[Transition metal accumulation and cellular senescence].

Aging refers to a progressive decline in biological functions, leading to age-related diseases and mortality. The transition metals, including iron, copper, and manganese, play important roles in human physiological and pathological processes. Substantial research has demonstrated that senescent cells accumulate higher levels of transition metals, which in turn accelerates the process of cellular senescence and related diseases through mechanisms such as production of excessive reactive oxygen species (ROS), induction of oxidative stress, DNA damage, and mitochondrial dysfunction. This review article provides a comprehensive overview of the causes of transition metal accumulation in senescent cells, as well as the mechanisms by which it further promotes cellular senescence and related diseases. The aim is to provide insights into anti-aging and treatment of aging-related diseases caused by transition metal accumulation.

Fe3O4-doped silk fibroin-polyacrylamide hydrogel for selective and highly efficient absorption of cationic dyes pollution in water.

Overuse of organic dyes has caused serious threats to the ecosystem and human health. However, the development of high-efficient, environmentally friendly, selective, and degradable cationic dye adsorbents remains a huge challenge. In this work, a novel Fe3O4nanoparticles doped silk fibroin-polyacrylamide magnetic hybrid hydrogel (Fe3O4@SF-PAAM) was successfully fabricated by combining free radical polymerization to prepare hydrogels andin situco-precipitation to prepare nanoparticles. The obtained Fe3O4@SF-PAAM hydrogel shows strong magnetic performance with saturated magnetic of 10.2 emu mg-1and excellent swelling properties with a swelling ratio of 55867%. In addition, Fe3O4@SF-PAAM can adsorb cationic dyes such as methylene blue (MB), crystal violet, and Rhodamine B, but has no adsorption effect on anionic dyes such as methyl orange, congo red, and carmine, indicating that Fe3O4@SF-PAAM has good selective adsorption properties for cationic dyes. Interestingly, the adsorption capacity of Fe3O4@SF-PAAM was approached 2025 mg g-1for MB (MB, a typical cation dye) at 25 °C and neutral. Meanwhile, the hybrid hydrogel is reusable, the removal rate for MB is still over 90% after the five adsorption-desorption cycles. The fabricated magnetic hybrid hydrogel is a kind of a highly-efficiency and eco-friendly adsorbent and presents great potential applications in water purification and environmental protection.

One-step synthesis of fluorescence-enhanced carbon dots for Fe (III) on-off-on sensing, bioimaging and light-emitting devices.

Carbon quantum dots (CDs), as one of the most potential fluorescent sensing materials, have attracted lots of attention in recent years. However, the low quantum yields, complicated separation and purification procedures have limited its application and large-scale production. In this paper, a facile and universal method was successfully developed to synthesize CDs-silica (SiO2) spheres composites (CS composites), which not only demonstrates 10-fold fluorescence enhancement compared with single CDs but also enables the purification with a simple centrifugation step. Meanwhile, fabricated composites also presented superior photoluminescence (PL) stability and high PL intensity, even in some tough environments such as acid/alkali aqueous solution, high/low temperature, and high ion concentration aqueous solution. This simple, fast, low-cost, and efficient synthesis method would potentially expand the application of CDs for clinical analysis, optical sensing (ferric ion (Fe3+) and pyrophosphate), bioimaging and light-emitting diodes (LEDs).

Water-stable perovskite-on-polymer fluorescent microspheres for simultaneous monitoring of pH, urea, and urease.

Perovskite materials have attracted attention due to their excellent optical and electrical properties; however, their unsatisfactory stability limits their application in biochemical detection. In this paper, CsPbBr3 perovskite quantum dots were successfully encapsulated in poly(styrene/acrylamide) microspheres, using a swelling-shrinking method. The manufactured perovskite microspheres (PDPS composites) not only maintained strong photoluminescence (PL) stability but also demonstrated great water solubility. Additionally, a real-time pH monitoring platform was constructed based on the prepared PDPS composites and dopamine, and the system showed a good linear relationship in a pH range of 4-12. Furthermore, urea could be hydrolyzed to produce hydroxyl groups, thereby increasing the pH of the solution. Therefore, this system was then extended for urea and urease detection. As a result, the detection limits of urea and urease were recorded as 1.67 µM and 2.1 mU/mL, respectively. This development provides an interesting demonstration of the expanding list of applications of perovskite materials.

[Effect and Mechanism of Treating Experimental Autoimmune Encephalomyelitis in Mice with Butylphthalide Combined with Bone Marrow Mesenchymal Stem Cells].

OBJECTIVE: To explore the efficacy and mechanism of using 3-n-butylphthalide (NBP) in combination with bone marrow mesenchymal stem cells (BMSCs) in the treatment of experimental autoimmune encephalomyelitis (EAE) in mice. METHODS: Myelin oligodendrocyte glycoprotein (MOG35-55) was used for the induction and establishment of the EAE model in C57BL/6 mice. The mice were randomly assigned to the EAE group, which received intraperitoneal injection of phosphate-buffered saline (PBS), the NBP-treated EAE group, or the NBP group, which received intraperitoneal injection of NBP, the BMSCs transplantion EAE group, or the BMSCs group, which received BMSCs injected into the lateral ventricle and intraperitoneal injection of PBS, and the BMSCs and NBP combination treatment EAE group, or the BMSCs+NBP group, which received BMSCs injected into the lateral ventricle and intraperitoneal injection of NBP. Each group had 10 mice, while ten normal mice were used as the blank control group receiving intraperitoneal injection of PBS. The neurological function scores were documented daily. The mice were sacrificed 22 days after EAE induction, and the demyelination state of of the spinal cords was observed through Luxol fast blue (LFB) staining. In addition, the levels of serum interleukin-6 (IL-6), IL-10, IL-17, IL-22 and transforming growth factor-ß (TGF-ß) were examined with ELISA. The levels of glial fibrillary acidic protein (GFAP), microtubule associated protein-2 (MAP-2) and myelin basic protein (MBP) in the brain were examined with immunofluorescence staining. Western blot was used to check the expressions of nuclear factor (NF)-κB pathway, phosphoinositide-3 kinase (PI3K)/protein kinase B (PKB or Akt) pathway, IL-17 and forkhead box P3 (Foxp3) in the spinal cords. RESULTS: The neurological function scores and average scores of each treatment group were significantly lower than those of the EAE group ( P<0.05). The scores of the BMSCs+NBP group decreased more significantly than those of the single treatment groups (the NBP group and the BMSCs group) ( P<0.05). LFB staining results of the spinal cords were consistent with the neurological function scores and the average scores. Compared with the EAE group, the levels of pro-inflammatory cytokines, including IL-6, IL-17 and IL-22, significantly decreased ( P<0.05), and the levels of anti-inflammatory cytokines IL-10 and TGF-ß significantly increased ( P<0.05). The change in cytokine expression was more significant in the BMSCs+NBP group ( P<0.05). The expressions of GFAP, MAP-2 and MBP in the BMSCs+NBP group were significantly higher than those of the BMSCs group ( P<0.05). Compared with the EAE group, the p-NF-κB/NF-κB ratio and the IL-17/Foxp3 ratio in NBP group, BMSCs group and BMSCs+NBP group decreased, while P-IκBα/IκBα, p-pI3k/PI3K and P-Akt/Akt ratios increased, especially in the BMSCs+NBP group( P<0.05). CONCLUSION: The combined treatment of NBP and BMSCs can help alleviate the symptoms of EAE model mice, showing better efficacy than treatment with NBP or BMSCs alone. The mechanism is related to the inhibition of the NF-κB pathway to regulate Th17/Foxp3 ratio and the activation of the PI3K/Akt pathway to promote the neurogenic differentiation of BMSCs.

Patients treatment with neuroglioma by teniposide and semustine and its influence on Twist and E-cadherin expression.

UNLABELLED: This study focuses on curative effects of teniposide combining with semustine on patients with neuroglioma and the influences on the expression of Twist and E-cadherin in tissue. Sixty-eight patients with neuroglioma taking operation in our hospital were divided into two groups randomly. Single radiotherapy was given to 34 patients in group A, and teniposide (VM-26) and semustine (Me-CCUN) were added to radiotherapy for 34 patients in group B. Then, curative effects, survival rate, living quality and adverse reaction rate after operation were compared between two groups. Moreover, the difference in positive expression rate of Twist and E-cadherin before and after treatment between two groups was analyzed by immunohistochemistry. RESULTS: In group B, the effective rate of treatment was 88.2%, and the disease control rate was 70.6%, higher than 52.9% and 32.4% in group A with statistical significance (P < 0.05). Moreover, the survival rate in three years of group B was 44.1%, and the score of living quality was 67.11 ± 4.32, and also higher than 23.5% and 63.79 ± 4.53 in group A with statistical significance (P < 0.05). However, the difference between two groups in adverse reaction rate has no statistical significance (P > 0.05). In addition, the difference in positive expression rate of Twist and E-cadherin between group A and group B has no statistical significance before treatment (P > 0.05). After treatment, however, the positive rate of Twist in group B is lower than that in group A, while the positive rate of E-cadherin is higher. Both differences have statistical significance (P < 0.05). Chemotherapy of VM-26 combining with Me-CCNU can inhibit Twist expression and improve the expression rate of E-cadherin to help improving the curative effects and living quality and increasing survival rate.

Role of GPER on proliferation, migration and invasion in ligand-independent manner in human ovarian cancer cell line SKOV3.

G protein-coupled estrogen receptor (GPER) is identified as a critical estrogen receptor, in addition to the classical estrogen receptors ERα and ERß. In ERα-negative ovarian cancer cells, our previous studies have found that estrogen stimulated cell proliferation and metastasis via GPER. However, the ligand-independent function of GPER in ovarian cancer cells is still not clear. Herein, we describe that GPER has a co-expression with ERα and ERß, which are first determined in SKOV3 ovarian cancer cell line. In the absence of estrogen, GPER depletion by specific siRNA inhibits the proliferation, migration and invasion of SKOV3 cells. Whereas abrogation of ERα or ERß by specific antagonist MPP and PHTPP has the opposite effects for stimulation of cell growth. Markedly, GPER knockdown attenuates MPP or PHTPP-induced cell proliferation, migration and invasion. Furthermore, GPER modulates protein expression of the cell cycle critical components, c-fos and cyclin D1 and factors for cancer cell invasion and metastasis, matrix metalloproteinase 2 (MMP-2) and MMP-9. These findings establish that GPER ligand-independently stimulates the proliferation, migration and invasion of SKOV3 cells. Knockdown of GPER attenuates the progression of ovarian cancer that caused by functional loss of ERα or ERß. Targeting GPER provides new aspect as a potential therapeutic strategy in ovarian cancer.

A novel estrogen receptor GPER mediates proliferation induced by 17ß-estradiol and selective GPER agonist G-1 in estrogen receptor α (ERα)-negative ovarian cancer cells.

G protein-coupled estrogen receptor (GPER) is recently identified as a membrane-associated estrogen receptor that mediates non-genomic effects of estrogen. Our previous immunohistochemistry study found an association between GPER and the proliferation of epithelial ovarian cancer. However, the contributions and mechanisms of GPER in the proliferation of ovarian cancers are not clear. We have examined the role of GPER in estrogen receptor α (ERα)-negative/GPER positive OVCAR5 ovarian cancer cell line. MTT assay was used to detect cell proliferation. BrdU incorporation assay was used to measure the cells in S-phase. Protein expression of marker genes of proliferation, cell cycle and apoptosis were examined by Western blot. The results showed that 17ß-estradiol and selective GPER agonist G-1 stimulated the proliferation of OVCAR5 cells and increased the cells in S-phase. Both ligands upregulated the protein levels of c-fos and cyclin D1. Small interfering RNA targeting GPER or G protein inhibitor pertussin toxin (PTX) inhibited basal cell proliferation and attenuated 17ß-estradiol- or G-1-induced cell proliferation. GPER mediated cell growth was also associated with the apoptosis of OVCAR5 cells. These findings suggest that GPER has an important function in the proliferation of ovarian cancer cells lacking ERα. GPER might be a promising therapeutic target in ovarian cancer.

Lab on skin: real-time metabolite monitoring with polyphenol film based subdermal wearable patches.

The advent of digital technologies has spurred the development of wearable sensing devices marking a significant shift in obtaining real-time physiological information. The principal objective is to transition from blood-centric monitoring to minimally invasive modalities, which will enable movement from specialised settings to more accessible environments such as the practices of general practitioners or even home settings. While subcutaneously implanted continuous monitoring devices have demonstrated this transition, detection of analytes from sample matrices like skin interstitial fluid (ISF), is a frontier that offers attractive minimally invasive routes for detection of biomarkers. This manuscript presents a comprehensive overview of our work in subdermal wearable biosensing patches for the simultaneous monitoring of glucose and lactate from ISF in ambulatory conditions. The performance of the subdermal wearable glucose monitoring patch was evaluated over a duration of three days, which is the longest reported duration reported till date. The subdermal wearable lactate sensing patch was worn for the duration of the exercise. Our findings highlight a critical observation that biofouling effects become apparent after a 24 h period. The data presented in this manuscript extends on the knowledge in the areas of continuous metabolite monitoring by introducing multifunctional polyphenol polymer films that can be used for both glucose and lactate monitoring with appropriate modifications. This study underscores the potential of subdermal wearable patches as versatile tools for real-time metabolite monitoring, positioning them as valuable assets in the evolution of personalised healthcare in diverse settings.

The novel estrogen receptor GPER regulates the migration and invasion of ovarian cancer cells.

G protein-coupled estrogen receptor (GPER) was identified as a new member of the estrogen receptor family in recent years. It has become apparent that GPER mediates the non-genomic signaling of 17ß-estradiol (E2) in a variety of estrogen-related cancers. Our previous study has found that GPER was overexpressed in human epithelial ovarian cancer and was positively correlated with the expression of matrix metalloproteinase 9 (MMP-9), which suggested GPER might promote the metastasis of ovarian cancer. However, the mechanisms underlying GPER-dependent metastasis of ovarian cancer are still not clear. In the present study, estrogen receptor α (ERα)-negative/GPER-positive OVCAR5 ovarian cancer cell line was used to investigate the role of GPER in the migration and invasion of ovarian cancer. Wound healing assay and transwell matrigel invasion assay were performed to determine the potentials of cell migration and invasion, respectively. The production and activity of MMP-9 in OVCAR5 cells were examined by Western blot and gelatin zymography analysis. The results showed that E2 and selective GPER agonist G-1 increased cell motility and invasiveness, and upregulated the production and proteolytic activity of MMP-9 in OVCAR5 cells. Small interfering RNA (siRNA) targeting GPER and G protein inhibitor pertussin toxin (PTX) inhibited the migration and invasion of OVCAR5 cells, and also reduced the expression and activity of MMP-9. Our data suggested that GPER promoted the migration and invasion of ovarian cancer cells by increasing the expression and activity of MMP-9. GPER might play an important role in the progression of ovarian cancer.

Decorin promotes myogenic differentiation and mdx mice therapeutic effects after transplantation of rat adipose-derived stem cells.

BACKGROUND AIMS: Adipose-derived stem cells (ADSC) have been considered as attractive candidates for the treatment of Duchenne muscular dystrophy (DMD), but the rate of ADSC myogenesis is very low. Myostatin (Mstn), a negative regulator of myogenesis, is known to be responsible for limiting skeletal muscle regeneration. Decorin could bind Mstn and deactivate it. Decorin has been shown to improve myogenic differentiation in mdx mice. We hypothesized that inhibition of Mstn by using decorin may ameliorate myogenic differentiation of ADSC. METHODS: Rat ADSC were transfected with the lentivirus-containing green fluorescence protein (GFP) and human decorin gene. The transfected ADSC were induced by 5-azacytidine (5-AzaC). The rates of myogenic differentiation and adipogenesis were detected. The transfected ADSC were injected into mdx mice and the expression of Mstn and decorin detected by Western blot. Dystrophin was detected after transfected ADSC transplantation by immunofluorescence staining and Western blot. Serum creatine kinase (CK) and histologic changes were also evaluated. RESULTS: The optimal multiplicity of infection of ADSC was 10. Decorin improved muscle mass. In accordance with the increased muscle mass, dystrophin expression increased. Following the level of decorin increase, the Mstn expression decreased. Furthermore, serum CK and histologic changes in centrally nucleated fiber (CNF) decreased. CONCLUSIONS: Improved myogenic differentiation of ADSC was observed by using decorin. This process was probably the result of decorin inhibiting Mstn. A new method of DMD therapy combining Mstn inhibition (using decorin) and ADSC transplantation is probably feasible.

Identification of zinc pollution in rice plants based on two characteristic variables.

Traditional chemical methods used to measure the zinc content in rice plants are time-consuming, laborious, requires reagents, and have a limited monitoring range, while the Raman spectroscopy method has the advantage of being fast, non-destructive, and requires no reagents. Unfortunately, the identification accuracy of the Raman partial least squares (PLS) model based on principal components is only 53.33%. To boost this, a One-Way ANOVA method was used to extract the characteristic variables in the Raman spectra. Based on these Raman variables, a model for identifying zinc stressed samples was established. The identification accuracy was improved to 70% but still fell short of the measurement requirements. To further enhance these results, the Raman spectrum was decomposed into components based on the Hilbert Vibration Decomposition (HVD) method. Using characteristic variables of the Raman spectrum and its HVD components to establish a PLS model, the identification accuracy of the test set is raised to 90.25%. These results are a significant improvement from those obtained using a model solely based on the Raman spectral characteristic variables, revealing that HVD components provide highly effective identification information. A Raman modeling method based on the characteristic variables of the HVD component is an innovative way for improving the accuracy of Raman detection, especially for the measurement of trace substances.

BMSCs differentiated into neurons, astrocytes and oligodendrocytes alleviated the inflammation and demyelination of EAE mice models.

Multiple sclerosis (MS) is a complex, progressive neuroinflammatory disease associated with autoimmunity. Currently, effective therapeutic strategy was poorly found in MS. Experimental autoimmune encephalomyelitis (EAE) is widely used to study the pathogenesis of MS. Cumulative research have shown that bone marrow mesenchymal stem Cells (BMSCs) transplantation could treat EAE animal models, but the mechanism was divergent. Here, we systematically evaluated whether BMSCs can differentiate into neurons, astrocytes and oligodendrocytes to alleviate the symptoms of EAE mice. We used Immunofluorescence staining to detect MAP-2, GFAP, and MBP to evaluate whether BMSCs can differentiate into neurons, astrocytes and oligodendrocytes. The effect of BMSCs transplantation on inflammatory infiltration and demyelination in EAE mice were detected by Hematoxylin-Eosin (H&E) and Luxol Fast Blue (LFB) staining, respectively. Inflammatory factors expression was detected by ELISA and RT-qPCR, respectively. Our results showed that BMSCs could be induced to differentiate into neuron cells, astrocytes and oligodendrocyte in vivo and in vitro, and BMSCs transplanted in EAE mice were easier to differentiate than normal mice. Moreover, transplanted BMSCs reduced neurological function scores and disease incidence of EAE mice. BMSCs transplantation alleviated the inflammation and demyelination of EAE mice. Finally, we found that BMSCs transplantation down-regulated the levels of pro-inflammatory factors TNF-α, IL-1ß and IFN-γ, and up-regulated the levels of anti-inflammatory factors IL-10 and TGF-ß. In conclusion, this study found that BMSCs could alleviate the inflammatory response and demyelination in EAE mice, which may be achieved by the differentiation of BMSCs into neurons, astrocytes and oligodendrocytes in EAE mice.

A fluorometric and colorimetric dual-signal nanoplatform for ultrasensitive visual monitoring of the activity of alkaline phosphatase.

Considering the limited sensitivity and accuracy of single-signal assay strategies, the multi-signal assay strategy has sparked significant excitement in recent years. In this study, for the first time, we reported a one-pot method in situ synthesis of carbon-containing nanoparticles (CNPs) via p-aminophenol (AP) and diethylenetriamine (DETA). The CNP solution exhibits yellow and light blue fluorescence under UV-light. Moreover, the CNPs exhibited excellent photoluminescence stability even under extreme conditions. Inspired by the alkaline phosphatase (ALP)-triggered specific catalytic reaction, we constructed an ultrasensitive fluorescence and colorimetric two-channel strategy for monitoring the ALP activity. By optimizing the detection parameters, the detection limits for both fluorometric and colorimetric were 0.05 mU mL-1. Moreover, the strategy showed high specificity and was successfully applied to monitor the ALP activity level in human serum samples. The analytical strategy opened a new window for the detection of the ALP activity, screening of the ALP inhibitor, and disease diagnosis.

[The expression of a novel estrogen receptor, GPR30, in epithelial ovarian carcinoma and its correlation with MMP-9].

The aim of the present study is to investigate the expression of a novel estrogen receptor, G protein-coupled receptor 30 (GPR30) and its correlation with matrix metalloproteinases-9 (MMP-9) in epithelial ovarian cancer (EOC). Ovary tissues were obtained from 39 female patients, including 30 cases of EOC and 9 cases of benign ovarian tumor. Four normal ovary tissues were used as control. Immunohistochemical staining was used to detect the expressions of GPR30 and MMP-9. Chi square test, Fisher's exact test and Spearman's rank correlation analysis were used for statistical analysis. The results showed that GPR30 overexpression rate in EOC cases was significantly higher than those in benign ovarian tumor and normal ovary cases. Whereas MMP-9 overexpression rate in EOC cases was significantly higher than that in normal ovary cases, without any difference to that in benign ovarian tumor cases. To demonstrate the relationship between GPR30 and clinicopathological variables of EOC, we further analyzed the pathology type, FIGO stage and age of patients sampled in our study. The analysis showed there were significant differences of GPR30 overexpression rate among various pathology types and different FIGO stages (P<0.05), and no significant difference of both GPR30 and MMP-9 among three age groups (P>0.05). Moreover, GPR30 expression was positively correlated with MMP-9 (r(s)=1.000, P=0.002). These results suggest that GPR30 may be involved in the invasion and metastasis of EOC, being a potential index of EOC early diagnosis and malignancy grade prediction.

Serum leptin is associated with first-ever ischemic stroke, lesion size and stroke severity in a Chinese cohort.

OBJECTIVE: Leptin may be associated with cardiovascular disease. We tested to determine whether leptin is a marker for first-ever acute ischemic stroke (AIS) in a nested case-referent study. METHODS: Consecutive patients with first-ever AIS from May 2017 to December 2017 were included. Referents were matched for sex, age and body mass index. Serum leptin levels and routine tests were examined in both groups. RESULTS: The median serum level of leptin in the stroke patients was 14.3 (interquartile range [IQR], 7.2-21.7) ng/ml, which was significantly higher (P < 0.001) than in the referents (10.7; 5.7-13.6 ng/ml). There was a positive correlation between serum level of leptin and National Institute of Health Stroke Scale score (r[Spearman] = 0.43, P < 0.001). In addition, serum leptin levels paralleled lesion size. Median serum level of leptin in patients with small lesions, medium lesions and large lesions was 7.3 (IQR, 5.3-14.3) ng/ml, 13.9 (IQR, 7.0-21.3) ng/ml, 20.5 (IQR, 12.4-32.7) ng/ml, respectively (analysis of variance: P < 0.001). In the univariate model matching for sex and age, leptin as a continuous variable was associated with AIS, after adjustment for possible confounders (odds ratio [OR] 1.07, 95% confidence interval [CI]: 1.04-1.11; P < 0.001). After adjusting for all other factors, leptin remained an independent stroke predictor with an adjusted OR of 1.03 (95% CI, 1.00-1.10; P = 0.006). Interestingly, the association between AIS and leptin level was more pronounced among men (adjusted OR = 1.05, 95% CI: 1.01-1.12; P < 0.001) when compared with women (adjusted OR = 1.03, 95% CI: 1.10-1.11; P = 0.009). CONCLUSION: Serum leptin is associated with first-ever AIS, lesion size and stroke severity in a Chinese cohort.

[Role of platelet-activating factor in progesterone synthesis and vascular endothelial growth factor expression in rat luteal cells].

The present study aimed to investigate the role of platelet-activating factor (PAF) in progesterone synthesis and vascular endothelial growth factor (VEGF) expression in rat luteal cells. Immature (25-28 days old) female Sprague-Dawley rats were injected subcutaneously with 50 IU pregnant mare serum gonadotrophin (PMSG), and 25 IU human chorionic gonadotrophin (hCG) 48 h later, to induce follicular development and luteum formation. On day 6 after hCG administration (the day of hCG administration was the first day), the rats were killed by guillotine and the ovarian luteal cells were collected. After incubation for 24 h, luteal cells were incubated without or with different doses (0.1 µg/mL, 1 µg/mL, 10 µg/mL) of PAF at 37 °C (5% CO(2)) for 24 h, and then progesterone concentration was evaluated by radioimmunoassay (RIA); apoptotic rate and VEGF mRNA expression in luteal cells were assessed by flow cytometry and RT-PCR, respectively. The results showed that PAF promoted progesterone production, with a maximal effect at 1 µg/mL (P<0.05); PAF increased apoptotic rate but not in a dose-dependent manner, and 10 µg/mL PAF enhanced apoptotic rate significantly (P<0.05); furthermore, PAF stimulated VEGF mRNA expression in luteal cells, especially at 1 µg/mL (P<0.01). It is suggested that PAF regulates progesterone synthesis and VEGF mRNA expression in luteal cells to mediate corpus luteum formation in rat ovary.

Pharmacological agents for improving sleep quality at high altitude: a systematic review and meta-analysis of randomized controlled trials.

Several hypnotic agents commonly recommended for improving sleep at sea level are discouraged at high altitude. We aimed to evaluate the efficacy and safety of drugs prescribed for improving sleep quality in patients with acute exposure to high altitudes by conducting a systematic review and meta-analysis. An electronic search was executed for randomized controlled trials comparing drug treatments with placebo and no-treatment conditions, which used objective sleep parameters or subjective sleep quality evaluations. Eight studies (152 participants) were included in the meta-analysis and involved trials using acetazolamide, temazepam, zolpidem, zaleplon, and theophylline. Generally, the nonbenzodiazepines were reported to be superior and safe in improving sleep quality. Participants who were administered zaleplon or zolpidem reported a significant improvement in subjective sleep quality. As measured by polysomnography, both zaleplon and zolpidem improved the total sleep time, sleep efficiency index, and stage 4 sleep duration, whereas they decreased the wake-after-sleep onset without impairing ventilation. In contrast, temazepam was not superior to placebo in terms of quicker onset of sleep and better sleep quality. On the other hand, acetazolamide and theophylline both reduced the sleep efficiency index. The present results favored zaleplon and zolpidem in improving both the objective and subjective quality of sleep without impairing ventilation.

Gene expression of transforming growth factor-beta receptors types I and II in rat endometrium during the estrous cycle and early pregnancy.

Roles of transforming growth factor-beta (TGF-beta) receptor types I (TbetaRI) and II (TbetaRII) during the estrous cycle and implantation of rodents are currently unclear. In the present study, the spatial and temporal expressions of TbetaRI and TbetaRII in rat endometrium during the estrous cycle, pre-, and peri-implantation were examined using in situ hybridization and semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). With in situ hybridization, TbetaRI and TbetaRII were expressed at weak levels in rat endometrium during the estrous cycle. During pre-implantation, both receptors were expressed in the luminal epithelium and glandular epithelium on Days 0.5 and 1.5 of pregnancy, but were down-regulated on Days 2.5 and 3.5. During peri-implantation, both TGF-beta receptors were localized in the luminal epithelium and subepithelial stroma to facilitate attachment reaction and trophoblast invasion. They were highly expressed on Day 4.5, whereas were down-regulated on Days 5.5 and 6.5. Semi-quantitative RT-PCR analysis confirmed the data obtained by in situ hybridization. These results suggest that during pre-implantation, both TGF-beta receptors are functional in the proliferation of endometrial epithelial cells. During peri-implantation, both TGF-beta receptors play important roles during the onset of the uterine receptivity and the attachment reaction. TGF-beta signaling is down-regulated when trophoblast invasion begins.

The association of serum 25-hydroxyvitamin D levels with multiple sclerosis severity and progression in a case-control study from China.

OBJECTIVE: Low vitamin D levels had been shown to play a role in the pathogenesis of multiple sclerosis (MS). Currently, there is little information regarding the correlation between levels of vitamin D and MS in Chinese. This study aimed at detection of association between serum 25-hydroxyvitamin D [25(OH) D] concentrations and MS and its relation to the disease severity in Chinese. METHODS: The present study was a case-control type, it included 141 patients with definitive MS on the basis of 'McDonald' criteria and 282 age-sex matched controls. All patients were clinically evaluated including disease severity using expanded disability status scale (EDSS) score and progression index (PI). Serum 25(OH) D measurements were performed at baseline. RESULTS: The median serum level of 25(OH) D in patients with MS was 15.9 (IQR, 11.4-24.4) ng/mL, which was significantly lower (P<0.0001) than those in healthy controls (20.6 [IQR, 15.3-27.7] ng/mL). There was a negative correlation between levels of 25(OH) D and the EDSS score (r=-0.549, P<0.0001). In multivariate conditional logistic analyses using dichotomous 25(OH) D levels, values less than or equal to 20ng/mL indicted higher risk of MS (OR 1.691, 95 CI: 1.058-2.394; P=0.024). Similarly, in binary logistic multivariate analyses using dichotomous 25(OH) D levels, values less than or equal to 20ng/mL indicted the MS high progression (OR 6.278, 95 CI: 2.662-15.659; P<0.001). CONCLUSION: Low serum 25(OH) D levels were associated with increased activity and progression in Chinese patients with MS. Further analytical work is required to establish a causal association between vitamin D status and MS risk and progression.