Enhanced efficacy with reduced toxicity of chemotherapy drug 5-fluorouracil by synergistic treatment with Abnormal Savda Munziq from Uyghur medicine.

BACKGROUND: Abnormal Savda Munziq (ASMq) is a traditional prescription in Uyghur Medicine, and its treatment of complex diseases such as tumors and asthma has been proven to be effective in Uyghur medical clinical practice. The efficacy-enhancing and toxicity-reducing properties of ASMq were studied on mice with transplanted cervical cancer (U27) tumors, which were treated with 5-fluorouracil (5-FU) in this work. METHODS: To investigate the synergistic effect of ASMq and 5-FU on U27 cells, inhibitory effects on cell proliferation were determined through a MTT assay. 48 Kunming mice which were randomly divided in to 6 groups: control group, model group, 5-FU group, 5-FU combine with ASMq low-dose group, 5-FU combine with ASMq medium-dose group, and 5-FU combine with ASMq high- dose group, the inhibition rate of the tumor, the viscera indexes, and the content of serum tumor necrosis factor-α (TNF-α), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined. The expression levels of transforming growth factor-ß1 (TGF-ß1) and human papillomavirus type 16 E2 (HPV16 E2) protein were assessed by Western blot. Pathological changes in the liver were observed. RESULT: The inhibition rates of tumors, the 5-FU + ASMq.H group(80.64%), 5-FU + ASMq.M group (90.67%), 5-FU + ASMq.L group (72.03%) and 5-FU group (66.89%), clearly indicated that the effects of tumor inhibition. The thymus index and spleen index were increased, and the serum concentration of TNF-α increased while ALT and AST concentrations were decreased, and TNF-α protein expression were increased while TGF-ß1 and HPV16 E2 were decreased. ASMq might can improve livers central vein hyperemia and interstitial edema, and preserve the radial structure of the hepatic cords. CONCLUSIONS: The results suggested that ASMq might reduce toxicity and enhance the efficacy of the chemotherapeutic drug 5-fluorouracil in the treatment of cervical carcinoma.

The disrupting effect of chlormequat chloride on growth hormone is associated with pregnancy.

Since chlormequat chloride is widely applied as a plant growth regulator in agriculture and horticulture, its exposure through food consumption is common. We demonstrated previously that chlormequat chloride exposure during pregnancy led to embryos with bigger sizes associated with higher levels of growth hormone (GH) on gestation day 11 (GD11). However, the dose-effect relationship of chlormequat chloride at a lower dose range was not established, and the underlying mechanisms of its promoting effects on embryonic growth and development were not fully elucidated. To address these, pregnant rats were orally exposed to chlormequat chloride at 0, 0.05, 0.5 and 5 mg/kg.bw from GD0 to 11 and the embryonic growth and growth related hormones were evaluated on GD11. We found that the growth and development of the embryos was significantly promoted in a dose dependent manner by chlormequat chloride. Chlormequat chloride also increased embryonic GH, GH releasing hormone (GHRH), and somatostatin (SRIF), and inhibited the embryonic cAMP dependent protein kinase A (PKA) signaling pathway. Chlormequat chloride increased GH synthesis modulated by GHRH/SRIF-PKA-Pituitary specific transcription factor 1 (Pit-1) in the maternal rats. Intriguingly, chlormequat chloride did not show any effects on GH and PKA signaling pathways in the non-pregnant female rats. These findings together suggest that the disrupting effect of chlormequat chloride on GH is associated with pregnancy.

Association between Antibiotic Exposure and Type 2 Diabetes Mellitus in Middle-Aged and Older Adults.

BACKGROUND: Although previous studies have shown an association between clinically used antibiotics and type 2 diabetes, the relationship between antibiotic exposure from food and drinking water and type 2 diabetes in middle-aged and older adults is unclear. OBJECTIVE: This study was aimed at exploring the relationship between antibiotic exposures from different sources and type 2 diabetes in middle-aged and older people, through urinary antibiotic biomonitoring. METHODS: A total of 525 adults who were 45-75 years of age were recruited from Xinjiang in 2019. The total urinary concentrations of 18 antibiotics in five classes (tetracyclines, fluoroquinolones, macrolides, sulfonamides and chloramphenicol) commonly used in daily life were measured via isotope dilution ultraperformance liquid chromatography coupled with high-resolution quadrupole time-of-flight mass spectrometry. The antibiotics included four human antibiotics, four veterinary antibiotics and ten preferred veterinary antibiotics. The hazard quotient (HQ) of each antibiotic and the hazard index (HI) based on the mode of antibiotic use and effect endpoint classification were also calculated. Type 2 diabetes was defined on the basis of international levels. RESULTS: The overall detection rate of the 18 antibiotics in middle-aged and older adults was 51.0%. The concentration, daily exposure dose, HQ, and HI were relatively high in participants with type 2 diabetes. After model adjustment for covariates, participants with HI > 1 for microbial effects (OR = 3.442, 95%CI: 1.423-8.327), HI > 1 for preferred veterinary antibiotic use (OR = 3.348, 95%CI: 1.386-8.083), HQ > 1 for norfloxacin (OR = 10.511, 96%CI: 1.571-70.344) and HQ > 1 for ciprofloxacin (OR = 6.565, 95%CI: 1.676-25.715) had a higher risk of developing type 2 diabetes mellitus. CONCLUSIONS: Certain antibiotic exposures, mainly those from sources associated with food and drinking water, generate health risks and are associated with type 2 diabetes in middle-aged and older adults. Because of this study's cross-sectional design, additional prospective studies and experimental studies are needed to validate these findings.

Hepatoprotective Effects of Total Triterpenoids and Total Flavonoids from Vitis vinifera L against Immunological Liver Injury in Mice.

Suosuo grape (the fruits of Vitis vinifera L) has been used for prevention and treatment of liver diseases in Uighur folk medicine in China besides its edible value. In this study, the hepatoprotective effects of total triterpenoids (VTT) and total flavonoids (VTF) from Suosuo grape were evaluated in Bacille-Calmette-Guerin- (BCG-) plus-lipopolysaccharide- (LPS-) induced immunological liver injury (ILI) in mice. Various dose groups (50, 150, and 300 mg/kg) of VTT and VTF alleviated the degree of liver injury of ILI mice, effectively reduced the BCG/LPS-induced elevated liver index and spleen index, hepatic nitric oxide (NO), and malondialdehyde (MDA) content, increased liver homogenate alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and restored hepatic superoxide dismutase (SOD) activity in ILI mice. VTT and VTF also significantly inhibited intrahepatic expression of Th1 cytokines (IFN-γ and IL-2) in ILI mice and increased intrahepatic expression of Th2 cytokines (IL-4 and IL-10). Moreover, the increased Bax/Bcl-2 ratio was significantly downregulated by VTT and VTF in liver tissue of ILI mice. These results are comparable to those of biphenyl dicarboxylate (DDB, the reference hepatoprotective agent) and suggest that VTT and VTF play a protective role against immunological liver injury, which may have important implications for our understanding of the immunoregulatory mechanisms of this plant.

Effect of PhenylEthanol Glycosides from Cistanche Tubulosa on Autophagy and Apoptosis in H22 Tumor-Bearing Mice.

An effectual remedy for hepatocellular carcinoma (HCC) and knowledge of the mechanism are urgently needed. Researchers have found that CPhGs, an extract from Cistanche tubulosa (Schenk) Wight, had better antitumor effects, but its mechanism is still unknown. In the present study, using an H22 tumor-bearing mouse as a model, we investigated the antitumor effects of CPhGs and the effect of CPhGs on autophagy and apoptosis. Besides, we also discussed the role of autophagy with the help of HCQ and rapamycin. Our results show that CPhGs inhibit tumor growth and induce apoptosis and autophagy of tumor tissue. TUNEL staining displayed that tumor apoptosis rate increased after the intervention of CPhGs, and immunohistochemistry and western blot showed that cleaved-PARP and cleaved-caspase 3 were upregulated after the intervention of CPhGs, and these results were most pronounced in the high-dose group. Autophagy results revealed that CPhGs increased the number of autophagosomes, increased the level of LC3B-II, and decreased the level of p62. Finally, our results showed that excessive autophagy suppresses tumor growth, whereas inhibition of autophagy does the opposite, which indicated that CPhGs induced autophagic death in H22 hepatoma-bearing mice. These data altogether confirmed the involvement of apoptosis and autophagy in CPhGs treatment for HCC.

Preventive effect of total flavonoids of Trollius altaicus on a chronic obstructive pulmonary disease rat model based on the TLR4/NF-κB pathway.

Background: Chronic obstructive pulmonary disease (COPD) is diagnosed based on the clinical symptoms, risk factors, and pulmonary function tests. Exposure to cigarette smoke (CS), microbial infection stimulates monocytes and macrophages to rapidly synthesise and release inflammatory factors. A previous study of Trollius altaicus (TAF) revealed that it had significant anti-inflammatory and anti-oxidation effects on a pneumonia disease. Based on recent studies of the inflammatory pathway of toll-like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB), we will explore the influence of TAF on COPD. Methods: Wistar rats were randomly divided into blank control group, Model Group, low-dose TAF + model group, middle-dose TAF + model group, high-dose TAF + model group, positive control + model group. Except for the blank control group, COPD inflammation models were established in all groups by CS poisoning and LPS. Prior to the daily poisoning, 125 mg/kg, 250 mg/kg, and 500 mg/kg of TAF were administered by gavage in the low-, middle-, and high-dose groups, respectively, and dexamethasone solution (1 mg/kg, once daily) was administered continuously in the positive control group on the last 5 days of modelling. General signs, lung function indices, lung imaging results, complete blood count, lung histopathological changes, inflammatory factors in the alveolar lavage fluid, relative expressions of TLR4, IκB kinase α (IKKα), p65, as well as IL-1ß proteins and their mRNA relative expressions were measured and compared between each group. Results: Compared with the blank control group, TAF effectively reduced pulmonary parenchymal oedema (wet-to-dry ratio) and respiratory secretions. It also significantly delayed lung function injury. Lung X-ray imaging and haematoxylin and eosin staining. Blood routine examination results showed that TAF effectively inhibited the increase of white blood cell, lymphocyte, and eosinophil counts, decreased the release of inflammatory cytokines [IL-1ß, IL-6, IL-8, TNF-α, and transforming growth factor-1ß (TGF-1ß)] and promoted the release of IL-10. It also inhibited the relative expressions of TLR4, IKKα, p65, IL-1ß proteins, as well as IL-1 receptor-associated kinase (IRAK-1), IKKɑ, p65, and IL-1ß mRNA. Conclusions: Early intervention of TAF can reduce the occurrence of COPD, reduce the development of inflammation via TLR/NF-κB pathway, and provide reference for further study of the medicinal value of TAF.

Urinary Antibiotics and Dietary Determinants in Adults in Xinjiang, West China.

The Xinjiang autonomous region, located in west China, has a unique ethnic structure and a well-developed livestock industry. People in this region have a high risk of exposure to antibiotics, but the exposure level to antibiotics in relation to dietary determinants is unknown. In this study, 18 antibiotics, including four human antibiotics (HAs), four veterinary antibiotics (VAs), and 10 preferred veterinary antibiotics (PVAs) were detected in the urine of approximately half of the 873 adults in Xinjiang, including Han Chinese (24.6%), Hui (25.1%), Uighur (24.6%), and Kazakh (25.7%). Logistic regression was used to analyze the association between antibiotic exposure levels and adult diet and water intake. The detection percentage of antibiotics in the urine of adults in Xinjiang ranged from 0.1% to 30.1%, with a total detection percentage of all antibiotics of 49.8%. HAs, VAs and PVAs were detected in 12.3%, 10.3%, and 40.5%, respectively. Fluoroquinolones were the antibiotics with the highest detection percentage (30.1%) and tetracyclines were the antibiotics with the highest detected concentration (17 ng/mL). Adults who regularly ate pork, consumed fruit daily, and did not prefer a plant-based diet were associated with thiamphenicol, norfloxacin, and fluoroquinolones, respectively. These results indicated that adults in the Xinjiang autonomous region were extensively exposed to multiple antibiotics, and some types of food were potential sources of exposure. Special attention should be paid to the health effects of antibiotic exposure in humans in the future.

[Effect of neonatal exposure to environmental pollutants on the DNA methylation of rat testis].

OBJECTIVE: To investigate the effects of neonatal exposure of DNA methylation inhibitor, Cadmium and PCB153 on DNA methylation, apoptosis and spermatogenesis in SD rats. METHODS: Neonatal SD rats were randomly divided into 10 groups and received oral administrations of PCB153 (0.025, 0. 250, 2.500 mg/kg), or Cadmium (1, 2, 4 mg/kg), or positive control 5-Aza-CdR (0.025, 0.250 mg/kg), or vehicle control for five days from PND3. Half of the rats were killed 24 h after the last administration. The remains were fed until 12 weeks. Sperm numbers, apoptosis and DNA methylation levels in testis were investigated. RESULTS: The daily sperm production was significantly decreased in each neonatal exposed group (P < 0.05). Neonatal rats exposed to 5-Aza-CdR and Cadmium reduced the global DNA methylation level, increased apoptosis, while PCB153 exposure did not significantly change DNA methylation and apoptosis. CONCLUSION: Neonatal rats exposed to chemicals could reduce spermatogenesis via multiple pathways. Lower DNA methylation and increased neonatal apoptosis were suggested as one of the causes.