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.

[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.

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.

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.

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.

[Extramedullary plasmacytoma of the head and neck: a clinicopathologic, immunohistochemistry study].

OBJECTIVE: To investigate the relation between histopathological feature, clinical behavior characters, immunoglobulin (Ig) secretory function and prognosis of the extramedullary plasmacytoma (EMP) of the head and neck. METHOD: 12 cases of EMP in the head and neck region were studied retrospectively. The clinicopathological records from January, 1977 to December, 1996 were reviewed. Immunohistochemical (IHC) stains for detecting intracytoplasmic immunoglobulin kappa (IgG kappa) and lambda (IgG lambda) were carried out. RESULT: 10 cases of the patients were male and 2 female; Their ages ranged from 32 to 67 years with an average of 57 years. The tumors were located in the nasosinus (6), nasopharynx (2), Larynx (3) and ear (1). Low-(I), intermediate (II) and high-grade (III) tumors were 3, 3 and 6 cases respectively. Two patients with EMP of nasopharynx were treated with radiotherapy, in others radiotherapy was administered after complete surgical resection. Follow-up time ranged from 10 to 76 months. IHC showed monoclonality of the plasma cell and was positive for IgG lambda (6 cases) and IgG kappa (6 cases, conferming the identical clonal origin of the plasma cells. The 5-year survival for grade I, II and III were 75.0%, 62.0% and 37.6%, 37.5% and 68.50% for IgG lambda positive and IgG kappa positive cases, respectively. There are statistically significance between them (P < 0.01). CONCLUSION: EMP in head and neck region are rare plasma cell tumors. IHC play an important role in differential diagnosis. The combination of surgery and radiotherapy proved to be an adequate and effective treatment. The grading and IgG secretory function may be valuable for predicting the prognosis of EMP.

[Preliminary clinical study on krypton laser photodynamic therapy for PWS].

OBJECTIVES: In order to explore an ideal PWS treatment, which could destroy the capillary of lesion without any damage to skin. Based on principle of improving elective therapeutic efficacy of photodynamic therapy, new Krypton laser PDT was introduced to this preliminary clinical trial. MATERIALS AND METHODS: The absorptive spectrum was measured on photosensitizer PsD-007. The therapeutic laser dosage and result and side effect were surveyed. Twenty cases of PWS were randomly selected by means of self-control. 413 nm wavelength laser PDT was carried on those patients. Lesion responses were investigated at different phases after treatment. More attention was paid to the result and side effect. Biopsy was taken from one case. RESULTS: PsD-007 has the soret peak at 408 nm. There was purplish reaction within a week, which disappeared spontaneously within two months. Lesion blanch with neither weeping soakage nor scar formation. All cases got dramatically blanch of lesions. Histological finding revealed red blood cells leaking through broken vessels, while dermal remained normal. CONCLUSION: 413 nm Krypton laser PDT had target elective effect, which had satisfactory result. It suggested good potential plication.

[Application of Continuous Wave Nd:YAG Laser Irradiation in the Management of Cavernous Hemangioma of Deep Oral-Maxillofacial Regions]

OBJECTIVE:Based on our previous clinical report of Nd:YAG laser irradiation as the means for deeling with cavernous hemangioma in deep oral-maxillofacial regions, this article detailed futher clinical application of this laser, trying to set up a non-surgical method for treatment of ang ioma. The relationship of laser dosage and therapeutic effect and possible surrounding tissue thermal damages were investigated.METHODS:Clinical study was carried out on 31 cases of deep hemangiomas involving different areas. Nd:YAG laser irradiation was delivered after surgical elevation of the flaps. All cases surveyed a follow up of 1.5 to 3 years.RESULTS:Posttherapeutic clinical and imaging examinations were taken to compare the findings before and after treatment. There are 29 cases with complete regression (93.55%), 2 cases with partial regression (6.45%). No complication occurred.CONCLUSION:Nd:YAG laser irradiation after flap elevation has been confirmed to be a valuable means to treat deep hemangiomas. It has the advantages of target tissue selection and normal tissue preservation, simplified manipulation and less bleeding, fewer complications and hihger successful rate.

[Evaluation of cryosurgery for the management of oral malignant mucomembranous melanoma-A survey of 107 cases reports]

OBJECTIVE:There were 13 cases underwent operation.24 cases underwent cryosurgery only and 70 cases received comprehensive management,which as cryosurgery,operation,chemotherapy and immuno-therapy.RESULTS:The 3'and 5' year survival rate of three groups were 0.0%,0.0%,37.50%,31.25% and 57.14%,36.07%.There are significant differences between operation group and cryosurgery group and between operation group and comprehensive treatment group.Although the third group got the better result,but the difference between late two groups was not statistical significant.CONCLUSION:It is suggested that comprehensive treatment be the routine regime of melanoma in head and neck. Our experience with review of literature covered the classification, surgical principle and complication was presented.

[Surgical approach plus Nd:YAG laser irradiation for the management of hemangioma in deep maxillofacial region]

This article introduces a new method for the management of cavernous hemangioma in deep maxillofacial region.Common surgical approach was carried out to expose the mass of hemangioma,then Nd:YAG laser was irradiated it without tumor removal.Immediatelly shrinking of hemangioma can be seen in all these seven cases.The therapeutic effect was satisfied in 3-12 months follow up.With the basic research of the rabbit facial nerve's Nd:YAG laser injured detecting experiment.We discussed its indication,advantage and interaction between laser and peripheral tissue.Our result shown that this new way is a good method for hemangioma in deep maxillofacial region as its advantages of skin preventing and peripheral normal tissue preserving

[A case-control study on relationship between hepatitis C infection and primary liver cancer].

All the cases and controls emerged from a cohort study held in the past years. They were male, more than 20 years of age at the time of their enrollment into the cohort study, with serum specimens taken and kept at -20 degrees C. Every death of primary liver cancer (PLC), occurred since then, as a 'case' (78 in total), was compared with no more than 4 matched controls chosen from cohort members who were still alive until the last follow-up. ELISA technique was used to test anti-HCV antibodies in the stored serum specimens of the cases and controls. The Results showed that anti-HCV prevalence rates were 33.3% (26/78) of the cases and 15.3% (40/262) of their matched controls, respectively (chi 2 = 11.86, P < 0.01, ORMH = 3.0, PAR% = 23.40%). The results suggest that HCV infection is another important factor in the aetiology of PLC in Guangxi, China. Because the serum specimens tested were drawn years before the occurrence of PLC deaths, our conclusion need not worry about the sequential problem, which occurs in most of other kinds of case-control studies.