ABSTRACT
PURPOSE: Long noncoding RNAs (lncRNAs) with abnormal expression are frequently seen in hepatocellular cancer patients (HCC). Previous studies have reported the correlation between lncRNA and prognosis processes of HCC patients. In this research, a graphical nomogram with lncRNAs signatures, T, M phases was developed using the rms R package to estimate the survival rates of HCC patients in year 1, 3, and 5. METHODS: To find the prognostic lncRNA and create the lncRNA signatures, univariate Cox survival analysis and multivariate Cox regression analysis were chosen. The rms R software package was used to build a graphical nomogram based on lncRNAs signatures to predict the survival rates in of HCC patients in 1, 3, and 5 years. Using "edgeR", "DEseq" R packages to find the differentially expressed genes (DEGs). RESULTS: Firstly, a total of 5581 DEGs including 1526 lncRNAs and 3109 mRNAs were identified through bioinformatic analysis, of which 4 lncRNAs (LINC00578, RP11-298O21.2, RP11-383H13.1, RP11-440G9.1) were identified to be strongly related to the prognosis of liver cancer (P < 0.05). Moreover, we constructed a 4-lncRNAs signature by using the calculated regression coefficient. 4-lncRNAs signature is identified to significantly correlated with clinical and pathological characteristics (such as T stage, and death status of HCC patients). CONCLUSIONS: A prognostic nomogram on the base of 4-lncRNAs markers was built, which is capable to accurately predict the 1-year, 3-year, and 5-year survival of HCC patients after the construction of the 4-lncRNAs signature linked with prognosis of HCC.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , RNA, Long Noncoding , Humans , Carcinoma, Hepatocellular/pathology , Prognosis , Liver Neoplasms/pathology , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Nomograms , Kaplan-Meier EstimateABSTRACT
BACKGROUND: Depression is a significant contributor to disability in Brazil, with most Brazilians affected by depression receiving no treatment. As the community, including family and friends, plays a crucial role in providing support for someone with depression, it is important that evidence-based resources are available to support people who wish to help. The aim of this study was to culturally adapt the English-language mental health first aid guidelines for assisting a person with depression for the Brazilian culture. METHODS: A Delphi expert consensus study was conducted, with two expert panels; health professionals (n = 29) and people with lived experience of depression (n = 28). One hundred and seventy-four statements from the English-language guidelines were translated into Brazilian Portuguese and administered as a survey. Participants were asked to rate statements based on how appropriate those statements were for the Brazilian culture and to suggest new statements if appropriate. RESULTS: Data were collected over two survey rounds. Consensus was achieved on 143 statements. A total of 133 statements were adopted from the English-language guidelines, whereas 10 new endorsed statements were generated from suggestions of the two expert panels. CONCLUSIONS: There were similarities between the English-language and Brazilian guidelines, mainly related to family involvement and the value of empathy. More research on dissemination and incorporation of the guidelines into the Mental Health First Aid (MHFA) training course for Brazil is required.
Subject(s)
Depression , Mental Health , Humans , Brazil , Depression/therapy , First Aid , Delphi Technique , Surveys and QuestionnairesABSTRACT
Rheum tanguticum is a perennial herb and an important medicinal plant, with anthraquinones as its main bioactive compounds. However, the specific pathway of anthraquinone biosynthesis in rhubarb is still unclear. The accumulation of anthraquinones in different tissues (root, leaf, stem and seed) of R. tanguticum revealed considerable variation, suggesting possible differences in metabolite biosynthetic pathways and accumulation among various tissues. To better illustrate the biosynthetic pathway of anthraquinones, we assembled transcriptome sequences from the root, leaf, stem and seed tissues yielding 157,564 transcripts and 88,142 unigenes. Putative functions could be assigned to 56,911 unigenes (64.57%) based on BLAST searches against annotation databases, including GO, KEGG, Swiss-Prot, NR, and Pfam. In addition, putative genes involved in the biosynthetic pathway of anthraquinone were identified. The expression profiles of nine unigenes involved in anthraquinone biosynthesis were verified in different tissues of R. tanguticum by qRT-PCR. Various transcription factors, including bHLH, MYB_related, and C2H2, were identified by searching unigenes against plantTFDB. This is the first transcriptome analysis of different tissues of R. tanguticum and can be utilized to describe the genes involved in the biosynthetic pathway of anthraquiones, understanding the molecular mechanism of active compounds in R. tanguticum.
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ABSTRACT
The wide use of antifungal agents has led to the development of resistance in the pathogenic yeast strain Candida albicans. Gain-of-function mutations in transcription factors such as Tac1p demonstrated their ability to control expression of the ABC transporter genes CDR1 and CDR2, and mediation of azole resistance. Previously, we obtained a series of azole-resistant isolates with high-level expression of CDR1 or/and CDR2, and identified the novel H741D mutation in Tac1p. In the present study, the TAC1 alleles from isolate C13 were introduced into tac1Δ/Δ mutant. The H741D change was seen in TAC1C13 in addition to several other amino acid differences. Hyperactive alleles TAC1C13 exhibited higher minimum inhibitory concentrations (MICs) of fluconazole and itraconazole than that observed in SN152 containing the wild-type TAC1 allele. And alleles TAC1C13 conferred constitutively high levels of Cdr1p and Cdr2p. Moreover, the importance of H741D in conferring hyperactivity to TAC1 was also confirmed by site-directed mutagenesis. Compared with SN152, the presence of H741D resulted in > 2-fold increase in CDR1 and CDR2 gene and protein expression, > 4-fold increase in fluconazole and itraconazole MICs and higher rates of Rhodamine 6G efflux by 43.24%.
Subject(s)
Candida albicans/genetics , Drug Resistance, Fungal/genetics , Fungal Proteins/metabolism , Membrane Transport Proteins/metabolism , Transcription Factors/genetics , Fluconazole/pharmacology , Gene Expression Regulation, Fungal , Itraconazole/pharmacology , MutationABSTRACT
This study aimed to establish the influence of biofilm from clinical isolates of Candida albicans on fluconazole resistance, focusing on efflux pumps and azole-targeted enzymes. Twenty-three C. albicans clinical isolates were collected from two hospitals in Shanghai, China. Antifungal susceptibility tests were performed on biofilm and planktonic cells. A crystal violet assay was used to monitor biofilm growth. Real-time RT-PCR was performed to quantify the expression of the transporter-related genes MDR1, CDR1, and CDR2 as well as ERG11, a gene encoding an enzyme targeted by antifungal drugs. Fluconazole resistance was shown to increase in biofilm in a time-dependent manner. No significant differences were observed between different strains of C. albicans. Genes encoding efflux pumps were overexpressed in early stages of biofilm formation and could also be induced by fluconazole. While ERG11 was not upregulated in biofilm, it was overexpressed upon the addition of fluconazole to biofilm and planktonic cells. Gene expression also appeared to be related to the original genotype of the strain. The upregulation of genes encoding efflux pumps demonstrates their role in the development of fluconazole resistance during the early stages of C. albicans biofilm formation.
Subject(s)
Antifungal Agents/pharmacology , Biofilms , Candida albicans/drug effects , Candida albicans/genetics , Drug Resistance, Fungal , Fluconazole/pharmacology , Fungal Proteins/genetics , Biofilms/drug effects , Candida albicans/isolation & purification , Candida albicans/physiology , China , Fungal Proteins/metabolism , Gene Expression Regulation, Fungal/drug effects , Humans , Membrane Transport Proteins/genetics , Membrane Transport Proteins/metabolism , Microbial Sensitivity TestsABSTRACT
A novel fucosylated chondroitin sulfate (HmG) was isolated from sea cucumber Holothuria mexicana, the structure of which was characterized by monosaccharide composition, disaccharide composition, IR, 1H and 13C NMR spectrum, additionally with two dimensional NMR spectrum of degraded HmG (DHmG). The backbone of HmG was identified as chondroitin 6-O sulfate, while the major O-4 sulfated fucose branches linked to O-3 position of glucuronic acid in almost every disaccharide unit. The anticoagulant activities of HmG and DHmG were assessed and compared with heparin and low molecular weight heparin. The results indicated that HmG and DHmG both could significantly prolong the activated partial thrombo-plastin time, and the properties were well related to its molecular weight. DHmG showed similar anticoagulant properties to low molecular weight heparin with less bleeding risks, making it a safer anticoagulant drug.
Subject(s)
Anticoagulants/chemistry , Anticoagulants/pharmacology , Chondroitin Sulfates/chemistry , Chondroitin Sulfates/pharmacology , Holothuria/chemistry , Animals , Anticoagulants/isolation & purification , Chondroitin Sulfates/isolation & purification , Molecular Weight , Monosaccharides/analysis , Structure-Activity RelationshipABSTRACT
BACKGROUND: Chronic urticaria (CU) can be provoked by a wide variety of causes. Some studies suggest contact sensitization may play a role in the disease. OBJECTIVE: To investigate the incidence and distribution characteristics of allergic contact sensitization in central Chinese subjects with CU, and assess contact allergen avoidance measures in managing CU. METHODS: Patch tests were performed, following the recommended standard procedure, with 20 selected allergens, in line with the European baseline series. All subjects with positive results were prescribed appropriate avoidance measures for the sensitizing substances, while subjects with negative results served as the control group. CU severity was assessed daily from week1 to week4 and for each subject, applying the Urticaria Activity Score. RESULTS: 42.9% (233/543) of subjects with CU showed positive reactions to one or more contact allergen(s). Potassium dichromate, benzene mix and carba mix were more common in male patients, while nickel sulfate was more frequent in females. The positive rates for different allergens varied with age and occupation. The median (interquartile range) severity scores at week 1 were 20 (14-21) and 15 (14-27) for the allergen avoidance group and control group, respectively (P>0.05); and 12 (7-15) and 14 (12-17) at week 4 (P<0.001). CONCLUSION: The incidence of allergic contact sensitization in CU patients was high, and appropriate contact allergen avoidance measures benefitted CU management. Contact allergens may play a role in the pathogenic mechanism of CU and patch tests are an option for CU patients.
Subject(s)
Allergens/immunology , Dermatitis, Allergic Contact/epidemiology , Dermatitis, Allergic Contact/etiology , Urticaria/complications , Urticaria/epidemiology , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Child , Child, Preschool , China/epidemiology , Chronic Disease , Female , Humans , Incidence , Male , Middle Aged , Occupations/statistics & numerical data , Patch Tests , Severity of Illness Index , Sex Distribution , Statistics, Nonparametric , Young AdultABSTRACT
Abstract BACKGROUND: Chronic urticaria (CU) can be provoked by a wide variety of causes. Some studies suggest contact sensitization may play a role in the disease. OBJECTIVE: To investigate the incidence and distribution characteristics of allergic contact sensitization in central Chinese subjects with CU, and assess contact allergen avoidance measures in managing CU. METHODS: Patch tests were performed, following the recommended standard procedure, with 20 selected allergens, in line with the European baseline series. All subjects with positive results were prescribed appropriate avoidance measures for the sensitizing substances, while subjects with negative results served as the control group. CU severity was assessed daily from week1 to week4 and for each subject, applying the Urticaria Activity Score. RESULTS: 42.9% (233/543) of subjects with CU showed positive reactions to one or more contact allergen(s). Potassium dichromate, benzene mix and carba mix were more common in male patients, while nickel sulfate was more frequent in females. The positive rates for different allergens varied with age and occupation. The median (interquartile range) severity scores at week 1 were 20 (14-21) and 15 (14-27) for the allergen avoidance group and control group, respectively (P>0.05); and 12 (7-15) and 14 (12-17) at week 4 (P<0.001). CONCLUSION: The incidence of allergic contact sensitization in CU patients was high, and appropriate contact allergen avoidance measures benefitted CU management. Contact allergens may play a role in the pathogenic mechanism of CU and patch tests are an option for CU patients.