ABSTRACT
Digestate is the anaerobic digestion by-product of biogas production that can be used as a phosphorus (P) fertilizer. To achieve the efficient utilization of digestate as a P fertilizer and evaluate P availability in digestate-amended soils, it is necessary to assess both available P in different digestates and digestate-amended soils. In this study, Fourier transform mid-infrared photoacoustic spectroscopy (FTIR-PAS) combined with multivariate analysis was applied to predict water-extractable P (WEP) in digestates and plant-available P in digestate-amended soils. The plant-available P was determined by the diffusive gradients in thin films (DGT) technique. 45 digestate samples were collected both from laboratory-scale digesters (26 samples) and operating biogas plants (19 samples) in Denmark for WEP determination. Three soils amended with the collected 19 digestate samples from biogas plants (that results to 57 digestate-amended soil samples in total) were deployed for DGT measurement of plant- available P. The WEP predicting model had a coefficient of determination (R2) of 0.80 and a root mean square error of 0.78 g kg-1 while the plant-available P predicting model exhibited an R2 of 0.70 and a root mean square error of 134.09 µg P L-1. Furthermore, regression coefficients with a significant contribution of the plant-available P predicting model were identified, indicating that FTIR-PAS is capable for correlating spectra information with plant-available P related chemical bonds. In conclusion, FTIR-PAS can be used as a faster and non-destructive alternative for the assessment of both WEP in digestates and plant-available P in digestate-amended soils.
Subject(s)
Fertilizers , Soil , Biofuels/analysis , Fertilizers/analysis , Fourier Analysis , Phosphorus/chemistry , Plants , Soil/chemistry , Spectrophotometry, InfraredABSTRACT
Bacillus subtilis is one of the most popular commercial probiotics used in farm animal production. However, its potential mechanisms are not very clear. The aim of this study was to investigate the effects of dietary Bacillus subtilis on intestinal histomorphology, innate immunity, microbiota composition, transcriptomics, and related metabolomics. Twenty-four 48-week-old Lohman Pink-shell laying hens were randomly divided into two groups: a basic diet and the basic diet supplemented with Bacillus subtilis (0.5 g/kg) for a 9-week experiment. At the end of the experiment, tissues of the duodenum, ileum, and jejunum as well as cecal content of each bird were collected for microstructure, PCR, transcriptome, metabolome, and 16S rRNA analyses. The results showed that dietary Bacillus subtilis supplement had no effect on the intestinal microstructure. However, Bacillus subtilis increased mRNA expression of tight junction protein occludin (P < 0.05), while reduced mRNA expression of lipopolysaccharide-induced TNF factor (P < 0.01) in the duodenum. Moreover, transcriptomic results indicated that most of Bacillus subtilis supplement-induced differential genes were associated with inflammation and immunity, including cytochrome b-245 beta chain, transferrin, and purinergic receptor P2X 7, resulting in a decrease in Malondialdehyde level (P < 0.05) in the duodenum. In addition, at the genus level, Bacillus subtilis supplement enriched the potential beneficial bacteria, Candidatus_Soleaferrea (P = 0.02) but inhibited the harmful bacteria including Lachnospiraceae_FCS020_group, Ruminiclostridium, Lachnospiraceae_UCG-010, and Oxalobacter. Metabolomic results revealed that N-Acetylneuraminic acid and ADP were increased by fed Bacillus subtilis. These results suggest that dietary Bacillus subtilis could inhibit gut inflammation and improve antioxidative status and barrier integrity of the duodenum via regulating gut microbial composition in laying hens.
Subject(s)
Gastrointestinal Microbiome , Probiotics , Animal Feed/analysis , Animal Nutritional Physiological Phenomena , Animals , Bacillus subtilis/metabolism , Chickens/physiology , Diet/veterinary , Dietary Supplements/analysis , Female , Inflammation/veterinary , Oxidative Stress , Probiotics/pharmacology , RNA, Ribosomal, 16S/metabolismABSTRACT
OBJECTIVE: Lung cancer is one of the leading causes of morbidity and mortality in the world. In the past decade, numerous studies focus on the prognostic nutritional index (i.e., a measure of serum albumin and lymphocyte in peripheral circulation) as a possible biomarker to predict the survival outcomes in cancer patients undergoing chemotherapy. Prognostic nutritional index can reliably predict the survivability outcomes by effectively quantifying the nutritional and immunological status of cancer patients. To date, only one review has attempted to evaluate the impact of the prognostic nutritional index on the survival outcomes in lung cancer patients with certain limitations. The goal of the present systematic review and meta-analysis is to bridge the gap in the literature and evaluate the capacity of the prognostic nutritional index for predicting the survivability outcomes in lung cancer patients undergoing chemotherapy. The aim of the study is to evaluate the impact of prognostic nutritional index scoring on survival outcomes in lung cancer patients undergoing chemotherapy. MATERIALS AND METHODS: A systematic academic literature search was performed based on the PRISMA guidelines across Web of Science, EMBASE, CENTRAL, Scopus, and MEDLINE databases. A random-effect meta-analysis was performed to evaluate the impact of prognostic nutritional index scoring (i.e., high/low) on survival outcomes (i.e., progression-free survival, overall survival) in lung cancer patients undergoing chemotherapy. RESULTS: From 963 studies, 16 eligible studies with 4250 lung cancer patients (62.32 ± 5.08 years) undergoing chemotherapy were included. Our meta-analysis revealed worse mortality outcomes in terms of progression-free survival (HR: 1.31) and overall survival (1.21) for the group with a low prognostic nutritional index score as compared to the group with a high prognostic nutritional index score in lung cancer patients undergoing chemotherapy. Subsequent subgroup analyses further demonstrated markedly worse outcomes for progression-free survival (1.32) and overall survival (1.52) in non-small lung cancer patients with lower prognostic nutritional index scores. CONCLUSIONS: We provide preliminary evidence suggesting that lower prognostic nutrition index scores are associated with worse survivability outcomes (progression-free survival and overall survival) in lung cancer patients undergoing chemotherapy. We also show that lower prognostic nutrition index scores correlate with even worse survival outcomes in patients with non-small lung cancer histological subtype of lung cancer. These findings should help clinicians to stratify the risks associated with the chemotherapeutic management of lung cancer patients.
Subject(s)
Antineoplastic Agents/therapeutic use , Lung Neoplasms/drug therapy , Lung Neoplasms/physiopathology , Nutrition Assessment , Nutritional Status , Aged , Female , Forecasting , Humans , Lung Neoplasms/immunology , Lung Neoplasms/mortality , Male , Middle Aged , Prognosis , Survival RateABSTRACT
Objective: To investigate the clinical efficacy and safety of compound wild chrysanthemum eye masks for mild and moderate dry eye. Methods: In this double-masked, multicenter, placebo-controlled, randomized trial, middle-aged and elderly patients with mild and moderate dry eye were enrolled from six hospitals (Xiamen Eye Center of Xiamen University, China-Japan Friendship Hospital, Peking Union Medical College Hospital, Wangjing Hospital of China Academy of Chinese Medical Sciences, Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine and Hebei Eye Hospital). The patients were assigned to the compound wild chrysanthemum eye mask group and the eye mask simulator group based on the random number table. Subjective symptoms of dry eye, visual acuity, break-up time (BUT), Schirmer â test, and corneal fluorescent staining were evaluated in all patients before treatment and at 1 and 2 weeks after treatment. All adverse reactions during the treatment and follow-up were recorded. Results: A total of 120 patients were enrolled. Among them, 112 subjects were included for statistical analyses after the exclusion of 8 subjects who were lost for follow-up or had an adverse event, with an age of (54.26±7.44) years. All the indicators were equally comparable between the two groups. Before treatment and at 1 and 2 weeks after treatment, the median (lower quartile, upper quartile) of total score of questionnaires in the eye mask group was 14.50 (10.00, 19.00), 9.00 (5.00, 14.00) and 7.00 (4.00, 10.00), respectively, and that in the control group was 14.00 (9.00, 22.50), 12.00 (6.00, 20.00) and 10.00 (3.50, 17.00), respectively. The score decreased significantly in both groups after 1 week (t=9.1604, S=398.00; P<0.01) and 2 weeks (S=681.00, 575.50; P<0.05) of treatment. The total score of questionnaires in the eye mask group was significantly lower than that in the control group (Z=3.27, 2.81; P<0.05) after treatment. After 1 week of treatment, the average BUT of the eye mask group was (5.71±2.31) s, which was significantly longer than that before treatment (5.06±2.00) s (S =208.50, P<0.05). But there was no significant difference in the control group (S=150.00, P>0.05). After 2 weeks of treatment, there was statistically significant difference in BUT between the two groups (S=407.00, t=3.07; P<0.01). After 1 week of the treatment, the amount of tear secretion in the eye mask group [(6.88±4.78) mm] was significantly larger than that before treatment (S=196.50, P<0.05), while the control group [(6.80±5.85) mm] showed no significant difference (S=55.00, P<0.05). After 2 weeks of the treatment, the amount increased significantly to (7.43±4.86) mm and (7.29±4.56) mm, respectively, in both groups (t=-3.29, -2.26; P<0.05). The difference in the average BUT, Schirmer â test result and corneal fluorescent staining between both groups was not statistically significant at each time point. Five mild adverse events occurred, including 2 adverse events (2 times, 3.51%) in the eye mask group and 3 adverse events (4 times, 5.36%) in the control group. Conclusions: Compound wild chrysanthemum eye masks can effectively improve the symptoms and physical signs of mild and moderate dry eye and can be used as an auxiliary treatment. (Chin J Ophthalmol, 2021, 57: 601-607).
Subject(s)
Chrysanthemum , Dry Eye Syndromes , Aged , China , Cornea , Double-Blind Method , Dry Eye Syndromes/drug therapy , Humans , Middle Aged , Ophthalmic Solutions , Tears , Treatment OutcomeABSTRACT
As a prescription for promoting blood circulation and removing blood stasis, Taohong Siwu Decoction(THSWD) has certain effects in delaying the progression of renal fibrosis. However, as a traditional Chinese medicine compound containing many monomer components, it has been a research hotspot in the field of exploring the research methods and targets for the complex pathological process. The method of activating blood circulation and removing blood stasis has certain clinical effect in retarding the process of IgA nephropathy(IgAN) fibrosis, but the mechanism of action is still unclear. In this study, the network pharmacology method was used to investigate the active ingredients, targets and molecular mechanisms of THSWD in the intervention of IgAN fibrosis. On this basis, in vitro experiments were conducted to verify the effect of THSWD on the expression of ERK factor in BALB/c 3 T3 cells. The active ingredients and targets in THSWD were collected through the TCMSP. Sixty-one active ingredients and 240 targets including luteolin and quercetin were screened, and 185 targets were obtained by intersecting with CTD database to search IgAN related targets. Cytoscape software and STRING database were used to construct "THSWD-active ingredients-targets" network and protein-protein interaction network, and 69 core targets were screened. In DAVID's GO enrichment analysis and KEGG pathway analysis of the core targets and cell experiments, the results showed that ERK was an important factor for THSWD to interfere with IgAN fibrosis, and THSWD intervention could significantly decrease cell activity, ERK1/2 mRNA expression, and p-ERK1/2 protein expression. This study preliminarily revealed that THSWD may delay the growth of fibroblasts by affecting ERK factor and its phosphorylation level.
Subject(s)
Drugs, Chinese Herbal , Medicine, Chinese Traditional , Drugs, Chinese Herbal/pharmacology , Fibroblasts , Protein Interaction MapsABSTRACT
Developing alternatives to antibiotics is an urgent need in livestock production. Antimicrobial peptides (AMPs) are regarded as powerful antibiotic substitutes (ASs) because AMPs have broad-spectrum antimicrobial activities and growth-promoting ability. Here, we aimed to comprehensively assess the effects of AMPs on the growth performance, diarrhea rate, intestinal morphology and immunity of healthy or challenged piglets, compared with an antibiotics group or negative control group. We performed a set of meta-analyses of feeding trials from database inception to 27 May 2019. Among the 1379 identified studies, 20 were included in our meta-analyses (56 arms and 4067 piglets). The meta-analyses revealed that (1) compared with the negative control group, AMPs significantly improved the healthy piglets' average daily gain (ADG), average daily feed intake (ADFI), gain : feed ratio (G/F), levels of immune globulin (Ig) IgM and IgG, and intestinal villus height : crypt depth ratio (V/C) (P < 0.05). Meanwhile, AMPs significantly increased the challenged piglets' ADG, ADFI, G/F and V/C of the jejunum and ileum, and notably deceased the diarrhea rate (P < 0.05); (2) compared with antibiotics group, the effects of AMPs were slightly weaker than those of antibiotics in the healthy piglets, but AMPs have similar effects to those of antibiotics in challenged piglets. In a higher purity, the optimal dose of AMPs may be approximately 0.01%. Our findings indicate that AMPs can improve piglet growth performance, enhance immunity, benefit intestinal morphology and decrease the diarrheal rate. AMPs could be great ASs especially under infection conditions.
Subject(s)
Diarrhea , Intestines , Swine , Animals , Anti-Bacterial Agents/pharmacology , Diarrhea/drug therapy , Diarrhea/veterinary , Dietary Supplements , Intestinal Mucosa , Pore Forming Cytotoxic Proteins , WeaningABSTRACT
Calcium depletion is a valuable non-invasive tool for studying skeletal system disorders. A low calcium diet (LCD) was used to examine the pathophysiological characteristics and molecular mechanisms of osteoporotic damage in caged laying hens. Sixty 64-wk-old laying hens were randomly housed in single-bird cages, and the cages were divided into 2 treatments: fed a regular calcium diet (RCD, 3.69%) or a LCD (1.56%) for 8 wk. The diet-induced changes of serum bone remodeling indicators, bone strength, microstructure of the distal femur, and the gene expression profiling of keel bone were measured. Compared to RCD hens, LCD hens had higher activity of serum alkaline phosphatase and tartrate resistant acid phosphatase but lower serum calcium concentrations with reduced tibial and femoral mass, width, and strength (P < 0.05). In addition, LCD hens had greater densities of osteoclasts, osteoblasts, connective tissue cells, and osteoid in the trabecular bone (P < 0.05). The transcriptome analysis revealed that 563 unigenes were differentially expressed in keel bone between LCD and RCD hens. The Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that these differentially expressed genes were mainly associated with the osteoporosis-related signaling pathways involved in the biological functions of the bone cellular and extracellular structural modulations. The real-time PCR analysis further confirmed that the LCD enhanced the mRNA expression of collagen type 1 alpha 2, integrin-binding sialoprotein and periostin, but inhibited sclerostin expression. These findings indicate that LCD hens have a higher bone turnover and micro-architectural damage compared to RCD hens. The results further evidence dietary supplement of calcium is a critical nutrient strategy for improving hen skeletal health.
Subject(s)
Bone and Bones/physiopathology , Calcium, Dietary/metabolism , Chickens/physiology , Transcription, Genetic/physiology , Animals , Bone Remodeling/genetics , Calcification, Physiologic/genetics , Chickens/genetics , Female , Femur/physiology , Random Allocation , Tibia/physiologyABSTRACT
OBJECTIVE: To analyze the clinical and imaging characteristics of the neurological damage caused by nitrous oxide (N2O). METHODS: In the study, 10 patients in the Department of Neurology of China-Japan Friendship Hospital from October 2015 to February 2018 were retrospectively analyzed for the demographic data, the history of inhaled N2O, clinical features, blood examination, electrophysiological examination, spinal magnetic resonance imaging and therapeutic efficacy profiles. RESULTS: The male-to-female ratio was 4:6 and it presented with an age-of-onset 17-26 years [the average age: (20.80±3.12) years]. The time from inhaled N2O to onset was 1 month to 1 year [the average time: (6.95±4.19) months]. Paralysis in all the patients and numbness in 9 patients were the main clinical features, while positive Lhermitte's sign in 3 patients, urinary and defecation disturbance in 4 patients were also found. Blood examination indicated anemia in 2 patients, giant cell anemia in 1 case and small cell hypochromic anemia in 1 case. 3 cases had been treated with vitamin B12 in an external hospital, and the other 7 cases had abnormal increase in homocysteine levels. Electrophysiological examinations showed sensory and motor nerve involvement in 9 patients, and motor nerve involvement in 1 patient. The severity of lower extremity lesion was significantly heavier than that of upper extremity. Spinal magnetic resonance imagings showed that long segmental lesions were present in the cervical spinal cord of all the patients, 3 cases with long segmental lesions of the thoracic cord and 2 cases with spinal cord swelling. In 6 cases, the horizontal axis had an "inverted V-type" T2 high signal, 1 case was classified as "crescent", and 3 cases were "eight-shaped". The symptoms in these 10 cases were alleviated in varying degrees after stopping the inhalation of nitrous oxide, actively supplementing high doses of vitamin B12 and doing early rehabilitation exercises. CONCLUSION: Myelopathy with nitrous oxide presents as paralysis and numbness in limb extremities. In imaging, cervical spinal cord damage is common, accompanied by thoracic spinal cord damage. The horizontal axis is more common in the "inverted V-type". Treatment with high doses of vitamin B12 is effective.
Subject(s)
Spinal Cord Diseases , Adolescent , China , Female , Humans , Magnetic Resonance Imaging , Male , Nitrous Oxide , Retrospective Studies , Young AdultABSTRACT
OBJECTIVE: We previously reported that genetic ablation of (Fibroblast Growth Factors Receptors) FGFR1 in knee cartilage attenuates the degeneration of articular cartilage in adult mice, which suggests that FGFR1 is a potential targeting molecule for osteoarthritis (OA). Here, we identified R1-P1, an inhibitory peptide for FGFR1 and investigated its effect on the pathogenesis of OA in mice induced by destabilization of medial meniscus (DMM). DESIGN: Binding ability between R1-P1 and FGFR1 protein was evaluated by enzyme-linked immuno sorbent assay (ELISA) and molecular docking. Alterations in cartilage were evaluated histologically. The expression levels of molecules associated with articular cartilage homeostasis and FGFR1 signaling were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting and immunohistochemistry (IHC). The chondrocyte apoptosis was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay. RESULTS: R1-P1 had highly binding affinities to human FGFR1 protein, and efficiently inhibited extracellular signal-regulated kinase (ERK)1/2 pathway in mouse primary chondrocytes. In addition, R1-P1 attenuated the IL-1ß induced significant loss of proteoglycan in full-thickness cartilage tissue from human femur head. Moreover, this peptide can significantly restore the IL-1ß mediated loss of proteoglycan and type II collagen (Col II) and attenuate the expression of matrix metalloproteinase-13 (MMP13) in mouse primary chondrocytes. Finally, intra-articular injection of R1-P1 remarkably attenuated the loss of proteoglycan and the destruction of articular cartilage and decreased the expressions of extracellular matrix (ECM) degrading enzymes and apoptosis in articular chondrocytes of mice underwent DMM surgery. CONCLUSIONS: R1-P1, a novel inhibitory peptide for FGFR1, attenuates the degeneration of articular cartilage in adult mice, which is a potential leading molecule for the treatment of OA.
Subject(s)
Arthritis, Experimental/prevention & control , Cartilage, Articular/metabolism , Oligopeptides/therapeutic use , Osteoarthritis/prevention & control , Receptor, Fibroblast Growth Factor, Type 1/metabolism , Animals , Apoptosis/drug effects , Arthritis, Experimental/metabolism , Arthritis, Experimental/pathology , Cartilage, Articular/drug effects , Cartilage, Articular/pathology , Cells, Cultured , Chondrocytes/drug effects , Chondrocytes/pathology , Drug Evaluation, Preclinical/methods , Extracellular Matrix/drug effects , Extracellular Matrix/pathology , Humans , MAP Kinase Signaling System/drug effects , Male , Mice, Inbred C57BL , Oligopeptides/pharmacology , Osteoarthritis/metabolism , Osteoarthritis/pathology , Proteoglycans/metabolism , Receptor, Fibroblast Growth Factor, Type 1/antagonists & inhibitors , Tissue Culture TechniquesABSTRACT
BACKGROUND: Anti-VEGF agent ranibizumab has been extensively used as a standard treatment for wet AMD. We investigated whether traditional Chinese medicine could serve as a complementary therapy for this disease. METHODS: 144 patients with neovascular age-related macular degeneration received either intravitreal ranibizumab treatment as needed plus placebo or intravitreal ranibizumab treatment as needed plus an FDA approved traditional Chinese patent medicine named ZQMT. Both groups received treatment for 24 weeks. The primary outcome was the mean change of visual acuity at week 24 as compared to the baseline. RESULTS: We found that intravitreal ranibizumab treatment plus ZQMT was non-inferior to the treatment with intravitreal ranibizumab alone in improving visual acuity scores at week 24 with patients in both groups who gained substantial numbers of letters. In addition, we found that ZQMT treatment resulted in significant improvements in reducing retinal hemorrhage, fluid, and lesion size. Importantly, administration of ZQMT reduced the number of needed ranibizumab injections (P<0.0001, analysis of variance) in wet AMD patients leading to a significant reduction of drug cost. CONCLUSION: The combinatory therapy of ranibizumab and traditional Chinese patent medicine ZQMT had equivalent effects on visual acuity improvement and safety profiles as the ranibizumab treatment alone. Ranibizumab injections coupled with ZQMT offer therapeutic advantages in terms of reduction of retinal lesions and ease the financial burden of patients undergoing treatment by reducing the frequency of necessary ranibizumab injections.
Subject(s)
Macular Degeneration/drug therapy , Medicine, Chinese Traditional , Ranibizumab/administration & dosage , Complementary Therapies/methods , Double-Blind Method , Drug Therapy, Combination/methods , Female , Humans , Macular Degeneration/pathology , Macular Degeneration/physiopathology , MaleABSTRACT
A 72-year-old woman presented with suspected parkinsonism and discolouration of the skin especially on sun-exposed areas. Thorough investigation revealed systemic zirconium intoxication due to intake of metallic colloids as a home remedy as a cause of the skin colour change. There may be an association between skin discolouration and her parkinsonism. This is unique in that various clinical manifestations developed following systemic ingestion of zirconium and this should serve as a warning on the risk of taking illicit dietary supplements.
Subject(s)
Parkinsonian Disorders/pathology , Skin Pigmentation/drug effects , Skin/pathology , Zirconium/toxicity , Aged , Dietary Supplements/toxicity , Female , Humans , Parkinsonian Disorders/chemically induced , Parkinsonian Disorders/complications , Ultraviolet Rays/adverse effectsABSTRACT
Selenium is essential for the normal life processes, and all animals, including fish, need this inorganic element. In order to research the pathology of selenium deficiency in common carp, Cyprinus carpio L., 360 juvenile carp were allocated to three treatments. Each treatment containing 120 fish was randomly divided into four groups, fed with purified diets containing selenium at 0, 0.15, 0.30 and 0.45 mg kg(-1). The results indicated that the morbidity and mortality rates of the test groups were negatively correlated with the level of selenium in the diets. The morbidity and mortality rates were, respectively, 46.7%, 33.3%, 13.3%, 0 and 26.7% 16.7%, 6.7%, 0. The affected fish exhibited pathological changes, such as 'thin back disease' and lordosis. Histologically, there was no abnormality observed in muscles, liver and pancreas. Ultrastructurally, there was swelling of the mitochondria of the cardiac muscle cells, the liver cells and renal tubular epithelial cells, with disintegration and lysis of the cristae of the mitochondria which vesiculated. Serum glutamic oxaloacetic transaminase and glutamic pyruvic transaminase levels were increased and the activity of the serum glutathione peroxidase and the serum superoxide dismutase was decreased; in contrast, the serum malonaldehyde concentration was increased.
Subject(s)
Carps/metabolism , Fish Diseases/pathology , Selenium/deficiency , Animals , Blood Chemical Analysis/veterinary , Dose-Response Relationship, Drug , Fish Diseases/blood , Fish Diseases/epidemiology , Lordosis/blood , Lordosis/epidemiology , Lordosis/pathology , Lordosis/veterinary , Selenium/administration & dosageABSTRACT
To explore the associations of SNPs within hsa-miR-605 (rs2043556) and hsa-miR-149 (rs2292832) and lifestyle-related factors with gastrointestinal cancer, a case-control study including 762 cases and 757 controls was conducted. Marginally significant associations were found both for hsa-miR-149 rs2292832 with gastric cancer risk (TC + CC vs. TT, OR = 0.68, 95% CI: 0.44-1.04) and for hsa-miR-605 rs2043556 with colorectal cancer risk (AG + GG vs. AA, OR = 0.70, 95% CI: 0.48-1.02) in males. Tea drinking showed a protective effect on gastric cancer risk (OR = 0.28, 95% CI: 0.13-0.60), while smoke inhalation increased the risk of gastric cancer (OR = 1.94, 95% CI: 1.08-3.47). Irritability was found to be a risk factor for both colorectal cancer (OR = 1.61, 95% CI: 1.02-2.53) and gastric cancer (OR = 1.96, 95% CI: 1.17-3.29). Among those that engaged in smoke inhalation, miR-149 CT/CC and miR-605 AG/GG genotype carriers had increased susceptibilities to colorectal cancer (OR = 1.90, 95% CI: 1.11-3.25) and gastric cancer (OR = 1.87, 95% CI: 1.03-3.42), respectively. Among the tea drinkers, there exists a marginally protective effect of miR-605 AG/GG genotypes on colorectal cancer incidence (OR = 0.71, 95% CI: 0.47-1.06) and a significantly protective effect of miR-149 CT/CC on gastric cancer incidence (OR = 0.47, 95% CI: 0.29-0.77). The SNPs of rs2292832 and rs2043556 might be able to modify the susceptibility to male gastric and colorectal cancers, respectively. Tea drinking is a protective factor, while smoke inhalation is a risk factor for gastric cancer, and they might have the potential to modify the associations between miR-149 and miR-605 polymorphisms with gastrointestinal cancer risk. In addition, irritability was shown to be a risk factor for both gastric and colorectal cancers.
Subject(s)
Gastrointestinal Neoplasms/genetics , Genetic Predisposition to Disease , MicroRNAs , Polymorphism, Single Nucleotide , Aged , Case-Control Studies , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/genetics , Female , Gene Expression , Humans , Irritable Mood , Life Style , Male , Middle Aged , Risk Factors , Smoking , Stomach Neoplasms/epidemiology , Stomach Neoplasms/genetics , TeaABSTRACT
To assist in distinguishing disease-causing mutations from nonpathogenic polymorphisms, we developed an objective algorithm to calculate an "estimate of pathogenic probability" (EPP) based on the prevalence of a specific variation, its segregation within families, and its predicted effects on protein structure. Eleven missense variations in the RPE65 gene were evaluated in patients with Leber congenital amaurosis (LCA) using the EPP algorithm. The accuracy of the EPP algorithm was evaluated using a cell-culture assay of RPE65-isomerase activity The variations were engineered into plasmids containing a human RPE65 cDNA and the retinoid isomerase activity of each variant was determined in cultured cells. The EPP algorithm predicted eight substitution mutations to be disease-causing variants. The isomerase catalytic activities of these RPE65 variants were all less than 6% of wild-type. In contrast, the EPP algorithm predicted the other three substitutions to be non-disease-causing, with isomerase activities of 68%, 127%, and 110% of wild-type, respectively. We observed complete concordance between the predicted pathogenicities of missense variations in the RPE65 gene and retinoid isomerase activities measured in a functional assay. These results suggest that the EPP algorithm may be useful to evaluate the pathogenicity of missense variations in other disease genes where functional assays are not available.
Subject(s)
Carrier Proteins/genetics , Eye Proteins/genetics , Mutation, Missense , Algorithms , Amino Acid Sequence , Base Sequence , Biocatalysis , Carrier Proteins/chemistry , Carrier Proteins/physiology , Cell Line , DNA Primers , DNA, Complementary , Eye Proteins/chemistry , Eye Proteins/physiology , Female , Humans , Male , Molecular Sequence Data , Mutagenesis, Site-Directed , Pedigree , Reverse Transcriptase Polymerase Chain Reaction , cis-trans-IsomerasesABSTRACT
The tolerant-selenium exopolysaccharide-producing bacterial strain Enterobacter cloacae Z0206 was batch cultured in PDA medium containing optimal concentration of sodium selenite. Selenium was accumulated efficiently in Enterobacter cloacae Z0206 during cultivation with selenium. Inorganic selenite could be transformed into organic forms. Selenium-enriched exopolysaccharide (Se-ECZ-EPS-1) was purified from the fermentation liquid. Selenium content of Se-ECZ-EPS-1 was 12.962microg/g. Se-ECZ-EPS-1 with Mw of 29,300Ka was composed of Glc, Gal and Mann with molar ratio of 8.530:0.061:0.706. Administration of Se-ECZ-EPS-1 to cyclophosphamide (CP)-exposed animals resulted in improvement of cellular and humoral immune responses. These findings indicated that Se-ECZ-EPS-1 may act as potent immunomodulatory agents.
Subject(s)
Enterobacter cloacae/metabolism , Immunologic Factors/pharmacology , Polysaccharides/pharmacology , Selenium/chemistry , Animals , Biotransformation , Chromatography, DEAE-Cellulose , Chromatography, High Pressure Liquid , Immunologic Factors/chemistry , Immunologic Factors/metabolism , Male , Mice , Mice, Inbred ICR , Microscopy, Atomic Force , Organ Size/drug effects , Polysaccharides/biosynthesis , Polysaccharides/chemistry , Spectroscopy, Fourier Transform Infrared , Spleen/drug effects , Spleen/immunology , Thymus Gland/drug effects , Thymus Gland/immunologyABSTRACT
OBJECTIVE: PG201 has been formulated using 12 herbs known to have anti-inflammatory and protective effects on damaged tissue and bone among other functions. The present study was done in order to assess the therapeutic effects of PG201 in collagen-induced arthritis (CIA) in mice. METHODS: DBA/1 mice were immunized with bovine type II collagen. After a second collagen immunization, mice were treated with PG201 orally at 10 mg/kg once a day for 18 days. Paws were evaluated macroscopically for redness, swelling and deformities. The levels of TNF-alpha and IL-1beta in the ankle were examined. The severity of arthritis within the knee joints was evaluated by histological assessment of cartilage destruction and pannus formation. Molecular indicators related to CIA pathology were analysed by measuring the serum levels of matrix metalloproteinase 2 (MMP-2), tissue inhibitor of matrix metalloproteinase 2 (TIMP-2) and the anti-inflammatory cytokines interleukin (IL)-4 and IL-10. RESULTS: Administration of PG201 significantly suppressed the progression of CIA and inhibited the production of TNF-alpha and IL-1beta in the paws. The erosion of cartilage was dramatically reduced in mouse knees after treatment with PG201. In the serum of PG201-treated mice, the level of TIMP-2 and the ratio of TIMP-2 to MMP-2 were significantly elevated, and the level of IL-4, but not of IL-10, was increased. CONCLUSION: Administration of PG201 has therapeutic effects on CIA. Protection of cartilage was particularly prominent. PG201 is a potential therapy for rheumatoid arthritis.
Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Experimental/prevention & control , Drugs, Chinese Herbal/therapeutic use , Phytotherapy , Plant Extracts/therapeutic use , Animals , Antirheumatic Agents/toxicity , Arthritis, Experimental/metabolism , Arthritis, Experimental/pathology , Collagen , Disease Progression , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/toxicity , Ethanol , Female , Interleukin-1/analysis , Interleukins/blood , Male , Matrix Metalloproteinase 2/blood , Mice , Mice, Inbred DBA , Phytotherapy/adverse effects , Rats , Rats, Sprague-Dawley , Tissue Inhibitor of Metalloproteinases/blood , Tumor Necrosis Factor-alpha/analysisABSTRACT
The erythrocytic growth stage of Plasmodium falciparum involves hemoglobin proteolysis as the primary nutrient source with the concomitant release of free heme. The liberated heme is processed by the parasite into hemozoin, a polymeric porphyrin dimer. Histidine-rich protein binds heme and mediates the formation of hemozoin, which is inhibited by the antimalarial drug chloroquine. Interference with heme binding was determined using a microtiterplate assay. Combinatorial libraries were screened and tested against parasite growth, revealing a good correlation between heme binding interference and the inhibition of parasite growth. Several of these compounds retain their potency against a chloroquine-resistant strain of Plasmodium falciparum. The most potent compounds have IC(50) values less than or equal to 50 nM against chloroquine-resistant and chloroquine-sensitive parasites.
Subject(s)
Antimalarials/chemistry , Heme/metabolism , Proteins/metabolism , Animals , Antimalarials/pharmacology , Combinatorial Chemistry Techniques , Drug Design , Drug Evaluation, Preclinical , Inhibitory Concentration 50 , Plasmodium falciparum/drug effects , Protein Binding/drug effects , Protozoan Proteins/metabolism , Structure-Activity RelationshipSubject(s)
Acetates/therapeutic use , Enzyme Inhibitors/therapeutic use , Indoles/therapeutic use , Liver/blood supply , Phospholipases A/antagonists & inhibitors , Reperfusion Injury/prevention & control , Animals , Blood Pressure/drug effects , Dogs , Drug Evaluation, Preclinical , Female , Group II Phospholipases A2 , SystoleSubject(s)
Dipyridamole/pharmacology , Liver/blood supply , Reperfusion Injury/prevention & control , Vasodilator Agents/pharmacology , Adenosine Triphosphate/metabolism , Animals , Cyclic AMP/metabolism , Dogs , Drug Evaluation, Preclinical , Female , Ischemia/drug therapy , Liver/metabolism , Reperfusion Injury/metabolismABSTRACT
Eighty-seven cases of intermediate and late rheumatoid arthritis were treated with Instant Shu Guan Wen Jing Granules ([symbol: see text] Relaxing Joints by Warming Channels) and Instant Shu Guan Qing Luo Granules ([symbol: see text] Relaxing Joints by Removing Heat from the Lung Channel) to tonify the kidney, resolve phlegm and remove blood stasis, and compared with 41 cases treated with Instant Wang Bi Granules ([symbol: see text] Prescription for Arthralgia-syndrome). The treatment produced a clinical cure rate of 54.0% and a total effective rate of 90.8% as in against 29.3% and 73.2% respectively in the control group. The difference was significant (P < 0.01). Improvement in main symptoms and laboratory findings in the treatment group was all more marked than that in the control group (P < 0.05 or P < 0.01), with no side effects observed.