORC1L1 and Vitamin K. Rapamycin significantly decreased the expression levels of p-mTOR and p-ERK, while FR180204 (p-ERK Inhibition) lead to a decrease in p-ERK level. Rapamycin and FR180202 attenuated the inhibitory effect of DHA-S on VKORC1, VKORC1L1 and vitamin K levels. In addition, DHA-S increased the expression levels of mTOR, p-mTOR and p-ERK in male and female rat livers and prolonged PT and APTT. In summary, this study indicated that DHA-S induced blood coagulation via the modulation of the mTOR/ERK pathway in rats.

Plasma growth hormone pulses induce male-biased pulsatile chromatin opening and epigenetic regulation in adult mouse liver.

Sex differences in plasma growth hormone (GH) profiles, pulsatile in males and persistent in females, regulate sex differences in hepatic STAT5 activation linked to sex differences in gene expression and liver disease susceptibility, but little is understood about the fundamental underlying, GH pattern-dependent regulatory mechanisms. Here, DNase-I hypersensitivity site (DHS) analysis of liver chromatin accessibility in a cohort of 18 individual male mice established that the endogenous male rhythm of plasma GH pulse-stimulated liver STAT5 activation induces dynamic, repeated cycles of chromatin opening and closing at several thousand liver DHS and comprises a novel mechanism conferring male bias to liver chromatin accessibility. Strikingly, a single physiological replacement dose of GH given to hypophysectomized male mice restored, within 30 min, liver STAT5 activity and chromatin accessibility at 83% of the dynamic, pituitary hormone-dependent male-biased DHS. Sex-dependent transcription factor binding patterns and chromatin state analysis identified key genomic and epigenetic features distinguishing this dynamic, STAT5-driven mechanism of male-biased chromatin opening from a second GH-dependent mechanism operative at static male-biased DHS, which are constitutively open in male liver. Dynamic but not static male-biased DHS adopt a bivalent-like epigenetic state in female liver, as do static female-biased DHS in male liver, albeit using distinct repressive histone marks in each sex, namely, H3K9me3 at male-biased DHS in female liver and H3K27me3 at female-biased DHS in male liver. Moreover, sex-biased H3K36me3 marks are uniquely enriched at static sex-biased DHS, which may serve to keep these sex-dependent hepatocyte enhancers free of H3K27me3 repressive marks and thus constitutively open. Pulsatile chromatin opening stimulated by endogenous, physiological hormone pulses is thus one of two distinct GH-determined mechanisms for establishing widespread sex differences in hepatic chromatin accessibility and epigenetic regulation, both closely linked to sex-biased gene transcription and the sexual dimorphism of liver function.

Plasma growth hormone pulses induce male-biased pulsatile chromatin opening and epigenetic regulation in adult mouse liver

Sex differences in plasma growth hormone (GH) profiles, pulsatile in males and persistent in females, regulate sex differences in hepatic STAT5 activation linked to sex differences in gene expression and liver disease susceptibility, but little is understood about the fundamental underlying, GH pattern-dependent regulatory mechanisms. Here, DNase-I hypersensitivity site (DHS) analysis of liver chromatin accessibility in a cohort of 18 individual male mice established that the endogenous male rhythm of plasma GH pulse-stimulated liver STAT5 activation induces dynamic, repeated cycles of chromatin opening and closing at several thousand liver DHS and comprises a novel mechanism conferring male bias to liver chromatin accessibility. Strikingly, a single physiological replacement dose of GH given to hypophysectomized male mice restored, within 30 min, liver STAT5 activity and chromatin accessibility at 83% of the dynamic, pituitary hormone-dependent male-biased DHS. Sex-dependent transcription factor binding patterns and chromatin state analysis identified key genomic and epigenetic features distinguishing this dynamic, STAT5-driven mechanism of male-biased chromatin opening from a second GH-dependent mechanism operative at static male-biased DHS, which are constitutively open in male liver. Dynamic but not static male-biased DHS adopt a bivalent-like epigenetic state in female liver, as do static female-biased DHS in male liver, albeit using distinct repressive histone marks in each sex, namely, H3K9me3 at male-biased DHS in female liver and H3K27me3 at female-biased DHS in male liver. Moreover, sex-biased H3K36me3 marks are uniquely enriched at static sex-biased DHS, which may serve to keep these sex-dependent hepatocyte enhancers free of H3K27me3 repressive marks and thus constitutively open. Pulsatile chromatin opening stimulated by endogenous, physiological hormone pulses is thus one of two distinct GH-determined mechanisms for establishing widespread sex differences in hepatic chromatin accessibility and epigenetic regulation, both closely linked to sex-biased gene transcription and the sexual dimorphism of liver function.

Metabolic dysfunction-associated steatotic liver disease criteria may underestimate the number of lean female nonalcoholic fatty liver disease patients with significant liver fibrosis.

It remains unclear whether the newly defined concept of metabolic dysfunction-associated steatotic liver disease (MASLD) appropriately includes patients with nonalcoholic fatty liver disease with significant liver fibrosis. A total of 4112 patients in whom nonalcoholic fatty liver disease was diagnosed by ultrasonography during medical checkups were enrolled. We defined a fibrosis-4 index ≥1.3 in patients aged <65years and ≥2.0 in patients aged ≥65years as significant liver fibrosis. The numbers of patients with a low, intermediate, and high probability of advanced fibrosis based on the fibrosis-4 index were 3360 (81.7%), 668 (16.2%), and 84 (2.0%). There were 3828 (93.1%) and 284 (6.9%) patients diagnosed with MASLD and non-MASLD. The non-MASLD group, compared with the MASLD group, was significantly younger (44 vs. 55years) and had a higher percentage of women (62.3% vs. 27.7%). Significant fibrosis, defined based on the fibrosis-4 index, was present in 18.5% of the MASLD group and 15.5% of the non-MASLD group. In a multivariable analysis, female sex (OR 6.170, 95% CI 3.180-12.000; p<0.001) was independently associated with non-MASLD in patients with a significant fibrosis. Among non-MASLD patients with a significant fibrosis (n=44), body mass index was significantly lower in females than in males (p<0.001). In a multivariable analysis of patients aged <65years, female sex (OR, 7.700; 95% CI, 3.750-15.800; p<0.001) remained independently associated with non-MASLD in patients with a significant fibrosis. MASLD may inappropriately exclude patients with significant fibrosis, especially lean females with nonalcoholic fatty liver disease.