Association of oxidative stress and Kashin-Beck disease integrated Meta and Bioinformatics analysis.

OBJECTIVE: To explore the association between oxidative stress (OS) and Kashin-Beck disease (KBD). METHODS: Terms associated with "KBD" and "OS" were searched in the six different databases up to October 2021. Stata 14.0 was used to pool the means and standard deviations using random-effect or fixed-effect model. The differentially expressed genes in the articular chondrocytes of KBD were identified, the OS related genes were identified by blasting with the GeneCards. The KEGG pathway and gene ontology enrichment analysis was conducted using STRING. RESULTS: The pooled SMD and 95% CI showed hair selenium (-4.59; -6.99, -2.19), blood selenium (-1.65; -2.86, -0.44) and glutathione peroxidases (-4.15; -6.97, -1.33) levels were decreased in KBD, whereas the malondialdehyde (1.12; 0.60, 1.64), nitric oxide (2.29; 1.31, 3.27), nitric oxide synthase (1.07; 0.81, 1.33) and inducible nitric oxide synthase (1.69; 0.62, 2.77) were increased compared with external controls. Meanwhile, hair selenium (-2.71; -5.32, -0.10) and glutathione peroxidases (-1.00; -1.78, -0.22) in KBD were decreased, whereas the malondialdehyde (1.42; 1.04, 1.80), nitric oxide (3.08; 1.93, 4.22) and inducible nitric oxide synthase (0.81; 0.00, 1.61) were elevated compared with internal controls. Enrichment analysis revealed apoptosis was significantly correlated with KBD. The significant biological processes revealed OS induced the release of cytochrome c from mitochondria. The cellular component of OS located in the mitochondrial outer membrane. CONCLUSIONS: The OS levels in KBD were significantly increased because of selenium deficiency, OS mainly occurred in mitochondrial outer membrane, released of cytochrome c from mitochondria, and induced apoptotic signaling pathway.

Effective adsorption of antimony (V) from contaminated water by a novel composite manganese oxide/oxyhydroxide as an adsorbent.

To obtain an efficient and low-cost adsorbent for the Sb(V) removal in Sb(V)-contaminated water, a novel composite manganese oxide/oxyhydroxide (CMO) was synthesized by a simple hydrothermal synthesis method. The synthesized adsorbent was characterized via scanning electron microscopy, X-ray diffraction, transmission electron microscopy, Brunauer-Emmett-Teller surface area, Fourier transform infrared, and X-ray photoelectron spectroscopy analyses. The results revealed that the as-prepared CMO adsorbent possessed a porous structure consisting of Mn3O4 nanoparticles and MnOOH nanorods. Batch experiments showed that the adsorption behaviours were well fitted by the Langmuir isotherm and the pseudo-second-order kinetic model, reaching the maximum adsorption capacity of 119.63 mg/g at 25 °C. The application of CMO adsorbent showed that the Sb(V) removal efficiency in 6.24 L Sb(V)-containing water with a concentration of 3.6 mg/L was more than 90%. The reusability of CMO adsorbent demonstrated that the Sb(V) removal efficiency was still more than 80% even after five times of regeneration. The adsorption mechanism for Sb(V) can be described as ligand exchange between hydroxyl groups on the adsorbent surface and hydroxyl groups in Sb(OH)6- molecules by forming inner-sphere complexes. Those results suggested that the CMO adsorbent can be considered as a potential adsorbent to remove Sb(V) from contaminated water.

[Threshold effects of body mass index on the bone mineral density of Chinese rural women in fluorosis area].

To explore the threshold effect of body mass index (BMI) on bone mineral density (BMD) in Chinese women living in the fluorosis area, we conducted a cross-sectional study and recruited 722 women in rural areas in Henan Province, China. After detection and analyses, we found that compared with the normal BMI group, the risk of osteoporosis in the overweight and obese groups were reduced by 32% and 69%, respectively. Threshold effect analysis showed that BMD was positively correlated with BMI when BMI was 16.8-31.2 kg/m2; while when BMI was greater than 31.2 kg/m2, the correlation reached saturation. The correlation observed between low-to-moderate fluoride exposure and BMD in rural women was not significant.

[The role of abnormal mitochondrial fusion and fission in PBDE-47-induced change in mitochondrial mass in PC12 cells].

Objective: To investigate the effect of 2, 2', 4, 4'-tetrabromodiphenyl ether (PBDE-47) on the mitochondrial mass in rat adrenal pheochromocytoma (PC12) cells and the potential mechanisms. Methods: Highly differentiated PC12 cells were divided into control, 1, 10 or 20 µmol/L PBDE-47-treated groups and cultured for 24 h. Transmission electron microscopy was employed to observe the changes in mitochondrial morphology and quantity in PC12 cells. Flow cytometry was used to measure the fluorescence intensity of Nonyl Acridine Orange (NAO) , a fluorescent indicator of mitochondrial membrane cardiolipin, to reflect mitochondria mass. Western blotting was used to determine the expression levels of Mitofusion 1 (Mfn1) and Fission 1 (Fis1) proteins. To further explore the role of abnormal mitochondrial fusion and fission in PBDE-47-induced mitochondrial mass changes, PC12 cells were divided into control group, 5 µmol/L M1 treatment group, 20 µmol/L PBDE-47 treatment group and 5 µmol/L M1+20 µmol/L PBDE-47 combined treatment group and cultured for 24 h, then the fluorescence intensity of NAO and expression levels of Mfn1 and Fis1 proteins were detected. Results: The control group showed numerous mitochondria with normal morphology, while the number of mitochondria decreased after PBDE-47 treatment. Especially, the disappeared cristae, swelling and vacuoles of mitochondria and decreased fluorescence intensity of NAO (P<0.05) were observed in 10 and 20 µmol/L PBDE-47-treated groups. Meanwhile, the expression levels of Mfn1 and Fis1 proteins in the 10 and 20 µmol/L PBDE-47-treated groups were significantly decreased compared with control group (P<0.05) . However, 5 µmol/L M1 co-treatment with 20 µmol/L PBDE-47 significantly increased the levels of Mfn1 and Fis1 proteins and fluorescence intensity of NAO compared with the 20 µmol/L PBDE-47 group (P<0.05) . Conclusion: PBDE-47 can inhibit the mitochondrial fusion and fission process, thus leading to damage of mitochondria mass in PC12 cells.

[The effects of resveratrol on mitochondrial biogenesis dysfunction induced by fluoride in human neuroblastoma SH-SY5Y cells].

Objective: To explore the role of mitochondrial biogenesis and the neuroprotective mechanism of resveratrol in fluoride neurotoxicity. Methods: SH-SY5Y cells in exponential phase were treated with different concentrations (20, 40, 60 mg/L) of sodium fluoride (NaF) for 24 h. Co-treatment with 60 mg/L NaF, 20 µmol/L resveratrol (RSV) was administrated in the resveratrol intervene trial. Western blotting was used to determine the expression levels of mitochondrial biogenesis key regulating factor of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) , nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM) in SH-SY5Y cells. The mRNA levels of PGC-1α, NRF1 and TFAM were determined by Quantitative Real-time PCR in SH-SY5Y cells, as well as the relative mitochondrial DNA (mtDNA) contents and mRNA expression of mitochondrial respiratory chain complexes subunit CO1 and ATP8. Flow cytometry was used to determine mitochondrial membrane potential in SH-SY5Y cells. Results: Both the protein and mRNA levels of PGC-1α, NRF1 and TFAM were decresed after 60 mg/L NaF treatment in SH-SY5Y cells (P<0.05) . The relative mtDNA contents and mRNA expression of complexes subunit CO1 and ATP8 were also significantly decreased compared with control (P<0.05) . Mitochondrial membrane potential were also significantly decreased after 60 mg/L NaF treatment in SH-SY5Y cells (P<0.05) . Compared with 60 mg/L NaF group, the protein and mRNA levels of PGC-1α, NRF1 and TFAM in 20 µmol/L RSV+60 mg/L NaF group were significantly increased (P<0.05) . The relative mtDNA contents, mitochondrial membrane potential and mRNA levels of complexes subunit CO1 and ATP8 in 20 µmol/L RSV+60 mg/L NaF group were also significantly higher than that in 60 mg/L NaF group (P<0.05) . Conclusion: Resveratrol may alleviate the fluoride-induced mitochondrial biogenesis dysfunction in SH-SY5Y cells.

Studies on the interference of ganciclovir to HCV liver fibrosis.

OBJECTIVE: To investigate the significance of the combined treatment with ganciclovir and interferon for patients with hepatitis C (HCV) liver fibrosis. PATIENTS AND METHODS: We retrospectively summarize 86 patients with hepatitis C treated in our hospital from October 2013 to October 2015. 49 cases, considered as control group, received combined treatment with α-interferon and ribavirin; 37 cases, considered as observation group, received combined treatment with ganciclovir and interferon. The changes of liver fibrosis, viral replication and liver function of both groups were compared for two weeks and six months. RESULTS: The levels of sera hyaluronic acid (HA), laminin (LN), type IV collagen (IVC) and type III procollagen (PIII NP) of both groups were reduced after treatment, and the observation group improved more significantly (p <0.05). Compared to the rate of antigen-positive after treatment and HCV copy number before and after treatment, the differences were not statistically significant (p > 0.05). The level of alanine aminotransferase (ALT) of the control group increased after treatment, compared with that before. This was done along with the decrease of the level of albumin. By contrast, the level of ALT in the observation group was reduced and the level of albumin was increased compared with that before (p < 0.05). CONCLUSIONS: Ganciclovir combined with interferon may further reduce the fibrosis process of patients with hepatitis C, and may improve liver function. The effect of antiviral was similar as ganciclovir combined with Interferon was comparatively good applied, safety and effectiveness.

Ultrafast Dynamics Evidence of High Temperature Superconductivity in Single Unit Cell FeSe on SrTiO_{3}.

We report the time-resolved excited state ultrafast dynamics of single unit cell (1 UC) thick FeSe films on SrTiO_{3} (STO), with FeTe capping layers. By measuring the photoexcited quasiparticles' density and lifetime, we unambiguously identify a superconducting (SC) phase transition, with a transition temperature T_{c} of 68 (-5/+2) K and a SC gap of Δ(0)=20.2±1.5 meV. The obtained electron-phonon coupling strength λ is as large as 0.48, demonstrating the likely crucial role of electron-phonon coupling in the high temperature superconductivity of the 1 UC FeSe on STO systems. We further find a 0.05 THz coherent acoustic phonon branch in the capping layer, which provides an additional decay channel to the gluing bosons.

Pilot study of DNA methylation in the pathogenesis of chronic rhinosinusitis with nasal polyps.

BACKGROUND: DNA methylation has been implicated in the pathogenesis of allergy and atopy. This study aimed to identify whether DNA methylation also plays an important role in the pathogenesis of nasal polyps (NP). METHODOLOGY: NP tissues were obtained from 32 patients with chronic rhinosinusitis with bilateral NP. Biopsies of inferior turbinate mucosa (ITM) were taken from 18 patients who underwent rhinoseptoplasty (control group). The methylated genes, which were detected by DNA methylation microarray, were validated by methylation-specific polymerase chain reaction, bisulphite sequencing, real-time polymerase chain reaction and immunohistochemistry. RESULTS: DNA methylation microarray identified 8,008 CpG islands in 2,848 genes. One hundred and ninety-eight genes were found to have a methylated signal in the promoter region in NP samples compared with ITM samples. The four top genes that changed, COL18A1, EP300, GNAS and SMURF1, were selected for further study. The methylation frequency of COL18A1 was significantly higher in NP samples than in ITM samples. CONCLUSIONS: DNA methylation might play an important role in the pathogenesis of NP. Promoter methylation of COL18A1 was found to be significantly increased in NP tissues, further studies are necessary to confirm the significance of these epigenetic factors in the mechanisms underlying the development or persistence of NP.

Study of the correlation between growth hormone deficiency and serum leptin, adiponectin, and visfatin levels in adults.

We aimed to determine the significance and changes in leptin, adiponectin (ADP), and visfatin levels in adults with growth hormone deficiency (GHD). Forty adults (19 men, 21 women) who had been diagnosed with GHD comprised the observation group, while 36 healthy adults (18 men, 18 women) were used as the control group. Fasting venous blood was collected to detect leptin, ADP, and visfatin levels. There was no statistically significant difference (P > 0.05) between the GHD group and the control group in terms of gender ratio, age, and body mass index. The waist-to-hip ratio (0.894 ± 0.061 vs 0.830 ± 0.481), cholesterol (4.99 ± 1.046 vs 4.18 ± 0.683), triglyceride (1.97 ± 1.428 vs 1.08 ± 0.403), LDL (2.91 ± 0.980 vs 2.29 ± 0.540), leptin (3.00 ± 1.233 vs 1.89 ± 1.554), ADP (15.26 ± 6.449 vs 10.24 ± 7.608), and visfatin levels (10.42 ± 3.715 vs 5.87 ± 3.90) in the GHD group were significantly higher than those in the control group (all P < 0.05). The levels of growth hormone (1.68 ± 1.67 vs 15.53 ± 6.23), insulin-like growth factor-1 (IGF-1, 22.64 ± 16.41 vs 61.85 ± 28.48), IGF-binding protein-3 (4889 ± 2962 vs 6866 ± 3823), and dehydroepiandrosterone sulfate (1.466 ± 1.804 vs 6.000 ± 2.767) in the GHD group were significantly lower than those in the control group (all P < 0.05). Correlation analysis demonstrated that leptin level was positively correlated to ADP and visfatin in both the GHD and control groups and negatively correlated to IGF-1 (r = 0.332, P < 0.05). Logistic regression analysis demonstrated that leptin, ADP, and visfatin were independent risk factors for adults with GHD.

dCTP pyrophosphohydrase exhibits nucleic accumulation in multiple carcinomas.

Nucleoside triphosphate pyrophosphohydrolase (NTP-PPase) functions as one of the mechanisms to guarantee the fidelity of DNA replication through the cleavage of non-canonical nucleotides into di- or monophosphates. Human NTP-PPase is poorly understood and investigated. In the present study, by using tissue microassays with the paired cancer and adjacent regions, we found that with the prevalent expression of dCTP pyrophosphohydrase (DCTPP1) in the cytosol and nucleus in tumors investigated, DCTPP1 was inclined to accumulate in the nucleus of cancer cells compared to the paired adjacent tissue cells in multiple carcinoma including lung, breast, liver, cervical, gastric and esophagus cancer. More significantly, the higher DCTPP1 expression in the nucleus of lung, gastric and esophagus cancer cells was associated with histological subtypes. The nucleic accumulation of DCTPP1 was apparently observed as well when cancer cell line MCF-7 was treated with H2O2 in vitro. Considering the roles of DCTPP1 on restricting the concentration of non-canonical nucleotides in the nucleotide pool, accumulation of DCTPP1 in the nucleus of cancer cells might suffice for maintaining the proper DNA replication in order to fulfill the requirement for the survival and proliferation of tumor cells.

The molecular mechanism of microRNA-145 to suppress invasion-metastasis cascade in gastric cancer.

Invasion and metastasis are the major features of malignant tumors that are responsible for 90% of cancer-related deaths. Recently, microRNAs have been discovered to have a role in suppressing tumor metastasis. This study's aim was to clarify the roles of miR-145 in gastric carcinomas and its underlying molecular mechanism in regulating tumor metastasis. Here, we demonstrate a stepwise downregulation of miR-145 level in nontumorous gastric mucosa, primary gastric cancers and their secondary metastases. In vitro analysis of miR-145's ectopic expression and loss-of-function suggests that it suppresses gastric cancer cell migration and invasion. In vivo spontaneous metastasis and experimental metastasis assay further confirm its function in suppressing the invasion-metastasis cascade, including impairing local invasion and inhibiting hematogenous metastasis in gastric cancers. Furthermore, we identified a novel mechanism of miR-145 to suppress metastasis. N-cadherin (CDH2) was proved to be a direct target of miR-145, using luciferase assay and western blot. Re-expressing N-cadherin in miR-145-transfected cells reverses their migration and invasion defects. Although not a direct target of miR-145, matrix metallopeptidase 9 (MMP9), but not MMP2, was also significantly decreased in miR-145-expressing cells. We suggest that miR-145 suppresses tumor metastasis by inhibiting N-cadherin protein translation, and then indirectly downregulates its downstream effector MMP9.

A liquid-filled tunable double-focus microlens.

A novel microlens design with tunable double-focus is presented. It is fabricated by adding only one SU-8 photolithography step to the well-developed liquid-filled microlens fabrication process. The thickness of this layer determines the thickness difference between the central and peripheral region of the membrane, the deformation of which is used to define the surface profile of the microlens. The stepped thickness variation is finally manifested as the difference in deformation contour at two different regions of the membrane when subjected to uniform applied pressure, thereby causing two focal lengths to appear. Experimental and simulation results are presented, from which the tunability of the focal lengths of the double-focus microlens is demonstrated to be effective over a wide range through combining the structural design with pressure control. The successful demonstration of this unconventional microlens design concept will potentially extend t application of liquid-filled microlens technology.

Selection of antisense oligonucleotides for reversal of multidrug resistance in breast carcinoma cells.

BACKGROUND: Multidrug resistance (MDR) is a major obstacle in cancer treatment. In the present study, six regions of the mdr1 gene associated with transcription control or translation initiation were selected as targets. Six antisense oligonucleotides (ASODN; AS1-AS6) complementary to the corresponding sequence of the mdr1 gene were synthesized to investigate whether or not blocking the transcription control sites with ASODN could reverse MDR and which ASODN had the best efficiency for reversing MDR in breast carcinoma cells. METHODS: Forty-eight hours after transfection, mdr1 mRNA and P-glycoprotein (Pgp) were determined by RT-PCR, flow cytometry and Rhodamine 123 (Rh123) retention assay. The chemosensitivity of the treated cells was evaluated by MTT assay. RESULTS: A significant reduction in expression of mdr1 mRNA and Pgp was found in four groups (AS1, AS3, AS5 and AS6), accompanying a dysfunction of Pgp. The lowest levels of mdr1 index and Pgp expression were observed in the AS6 group. MTT assay showed that a significant reduction of drug resistance was found in the four groups, especially in the AS6 group, which showed an 8.4-fold reduction in drug resistance for adriamycin and a 10.5-fold reduction in drug resistance for vinblastine. DISCUSSION: These data suggest that the MDR phenotype of breast carcinoma cells could be reversed by ASODN complementary to the transcription control site or translation initiation region. AS6, which is complementary to the translation initiation codon (ATG) of mdr1 cDNA, has the best reversal efficiency.

Suppression of glucosylceramide synthase by RNA interference reverses multidrug resistance in human breast cancer cells.

Glucosylceramide synthase (GCS), the enzyme that converts ceramide to glucosylceramide, induce multidrug resistance (MDR) in cancer cells. Recently, RNA interference (RNAi) is a powerful strategy for gene therapy by introducing double-stranded RNA and leading to the sequence-specific destruction. We have designed two different short hairpin RNAs (shRNAs) targeting GCS and introduced them into adriamycin- resistant human breast cancer cells (MCF-7/AdrR cells) to inhibit GCS expression. The results demonstrated that the shRNAs targeting GCS decreased GCS mRNA, abolished GCS protein levels and restored the sensitivity of MCF-7/AdrR cells to several antineoplastic drugs. This study revealed that this approach can reverse MDR effectively and it may be applicable to cancer patients as a specific means to restore the sensitivity to chemotherapy.

Modulation of BCRP mediated atypical multidrug resistance phenotype by RNA interference.

Multidrug resistance (MDR) in human cancers is one of the major causes of failure of chemotherapy. The emergence of breast cancer resistance protein (BCRP), a member of the ABC transporter family, has necessitated the development of antagonists. To overcome the BCRP-mediated atypical multidrug drug resistance, two small interfering RNA constructs (RNAi) targeting two different regions of BCRP mRNA were designed to inhibit the atypical MDR expression by transfecting them into MCF-7/MX100 cell lines. The multidrug resistance index to mitoxantrone and the intensity of mitoxantrone fluorescence of MCF-7/MX100 decreased after transfected by pSUPER-BCRP-A and pSUPER-BCRP-B respectively; the BCRP mRNA level and the BCRP protein level of MCF-7/MX100 decreased after treated with pSUPER-BCRPs. The two constructed RNAi plasmids could reverse the atypical mutidrug resistance mediated by BCRP, but neither can reversed it completely, this may be due to low transfection efficiency and transient transfection.