Effect of total flavonoids from Drynaria rhizome on bone loss in ovariectomized rats

Purpose: To determine the potential effect of total flavonoids from Drynaria rhizome on bone loss in ovariectomized (OVX) rats. Methods: The rats were divided into four groups: normal control, ovariectomized (OVX) control, and two Drynaria rhizome (DR) flavonoids treatments. Post-operation, osteoporotic OVX rats were given Drynaria rhizome total flavonoids for 3 months. Thereafter, the expressions of bone-related genes and biochemical indices were investigated in samples taken from the serum and bone of the rats. Results: Treatment with total flavonoids from Drynaria rhizome prevented bone mineral loss and improved some related biochemical indices associated with osteoporosis: alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP), bone gla protein (BGP) and estradiol (E2). Reverse transcription-polymerase chain reaction (RT-PCR) data showed that treatment with the total flavonoids significantly downregulated mRNA expression of Wnt10b, β-catenin, recombinant human bone morphogenetic protein-2 (BMP2) and BMP4 in OVX rats, but significantly reversed OVX-induced downregulation of dickkopf1 (Dkk1) mRNA expression. Conclusion: These results indicate that total flavonoids from Drynaria rhizome exert anti-osteoporotic effects in rats via WNT signaling and BMP-2 signaling pathways

Extraction optimization of Eucommia ulmoides Oliver and its effect on bone quality in OVX rats

Purpose: To maximize the yield of extract from Eucommia ulmoides Oliver and its effect on bone quality. Methods: Different extraction indices were optimized with response surface methodology (RSM) for maximization of extract yield from Eucommia ulmoides Oliver. Box–Behnken design (BBD) was used to identify the effects of temperature, time, and liquid to solid ratio on extract yield from Eucommia ulmoides Oliver. After 4-week acclimatization, thiry-two rats were randomly assigned to 4 groups (n = 8): group 1 (sham) given vehicle only; group 2 (OVX rats given Eucommia ulmoides Oliver extract at a dose of 4 g/kg; group 3 (OVX + vehicle); group 4 (OVX + EUOE), i.e., OVX rats given Eucommia ulmoides Oliver extract (4 g/kg). Sham rats had intact ovaries. After surgery, the rats received gentamicin intramuscularly for 3 successive days. Two months after surgery, blood and trabecular bones was taken for analysis. Results: Temperature and liquid-to-solid ratio had marked impact on extract yield from Eucommia ulmoides Oliver, with the best conditions being temperature of 88 °C, time of 137 min, and liquid to solid ratio 16:1. Using these optimized conditions, the maximum yield of extract obtained experimentally (2.53%) was very close to the predicted value of 2.49 %. There was a good fit between the mathematical model evolved and the data on extract yield. The extract significantly (p < 0.01) increased the Ca and P and Cr levels in OVX + EUOE group compared to those in OVX control. Moreover, the extract significantly (p < 0.01) increased macro-mechanical indices of trabecular bone in OVX+EUOE group, relative to those in OVX control. Conclusion: The yield of Eucommia ulmoides Oliver extract has been successfully optimized using RSM. The extract exhibited strong effects on bone quality. Keywords: Optimization, Eucommia ulmoides, Box–Behnken design, Response surface methodology, Bone loss, Gen

Epigenetics in ovarian cancer: premise, properties, and perspectives.

Malignant ovarian tumors bear the highest mortality rate among all gynecological cancers. Both late tumor diagnosis and tolerance to available chemical therapy increase patient mortality. Therefore, it is both urgent and important to identify biomarkers facilitating early identification and novel agents preventing recurrence. Accumulating evidence demonstrates that epigenetic aberrations (particularly histone modifications) are crucial in tumor initiation and development. Histone acetylation and methylation are respectively regulated by acetyltransferases-deacetylases and methyltransferases-demethylases, both of which are implicated in ovarian cancer pathogenesis. In this review, we summarize the most recent discoveries pertaining to ovarian cancer development arising from the imbalance of histone acetylation and methylation, and provide insight into novel therapeutic interventions for the treatment of ovarian carcinoma

A Novel Derivative of the Natural Product Danshensu Suppresses Inflammatory Responses to Alleviate Caerulein-Induced Acute Pancreatitis

Acute pancreatitis (AP), a common abdominal inflammatory disorder, is characterized by premature intracellular activation of digestive proteases within pancreatic acini and a consecutive systemic inflammatory response. Although the mechanism remains to be fully understood, inflammation is the main cause of pancreatic damage in AP. A novel compound [4-(2-acetoxy-3-((R)-3-(benzylthio)-1-methoxy-1-oxopropan-2-ylamino)-3-oxopropyl)-1,2-phenylene diacetate (DSC)], derived from danshensu, exhibits anti-inflammatory and anti-apoptotic properties in vitro. However, its potential beneficial effect in AP has not been demonstrated. This study aimed to investigate the effects and underlying mechanisms of DSC in experimental AP in mice. We found that DSC suppressed inflammatory responses in AP by inhibiting the activation of nuclear factor-κB (NF-κB), signal transducer and activator of transcription 3 (STAT3) and nucleotide-binding domain leucine-rich repeat containing family, pyrin domain-containing 3 (NLRP3) inflammasome. Furthermore, treatment with DSC modulated the infiltration of neutrophils and the phenotypes of macrophages in mice induced with AP. Interestingly, we found that the expression of nuclear factor-erythroid 2 related factor 2 (Nrf2) and its regulated antioxidant enzyme heme oxygenase-1 (HO-1), which modulate inflammatory activities, was significantly increased in DSC-treated groups. Together, our findings demonstrate that DSC alleviates pancreatic inflammation and damage in AP by inhibiting the activation of NF-κB, STAT3, and NLRP3 inflammasome and modulating immune cell responses

The association between a body shape index and elevated urinary albumin–creatinine ratio in Chinese community adults

BackgroundObesity, especially visceral obesity, seems to be one of the most decisive risk factors for chronic kidney disease. A Body Shape Index (ABSI) is an emerging body size measurement marker of visceral obesity. This study aimed to explore whether ABSI is associated with albuminuria in Chinese community adults.MethodsThis cross-sectional study enrolled 40,726 participants aged 40 or older from seven provinces across China through a cluster random sampling method. ABSI was calculated by body mass index, waist circumference, and height. Increased albuminuria was defined as urinary albumin–creatinine ratio (UACR) ≥ 30 mg/g, indicating kidney injury. For ABSI, we divided it by quartile cutoff points and tried to determine the association between ABSI levels and UACR by multiple regression analysis. DAG (Directed Acyclic Graph) was plotted using literature and expert consensus to identify potential confounding factors.ResultsThe average age of subjects with elevated UACR was 61.43 ± 10.07, and 26% were men. The average age of subjects with normal UACR was 57.70 ± 9.02, and 30.5% were men. Multiple logistic regression analysis was conducted and demonstrated that the ABSI quartiles were related to elevated UACR positively (OR [95% CI] Q2 vs. Q1: 1.094 [1.004, 1.197]; OR [95% CI] Q3 vs. Q1: 1.126 [1.030, 1.231]; OR [95% CI] Q4 vs. Q1: 1.183 [1.080, 1.295], p for trend < 0.001) after adjustments for confounding factors. The stratified analysis further showed that with the mounting for ABSI levels, elevated UACR more easily occurred in the people characterized by the elderly, men, and hypertension.ConclusionsIn Chinese community adults, people with higher ABSI levels can be deemed as high-risk individuals with UACR elevation, and it will be beneficial for them to lose weight and significantly reduce visceral fat

Modification effect of changes in cardiometabolic traits in association between kidney stones and cardiovascular events

BackgroundsWhether longitudinal changes in metabolic status influence the effect of kidney stones on cardiovascular disease (CVD) remains unclarified. We investigated the modification effect of status changes in metabolic syndrome (MetS) in the association of kidney stones with risk of incident CVD events.MethodsWe performed a prospective association and interaction study in a nationwide cohort including 129,172 participants aged ≥ 40 years without CVDs at baseline and followed up for an average of 3.8 years. Kidney stones information was collected by using a questionnaire and validated by medical records. The repeated biochemical measurements were performed to ascertain the metabolic status at both baseline and follow-up.Results4,017 incident total CVDs, 1,413 coronary heart diseases (CHDs) and 2,682 strokes were documented and ascertained during follow-up. Kidney stones presence was significantly associated with 44%, 70% and 31% higher risk of CVDs, CHDs and stroke, respectively. The stratified analysis showed significant associations were found in the incident and sustained MetS patients, while no significant associations were found in the non-MetS at both baseline and follow-up subjects or the MetS remission ones, especially in women. For the change status of each single component of the MetS, though the trends were not always the same, the associations with CVD were consistently significant in those with sustained metabolic disorders, except for the sustained high blood glucose group, while the associations were consistently significant in those with incident metabolic disorders except for the incident blood pressure group. We also found a significant association of kidney stone and CVD or CHD risk in the remain normal glucose or triglycerides groups; while the associations were consistently significant in those with incident metabolic disorders except for the incident blood pressure group. We also found a significant association of kidney stone and CVD or CHD risk in the remain normal glucose or triglycerides groups.ConclusionsA history of kidney stones in women with newly developed MetS or long-standing MetS associated with increased risk of CVD. The mechanisms link kidney stones and CVD risk in the metabolic and non-metabolic pathways were warranted for further studies

The Relative Body Weight Gain From Early to Middle Life Adulthood Associated With Later Life Risk of Diabetes: A Nationwide Cohort Study

AimTo determine the effect of decade-based body weight gain from 20 to 50 years of age on later life diabetes risk.Methods35,611 non-diabetic participants aged ≥ 50 years from a well-defined nationwide cohort were followed up for average of 3.6 years, with cardiovascular diseases and cancers at baseline were excluded. Body weight at 20, 30, 40, and 50 years was reported. The overall 30 years and each 10-year weight gain were calculated from the early and middle life. Cox regression models were used to estimate risks of incident diabetes.ResultsAfter 127,745.26 person-years of follow-up, 2,789 incident diabetes were identified (incidence rate, 2.18%) in 25,289 women (mean weight gain 20-50 years, 7.60 kg) and 10,322 men (7.93 kg). Each 10-kg weight gain over the 30 years was significantly associated with a 39.7% increased risk of incident diabetes (95% confidence interval [CI], 1.33-1.47); weight gain from 20-30 years showed a more prominent effect on the risk of developing diabetes before 60 years than that of after 60 years (Hazard ratio, HR = 1.084, 95% CI [1.049-1.121], P <0.0001 vs. 1.015 [0.975-1.056], P = 0.4643; PInteraction=0.0293). It showed a stable effect of the three 10-year intervals weight gain on risk of diabetes after 60 years (HR=1.055, 1.038, 1.043, respectively, all P < 0.0036).ConclusionsThe early life weight gain showed a more prominent effect on developing diabetes before 60 years than after 60 years; however, each-decade weight gain from 20 to 50 years showed a similar effect on risk developing diabetes after 60 years

Quantifying the Influences of Driving Factors on Vegetation EVI Changes Using Structural Equation Model: A Case Study in Anhui Province, China

Vegetation cover is important to the stability of regional ecosystems and is a focus of research on the relationship between natural and human environments. Although some studies have investigated the association between changes in vegetation cover and various influencing factors, these have shortcomings in quantifying direct and indirect effects. In this study, MOD13Q1 enhanced vegetation index (EVI) data for Anhui Province, China, were acquired between 2000 and 2020. The univariate linear regression, coefficient of variation and Hurst index methods were used to analyze spatial and temporal trends and fluctuations in the EVI between 2000 and 2020 and predict future trends. The impact of land-use change on EVI change was explored using 2000 and 2020 land-use data. Finally, a structural equation model (SEM) was used to quantify the effects of topography, annual average temperature, annual precipitation and human activity changes on EVI variation in Anhui Province. The results show that (1) from 2000 to 2020, the overall EVI in Anhui Province showed a fluctuating trend that increased at a rate of 0.0181·10a−1, and 67.1% of the study area showed a greening trend. The EVI was relatively stable in most regions, with regions of fluctuating EVI being mostly affected by urbanization. For a period after 2020, the overall EVI change will exhibit anti-sustainability and will likely decrease. (2) Among the regions of EVI increase, 72.2% had no change in land-use type, while 10.8% and 6.6% changed to farmland and woodland land uses, respectively. Among the regions where EVI decreased, 69.9% had no change in land-use type, while 13.7% changed from farmland to construction land. (3) Overall, human activity change was the main influence on EVI change, which was mainly reflected in the negative impacts of accelerated urbanization. Topography had direct and indirect effects on EVI variations in Central and Southern Anhui. Annual precipitation change had a stronger impact on EVI variation in Northern and Central Anhui than in Southern Anhui, while annual average temperature change had a small impact in the entire province. Compared with other study methods, SEM provides a new approach to quantifying the influences of vegetation cover dynamics. In addition, the results of this study have important implications for ecological environmental protection and sustainable development in Anhui Province

MicroRNA‐215‐5p promotes proliferation, invasion, and inhibits apoptosis in liposarcoma cells by targeting MDM2

Abstract Background Liposarcoma (LPS) is one of the most common soft tissue malignancies in adults, and it is characterized by dysregulation of multiple signaling pathways, including MDM2 proto‐oncogene (MDM2) amplification. MicroRNA (miRNA) regulates gene expression through incomplete complementary pairing with the 3' untranslated region of mRNAs involved in tumor progression. Methods In this study, bioinformatics analysis, RT‐qPCR, dual‐luciferase reporter gene, MTT, flow cytometry, cell scratches, chamber migration, colony formation, FISH, WB, and CCK8 were used. Results RT‐qPCR showed that the expression of MDM2 was increased when miR‐215‐5p was overexpressed compared with the control group. The dual‐luciferase reporter gene showed that the Renilla ratio firefly fluorescence intensity was decreased in the overexpression group compared with the control group. Cell phenotype experiments revealed that the overexpression group had increased cell proliferation rate, increased apoptosis rate, increased colony formation rate, increased cell healing area ratio, and increased number of cell invasions. FISH revealed increased MDM2 expression in the overexpression group. WB suggested decreased Bax expression, increased PCNA, Bcl‐2, and MDM2 expression, and decreased P53 and P21 expression in the overexpression group. Conclusions In this study, we suggest that miR‐215‐5p can target and promote MDM2 expression, promote the proliferation and invasion of LPS cells SW‐872, and inhibit apoptosis.Targeting miR‐215‐5p may be a novel therapeutic strategy for the treatment of LPS