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International Immunopharmacology Jul 2024Osteoporosis (OP) is a common systemic skeletal disorder characterized by an imbalance in bone homeostasis, involving increased osteoclastic bone formation and decreased...
BACKGROUND
Osteoporosis (OP) is a common systemic skeletal disorder characterized by an imbalance in bone homeostasis, involving increased osteoclastic bone formation and decreased osteoblastic bone resorption. Quercetin is a plant polyphenol that has been found to exhibit various biological activities, including antioxidant, anti-inflammatory, and antimicrobial effects. Previous studies have demonstrated its potential to improve postmenopausal OP, although the exact mechanism remains unclear. This study aims to investigate the anti-osteoporotic mechanism of quercetin based on the "intestinal flora - short-chain fatty acids (SCFAs) - inflammatory" signaling axis.
METHODS
In this study, we established an ovariectomized (OVX)-induced rat model, quercetin intervention and evaluated the effects on rats following antibiotic (ABX) treatment and fecal microbiota transplantation (FMT). After 6 weeks of intervention, the rats were euthanized, and samples from their femur, tibia, lumbar spine, serum, colon and feces were collected, and bone strength, intestinal flora structure, SCFAs levels and cytokine levels were assessed.
RESULTS
Quercetin modulates the intestinal flora by increasing potentially probiotic bacteria (i.e., Lactobacillales, Prevotellaceae, and Blautia) and decreasing potentially pathogenic bacteria (Desulfobacterota, Erysipelotrichales, Romboutsia, and Butyricoccaceae). It also increases SCFAs content and reduces colonic permeability by enhancing tight junction proteins (ZO-1, Occludin). Furthermore, quercetin lowers proinflammatory cytokine levels (LPS, IL-1β, and TNF-α), which enhances bone strength and prevents OVX-induced bone loss.
CONCLUSIONS
Quercetin may effectively reduce bone loss in OVX rats via the "intestinal flora - SCFAs - inflammatory" signaling pathway.
Topics: Animals; Gastrointestinal Microbiome; Quercetin; Female; Fatty Acids, Volatile; Rats; Rats, Sprague-Dawley; Ovariectomy; Signal Transduction; Cytokines; Fecal Microbiota Transplantation; Osteoporosis; Disease Models, Animal; Anti-Inflammatory Agents; Humans; Inflammation
PubMed: 38810309
DOI: 10.1016/j.intimp.2024.112341 -
Journal of Biomedical Research May 2024Previous studies have shown that differentiated embryo-chondrocyte expressed gene 1 (DEC1) promotes osteoblast osteogenesis. To investigate the role of DEC1 in...
Previous studies have shown that differentiated embryo-chondrocyte expressed gene 1 (DEC1) promotes osteoblast osteogenesis. To investigate the role of DEC1 in postmenopausal osteoporosis (PMOP), we utilized the two types (DEC1 , DEC1 ) mice to establish an ovariectomy (OVX) model and found that the bone loss in DEC1 OVX mice were much less than that in DEC1 OVX mice. The expression levels of RUNX2 and OSX significantly increased in DEC1 OVX mice compared with those in DEC1 OVX mice. Whereas, NFATc1, c-Fos, CTSK and RANKL/OPG significantly decreased in DEC1 OVX mice compared with those in DEC1 OVX mice. Likewise, DEC1 deficiency suppressed IL-6 and IL-1β. Further study showed , , and significantly increased in DEC1 OVX BMSCs compared with those in DEC1 OVX BMSCs. And the mRNA levels of , and increased significantly in DEC1 OVX BMMs compared with those in DEC1 sham BMMs, but not in DEC1 OVX BMMs compared with those in DEC1 sham BMMs. Furthermore, the p-IκBα and p-P65 significantly increased in DEC1 OVX BMMs compared with those in DEC1 sham BMMs, but did not increase in DEC1 OVX BMMs compared with those in DEC1 sham BMMs. Taken together, DEC1 deficiency inhibits the NF-κB pathway induced by OVX, thereby decreasing cytokines, and subsequently, inhibits the decrease of osteogenesis and the increase of osteoclastogenesis caused by OVX. The findings provide a novel understanding of postmenopausal osteoporosis development, which offers potential avenues for the intervention strategies.
PubMed: 38807374
DOI: 10.7555/JBR.38.20240069 -
The American Journal of Case Reports May 2024BACKGROUND Malignant peritoneal mesothelioma is a rare disease with a poor prognosis that often presents with vague symptoms and inconclusive laboratory test results....
BACKGROUND Malignant peritoneal mesothelioma is a rare disease with a poor prognosis that often presents with vague symptoms and inconclusive laboratory test results. Causes include industrial pollutants, primarily asbestos, and certain genetic mutations, such as BAP1. Due to the nonspecific symptoms, it is often incidentally diagnosed during or after other surgical procedures. CASE REPORT A 35-year-old healthy woman underwent an uncomplicated laparoscopic left salpingo-oophorectomy for a symptomatic large ovarian mature cystic teratoma. She subsequently presented with late-onset postoperative fever, leukocytosis, and multiple intra-abdominal masses. Following an exploratory laparotomy, extensive infectious disease evaluation, and multiple biopsies requiring interdisciplinary collaboration, malignant peritoneal mesothelioma was diagnosed by positive histologic staining of an omental biopsy for D2-40 and CK5/6. This first specimen was positive for BAP1, with the second, a liver biopsy, testing negative for BAP1. The tumor cell testing was also notable for mutations in NF2, MLL2, and ARID1A, and the hereditary cancer genetic testing was overall unremarkable. Her disease progressed rapidly, and she died 6 months after her initial procedure. CONCLUSIONS This case of rapidly developing malignant peritoneal mesothelioma following surgical management of an ovarian mature teratoma highlights the complexity in diagnosing a rare disease that presents with nonspecific symptoms in an otherwise young and healthy woman. The rapid disease course was likely accelerated by expansive intraperitoneal spread and multiple somatic oncogenic mutations in BAP1, NF2, MLL2, and ARID1A. Gynecologists should keep a broad differential for postoperative complications, as occult malignancies can present with symptoms that mimic postoperative complications.
Topics: Humans; Female; Adult; Peritoneal Neoplasms; Postoperative Complications; Ovarian Neoplasms; Mesothelioma, Malignant; Fatal Outcome; Diagnosis, Differential; Disease Progression; Teratoma; Salpingo-oophorectomy; Mesothelioma
PubMed: 38803090
DOI: 10.12659/AJCR.942948 -
PeerJ 2024We propose a new mouse (C57Bl6/J) model combining several features of heart failure with preserved ejection fraction encountered in older women, including hypertension...
We propose a new mouse (C57Bl6/J) model combining several features of heart failure with preserved ejection fraction encountered in older women, including hypertension from Angiotensin II infusion (AngII), menopause, and advanced age. To mimic menopause, we delayed ovariectomy (Ovx) at 12 months of age. We also studied the effects of AngII infusion for 28 days in younger animals and the impact of losing gonadal steroids earlier in life. We observed that AngII effects on heart morphology were different in younger and adult mice (3- and 12-month-old; 20 and 19% increase in heart weight. < 0.01 for both) than in older animals (24-month-old; 6%; not significant). Ovariectomy at 12 months restored the hypertrophic response to AngII in elderly females (23%, = 0.0001). We performed a bulk RNA sequencing study of the left ventricle (LV) and left atrial gene expression in elderly animals, controls, and Ovx. AngII modulated (|Log fold change| ≥ 1) the LV expression of 170 genes in control females and 179 in Ovx ones, 64 being shared. In the left atrium, AngII modulated 235 genes in control females and 453 in Ovx, 140 shared. We observed many upregulated genes associated with the extracellular matrix regulation in both heart chambers. Many of these upregulated genes were shared between the ventricle and the atrium as well as in control and Ovx animals, namely for the most expressed , and . Several circadian clock LV genes were modulated differently by AngII between control and Ovx females ( and ). In conclusion, sex hormones, even in elderly female mice, modulate the heart's hypertrophic response to AngII. Our study identifies potential new markers of hypertensive disease in aging female mice and possible disturbances of their cardiac circadian clock.
Topics: Animals; Female; Angiotensin II; Disease Models, Animal; Mice; Hypertension; Mice, Inbred C57BL; Ovariectomy; Aging; Heart Ventricles; Menopause; Humans; Connective Tissue Growth Factor; Heart Atria; Collagen Type III
PubMed: 38799057
DOI: 10.7717/peerj.17434 -
Particle and Fibre Toxicology May 2024Rural regions of the western United States have experienced a noticeable surge in both the frequency and severity of acute wildfire events, which brings significant...
BACKGROUND
Rural regions of the western United States have experienced a noticeable surge in both the frequency and severity of acute wildfire events, which brings significant challenges to both public safety and environmental conservation efforts, with impacts felt globally. Identifying factors contributing to immune dysfunction, including endocrinological phenotypes, is essential to understanding how hormones may influence toxicological susceptibility.
METHODS
This exploratory study utilized male and female C57BL/6 mice as in vivo models to investigate distinct responses to acute woodsmoke (WS) exposure with a focus on sex-based differences. In a second set of investigations, two groups were established within the female mouse cohort. In one group, mice experienced ovariectomy (OVX) to simulate an ovarian hormone-deficient state similar to surgical menopause, while the other group received Sham surgery as controls, to investigate the mechanistic role of ovarian hormone presence in driving immune dysregulation following acute WS exposure. Each experimental cohort followed a consecutive 2-day protocol with daily 4-h exposure intervals under two conditions: control HEPA-filtered air (FA) and acute WS to simulate an acute wildfire episode.
RESULTS
Metals analysis of WS particulate matter (PM) revealed significantly increased levels of Cu, W, Pb, and U, compared to filtered air (FA) controls, providing insights into the specific metal components most impacted by the changing dynamics of wildfire occurrences in the region. Male and female mice exhibited diverse patterns in lung mRNA cytokine expression following WS exposure, with males showing downregulation and females displaying upregulation, notably for IL-1β, TNF-α, CXCL-1, CCL-5, TGF-β, and IL-6. After acute WS exposure, there were notable differences in the responses of macrophages, neutrophils, and bronchoalveolar lavage (BAL) cytokines IL-10, IL-6, IL-1β, and TNF-α. Significant diverse alterations were observed in BAL cytokines, specifically IL-1β, IL-10, IL-6, and TNF-α, as well as in the populations of immune cells, such as macrophages and polymorphonuclear leukocytes, in both Sham and OVX mice, following acute WS exposure. These findings elucidated the profound influence of hormonal changes on inflammatory outcomes, delineating substantial sex-related differences in immune activation and revealing altered immune responses in OVX mice due to ovarian hormone deficiency. In addition, the flow cytometry analysis highlighted the complex interaction between OVX surgery, acute WS exposure, and their collective impact on immune cell populations within the hematopoietic bone marrow niche.
CONCLUSIONS
In summary, both male and female mice, alongside females subjected to OVX and those who had sham surgery, exhibit significant variations in the expression of proinflammatory cytokines, chemokines, lung mRNA gene expression, and related functional networks linked to signaling pathways. These differences potentially act as mediators of sex-specific and hormonal influences in the systemic inflammatory response to acute WS exposure during a wildfire event. Understanding the regulatory roles of genes expressed differentially under environmental stressors holds considerable implications, aiding in identifying sex-specific therapeutic targets for addressing acute lung inflammation and injury.
Topics: Animals; Female; Male; Mice, Inbred C57BL; Inhalation Exposure; Wildfires; Particulate Matter; Sex Factors; Cytokines; Lung; Smoke; Air Pollutants; Bronchoalveolar Lavage Fluid; Ovariectomy; Mice; Ovary
PubMed: 38797836
DOI: 10.1186/s12989-024-00587-5 -
Nutrients May 2024Recent interest in preventing the development of osteoporosis has focused on the regulation of redox homeostasis. However, the action of lycopene (LYC), a strong natural...
Recent interest in preventing the development of osteoporosis has focused on the regulation of redox homeostasis. However, the action of lycopene (LYC), a strong natural antioxidant compound, on osteoporotic bone loss remains largely unknown. Here, we show that oral administration of LYC to OVX rats for 12 weeks reduced body weight gain, improved lipid metabolism, and preserved bone quality. In addition, LYC treatment inhibited ROS overgeneration in serum and bone marrow in OVX rats, and in BMSCs upon HO stimulation, leading to inhibiting adipogenesis and promoting osteogenesis during bone remodeling. At the molecular level, LYC improved bone quality via an increase in the expressions of FoxO1 and Runx2 and a decrease in the expressions of PPARγ and C/EBPα in OVX rats and BMSCs. Collectively, these findings suggest that LYC attenuates osteoporotic bone loss through promoting osteogenesis and inhibiting adipogenesis via regulation of the FoxO1/PPARγ pathway driven by oxidative stress, presenting a novel strategy for osteoporosis management.
Topics: Animals; Osteogenesis; Adipogenesis; Lycopene; PPAR gamma; Mesenchymal Stem Cells; Female; Ovariectomy; Signal Transduction; Rats; Rats, Sprague-Dawley; Osteoporosis; Oxidative Stress; Forkhead Box Protein O1; Antioxidants; Reactive Oxygen Species
PubMed: 38794681
DOI: 10.3390/nu16101443 -
Medicina (Kaunas, Lithuania) Apr 2024: The hormonal state of hypoestrogenism is associated with the accumulation of white adipose tissue, which can induce an increase in pro-inflammatory markers, leading to...
: The hormonal state of hypoestrogenism is associated with the accumulation of white adipose tissue, which can induce an increase in pro-inflammatory markers, leading to progressive health complications. Melatonin can act on adipose tissue mass, promoting its reduction and influencing inflammation, reducing IL-6 and releasing IL-10, pro- and anti-inflammatory markers, respectively. However, the role of melatonin regarding such parameters under the context of hypoestrogenism remains unknown. The aim of this study was to determine the effect of 12 weeks of hypoestrogenism and melatonin on white adipose tissue mass and circulating levels of IL-6, IL-10, TGF-β-1, and leukotriene C4 (LTC4). : The animals (Wistar rats with sixteen weeks of age at the beginning of the experiment) under hypoestrogenism were submitted to the surgical technique of bilateral ovariectomy. The animals received melatonin (10 mg·kg) or vehicles by orogastric gavage every day for 12 weeks and administration occurred systematically 1 h after the beginning of the dark period. White adipose tissue (perigonadal, peritoneal, and subcutaneous) was collected for mass recording, while blood was collected for the serum determination of IL-6, IL-10, TGF-β-1, and LTC4. : Hypoestrogenism increased the perigonadal and subcutaneous mass and IL-6 levels. Melatonin kept hypoestrogenic animals in physiological conditions similar to the control group and increased thymus tissue mass. : Hypoestrogenism appears to have a negative impact on white adipose tissue mass and IL-6 and although melatonin commonly exerts a significant effect in preventing these changes, this study did not have a sufficiently negative impact caused by hypoestrogenism for melatonin to promote certain benefits.
Topics: Animals; Melatonin; Rats, Wistar; Rats; Female; Interleukin-6; Biomarkers; Adipose Tissue; Interleukin-10; Ovariectomy; Inflammation; Transforming Growth Factor beta1; Estrogens; Adipose Tissue, White
PubMed: 38792922
DOI: 10.3390/medicina60050740 -
International Journal of Molecular... May 2024Heart failure with preserved ejection fraction (HFpEF) is more prevalent in post- compared to pre-menopausal women. The underlying mechanisms are not fully understood....
Cardiac Left Ventricular miRNA-26a Is Downregulated in Ovariectomized Mice, Upregulated upon 17-Beta Estradiol Replacement, and Inversely Correlated with Collagen Type 1 Gene Expression.
Heart failure with preserved ejection fraction (HFpEF) is more prevalent in post- compared to pre-menopausal women. The underlying mechanisms are not fully understood. Data in humans is confounded by age and co-morbidities. We investigated the effects of ovariectomy and estrogen replacement on the left ventricular (LV) gene expression of pro-inflammatory and pro-fibrotic factors involved in HFpEF and putative regulating miRNAs. Nine-week-old C57BL/6 female mice were subjected to ovariectomy (OVX) or SHAM operation. OVX and SHAM groups were sacrificed 1-, 6-, and 12-weeks post-surgery (T1/SHAM; T1/OVX; T6/SHAM; T6/OVX, T12/SHAM). 17β-estradiol (E) or vehicle (VEH) was then administered to the OVX groups for 6 weeks (T12/OVX/E2; T12/OVX/VEH). Another SHAM group was sacrificed 12-weeks post-surgery. RNA and miRNAs were extracted from the LV apex. An early 3-fold increase in the gene expression of , , , , , and was observed one-week post-surgery in T1/OVX vs. T1/SHAM, but not at later time points. miRNA-26a was lower in T1/OVX vs. T1/SHAM and was inversely correlated with and expression 1-week post-surgery (r = -0.79 < 0.001; r = -0.6 = 0.007). miRNAs-26a, 29b, and 133a were significantly higher, while , , , , , , and gene expression was significantly lower in E- compared to vehicle-treated OVX mice. miRNA-26a was inversely correlated with in T12/OVX/ E (r = -0.56 = 0.02). OVX triggered an early increase in the gene expression of pro-inflammatory and pro-fibrotic factors, highlighting the importance of the early phase post-cessation of ovarian function. E replacement therapy, even if it was not immediately initiated after OVX, reversed these unfavorable changes and upregulated cardiac miRNA-26a, previously unknown to be affected by menopausal status.
Topics: Animals; MicroRNAs; Ovariectomy; Female; Estradiol; Mice; Collagen Type I; Heart Ventricles; Mice, Inbred C57BL; Collagen Type III; Gene Expression Regulation; Down-Regulation; Heart Failure; Collagen Type I, alpha 1 Chain; Up-Regulation; Interleukin-6; Interleukin-1alpha; Estrogen Replacement Therapy
PubMed: 38791190
DOI: 10.3390/ijms25105153 -
International Journal of Molecular... May 2024Menopause is characterized by a reduction in sex hormones in women and is associated with metabolic changes, including fatty liver and insulin resistance. Lifestyle...
Menopause is characterized by a reduction in sex hormones in women and is associated with metabolic changes, including fatty liver and insulin resistance. Lifestyle changes, including a balanced diet and physical exercise, are necessary to prevent these undesirable changes. Strength training (ST) has been widely used because of the muscle and metabolic benefits it provides. Our study aims to evaluate the effects of ST on hepatic steatosis and insulin resistance in ovariectomized mice fed a high-fat diet (HFD) divided into four groups as follows: simulated sedentary surgery (SHAM-SED), trained simulated surgery (SHAM-EXE), sedentary ovariectomy (OVX-SED), and trained ovariectomy (OVX-EXE). They were fed an HFD for 9 weeks. ST was performed thrice a week. ST efficiently reduced body weight and fat percentage and increased lean mass in OVX mice. Furthermore, ST reduced the accumulation of ectopic hepatic lipids, increased AMPK phosphorylation, and inhibited the de novo lipogenesis pathway. OVX-EXE mice also showed a better glycemic profile, associated with greater insulin sensitivity identified by the euglycemic-hyperinsulinemic clamp, and reduced markers of hepatic oxidative stress compared with sedentary animals. Our data support the idea that ST can be indicated as a non-pharmacological treatment approach to mitigate metabolic changes resulting from menopause.
Topics: Animals; Insulin Resistance; Female; Ovariectomy; Diet, High-Fat; Mice; Resistance Training; Fatty Liver; Physical Conditioning, Animal; Oxidative Stress; Liver; Mice, Inbred C57BL; Body Weight; Lipogenesis
PubMed: 38791103
DOI: 10.3390/ijms25105066 -
Biomedicine & Pharmacotherapy =... Jul 2024Obesity is a multifaceted medical condition characterized by the pathological accumulation of excessive lipids in the body. We investigated the effects of morroniside, a...
Obesity is a multifaceted medical condition characterized by the pathological accumulation of excessive lipids in the body. We investigated the effects of morroniside, a bioactive compound derived from Cornus officinalis, on adipogenesis. We used a preadipocyte 3T3-L1 stable cell line and primary cultured adipose-derived stem cells (ADSCs) in vitro and ovariectomized (OVX) and a high-fat diet (HFD)-fed obese mouse model in vivo. Preadipocyte 3T3-L1 cells and ADSCs incubated with morroniside during adipocyte differentiation and obese mice subjected to OVX and HFD received oral morroniside treatment for 12 weeks. Morroniside treatment significantly reduced adipocyte differentiation and fatty acid accumulation and downregulated adipogenesis-related gene expression, concomitant with a decrease in triglyceride content and an increase in glycerol release in cells. The results of the in vivo study showed that morroniside ameliorated obesity-related phenotypes by reducing body weight gain, hepatic steatosis, and adipose tissue in obese mice. These findings suggest that morroniside is a promising compound for preventing and treating obesity.
Topics: Animals; Mice; Adipogenesis; 3T3-L1 Cells; Obesity; Anti-Obesity Agents; Female; Diet, High-Fat; Mice, Inbred C57BL; Adipocytes; Glycosides; Adipose Tissue; Cell Differentiation; Mice, Obese; Triglycerides; Ovariectomy; Fatty Liver
PubMed: 38788597
DOI: 10.1016/j.biopha.2024.116762