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.

Randomised clinical trial: an assessment of acupuncture on specific meridian or specific acupoint vs. sham acupuncture for treating functional dyspepsia.

BACKGROUND: Functional dyspepsia (FD) is a common disease without an established optimal treatment. AIM: To determine (i) the effect of acupuncture in relieving FD symptoms and improving life quality; (ii) the effect difference between acupoint and non-acupoint; and (iii) the effect difference among different acupoints. METHODS: A total of 712 eligible patients were included and randomly assigned to six groups (Group A: specific acupoints of the stomach meridian; Group B: non-specific acupoints of the stomach meridian; Group C: specific acupoints of alarm and transport points; Group D: specific acupoints of the gallbladder meridian; Group E: sham acupuncture of non-acupoints; and Group F: itopride). A treatment period of 4 weeks (continuous five sessions per week), and a follow-up period of 12 weeks were arranged. The outcomes were the (i) patients' response, (ii) symptoms improvement measured using the Symptom Index of Dyspepsia and (iii) quality-of-life improvement based on Nepean Dyspepsia Index. RESULTS: All groups had an improvement in dyspepsia symptoms and the QoL at the end of treatment, and the improvement was sustained for 4 weeks and 12 weeks. The overall response rate was significantly higher in acupuncture group A (70.69%), and lower in sham acupuncture group (34.75%), compared with itopride and other acupuncture groups. Similarly, the difference in symptoms and QoL improvement was significant between group A and the other acupuncture groups. CONCLUSIONS: Acupuncture is effective in the treatment of functional dyspepsia, and is superior to non-acupoint puncture. The benefit of acupuncture relies on acupoint specificity.

Establishment and characterization of a cell line (HCDB-1) derived from a hamster buccal pouch carcinoma induced by DMBA and Taiwanese betel quid extract.

This study identified that the carcinogenesis of hamster buccal pouch (HBP) induced by 7,12-dimethylbenz[a]anthracene (DMBA) was greatly enhanced (18 folds) by a combination treatment with Taiwanese betel quid (BQ) extract. A new cell line, HCDB-1, has been established from induced carcinomas. The cultured monolayer cells were epithelioid in shape with irregular nuclei. They demonstrated abundant cytokeratin and tonofilaments; however, ultrastructural well-organized desmosomes were lacking. The HCDB-1 cell exhibited population doubling in 19 h and was highly tumorigenic in nude mice. A C-->T transition at codon 141 (Ala to Val) of the p53 gene was detected in this cell. This mutation is equivalent to a specific temperature-sensitive mouse p53Ala135Val mutant that causes transformation by shifting to 37.5 degrees C. HCDB-1 is the first cell line established from the HBP model of oral carcinogenesis induced by DMBA/Taiwanese BQ extract. It might be valuable for exploring the molecular pathogenesis of oral cancer.

Protective role of selenium against hepatitis B virus and primary liver cancer in Qidong.

High rates of hepatitis B virus (HBV) infection and primary liver cancer (PLC) are present in Qidong county. Epidemiological surveys demonstrated an inverse association between selenium (Se) level and regional cancer incidence, as well as HBV infection. Four-year animal studies showed that dietary supplement of Se reduced the HBV infection by 77.2% and liver precancerous lesion by 75.8% of ducks, caused by exposure to natural environmental etiologic factors. An intervention trial was undertaken among the general population of 130,471. Individuals in five townships were involved for observation of the preventive effect of Se. The 8-yr follow-up data showed reduced PLC incidence by 35.1% in selenized table salt supplemented vs the nonsupplemented population. On withdrawal of Se from the treated group, PLC incidence rate began to increase. However, the inhibitory response to HBV was sustained during the 3-yr cessation of treatment. The clinical study among 226 Hepatitis B Surface Antigen (HBsAg)-positive persons provided either 200 micrograms of Se in the form of selenized yeast tablet or an identical placebo of yeast tablet daily for 4 yr showed that 7 of 113 subjects were diagnosed as having PLC in the placebo group, whereas no incidence of PLC was found in 113 subjects supplemented with Se. Again on cessation of treatment, PLC developed at a rate comparable to that in the control group, demonstrating that a continuous intake of Se is essential to sustain the chemopreventive effect.

Inhibitory effect of rikkunshi-to, a traditional Chinese herbal prescription, on tumor promotion in two-stage carcinogenesis in mouse skin.

We report the inhibitory effect of topical application of extracts of a traditional Chinese herbal prescription on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice. Methanol and water extracts obtained from 22 traditional Chinese herbal prescriptions were assayed and their inhibition ratios calculated. In general, the methanol extracts produced more effective inhibition than the water extracts. Of the various traditional Chinese herbal prescriptions, the methanol extract of Rikkunshi-to was more effective than other prescriptions as far as inhibition of TPA-induced inflammation was concerned. Hoelen, Glycyrrhizae Radix, Atractylodis Rhizoma, components of Rikkunshi-to markedly inhibited the inflammatory activity involved by TPA in mice. Furthermore, topical application of the methanol extract of Rikkunshi-to markedly inhibited TPA-induced tumor promotion in two-stage carcinogenesis in mouse skin.

A preliminary report on the intervention trials of primary liver cancer in high-risk populations with nutritional supplementation of selenium in China.

The purpose of this study was to evaluate the effect of selenium (Se) in the prevention of human primary liver cancer. Three intervention trials were conducted among the residents at high risk to primary liver cancer (PLC) in Qidong county, Jiang-su province, the People's Republic of China. This area has the second highest rate of PLC in China. One trial was undertaken among the general population in a township with supplement of table salt fortified with 15 ppm anhydrous sodium selenite (Se-salt) for 5 y and the other four townships with similar PLC incidence rate served as the controls using normal table salt. The second trial was undertaken among hepatitis B virus surface antigen carriers (HBVsAg+) receiving supplement of 200 micrograms Se in form of selenized yeast (Se-yeast) daily vs placebo for 4 y. The third trial was carried out in members of families with high PLC incidence using Se-yeast (200 micrograms of Se daily) vs placebo for 2 y. The results showed that nutritional supplement of Se could reduce the PLC incidence significantly.

Dialectic classification of syndrome diagnosis in traditional Chinese medicine used as new criterion for evaluating prognosis of patients with cervical cancer.

254 patients with cervical cancer were treated by radiotherapy from Jan 1979 to Dec 1984. All the patients were followed up at least for more than 3 years, of them 180 for over 5 years. According to various symptoms, picture of the tongue and pulse condition, the disease was classified into 4 types, namely: 1) deficiency of liver-yin and kidney-yin, 2) deficiency of splenic qi, 3) internal retention of damp-heat, and 4) stagnation of qi and blood or stagnation of liver qi. The survival rate of the various types was quite different. The patients of type 4 had the worst prognosis. The prognosis of patients with type 1 was significantly better than that of patients with type 4. The difference was of statistical significance (P less than 0.01).

Intervention trial with selenium for the prevention of lung cancer among tin miners in Yunnan, China. A pilot study.

This pilot study evaluated the feasibility and effectiveness of conducting a double-blind clinical trial for the prevention of lung cancer with selenium (Se) in Yunnan Tin Corporation, the People's Republic of China, where the incidence rates of lung cancer are extraordinarily high among the miners. Forty healthy miners were randomized to either 300 micrograms of Se in high Se malt cakes or an identical placebo of malt cakes daily for one year. Subjects consumed their usual daily diet. The low Se concentrations in plasma (0.05 +/- 0.008 microgram/mL) and hair (0.442 +/- 0.085 microgram/g) reflected their low dietary Se intake in the control subjects. In Se-supplemented group, the Se status was increased by 178% for serum and 194.8% for hair. The serum GSHpx activity was increased by 155.7%, whereas the lipid peroxide level was reduced by 74.5% compared to the placebo. The results of UDS assay indicated that the lymphocyte DNA damage induced by ultraviolet irradiation and carcinogen 3,4-benzpyrene could be protected by Se supplementation. Se-supplementation did not affect the liver function test (SGPT), as well as the concentrations of hemoglobin, albumin, and cholesterol. Thus, daily intake of 300 micrograms Se in form of Se-malt as a chemopreventive measure is safe and effective to humans with low Se status.

Chemoprevention trial of human hepatitis with selenium supplementation in China.

A three-year study has been conducted for prevention of infectious hepatitis with supplementation of table salt fortified with 15 ppm anhydrous sodium selenite to the general population of 20,847 persons in a township M.Z. at Qidong County, Jiangsu Province, China. The results showed that the incidence of virus hepatitis infection in the test township was significantly lower than that of controls provided with normal table salt. The incidence rate of infectious hepatitis in the treated township M.Z. was 1.20 and 4.52 per 1,000, whereas the average incidence in the 6 surrounding control townships was 2.96 and 10.48 per 1,000 in 1986 and 1987, respectively. The incidence of hepatitis B surface antigen (HBsAg+) was 13.2% vs 19.23% for males and 10.42% vs 12.24% for females in the supplemented vs nonsupplemented neighboring township, respectively. Epidemiological studies have demonstrated that a low grain Se content is associated with a high regional incidence of hepatitis B virus infections.

Selenium chemoprevention of liver cancer in animals and possible human applications.

An inverse correlation between geographic distribution of liver cancer incidence and the selenium (Se) contents of whole blood and grains was observed in Qidong county, Jiangsu province, a high liver cancer area of the People's Republic of China. Animal experiments demonstrated that supplementation of Se reduced the incidence of liver cancer in rats exposed to aflatoxin B1. Se was also shown to inhibit the growth of transplanted tumors. A lower incidence of liver preneoplastic alterations and reduction of hepatitis B virus infection in ducks by Se-supplementation was observed, and three pilot studies for a Se-intervention trial on human liver cancer were carried out on the residents of Qidong county. A protective effect on the cellular DNA damage induced by aflatoxin B1 was observed in lympocytes from human with Se-supplements.

Biochemical and cellular aspects of the anticancer activity of selenium.

Aberrant differentiation is a frequent hallmark of tumors, suggesting that modulators for differentiation and proliferation play a role in multistage carcinogenesis and that their use can also be exploited in cancer chemoprevention and therapy. We have demonstrated that selenium (Se) may be a modulator for the differentiation and proliferation of tumor cells. Evidence has been obtained that Se exerts the following effects: reversing changes of biochemical phenotypes toward normal levels, including reduction of cGMP level and cAMP-dependent protein kinase isozyme type I; increase in cAMP level and cAMP-dependent protein kinase isozyme type II, and altering membrane properties. Furthermore, we have obtained support for this hypothesis utilizing experiments on cultured human liver cell lines. It is demonstrated that Se can lead to the following changes: a. reduction of mitotic index; b. increase in the adhesiveness of cells; c. decrease in confluent saturation density and induction of an early contact inhibition; and d. decrease in tumorigenicity. For the purpose of comparison, the effects of Se on the normal counterparts was also studied. Contrary to what was observed above, there was no significant change in both biochemical and cellular aspects of normal cells treated analogously.

[Different effects of selenium on proliferation of human lung adenocarcinoma cells and human embryonic lung diploid cells in vitro].

After treating human lung adenocarcinoma cells by Na2SeO3 (1 microgram/ml) for 24 hours, its mitotic index decreased by 50%. The reduction rate was directly proportional to selenite concentration (1-5 micrograms/ml). In the meantime, the labelling index, growth rate and progression of the cell cycle were also inhibited. In contrast to the above observation, there was no marked change in the cell count, mitotic index, labelling index and the average silver granule number in the human embryonic lung diploid cells treated by Na2SeO3 (1-5 micrograms/ml) for 1-3 days. When human embryonic lung diploid cells were mix-cultured with human lung adenocarcinoma cells in the presence of 5 micrograms/ml Na2SeO3 for 24 hours, the former maintained a normal morphology, while the lung cancer cells showed heavily vacuolated cytoplasms and distorted nuclei.

[Mechanism of the anticancer action of selenium--influence on glycolysis and its key enzyme].

The aerobic glycolysis rate and mitochondria-bound hexokinase activity of ascitic liver cancer cells are 8 and 50 times as high as those of the normal liver cells, and they can be inhibited by Na2SeO3 in concentration below 10 micrograms/ml. The inhibitory effect increases with selenium concentration. In contrast, Na2SeO3 at the same concentration does not significantly affect the glycolysis rate and mitochondria-bound hexokinase activity of the normal liver cells. The selective action of selenium on energy metabolism of the liver cancer cells may account for its inhibitory effect on cancer cells.

[Level of cyclic AMP-dependent protein kinase isozyme in normal liver and hepatoma tissue and the effect of sodium selenite].

Sodium selenite in normal saline was administered intraperitoneally (1 mg/kg) into mice bearing ascitic hepatocarcinoma for 4 days. The cyclic AMP-dependent protein kinase isozymes (type I and type II) in normal liver and hepatocarcinoma cells were separated and assayed. The results show that the level of type I/II is markedly higher in hepatocarcinoma than in the normal liver cells. Sodium selenite is able to reduce it towards the normal level. Further analysis shows that the chief function of sodium selenite is to reduce the raised level of type I/II in hepatocarcinoma cells which, in fact, is due to the increase of total amount of type I cyclic AMP-dependent protein kinase. This paper presents the speculation that one of the mechanisms of the inhibitory effect of sodium selenite on carcinogenesis may be due to the selective action of this compound on the cyclic AMP-dependent protein kinase isozymes in tumor cells, thus inhibiting cancer cell division and facilitating differentiation and reversion.

[Regional distribution of liver cancer and its relation to selenium levels in Qidong County, China].

The selenium (Se) level in barley and maize from 43 communes of Qidong county, a high risk area of liver cancer in China, were assayed. An inverse correlation between the Se level and the liver cancer incidence was observed. An inverse correlation was also observed between the blood Se level and liver cancer incidence of the local residents. When selenite solution was sprayed on the crops during their preflowering, the content of Se in barley and maize was increased by 6 fold over the control. It is suggested that the increase of blood Se level of the residents who live in the low-Se areas by this method be useful in the prevention of liver cancer.

Regional variation of cancer mortality incidence and its relation to selenium levels in China.

The epidemiological relationship between selenium level and age-adjusted human cancer mortality (incidence) was studied in 24 regions located in eight provinces of China. Statistically significant inverse correlation was found between age-adjusted total cancer death rates and selenium levels in whole blood from local residents. In the areas with high selenium levels, there was significantly lower mortality in both males and females from cancer of the stomach and esophagus. In addition, an inverse correlation between regional distribution of liver cancer incidence and selenium contents in blood and grains in Qidong county, an area with high risk of hepatoma, was observed. With the intention of providing selenium supplements to residents living in low selenium regions, the selenium content in grains was raised by means of foliar spraying of crops with Na2SeO3 solution.

Peplomycin sulfate and pulmonary fibrosis: hydroxyproline, uronic acid, proline hydroxylase and glucosamine 6-phosphate synthetase in lungs of hamsters treated with peplomycin.

Effect of peplomycin sulfate (PLM) on pulmonary fibrosis was examined. Hydroxyproline, uronic acid, proline hydroxylase (EC 1.14.11.2) and glucosamine 6-phosphate synthetase (EC 2.6.1.16) in lungs of hamsters treated with PLM were studied and compared with those of hamsters treated with bleomycin (BLM). PLM, when administered intraperitoneally, one injection daily for 10 consecutive days, at either a high- (5 mg/kg) or low- (2.8 mg/kg) dosage-level, caused no significant increase of lung hydroxyproline and uronic acid as compared with controls. BLM on the other hand effected a significant increase in lung hydroxyproline on the high-dosage level (5 mg/kg) but not on the low-dosage level (2.8 mg/kg). In contrast, when administering PLM intratracheally, the concentrations of hydroxyproline in lungs increased 20% over the control levels. A transient increase of proline hydroxylase and glucosamine 6-phosphate synthetase also occurred shortly after the instillation. These increases were also observed in the corresponding groups treated with BLM, which confirmed the previous observations by other investigators. However, the magnitude of the increase was relatively lower in those values of PLM as compared with those of BLM. These data suggested that (1) PLM, when administered with multiple dosages intraperitoneally, showed no significant effect on the elevation of lung hydroxyproline; (2) PLM, when administered with a dose intratracheally, induced pulmonary fibrosis similar to that caused by BLM. However, the hydroxyproline accumulation in lungs of PLM-treated hamsters was less than in those of the BLM-treated; (3) The fibrotic effect on the lungs caused by either PLM or BLM was probably attributed to acceleration of the syntheses of collagen and acidic glycosaminoglycans.