Inhibition of tartrate-resistant acid phosphatase 5 can prevent cardiac fibrosis after myocardial infarction.

BACKGROUND: Myocardial infarction (MI) leads to enhanced activity of cardiac fibroblasts (CFs) and abnormal deposition of extracellular matrix proteins, resulting in cardiac fibrosis. Tartrate-resistant acid phosphatase 5 (ACP5) has been shown to promote cell proliferation and phenotypic transition. However, it remains unclear whether ACP5 is involved in the development of cardiac fibrosis after MI. The present study aimed to investigate the role of ACP5 in post-MI fibrosis and its potential underlying mechanisms. METHODS: Clinical blood samples were collected to detect ACP5 concentration. Myocardial fibrosis was induced by ligation of the left anterior descending coronary artery. The ACP5 inhibitor, AubipyOMe, was administered by intraperitoneal injection. Cardiac function and morphological changes were observed on Day 28 after injury. Cardiac CFs from neonatal mice were extracted to elucidate the underlying mechanism in vitro. The expression of ACP5 was silenced by small interfering RNA (siRNA) and overexpressed by adeno-associated viruses to evaluate its effect on CF activation. RESULTS: The expression of ACP5 was increased in patients with MI, mice with MI, and mice with Ang II-induced fibrosis in vitro. AubipyOMe inhibited cardiac fibrosis and improved cardiac function in mice after MI. ACP5 inhibition reduced cell proliferation, migration, and phenotypic changes in CFs in vitro, while adenovirus-mediated ACP5 overexpression had the opposite effect. Mechanistically, the classical profibrotic pathway of glycogen synthase kinase-3ß (GSK3ß)/ß-catenin was changed with ACP5 modulation, which indicated that ACP5 had a positive regulatory effect. Furthermore, the inhibitory effect of ACP5 deficiency on the GSK3ß/ß-catenin pathway was counteracted by an ERK activator, which indicated that ACP5 regulated GSK3ß activity through ERK-mediated phosphorylation, thereby affecting ß-catenin degradation. CONCLUSION: ACP5 may influence the proliferation, migration, and phenotypic transition of CFs, leading to the development of myocardial fibrosis after MI through modulating the ERK/GSK3ß/ß-catenin signaling pathway.

Gd3 TeBO9 : A Rare-Earth Borate with Significant Magnetocaloric Effect.

Magnetic refrigeration technology based on Gd-based paramagnets is expected to be applied to refrigeration in extremely low temperatures, thereby reducing the consumption of liquid helium. Here, we obtained a compound, Gd3 TeBO9 with high Gd3+ concentration through element substitution. The Gd3+ concentration in this compound is as high as 2.4×1024  ions/kg, which is 33 % higher than the commercial Gd3 Ga5 O12 (GGG), and further magnetic tests show that Gd3 TeBO9 has a large magnetic entropy change (57.44 J/(kg K) and 408 mJ/(cm3 K) at 2.6 K and 7 T), which is 1.5 times that of GGG, implying the possibility of its further development as an potential magnetocaloric material.

Protective properties of extracellular vesicles in sepsis models: a systematic review and meta-analysis of preclinical studies.

BACKGROUND: Multiple preclinical studies have reported a beneficial effect of extracellular vesicles (EVs), especially mesenchymal stem cells derived EVs (MSC-EVs), in the treatment of sepsis. However, the therapeutic effect of EVs is still not universally recognized. Therefore, we conducted this meta-analysis by summarizing data from all published studies that met certain criteria to systematically review the association between EVs treatment and mortality in animal models of sepsis. METHODS: Systematic retrieval of all studies in PubMed, Cochrane and Web of Science that reported the effects of EVs on sepsis models up to September 2022. The primary outcome was animal mortality. After screening the eligible articles according to inclusion and exclusion criteria, the inverse variance method of fixed effect model was used to calculate the joint odds ratio (OR) and 95% confidence interval (CI). Meta-analysis was performed by RevMan version 5.4. RESULTS: In total, 17 studies met the inclusion criteria. Meta-analysis of those studies showed that EVs treatment was associated with reduced mortality in animal models of sepsis (OR 0.17 95% CI: 0.11,0.26, P < 0.001). Further subgroup analysis showed that the mode of sepsis induction, the source, dose, time and method of injection, and the species and gender of mice had no significant effect on the therapeutic effect of EVs. CONCLUSION: This meta-analysis showed that MSC-EVs treatment may be associated with lower mortality in animal models of sepsis. Subsequent preclinical studies will need to address the standardization of dose, source, and timing of EVs to provide comparable data. In addition, the effectiveness of EVs in treating sepsis must be studied in large animal studies to provide important clues for human clinical trials.

Elabela, a Novel Peptide, Exerts Neuroprotective Effects Against Ischemic Stroke Through the APJ/miR-124-3p/CTDSP1/AKT Pathway.

Elabela (ELA), which is the second endogenous peptide ligand of the apelin receptor (APJ) to be discovered, has been widely studied for potential use as a therapeutic peptide. However, its role in ischemic stroke (IS), which is a leading cause of disability and death worldwide and has limited therapeutic options, is uncertain. The aim of the present study was to investigate the beneficial effects of ELA on neuron survival after ischemia and the underlying molecular mechanisms. Primary cortical neurons were isolated from the cerebral cortex of pregnant C57BL/6J mice. Flow cytometry and immunofluorescence showed that ELA inhibited oxygen-glucose deprivation (OGD) -induced apoptosis and axonal damage in vitro. Additionally, analysis of the Gene Expression Omnibus database revealed that the expression of microRNA-124-3p (miR-124-3p) was decreased in blood samples from patients with IS, while the expression of C-terminal domain small phosphatase 1 (CTDSP1) was increased. These results indicated that miR-124-3p and CTDSP1 were related to ischemic stroke, and there might be a negative regulatory relationship between them. Then, we found that ELA significantly elevated miR-124-3p expression, suppressed CTDSP1 expression, and increased p-AKT expression by binding to the APJ receptor under OGD in vitro. A dual-luciferase reporter assay confirmed that CTDSP1 was a direct target of miR-124-3p. Furthermore, adenovirus-mediated overexpression of CTDSP1 exacerbated neuronal apoptosis and axonal damage and suppressed AKT phosphorylation, while treatment with ELA or miR-124-3p mimics reversed these effects. In conclusion, these results indicated that ELA could alleviate neuronal apoptosis and axonal damage by upregulating miR-124-3p and activating the CTDSP1/AKT signaling pathway. This study, for the first time, verified the protective effect of ELA against neuronal injury after ischemia and revealed the underlying mechanisms. We demonstrated the potential for the use of ELA as a therapeutic agent in the treatment of ischemic stroke.

Efficacy and safety of non-ergot dopamine-receptor agonists as an adjunct to levodopa in advanced Parkinson's disease: A network meta-analysis.

BACKGROUND AND PURPOSE: Non-ergot dopamine agonists (NEDAs) have been used as an adjunct therapy to levodopa in advanced Parkinson's disease (PD) for many years. However, there is no strong evidence that a given NEDA is more potent than another. To compare and rank the efficacy, tolerability, and safety of six commonly used NEDAs as an adjunct to levodopa in advanced PD, which includes long-acting and standard formulations, a network meta-analysis was performed. METHODS: The MEDLINE, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Wanfang databases were searched from January 1996 to June 2022 for eligible randomized controlled trials (RCTs). Six NEDAs, including rotigotine transdermal patch, ropinirole immediate-release (IR)/prolonged-release (PR), pramipexole IR/extended-release (ER), and piribedil, were investigated. RESULTS: A total of 34 RCTs (7868 patients) were included in the current study. The surface under the cumulative ranking curve indicated that ropinirole PR was associated with the best improvement in Unified Parkinson's Disease Rating Scale (UPDRS)-II, UPDRS-III, and UPDRS-II + III (0.811, 0.742, and 0.827). For OFF time reduction, pramipexole IR ranked first (0.979), and ropinirole PR ranked first in OFF time responder rate (0.927). Pramipexole ER ranked first in overall withdrawals, and rotigotine transdermal patch ranked first in the incidence of adverse events (≥1 AEs). CONCLUSIONS: This network meta-analysis suggests six commonly used NEDAs are effective as an adjunct to levodopa in advanced PD. In comprehensive consideration of better symptomatic management, ropinirole PR may be a better choice than other NEDAs in advanced PD. Six NEDAs showed different profiles of AEs.

Large Difference in Nonlinear Optical Activity of Rare Earth Ion Substitution of Bi3+ in A3TeBO9 (A = Bi, La, Pr, Nd, Sm-Dy).

A series of oxides with high rare earth contents, RE3TeBO9 (RE = La, Pr, Nd, Sm-Dy), were synthesized, and they all crystallize in the noncentrosymmetric space group P63 resembling that of a previously reported Bi3TeBO9 (J. Am. Chem. Soc. 2016, 138, 14190-14193), which showed a very strong second harmonic generation (SHG) signal believed to come from all three structural units [BO3], [TeO6], and [BiO6]. Surprisingly, compared with the isostructural compound Bi3TeBO9, both theoretical calculations and powder SHG tests show that RE3TeBO9 has an abnormally small SHG effect (0.2 × KDP). Based on the group theory analysis, the possible reasons are attributed to the misalignments and lack of distortions of the [BO3], [TeO6], and [REO8] groups in the unit cell. The 21 symmetric operation (a subset operation of the 63-screw axis) of the [TeO6], [BO3], and [REO8] groups leads to complete cancellation of their contributions to the xy directions, while the absence of lone pair electrons in RE3+ and Te6+ results in small distortion in the c axis, hence small contributions to the SHG coefficients dijk involving the z axis. Diffuse reflectance spectra of RE3TeBO9 (RE = La, Pr, Nd, Sm-Dy) show typical absorption of different RE3+, and the similarity of their infrared spectra is due to the same crystal structure and same structural units of the [TeO6] and [BO3] groups. The strong fluorescence intensities of Eu3TeBO9 and Tb3TeBO9 show the characteristic emissions of Eu3+ and Tb3+, which may serve as luminescence materials with proper doping.

Repeated intravenous thrombolysis in recurrent ischemic stroke within 3 months: a systematic review.

BACKGROUND: Repeated intravenous thrombolysis (RIVT) within 3 months is an off-guideline therapy, however, may be an effective and safe way to treat early recurrent ischemic stroke. This study was conducted to assess the potential influencing factors on the efficacy and safety of RIVT in recurrent ischemic stroke within 3 months and to explore the strategy of RIVT within 3 months. METHODS: PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, and Wanfang Database were searched for cases of RIVT in recurrent ischemic stroke within 3 months up to February 1, 2023. Clinical characteristics were compared and analyzed between the good-outcome and poor-outcome groups and between the symptomatic intracranial hemorrhage (sICH) and non-sICH groups respectively. RESULTS: A total of 16 studies including 24 cases of RIVT within 3 months were retrospectively analyzed in the present study. The patients' ages ranged from 42 to 87 years (median 73.5 years) and the intervals between thrombolysis were from 0.25 to 90 days (median 9.5 days). Comparing the clinical characteristics between the good-outcome group and the poor-outcome group, no statistically significant differences were found (P > 0.05), but the differences in baseline National Institutes of Health stroke scale (NIHSS) score of the recurrent stroke (P = 0.056) and good outcome after the previous IVT (P = 0.054) nearly reached statistical significance. Comparing the data between the non-sICH group and the sICH group, statistically significant differences were found in terms of the proportion of cardiogenic embolism (P = 0.036), baseline NIHSS score in the recurrent stroke (P = 0.007) and the interval between thrombolysis (P = 0.041), but no significant difference was found by regression analysis. CONCLUSION: In patients with recurrent ischemic stroke within 3 months, those with a good outcome after the previous IVT and a low baseline NIHSS score in the recurrent stroke may be considered for RIVT, whereas those with a high baseline NIHSS score, a short interval between thrombolysis, and cardiogenic embolism may suffer a higher risk of sICH. Due to sample size and publication bias, more studies with larger sample sizes and more rigorous designs are needed to confirm this conclusion.

Comprehensive Analysis of Microbiome, Metabolome, and Transcriptome Revealed the Mechanisms of Intestinal Injury in Rainbow Trout under Heat Stress.

Global warming is one of the most common environmental challenges faced by cold-water fish farming. Intestinal barrier function, gut microbiota, and gut microbial metabolites are significantly altered under heat stress, posing serious obstacles to the healthy artificial culture of rainbow trout. However, the molecular mechanisms underlying intestinal injury in rainbow trout under heat stress remain unclear. In the present study, the optimal growth temperature for rainbow trout (16 °C) was used for the control group, and the maximum temperature tolerated by rainbow trout (24 °C) was used for the heat stress group, which was subjected to heat stress for 21 days. The mechanism of intestinal injury in rainbow trout under heat stress was explored by combining animal histology, 16S rRNA gene amplicon sequencing, ultra-high performance liquid chromatography-mass spectrometry, and transcriptome sequencing. The results showed that the antioxidant capacity of rainbow trout was enhanced under heat stress, the levels of stress-related hormones were significantly increased, and the relative expression of genes related to heat stress proteins was significantly increased, indicating that the heat stress model of rainbow trout was successfully established. Secondly, the intestinal tract of rainbow trout showed inflammatory pathological characteristics under heat stress, with increased permeability, activation of the inflammatory factor signaling pathway, and increased relative expression of inflammatory factor genes, suggesting that the intestinal barrier function was impaired. Thirdly, heat stress caused an imbalance of intestinal commensal microbiota and changes in intestinal metabolites in rainbow trout, which participated in the stress response mainly by affecting lipid metabolism and amino acid metabolism. Finally, heat stress promoted intestinal injury in rainbow trout by activating the peroxisome proliferator-activated receptor-α signaling pathway. These results not only expand the understanding of fish stress physiology and regulation mechanisms, but also provide a scientific basis for healthy artificial culture and the reduction of rainbow trout production costs.

A retrospective analysis of maternal complications and newborn outcomes of general anesthesia for cesarean delivery in a single tertiary hospital in China.

BACKGROUND: Either neuraxial anesthesia or general anesthesia can be performed for cesarean delivery. Generally, neuraxial anesthesia is the first choice with the risk and benefit balance for both the mother and fetus. However, general anesthesia is also applicable most commonly in the emergent setting. This study analyzed maternal complications associated with general anesthesia for cesarean delivery and suggested lowering pregnancy-related maternal and newborn adverse outcomes. METHODS: With the approval of the Institutional Ethics Review Board (No: 2017016), data on cesarean delivery and related anesthesia were collected from the Electronic Health Record System from 1/1/2013 to 12/31/2016. Statistical software STATA version 15.1 was used for data analyses. All statistical tests were two-sided, and a level significance of 0.05 was assumed. RESULTS: The rate of general anesthesia for cesarean delivery increased steadily during 2013-2016, 3.71% in 2013 to 10.23% in 2016 (p < 0.001). Repeat cesarean delivery among general anesthesia group increased significantly from 16.22% in 2013 to 54.14% in 2016 (p < 0.001). Morbidly adherent placenta (MAP) was the first reason among pregnancy-related complications, which accounted for 33% in total in general anesthesia group (38% in 2013 to 44% in 2016). The laryngeal mask airway (LMA) was used in airway management, and the proportion of LMA increased from 28.38% in 2013 to 92.99% in 2016 (p < 0.001). There were significant differences in newborn outcomes between general anesthesia and neuraxial anesthesia groups, including newborn weight, newborn Apgar score at 1 min and 5 min and newborn admission to the NICU (p < 0.001). CONCLUSIONS: The growing incidence of general anesthesia was consistent with the trend of rising repeat cesarean delivery and MAP. low newborn Apgar score and high newborn admission to the NICU in general anesthesia group compared with neuraxial anesthesia group. The LMA was performed safely for airway management with enough fasting and careful gastric volume evaluation.

The effect of acute heat stress on the innate immune function of rainbow trout based on the transcriptome.

Heat stress is a condition in which the body's homeostasis is disturbed as a result of the rise in water temperature, resulting in the decline or even death of growth, immunity, and other functions. The mechanisms directing this response are not fully understood. To better characterize the effects of acute heat stress on the innate immune function of rainbow trout, we identified differentially regulated messenger RNA (mRNA) and non-coding RNA (ncRNA) in rainbow trout exposed to acute heat stress. Next-generation RNA sequencing and comprehensive bioinformatics analysis were conducted to characterize the transcriptome profiles, including mRNA, microRNA (miRNA), and long non-coding RNA (lncRNA). The head kidney of rainbow trout were exposed to acute heat stress at 22.5 °C for 24 h. A total of 2605 lncRNAs, 214 miRNAs, and 5608 mRNAs were identified as differentially regulated. Among these expressed genes differentially, 45 lncRNAs and 2 target genes, as well as 38 miRNAs and 14 target genes were significantly enriched in the innate immune response of rainbow trout. LncRNA is used as competitive endogenous RNA (ceRNA) to construct the ceRNA-miRNA-mRNA interaction network. Enrichment analysis of the Kyoto encyclopedia of genes and genomes (KEGG) of ceRNA, the differentially expressed genes related to the innate immune function of rainbow trout, were significantly enriched in the signaling pathway mediated by mitogen-activated protein kinase (MAPK). Overall, these analyses showed the effects of heat stress on the innate immune function in rainbow trout at the transcriptome level, providing a theoretical basis to improve the production and breeding of rainbow trout and the selection of new heat-resistant varieties.

Physiological response and miRNA-mRNA interaction analysis in the head kidney of rainbow trout exposed to acute heat stress.

The rainbow trout is a cold-water fish cultured in China. Heat stress has a serious impact on the summer survival and the yield of rainbow trout. A better understanding of the regulatory response of rainbow trout to heat stress will help in determining the relationship between heat stress signaling pathways and adaption mechanisms and help contribute to breeding new high-temperature tolerant strains of rainbow trout. In this study, the 48-h median lethal temperature (48h-LT50) of rainbow trout was determined as 22.5°C. We developed control (16°C) and heat-treated (22.5°C) groups and extracted RNA from the head kidney tissues for high-throughput sequencing to study the microRNA (miRNA) expression profiles. Twelve up-regulated and five down-regulated miRNAs were identified between the control and heat-treated groups. A total of 22 target genes were predicted for 6 of the differentially expressed miRNAs, including 31 negative miRNA-mRNA interactions. Important regulatory pathways under heat stress are related to the metabolism and immune responses of the rainbow trout. Our findings provide preliminary data for investigating the high-temperature molecular mechanism of the rainbow trout and can help producers to reduce the economic losses caused by high temperature weather.

Prenatal exposure to an environmentally relevant phthalate mixture disrupts reproduction in F1 female mice.

Phthalates are used in a large variety of products, such as building materials, medical devices, and personal care products. Most previous studies on the toxicity of phthalates have focused on single phthalates, but it is also important to study the effects of phthalate mixtures because humans are exposed to phthalate mixtures. Thus, we tested the hypothesis that prenatal exposure to an environmentally relevant phthalate mixture adversely affects female reproduction in mice. To test this hypothesis, pregnant CD-1 dams were orally dosed with vehicle (tocopherol-stripped corn oil) or a phthalate mixture (20 and 200µg/kg/day, 200 and 500mg/kg/day) daily from gestational day 10 to birth. The mixture was based on the composition of phthalates detected in urine samples from pregnant women in Illinois. The mixture included 35% diethyl phthalate, 21% di(2-ethylhexyl) phthalate, 15% dibutyl phthalate, 15% diisononyl phthalate, 8% diisobutyl phthalate, and 5% benzylbutyl phthalate. Female mice born to the exposed dams were subjected to tissue collections and fertility tests at different ages. Our results indicate that prenatal exposure to the phthalate mixture significantly increased uterine weight and decreased anogenital distance on postnatal days 8 and 60, induced cystic ovaries at 13months, disrupted estrous cyclicity, reduced fertility-related indices, and caused some breeding complications at 3, 6, and 9months of age. Collectively, our data suggest that prenatal exposure to an environmentally relevant phthalate mixture disrupts aspects of female reproduction in mice.

Apelin promotes mesenchymal stem cells survival and vascularization under hypoxic-ischemic condition in vitro involving the upregulation of vascular endothelial growth factor.

BACKGROUND: Mesenchymal stem cells (MSCs) transplantation has been regarded as an optimal therapeutic approach for cardiovascular disease. However, the inferior survival and low vascularization potential of these cells in the local infarct site reduce the therapeutic efficacy. In this study, we investigated the influence of apelin on MSCs survival and vascularization under hypoxic-ischemic condition in vitro and explored the relevant mechanism. METHODS: MSCs were obtained from C57BL/6 mice and cultured in vitro. Cells of the third passage were divided into MSCs and MSCs+apelin groups. In the MSCs+apelin group, MSCs were stimulated with apelin-13 (5µM). The two groups experienced exposure to hypoxia (1% O2) and serum deprivation for 24h, using normoxia (20% O2) as a negative control during the process. Human umbilical vein endothelial cells (HUVECs) were used and incubated with conditioned media from both groups to promote vascularization for another 6h. Vascular densities were assessed and relevant biomarkers were detected thereafter. RESULTS: Compared with MSCs group, MSCs+apelin group presented more rapid growth. The proliferation rate was much higher. Cells apoptosis percentage was significantly declined both under normoxic and hypoxic conditions. Media produced from MSCs+apelin group triggered HUVECs to form a larger number of vascular branches on matrigel. The expression and secretion of vascular endothelial growth factor (VEGF) were significantly increased. CONCLUSION: Apelin could effectively promote MSCs survival and vascularization under hypoxic-ischemic condition in vitro, and this procedure was associated with the upregulation of VEGF. This study provides a new perspective for exploring novel approaches to enhance MSCs survival and vascularization potential.

Promoted Effect of Pernigraniline as Electrons Accepter on RhB Degradation Over TiO2/ITO Film.

The pernigraniline (PNA)/TiO2 composite film has been synthesized by the combination of hydrothermal and electro-polymerization methods. The as-prepared PNA/TiO2 composite film was characterized by XRD, SEM, FTIR and XPS as well as photocatalytic degradation of Rhodamine B (RhB). And the roles of actives species in the photocatalytic process were investigated by using different types of active species scavengers. It was found that PNA/TiO2 film was reduced towards to the emeraldine (EM)/TiO2 in the photocatalytic reaction process and the roles of actives species in PNA/TiO2 system were different to EM/TiO2 system. The enhanced photocatalytic performance was attributed to that the PNA acted as the electrons acceptor, which was favorable for the separation of the photoinduced electron­hole pairs and could enhance the activity of the photocatalysts.

Long noncoding RNAs: Novel molecules in cardiovascular biology, disease and regeneration.

Remarkable breakthroughs made in genomic technologies have facilitated the discovery of thousands of novel transcripts that do not template protein synthesis. Numerous RNAs termed as long noncoding RNAs (lncRNAs) generated from this pervasive transcription function vividly in gene regulatory networks and a variety of biological and cellular processes. Here, we make a brief description of the known and putative functions of lncRNAs in cardiovascular biology and disease. The association between lncRNAs and stem cells mediated cardiomyocytes differentiation and neovascularization is discussed then. It will provide a new clue for further studies on these novel molecules in cardiovascular disease and bring bright prospects for their future applications in cardiac regenerative medicine.

Effects of Endocrine-Disrupting Chemicals on the Ovary.

Endocrine-disrupting chemicals (EDCs) are found abundantly in the environment, resulting in daily human exposure. This is of concern because many EDCs are known to target the female reproductive system and, more specifically, the ovary. In the female, the ovary is the key organ responsible for reproductive and endocrine functions. Exposure to EDCs is known to cause many reproductive health problems such as infertility, premature ovarian failure, and abnormal sex steroid hormone levels. Some EDCs and their effects on adult ovarian function have been studied extensively over the years, whereas the effects of others remain unclear. This review covers what is currently known about the effects of selected EDCs (bisphenol A, methoxychlor, 2,3,7,8-tetrachlorodibenzo-p-dioxin, phthalates, and genistein) on the adult ovary and the mechanisms by which they act upon the ovary, focusing primarily on their effects on folliculogenesis and steroidogenesis. Furthermore, this review discusses future directions needed to better understand the effects of EDCs, including the need to examine the effects of multiple and more consistent doses and to study different mechanisms of action.

The effects of in utero bisphenol A exposure on reproductive capacity in several generations of mice.

In utero bisphenol A (BPA) exposure affects reproductive function in the first generation (F1) of mice; however, not many studies have examined the reproductive effects of BPA exposure on subsequent generations. In this study, pregnant mice (F0) were orally dosed with vehicle, BPA (0.5, 20, and 50 µg/kg/day) or diethylstilbestrol (DES; 0.05 µg/kg/day) daily from gestation day 11 until birth. F1 females were used to generate the F2 generation, and F2 females were used to generate the F3 generation. Breeding studies at the ages of 3, 6, and 9 months were conducted to evaluate reproductive capacity over time. Further, studies were conducted to evaluate pubertal onset, litter size, and percentage of dead pups; and to calculate pregnancy rate, and mating, fertility, and gestational indices. The results indicate that BPA exposure (0.5 and 50 µg/kg/day) significantly delayed the age at vaginal opening in the F3 generation compared to vehicle control. Both DES (0.05 µg/kg/day) and BPA (50 µg/kg/day) significantly delayed the age at first estrus in the F3 generation compared to vehicle control. BPA exposure reduced gestational index in the F1 and F2 generations compared to control. Further, BPA exposure (0.5 µg/kg/day) compromised the fertility index in the F3 generation compared to control. Finally, in utero BPA exposure reduced the ability of female mice to maintain pregnancies as they aged. Collectively, these data suggest that BPA exposure affects reproductive function in female mice and that some effects may be transgenerational in nature.

Cardiac stem cells transplantation enhances the expression of connexin 43 via the ANG II/AT1R/TGF-beta1 signaling pathway in a rat model of myocardial infarction.

BACKGROUND: In this study, we hypothesized that CSCs mediated the expression of Cx43 after transplantation post MI via the ANG II/AT1R/TGF-beta1 signaling pathway. METHODS: Myocardial infarction (MI) was induced in twenty male Sprague-Dawley rats. The rats were randomized into two groups and were then received the injection of 5 × 10(6) CSCs labeled with PKH26 in phosphate buffer solution (PBS) or equal PBS alone into the infarct anterior ventricular free wall two weeks after MI. Six weeks later, relevant signaling molecules involved were all examined. RESULTS: In the CSCs group, an increased expression of Cx43 could be observed in different zones of the left ventricle (P<0.01). There was a significant reduction of the angiotensin II (ANG II) level in plasma and different regions of the left ventricular cardiac tissues (P<0.05; P<0.01). The angiotensin II type I receptor (AT1R) was decreased accompanied with an enhanced expression of angiotensin II type II receptor (AT2R) (P<0.01). Transforming growth factor beta-1(TGF-beta1) was downregulated (P<0.01). The expression of mothers against decapentaplegic homolog (SMAD) proteins including SMAD2 and SMAD3 was attenuated whereas SMAD7 was elevated (P<0.01, P<0.01, P<0.05). In addition, the expression of mitogen-activated protein kinases (MAPKs) including extracellular kinases 1/2 (ERK1/2) and p38 was also found to be reduced (P<0.01). CONCLUSION: CSCs transplantation could enhance the level of Cx43 after MI. They might function through intervening the ANGII/AT1R/TGF-beta1 signaling pathway to regulate the expression of Cx43.

[Clinical application of perforator flap in extended radical vulvectomy of vulvar carcinoma].

OBJECTIVE: To evaluate the clinical application of perforator flap in extended radical vulvectomy of vulvar carcinoma. METHODS: Retrospectively, twelve cases of vulva carcinoma were treated by radical extensive excision, and the defects were repaired with perforator flap. RESULTS: All the flaps were survived and healed with first intention except one infection. The wound infection patient was treated with change of the dressing and antibiotics. The reconstructed vulvae were plump and elastic. It appeared like the normal vulvae and there was no contraction of the vagina. CONCLUSIONS: Vulvar reconstruction with the perforator flap after the radical vulvectomy could make the patients recover easily, which produces almost normal appearance and function of the vulvae, reduces the time of wound healing, the patient could get the next therapy more quickly and the quality of life improving. It has wide clinical application value.