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International Journal of Molecular... Apr 2024This study explores low-intensity extracorporeal shock wave therapy (LiESWT)'s efficacy in alleviating detrusor hyperactivity with impaired contractility (DHIC) induced...
Low-Intensity Extracorporeal Shock Wave Therapy Ameliorates Detrusor Hyperactivity with Impaired Contractility via Transient Potential Vanilloid Channels: A Rat Model for Ovarian Hormone Deficiency.
This study explores low-intensity extracorporeal shock wave therapy (LiESWT)'s efficacy in alleviating detrusor hyperactivity with impaired contractility (DHIC) induced by ovarian hormone deficiency (OHD) in ovariectomized rats. The rats were categorized into the following four groups: sham group; OVX group, subjected to bilateral ovariectomy (OVX) for 12 months to induce OHD; OVX + SW4 group, underwent OHD for 12 months followed by 4 weeks of weekly LiESWT; and OVX + SW8 group, underwent OHD for 12 months followed by 8 weeks of weekly LiESWT. Cystometrogram studies and voiding behavior tracing were used to identify the symptoms of DHIC. Muscle strip contractility was evaluated through electrical-field, carbachol, ATP, and KCl stimulations. Western blot and immunofluorescence analyses were performed to assess the expressions of various markers related to bladder dysfunction. The OVX rats exhibited significant bladder deterioration and overactivity, alleviated by LiESWT. LiESWT modified transient receptor potential vanilloid (TRPV) channel expression, regulating calcium concentration and enhancing bladder capacity. It also elevated endoplasmic reticulum (ER) stress proteins, influencing ER-related Ca channels and receptors to modulate detrusor muscle contractility. OHD after 12 months led to neuronal degeneration and reduced TRPV1 and TRPV4 channel activation. LiESWT demonstrated potential in enhancing angiogenic remodeling, neurogenesis, and receptor response, ameliorating DHIC via TRPV channels and cellular signaling in the OHD-induced DHIC rat model.
Topics: Animals; Female; Rats; TRPV Cation Channels; Extracorporeal Shockwave Therapy; Disease Models, Animal; Muscle Contraction; Urinary Bladder; Urinary Bladder, Overactive; Ovariectomy; Rats, Sprague-Dawley; Ovary
PubMed: 38732143
DOI: 10.3390/ijms25094927 -
Animals : An Open Access Journal From... May 2024The purpose of this study was to evaluate the quality of recovery from general anesthesia with the administration of two low doses of dexmedetomidine in canine patients....
The purpose of this study was to evaluate the quality of recovery from general anesthesia with the administration of two low doses of dexmedetomidine in canine patients. For this blind randomized clinical trial study, 30 dogs undergoing general anesthesia for diagnostic procedures or elective surgery (ovariectomy/castration) were included. The patients were randomly divided into three groups, and at the end of anesthesia, they received a bolus of dexmedetomidine at 1 mcg/kg IV (D1), or a bolus of dexmedetomidine at 0.5 mcg/kg (D0.5), or a bolus of NaCl, in a total of 0.5 mL of solution for all three groups. After administration of the bolus, the anesthetist monitored the patients every 5 min by measuring heart rate, systolic and mean blood pressure, respiratory rate, and oxygen saturation. The quality of recovery was also assessed using 4 different scales. The extubation time, time of headlift, and standing position were also recorded. Both groups receiving dexmedetomidine had better awakening and a lower incidence of delirium when compared to saline administration. The heart rate was lower, while the systolic pressure was higher in the two groups D1 and D0.5 compared to the NaCl with a low presence of atrioventricular blocks. The extubation time resulted significantly higher in the D1 (17 ± 6 min) compared to the D0.5 (10 ± 4 min) and NaCl (8 ± 3 min) ( < 0.0001); the headlift time D1 (25 ± 10 min) resulted significantly longer than the NaCl group (11 ± 5 min) ( = 0.0023) but not than the D0.5 (18 ± 9 min). No significant differences were found among the three groups for standing positioning (D1 50 ± 18 min, D0.5 39 ± 22 min, NaCl 28 ± 17 min). The preventive administration of a bolus of dexmedetomidine at a dosage of 0.5 mcg/kg or 1 mcg/kg IV during the recovery phase improves the quality of recovery in patients undergoing general anesthesia.
PubMed: 38731387
DOI: 10.3390/ani14091383 -
Animals : An Open Access Journal From... Apr 2024Ovarian tumors in mares are uncommon in comparison to other neoplasms and are classified into three categories: gonadal stromal tumors, coelomic epithelium surface...
Ovarian tumors in mares are uncommon in comparison to other neoplasms and are classified into three categories: gonadal stromal tumors, coelomic epithelium surface tumors, and germinal cell tumors. Some ovarian neoplasms histologically show a mixture of multiple cell types in the same tumor, such as fibrothecoma; therefore, the differentiation between fibroma and thecoma is often difficult. According to the World Health Organization, fibrothecomas are classified as sex-cord stromal tumors (pure stromal tumors). Neoplasms such as fibrothecoma present with limited morphological, clinical, ultrasonographic, and endocrine profile characteristics. To diagnose this type of tumor, a broad clinical examination is needed, but histopathology remains the most accurate. Herein, we report a case of incidentally found ovarian fibrothecoma during a diagnostic laparotomy in a 6-year-old Dutch Warmblood (KWPN) mare who presented to the clinic with colic symptoms. After a unilateral ovariectomy, the altered right ovary was diagnosed as fibrothecoma based on histopathological features.
PubMed: 38731310
DOI: 10.3390/ani14091307 -
The Journal of Steroid Biochemistry and... Sep 2024Inflammatory bowel disease (IBD) describes a group of clinically common autoimmune diseases characterized by chronic intestinal inflammation, with gender differences in...
Inflammatory bowel disease (IBD) describes a group of clinically common autoimmune diseases characterized by chronic intestinal inflammation, with gender differences in prevalence. Estrogen has been previously shown to exert anti-inflammatory action in IBD development, however, the mechanisms remain obscure. Recent research has revealed that myeloid-derived suppressor cells (MDSCs) play a protective role in IBD pathogenesis. To investigate the molecular mechanisms of estrogen steroid 17β-estradiol (E2) in IBD progression, we established IBD mouse models (DNB-induced) with or without prior ovariectomy (OVX) and E2 implantation. We found that OVX led to worse IBD symptoms and reduced MDSCs frequency, whereas E2 significantly alleviated these effects in vivo. Moreover, in vitro experiments showed that E2 promoted the proliferation and immunosuppressive function of MDSCs through phosphorylation of Stat3 and p65. Mechanistically, E2-mediated Stat3/p65 phosphorylation depends on the interaction between HOTAIR, a long non-coding RNA that are well-known in MDSCs proliferation, and Stat3/p65 respectively. In conclusion, our study revealed that E2 promotes the expansion and immunosuppressive function of MDSCs, and thus diminished the occurrence and development of IBD.
Topics: Animals; STAT3 Transcription Factor; Estradiol; Myeloid-Derived Suppressor Cells; Inflammatory Bowel Diseases; Mice; Female; Signal Transduction; Mice, Inbred C57BL; NF-kappa B; Cell Proliferation; Estrogens; Phosphorylation; Ovariectomy; RNA, Long Noncoding
PubMed: 38719162
DOI: 10.1016/j.jsbmb.2024.106540 -
Drug Design, Development and Therapy 2024Estrogen deficiency is the main reason of postmenopausal osteoporosis. Eldecalcitol (ED-71) is a new active vitamin D analogue clinically used in the treatment of...
PURPOSE
Estrogen deficiency is the main reason of postmenopausal osteoporosis. Eldecalcitol (ED-71) is a new active vitamin D analogue clinically used in the treatment of postmenopausal osteoporosis. We aimed to investigate whether EphrinB2-EphB4 and RANKL/RANK/OPG signaling cooperate in mediating the process of osteoporosis by ED-71.
METHODS
In vivo, the ovariectomized (OVX) rats were administered orally with 30 ng/kg ED-71 once a day for 8 weeks. HE staining, Masson staining and Immunofluorescence staining were used to evaluate bone mass, bone formation, osteoclastogenesis associated factors and the expression of EphrinB2, EphB4, RANKL and OPG. In vitro, HO stimulation was used to simulate the cell environment in osteoporosis. Immunofluorescence, quantitative real time PCR (qRT-PCR), enzyme-linked immunosorbent assay (ELISA) and Western Blot were applied to detect the expression of EphrinB2, EphB4, RANKL and OPG. In osteoblasts, EphB4 was knocked down by EphB4 small-interfering RNA (siRNA) transfection. LY294002 (PI3K inhibitor) or ARQ092 (AKT inhibitor) was used to block PI3K/AKT pathway. An indirect co-culture system of osteoblasts and osteoclasts was established. The mRNA and protein expression of osteoclastogenes is associated factors were tested by qRT-PCR and Western Blot.
RESULTS
ED-71 increased bone mass and decreased the number of osteoclasts in OVX rats. Moreover, ED-71 promoted the expression of EphrinB2, EphB4, and decreased the RANKL/OPG ratio in osteoblasts. Osteoclastogenesis was restrained when osteoclasts were indirectly co-cultured with ED-71-treated osteoblasts. After silencing of EphB4 expression in osteoblasts, ED-71 inhibited the expression of P-PI3K and P-AKT and increased the ratio of RANKL/OPG. This reversed the inhibitory effect of ED-71 on osteoclastogenes. Therefore, in ED-71-inhibited osteoclastogenes, EphB4 is a key factor affecting the secretion of RANKL and OPG by osteoblasts. EphB4 suppressed the RANKL/OPG ratio through activating PI3K/AKT signaling in osteoblasts.
CONCLUSION
ED-71 inhibits osteoclastogenesis through EphrinB2-EphB4-RANKL/OPG axis, improving bone mass in ovariectomized rats. PI3K/AKT pathway is involved this process.
Topics: Animals; Female; Rats; Bone Density; Cells, Cultured; Ephrin-B2; Osteoclasts; Osteogenesis; Osteoprotegerin; Ovariectomy; RANK Ligand; Rats, Sprague-Dawley; Receptor, EphB4; Signal Transduction; Vitamin D
PubMed: 38716369
DOI: 10.2147/DDDT.S454116 -
American Journal of Veterinary Research Jul 2024To investigate differences in pain management between dogs and cats after surgical sterilization. We hypothesized that dogs would be more likely to be discharged with...
OBJECTIVE
To investigate differences in pain management between dogs and cats after surgical sterilization. We hypothesized that dogs would be more likely to be discharged with analgesics after sterilization compared to cats and that owner compliance would be better in dogs.
ANIMALS
175 respondents owning 92 dogs and 83 cats from a high-volume, low-cost veterinary clinic in Michigan during August 2022.
METHODS
Owners received an online survey designed to assess their pet's postoperative analgesic care. They were asked demographic information about themselves and their pets. Additionally, they were asked if their pet was discharged with analgesics, if they were administered as prescribed, and if their pet was painful at home. Dogs and cats were included if they were sterilized within 6 months of survey completion and in the owner's care at the time of the procedure.
RESULTS
The survey was distributed to 5,241 owners and received 227 responses, a response rate of 4.4%. Analgesics were prescribed for 19 of 162 (12%) pets: 14 of 88 (16%) dogs and 5 of 74 (6.7%) cats. There was no difference in the prescription of analgesics between dogs and cats after ovariohysterectomy (P = .09) or orchiectomy (P = .73). 15 of 19 owners reported their compliance in administering analgesics at 78.9%. Owners' subjective assessments showed that 24 of 86 (28%) dogs and 12 of 68 (17%) cats appeared painful at home.
CLINICAL RELEVANCE
Postoperative pain in cats may not be appropriately managed.
Topics: Cats; Animals; Dogs; Hysterectomy; Orchiectomy; Male; Female; Ovariectomy; Pain, Postoperative; Analgesics; Surveys and Questionnaires; Ownership; Dog Diseases; Michigan; Cat Diseases; Humans; Pain Management
PubMed: 38710204
DOI: 10.2460/ajvr.24.03.0055 -
Aging May 2024BMP9 has demonstrated significant osteogenic potential. In this study, we investigated the effect of Leptin on BMP9-induced osteogenic differentiation. Firstly, we found...
BMP9 has demonstrated significant osteogenic potential. In this study, we investigated the effect of Leptin on BMP9-induced osteogenic differentiation. Firstly, we found Leptin was decreased during BMP9-induced osteogenic differentiation and serum Leptin concentrations were increased in the ovariectomized (OVX) rats. Both and , exogenous expression of Leptin inhibited the process of osteogenic differentiation, whereas silencing Leptin enhanced. Exogenous Leptin could increase the malonylation of β-catenin. However, BMP9 could increase the level of Sirt5 and subsequently decrease the malonylation of β-catenin; the BMP9-induced osteogenic differentiation was inhibited by silencing Sirt5. These data suggested that Leptin can inhibit the BMP9-induced osteogenic differentiation, which may be mediated through reducing the activity of Wnt/β-catenin signalling via down-regulating Sirt5 to increase the malonylation level of β-catenin partly.
Topics: Animals; beta Catenin; Sirtuins; Female; Rats; Osteogenesis; Leptin; Down-Regulation; Growth Differentiation Factor 2; Wnt Signaling Pathway; Ovariectomy; Cell Differentiation; Rats, Sprague-Dawley
PubMed: 38709288
DOI: 10.18632/aging.205790 -
Frontiers in Bioengineering and... 2024This study aims to develop and evaluate the biocompatibility and osteogenic potential of a novel injectable strontium-doped hydroxyapatite bone-repair material. The...
This study aims to develop and evaluate the biocompatibility and osteogenic potential of a novel injectable strontium-doped hydroxyapatite bone-repair material. The properties of strontium-doped hydroxyapatite/chitosan (Sr-HA/CS), hydroxyapatite/chitosan (HA/CS) and calcium phosphate/chitosan (CAP/CS) were assessed following their preparation via physical cross-linking and a one-step simplified method. Petri dishes containing and were inoculated with the material for investigations. The material was also co-cultured with stem cells derived from human exfoliated deciduous teeth (SHEDs), to assess the morphology and proliferation capability of the SHEDs, Calcein-AM staining and the Cell Counting Kit-8 assay were employed. Osteogenic differentiation of SHEDs was determined using alkaline phosphatase (ALP) staining and Alizarin Red staining. For studies, Sr-HA/CS was implanted into the muscle pouch of mice and in a rat model of ovariectomy-induced femoral defects. Hematoxylin-eosin (HE) staining was performed to determine the extent of bone formation and defect healing. The formation of new bone was determined using Masson's trichrome staining. The osteogenic mechanism of the material was investigated using Tartrate-resistant acid phosphatase (TRAP) staining and immunohistochemical studies. X-ray diffraction (XRD) and energy-dispersive spectroscopy (EDS) showed that strontium was successfully doped into HA. The Sr-HA/CS material can be uniformly squeezed using a syringe with a 13% swelling rate. Sr-HA/CS had a significant antibacterial effect against both and ( < 0.05), with a stronger effect observed against . The Sr-HA/CS significantly improved cell proliferation and cell viability studies ( < 0.05). Compared to CAP/CS and CS, Sr-HA/CS generated a substantially greater new bone area during osteoinduction experiments ( < 0.05, < 0.001). The Sr-HA/CS material demonstrated a significantly higher rate of bone repair in the bone defeat studies compared to the CAP/CS and CS materials ( < 0.01). The OCN-positive area and TRAP-positive cells in Sr-HA/CS were greater than those in control groups ( < 0.05). A novel injectable strontium-doped HA bone-repair material with good antibacterial properties, biocompatibility, and osteoinductivity was successfully prepared.
PubMed: 38707496
DOI: 10.3389/fbioe.2024.1390337 -
Hepatology Communications May 2024Alcohol-associated liver disease is a complex disease regulated by genetic and environmental factors such as diet and sex. The combination of high-fat diet and alcohol...
BACKGROUND
Alcohol-associated liver disease is a complex disease regulated by genetic and environmental factors such as diet and sex. The combination of high-fat diet and alcohol consumption has synergistic effects on liver disease progression. Female sex hormones are known to protect females from liver disease induced by high-fat diet. In contrast, they promote alcohol-mediated liver injury. We aimed to define the role of female sex hormones on liver disease induced by a combination of high-fat diet and alcohol.
METHODS
Wild-type and protein arginine methyltransferase (Prmt)6 knockout female mice were subjected to gonadectomy (ovariectomy, OVX) or sham surgeries and then fed western diet and alcohol in the drinking water.
RESULTS
We found that female sex hormones protected mice from western diet/alcohol-induced weight gain, liver steatosis, injury, and fibrosis. Our data suggest that these changes are, in part, mediated by estrogen-mediated induction of arginine methyltransferase PRMT6. Liver proteome changes induced by OVX strongly correlated with changes induced by Prmt6 knockout. Using Prmt6 knockout mice, we confirmed that OVX-mediated weight gain, steatosis, and injury are PRMT6 dependent, while OVX-induced liver fibrosis is PRMT6 independent. Proteomic and gene expression analyses revealed that estrogen signaling suppressed the expression of several components of the integrin pathway, thus reducing integrin-mediated proinflammatory (Tnf, Il6) and profibrotic (Tgfb1, Col1a1) gene expression independent of PRMT6 levels. Integrin signaling inhibition using Arg-Gly-Asp peptides reduced proinflammatory and profibrotic gene expression in mice, suggesting that integrin suppression by estrogen is protective against fibrosis development.
CONCLUSIONS
Taken together, estrogen signaling protects mice from liver disease induced by a combination of alcohol and high-fat diet through upregulation of Prmt6 and suppression of integrin signaling.
Topics: Animals; Mice; Estradiol; Mice, Knockout; Female; Signal Transduction; Protein-Arginine N-Methyltransferases; Integrins; Diet, High-Fat; Ovariectomy; Ethanol; Liver Cirrhosis, Alcoholic; Liver; Mice, Inbred C57BL; Disease Models, Animal
PubMed: 38704651
DOI: 10.1097/HC9.0000000000000428 -
Scientific Reports May 2024Hydrolyzed egg yolk peptide (YPEP) was shown to increase bone mineral density in ovariectomized rats. However, the underlying mechanism of YPEP on osteoporosis has not...
Hydrolyzed egg yolk peptide (YPEP) was shown to increase bone mineral density in ovariectomized rats. However, the underlying mechanism of YPEP on osteoporosis has not been explored. Recent studies have shown that Wnt/β-catenin signaling pathway and gut microbiota may be involved in the regulation of bone metabolism and the progression of osteoporosis. The present study aimed to explore the preventive effect of the YPEP supplementation on osteoporosis in ovariectomized (OVX) rats and to verify whether YPEP can improve osteoporosis by regulating Wnt/β-catenin signaling pathway and gut microbiota. The experiment included five groups: sham surgery group (SHAM), ovariectomy group (OVX), 17-β estradiol group (E2: 25 µg /kg/d 17β-estradiol), OVX with low-dose YPEP group (LYPEP: 10 mg /kg/d YPEP) and OVX with high-dose YPEP group (HYPEP: 40 mg /kg/d YPEP). In this study, all the bone samples used were femurs. Micro-CT analysis revealed improvements in both bone mineral density (BMD) and microstructure by YPEP treatment. The three-point mechanical bending test indicated an enhancement in the biomechanical properties of the YPEP groups. The serum levels of bone alkaline phosphatase (BALP), bone gla protein (BGP), calcium (Ca), and phosphorus (P) were markedly higher in the YPEP groups than in the OVX group. The LYPEP group had markedly lower levels of alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) and C-terminal telopeptide of type I collagen (CTX-I) than the OVX group. The YPEP groups had significantly higher protein levels of the Wnt3a, β-catenin, LRP5, RUNX2 and OPG of the Wnt/β-catenin signaling pathway compared with the OVX group. Compared to the OVX group, the ratio of OPG/RANKL was markedly higher in the LYPEP group. At the genus level, there was a significantly increase in relative abundance of Lachnospiraceae_NK4A136_group and a decrease in Escherichia_Shigella in YPEP groups, compared with the OVX group. However, in the correlation analysis, there was no correlation between these two bacteria and bone metabolism and microstructure indexes. These findings demonstrate that YPEP has the potential to improve osteoporosis, and the mechanism may be associated with its modulating effect on Wnt/β-catenin signaling pathway.
Topics: Animals; Female; Rats; Alkaline Phosphatase; beta Catenin; Bone Density; Egg Proteins; Egg Yolk; Femur; Low Density Lipoprotein Receptor-Related Protein-5; Osteoporosis; Ovariectomy; Peptides; Rats, Sprague-Dawley; Wnt Signaling Pathway; X-Ray Microtomography
PubMed: 38702443
DOI: 10.1038/s41598-024-60514-8