Association of serum 25-hydroxyvitamin D levels with all-cause and cause-specific mortality among postmenopausal females: results from NHANES.

BACKGROUND: Vitamin D deficiency is common among the population, but its relationship with mortality of postmenopausal females is unclear. The aim of this study is to explore the association between serum 25-Hydroxyvitamin D (25(OH)D) and all-cause and cause-specific mortality among postmenopausal women in the United States. METHODS: 6812 participants of postmenopausal females from the National Health and Nutrition Examination Survey (2001-2018) were included in this study. The mortality status of the follow-up was ascertained by linkage to National Death Index (NDI) records through 31 December 2019. We used cox proportional hazards models to estimate the association of serum 25(OH)D concentrations and mortality of postmenopausal females. RESULTS: The mean level of serum 25(OH)D was 72.57 ± 29.93 nmol/L, and 65.34% had insufficient vitamin D. In postmenopausal females, low serum 25(OH)D concentrations were significantly associated with higher levels of glycohemoglobin, glucose, and lower levels of HDL. During follow-up, 1448 all-cause deaths occurred, including 393 cardiovascular disease (CVD)-related deaths and 263 cancer deaths. After multivariate adjustment, higher serum 25(OH)D levels were significantly related with lower all-cause and CVD mortality. In addition, serum 25(OH)D presented a L-shaped relationship with all-cause mortality, while appeared a U-shaped with CVD mortality, and the cut-off value is 73.89 nmol/L and 46.75 nmol/L respectively. CONCLUSIONS: Low serum 25(OH)D levels are associated with the higher risk of all-cause and CVD mortality in postmenopausal females. These findings provide new ideas and targets for the health management of postmenopausal women.

The Advance of Magnetic Resonance Elastography in Tumor Diagnosis.

The change in tissue stiffness caused by pathological changes in the tissue's structure could be detected earlier, prior to the manifestation of their clinical features. Magnetic resonance elastography (MRE) is a noninvasive imaging technique that uses low-frequency vibrations to quantitatively measure the elasticity or stiffness of tissues. In tumor tissue, stiffness is directly related to tumor development, invasion, metastasis, and chemoradiotherapy resistance. It also dictates the choice of surgical method. At present, MRE is widely used in assessing different human organs, such as the liver, brain, breast, prostate, uterus, gallbladder, and colon stiffness. In the field of oncology, MRE's value lies in tumor diagnosis (especially early diagnosis), selection of treatment method, and prognosis evaluation. This article summarizes the principle of MRE and its research and application progress in tumor diagnosis and treatment.

Erythropoietin reduces white matter damage in two-day-old rats exposed to hypoxic/ischemia injury.

OBJECTIVE: The aim of the study was to investigate whether erythropoietin (EPO) could protect against white matter damage (WMD) in a preterm equivalent neonatal rat hypoxic-ischemia (HI) model. METHODS: 113 two-day-old male rat pups were divided randomly into three groups: sham-treated, bilateral carotid artery occlusion (BCAO)-treated, BCAO + EPO-treated group. EPO (50 U/10 g body weight) or saline alone was administered intraperitoneally immediately after BCAO surgery. Body weight, brain weight, brain water content, and expression of myelin basic protein (MBP) were assessed at day 1, 3, 7, and 14 after HI insult. Morris water-maze (MWM) test was used to assess neurological behavior from day 31 to 35 after HI insult. RESULTS: Body weights of BCAO + EPO group were greater than those of BCAO group rats (P < 0.05). Specifically, at day 3 and 7 after HI, brain weights of BCAO + EPO-treated rats were higher than BCAO-treated animals (P < 0.05); at day 7 and 14 after HI, MBP of BCAO + EPO-treated rats were higher than BCAO-treated animals (P < 0.05). Similarly, the brain water content at day 3 after HI in BCAO + EPO-treated rats was lower than BCAO-treated animals (P < 0.05). The body weight, brain weight, brain water content, and MBP expression in BCAO + EPO-treated group were comparable to those in the sham-treated group. Spatial learning and memory of BCAO + EPO-treated rats was significantly improved over the BCAO-treated group and was comparable to the sham-operated animals. CONCLUSION: EPO treatment could be a potential intervention in treating WMD for preterm infants.

Anti-biofouling properties of amphiphilic phosphorylcholine polymer films.

Surfaces of amphiphilic phosphorylcholine polymer (PC1036) prepared by spin-coating were characterized by spectroscopic ellipsometry, water contact angle and atomic force microscopy. The antifouling properties of the PC1036 films to marine benthic diatom Nitzschia closterium MMDL533 were also investigated. The results showed that the dry PC1036 film promoted the adhesion of N. closterium MMDL533 because the hydrophobic lauryl groups were present in the film surface. The 2 h-swelled PC1036 films had excellent anti-fouling properties with extremely low attachment densities and retention densities no matter what the annealing temperature was. The thickness of the coated films lower than 147 Å had a profound effect on the film anti-fouling properties. Otherwise, when the film thickness was higher than that value, there was no more improvement of diatom cell reduction observed. The annealing temperature had only a little effect on the film resistant to diatom adhesion, which might be attributed to two factors including the PC group packing densities in the outer PC layer and the equilibrated water volume fraction in the 2 h-swelled PC1036 films.

Influence of surface free energy on the adhesion of marine benthic diatom Nitzschia closterium MMDL533.

The self-assembled monolayers (SAMs) with gradient surface free energies were prepared by surface grafting of a binary mixture of methyl and vinyl terminated trimethoxysilanes on hydrophilic glass slides followed by in situ oxidation of vinyl groups into carboxyl groups. Characterized by contact angles, the SAMs combined with freshly cleaned glass slides bearing hydroxyl groups were used to study the adhesion behavior of marine benthic diatom Nitzschia closterium MMDL533. The attachment densities were much higher on hydrophobic CH3-SAMs and lower on mixed SAMs with surface free energy of 40.1-50.4 mJ/m2. More gregarious adhesion had been found on hydrophobic CH3-SAMs. The percentage removal was in a narrow range of 63-80% on the engineered surfaces and was much lower with a value of 54% on the hydrophilic slides. Our studies have revealed some subtle but interesting differences in attachment and adhesion from the features reported for these benthic species, indicating the possible links to different diatom species.

Cyclosporin A promotes growth and invasiveness in vitro of human first-trimester trophoblast cells via MAPK3/MAPK1-mediated AP1 and Ca2+/calcineurin/NFAT signaling pathways.

Cyclosporin A (CsA) has provided the pharmacologic foundation for organ transplantation as a calcineurin inhibitor blocking T-cell activation. We have demonstrated that CsA promoted trophoblast viability/proliferation and invasion in vitro. In the present study, we further investigated the intracellular signalling pathways involved in enhancing cell viability/proliferation and invasiveness of the human trophoblast induced by CsA. We showed that blocking mitogen-activated protein kinase 3 (MAPK3)/MAPK1 signaling by U0126 attenuated CsA-increased cell viability and invasiveness of trophoblasts. Cyclosprin A inhibited ionomycin-stimulated nuclear factor of activated T-cells (NFAT) transactivation in JAR cells and reversed the ionomycin-inhibited trophoblast invasiveness. However, either activating calcineurin by ionomycin, resulting in NFAT transactivation, or inhibiting NFAT using an NFAT inhibitor had no effect on trophoblast cell viability/proliferation and apoptosis in vitro. Hence, the CsA-induced promotion of trophoblast growth and invasion occurred by overlapping but independent pathways. The MAPK3/MAPK1 pathway was essential for both trophoblast growth and invasion, whereas the Ca(2+)/calcineurin/NFAT pathway was only involved in the CsA-promoted trophoblast invasiveness. Finally, potential cross-talk between MAPK3/MAPK1 and Ca(2+)/calcineurin/NFAT and its relationship to activator protein 1 activation was investigated. Our findings explored possible signal transduction pathways modulated by CsA, which may lead to the expansion of the clinical applications of this drug.

Cyclosporine A induces titin expression via MAPK/ERK signalling and improves proliferative and invasive potential of human trophoblast cells.

BACKGROUND: Cyclosporin A (CsA) is a powerful immunosuppressive that has been widely used to prevent organ rejection and to treat certain autoimmune diseases. Our previous study showed that CsA at low concentrations could promote proliferation and invasion, and inhibit apoptosis, of human first trimester trophoblasts. In the present study, we further explored the potential mechanism and signal pathway. METHODS: After treatment of JAR cells with CsA, we screened the differentially expressed genes by suppression subtractive hybridization (SSH), and characterized the differentially expressed gene, titin, in human first-trimester trophoblasts by reverse transcription-polymerase chain reaction and Western blot. Mitogen-activated protein kinase (MAPK) activity was evaluated by ELISA. RESULTS: CsA stimulated proliferation and invasion of human trophoblasts in a dose-dependent manner, and this appeared to be positive correlated with titin transcription, suggesting that CsA regulates biological functions of human trophoblast by inducing titin expression. Furthermore, the CsA treatment increased the MAPK activity, and blocking of the signaling pathway by Mitogen-activated protein MAPK (MEK) inhibitor, U0126, inhibited CsA-induced titin transcription in trophoblasts. CONCLUSIONS: Our results indicate that titin expression is induced by CsA via activation of MAPK pathways and this may possibly be involved in promoting human trophoblast growth and invasiveness, which is beneficial to embryo viability.

Cyclosporin A increases expression of matrix metalloproteinase 9 and 2 and invasiveness in vitro of the first-trimester human trophoblast cells via the mitogen-activated protein kinase pathway.

BACKGROUND: Cyclosporin A (CsA) is an immunosuppressent which is used for preventing allograft rejection. Little is known, however, about the effect of CsA on the materno-fetal relationship. Our aim was to probe into the effect of CsA on the invasiveness of human first-trimester trophoblast cells and explore possible molecules involved, with a view to providing a new therapeutic approach for pregnancy complications with trophoblast disorder. METHODS: The effects of CsA on invasion of the first-trimester human trophoblasts were examined by matrigel invasion assay, and the transcription, translation and proteolytic activity of matrix metalloproteinase (MMP-9) and MMP-2 in these cells were estimated by RT-PCR, in-cell Western and zymography, respectively. The phosphorylation level of extracellular-signal related kinase (ERK) 1/2 in trophoblasts induced by CsA was also evaluated by in-cell Western. RESULTS: CsA increased the invasive index of first-trimester human trophoblasts (P < 0.01), as well as the messenger RNA, protein levels (both P < 0.01) and proteolytic activity (P < 0.05) of MMP-9 and MMP-U0126, a mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor, inhibited the enhanced invasiveness and activity of MMP-9 and MMP-in these cells induced by CsA. In addition, CsA activated the ERK1/2 in a time-dependent manner. CONCLUSIONS: CsA improves the invasiveness and activity of MMP 9 and MMP 2 in vitro of the first-trimester human trophoblast cells through activation of mitogen-activated protein kinase/extracellular-signal related kinase (ERK) 1/2 signaling pathway, which suggests this drug has a favorable modulation on the function of human first-trimester trophoblast cells.

The involvement of chloroplast HSP100/ClpB in the acquired thermotolerance in tomato.

The chloroplast HSP100/ClpB is a newly documented member of the ClpB family, but little was known about its role in imparting thermotolerance to cells. A cDNA coding for a HSP100/ClpB homolog has been cloned from Lycopersicon esculentum and termed as Lehsp100/ClpB (the cDNA sequence of Lehsp100/ClpB has been submitted to the GenBank database under accession number: AB219939). The protein encoded by the cDNA was most similar to the putative chloroplast HSP100/ClpBs in higher plants and the ClpB from Cyanobacterium Synechococcus sp. A 97 kDa protein, which matched the predicted size of mature LeHSP100/ClpB, was immunologically detected in chloroplast isolated from heat-treated tomato plants. In addition, the fusion protein, combining the transit sequence of LeHSP100/ClpB and GFP, was found to be located in chloroplast based on the observations of fluorescent microscope images. These results indicated the chloroplast-localization of LeHSP100/ClpB. Both the transcript and the protein of Lehsp100/ClpB were not detected under normal growth conditions, but they were induced by increasingly higher temperatures. An antisense Lehsp100/ClpB cDNA fragment was introduced into the tomato by Agrobacterium-mediated transformation. Antisense lines exhibited an extreme repression of heat-induced expression of Lehsp100/ClpB. The levels of chloroplast HSP60 and small HSP in antisense lines were identical to those of the control plants. After plants preconditioned at 38 degrees C for 2 h were exposed to a lethal heat shock at 46 degrees C for 2 h, the antisense lines were greatly impaired and withered in 21 days of the recovery phase, whereas the untransformed control plants and the vector-transformed plants survived. Furthermore, chlorophyll fluorescence measurements showed that PS II in antisense lines were more susceptible to the thermal irreversible inactivation than the untransformed and vector-transformed control plants. This work provides the first example that induction of chloroplast LeHSP100/ClpB contributes to the acquisition of thermotolerance in higher plants.

[Molecular cloning of tomato LeHsp110/ClpB gene and its effect on the thermotolerance in plant].

The heat shock protein ClpB is a member of the Clp family and functions as molecular chaperones. ClpB is related to the acquired thermotolerance in organisms. A cDNA of 3144 bp was screened out of a tomato cDNA library. The polypeptide deduced from the longest ORF contains 980 amino acid residues, and was classified into HSP100/ClpB family based on the result of molecular phylogenesis analysis. Thus it was named as LeHSP110/ClpB according to its calculated molecular weight. LeHSP110/ClpB was characteristic of heat-inducibility but no constitutive expression, and was demonstrated to locate in chloroplastic stroma. An antisense cDNA fragment of LeHsp110/ClpB under the control of CaMV 35S promoter was introduced into tomato by Agrobacterium tumefactions-mediated method. At high temperature, the mRNA levels of LeHsp110/ClpB in antisense transgenic plants were lower than those in control plants. The PS II of transgenic plants is more sensitive to high temperature than that of control plants according to data of Fv/Fm. These results clearly showed that HSP110/ClpB plays an important role in thermotolerance of high plants.

Cloning and molecular characteristic of the metalloprotease gene LeftsH6 from tomato.

The full-length 2213-bp ftsH (filamentation temperature-sensitive H) cDNA was cloned from the cDNA library of heat-shocked tomato leaves. According to an open reading frame of 2019-bp, the deduced protein precursor was predicted to target chloroplast. The putative AAA (ATPases associated with diverse cellular activities) domain and the Zn(2+)-binding domain, characteristic of FtsH metalloproteases family, were found in the FtsH-like protein. Most similar to the FtsH6 of Arabidopsis thaliana, the tomato ftsH-like gene was named as Lycopersicon esculentum filamentation temperature-sensitive H6 (LeftsH6). Purified FtsH degraded casein but not BSA in vitro, whereas a FtsH mutant with the Glu(472) in the zinc-binding motif replaced by Gln had lost the protease activity. A single copy of LeftsH6 was detected in tomato genome by Southern blot analysis. Northern and Western blot analyses revealed consistently the heat-inducible character of the LeftsH6 gene. No LeftsH6 expression was detected after cold, salt, drought or light stress. The results provided the first experimental evidence of the existence of heat-inducible ftsH gene in higher plants.

Differential regulation of Lehsp23.8 in tomato plants: Analysis of a multiple stress-inducible promoter.

Small heat shock proteins (sHSPs) are the major family of HSP induced by heat stress in plants. In this report, an approximately 1.9kb of Lehsp23.8 5'-flanking sequence was isolated from tomato genome. By using the ß-glucuronidase (GUS) reporter gene system, the developmental and tissue specific expression of the gus gene controlled by the Lehsp23.8 promoter was characterized in transgenic tomato plants. Strong GUS staining was detected in the roots, leaves, flowers, fruits and germinated seeds after heat shock. The heat-induced GUS activity was different in the floral tissues at various developmental stages. Fluorometric GUS assay showed that the heat-induced GUS activity was higher in the pericarp than in the placenta, and it was the lowest in the locular gel. The heat-shock induction of the Lehsp23.8 promoter depended on the different stages of fruit development. The optimal heat-shock temperatures leading to the maximal GUS activity in the pericarp of green, breaker, pink and red fruits were 42, 36, 39 and 39°C, respectively. The heat-induced GUS activity in tomato fruits increased gradually within 48h of treatment and weakened during tomato fruit ripening. Obvious GUS activities under cold, exogenous ABA and heavy metal (Cd(2+), Cu(2+), Pb(2+) or Zn(2+)) stress conditions were also detected. These results show that the Lehsp23.8 promoter is characterized as strongly heat-inducible and multiple-stress responsive.

[Effect of oxymatrine on pathological change in brain tissue of newborn mice infected by cytomegalovirus].

OBJECTIVE: To study the effect of oxymatrine on pathological change in brain tissue of newborn mice infected by cytomegalovirus (CMV). METHODS: CMV of TCID50 was inoculated into the brain of the newborn mice, and the morphological change in the brain tissue infected by CMV was observed with light microscope and transmission electron microscope. RESULTS: In the model control group, the results showed that there were some inflammatory cellular infiltration and focal necrosis in the brain tissue of newborn mice infected by CMV. The ultrastructure change in the brain tissue showed that the nuclear membrane of cerebral neurons sunk, the chromatin deformed and fused into masses, the cytoplasm vacuolated, the endoplasmic reticulum disarranged and the Nissl's body was blurred or disappeared. After being treated with oxymatrine (50 mg/kg, ip) for 15 days, those pathological changes of the brain tissue in the newborn mice could be significantly improved. CONCLUSION: Oxymatrine has an obvious inhibition on CMV in vivo.