Healing effect of Terminalia chebula Retz extract on second-degree burns in rats

Purpose: To investigate the healing effect of Terminalia chebula Retz. Extract (TCRE) on seconddegree burns in rats.Methods: Male Sprague Dawley (SD) rats, weighing 200 – 220 g, were subjected to deep seconddegree skin burns by electrical scald instrument. The animals were divided into three groups as follows: (1) second-degree burns model (control) group, (2) burns model treated with 1 % silver sulfadiazine (SSD) group, and (3) burns model treated with 100 mg·mL-1 TCRE group. On days 3, 7 and 14 following the administration of the drug/extract, the wound area and histopathological changes in rat epidermis were evaluated for the various groups. The minimum inhibitory concentration (MIC) of TCRE on Staphyloccocus aureus, Pseudomonas aeruginosa and Escherichia coli were also assessed separately.Results: On day 14, the mean wound area of TCRE treatment group (0.25 ± 0.06 cm2) was significantly smaller than that of the control rats (2.71 ± 0.20 cm2, p < 0.01). The histological results indicate that the inflammatory cells disappeared and were replaced by new granulation tissue in the group treated with 100 mg·mL-1 TCRE by day 14. Compared with SSD group rats, the inflammatory cells and fibroblast and granulation tissues of burnt rats treated with 100 mg·mL-1 TCRE were same as those of rats that had no burns. The antibacterial results revealed that the MIC of TCRE on Staphyloccocus aureus, Pseudomonas aeruginosa and Escherichia coli was 3.13, 12.5 and 6.25 mg·mL-1, respectively.Conclusion: Terminalia chebula Retz. has potentials to be developed as an effective medicinal herb for the treatment of second-degree burns.Keywords: Terminalia chebula, Second-degree burns, Burn wound, Healing, Granulation tissues, Fibroblast, Antibacterial, Inflammatory cell

Identification of a diagnostic model and molecular subtypes of major depressive disorder based on endoplasmic reticulum stress-related genes

SubjectMajor depressive disorder (MDD) negatively affects patients’ behaviours and daily lives. Due to the high heterogeneity and complex pathological features of MDD, its diagnosis remains challenging. Evidence suggests that endoplasmic reticulum stress (ERS) is involved in the pathogenesis of MDD; however, relevant diagnostic markers have not been well studied. This study aimed to screen for ERS genes with potential diagnostic value in MDD.MethodsGene expression data on MDD samples were downloaded from the GEO database, and ERS-related genes were obtained from the GeneCards and MSigDB databases. Differentially expressed genes (DEGs) in MDD patients and healthy subjects were identified and then integrated with ERS genes. ERS diagnostic model and nomogram were developed based on biomarkers screened using the LASSO method. The diagnostic performance of this model was evaluated. ERS-associated subtypes were identified. CIBERSORT and GSEA were used to explore the differences between the different subtypes. Finally, WGCNA was performed to identify hub genes related to the subtypes.ResultsA diagnostic model was developed based on seven ERS genes: KCNE1, PDIA4, STAU1, TMED4, MGST1, RCN1, and SHC1. The validation analysis showed that this model had a good diagnostic performance. KCNE1 expression was positively correlated with M0 macrophages and negatively correlated with resting CD4+ memory T cells. Two subtypes (SubA and SubB) were identified, and these two subtypes showed different ER score. The SubB group showed higher immune infiltration than the SubA group. Finally, NCF4, NCF2, CSF3R, and FPR2 were identified as hub genes associated with ERS molecular subtypes.ConclusionOur current study provides novel diagnostic biomarkers for MDD from an ERS perspective, and these findings further facilitate the use of precision medicine in MDD

Long-term trends in the incidence of depressive disorders in China, the United States, India and globally: A comparative study from 1990 to 2019

BackgroundDepressive disorders have become an increasingly significant public health issue. This study is intended to show the trend of the incidence of depressive disorders in China, the United States, India and the world from 1990 to 2019, as well as the impact of age, period and cohort on it.MethodsExtracting incidence data from the Global Burden of Disease Study 2019, we determined trends in the age-standardized incidence rate (ASIR) using Joinpoint regression. An age-period-cohort analysis was implemented to describe the effects of age, period, and cohort, as well as the long-term tendencies.ResultsFrom 1990 to 2019, the ASIR of depressive disorders in China was lower than that in the United States; India is lower than the United States in the first 5 years, showing a downward trend. The incidence in India and the United States is higher than the global average. The ASIR of women in the three countries is higher than that of men. In China, the elderly, early period and people born around 1954 have a higher risk of depressive disorders. In the United States, young people born around 1999 have a higher risk of depressive disorders. India is similar to China.ConclusionFrom 1990 to 2019, the age effect of China as a whole increased, and the period became stable, and the cohort effect declined. The overall age and period effects of the United States reduced, while the cohort effect increased. The age effect in India increased, while the period and cohort effects decreased. Depressive disorders are becoming ever more serious worldwide, and we’d better take measures to reduce its incidence according to the cohort effect of each age group

Genome wide association study on feed conversion ratio using imputed sequence data in chickens

Objective Feed consumption contributes a large percentage for total production costs in the poultry industry. Detecting genes associated with feeding traits will be of benefit to improve our understanding of the molecular determinants for feed efficiency. The objective of this study was to identify candidate genes associated with feed conversion ratio (FCR) via genome-wide association study (GWAS) using sequence data imputed from single nucleotide polymorphism (SNP) panel in a Chinese indigenous chicken population. Methods A total of 435 Chinese indigenous chickens were phenotyped for FCR and were genotyped using a 600K SNP genotyping array. Twenty-four birds were selected for sequencing, and the 600K SNP panel data were imputed to whole sequence data with the 24 birds as the reference. The GWAS were performed with GEMMA software. Results After quality control, 8,626,020 SNPs were used for sequence based GWAS, in which ten significant genomic regions were detected to be associated with FCR. Ten candidate genes, ubiquitin specific peptidase 44, leukotriene A4 hydrolase, ETS transcription factor, R-spondin 2, inhibitor of apoptosis protein 3, sosondowah ankyrin repeat domain family member D, calmodulin regulated spectrin associated protein family member 2, zinc finger and BTB domain containing 41, potassium sodium-activated channel subfamily T member 2, and member of RAS oncogene family were annotated. Several of them were within or near the reported FCR quantitative trait loci, and others were newly reported. Conclusion Results from this study provide valuable prior information on chicken genomic breeding programs, and potentially improve our understanding of the molecular mechanism for feeding traits

Prevalence and Characterization of Staphylococcus aureus Isolated From Women and Children in Guangzhou, China

The prevalent Staphylococcus aureus clones and antibiotic susceptibility profiles are known to change dynamically and geographically; however, recent S. aureus strains causing infections in women and children in China have not been characterized. In this study, we analyzed the molecular epidemiology and antimicrobial resistance of S. aureus isolated from patients in four centers for women and children in Guangzhou, China. In total, 131 S. aureus isolates (100 from children and 31 from women) were analyzed by spa typing, multi-locus sequence typing, virulence gene and antimicrobial resistance profiling, staphylococcal chromosomal cassette mec typing, and mutation analyses of rpoB. A total of 58 spa types, 27 sequence types (STs), and 10 clonal complexes (CCs) were identified. While CC59 (ST59-IV, 48.8%; ST338-III, 35.7%) and CC45 (ST45-IV, 100%) were the major clones (84.4%) among MRSA isolates, CC5 (ST188, 24.3%; ST1, 21.6%) and CC398 (ST398, 70%) were the major ones (70.1%) among MSSA isolates. ST338-MRSA-III mostly found in pus but hardly in respiratory tract samples while ST45-MRSA-IV was on the opposite, even though they both found in blood and cerebrospinal fluid sample frequently. Staphylococcal enterotoxin genes seb-seq-sek were strongly associated with ST59 and ST338, while sec was associated with ST45, ST121, ST22, and ST30. All ST338, ST1232, and SCCmec III isolates carried lukF/S-PV genes. A total of 80% of ST338 isolates were resistant to erythromycin, clindamycin, and tetracycline. All ST45 isolates exhibited intermediate or complete resistance to rifampicin. In total, 481 HIS/ASN mutations in rpoB were found in rifampicin-resistant or intermediate-resistant isolates. ST338-III and ST45-IV emerged as two of three major clones in MRSA isolates from women and children in Guangzhou, China, though ST59-MRSA-IV remained the most prevalent MRSA clone. Clonal distribution of S. aureus varied, depending on the specimen source. Virulence genes and antibiograms were closely associated with the clonal lineage. These results clarified the molecular epidemiology of S. aureus from women and children in Guangzhou, China, and provide critical information for the control and treatment of S. aureus infections

Susceptibility of HIV-1 Subtypes B′, CRF07_BC and CRF01_AE that Are Predominantly Circulating in China to HIV-1 Entry Inhibitors

The B', CRF07_BC and CRF01_AE are the predominant HIV-1 subtypes in China. It is essential to determine their baseline susceptibility to HIV entry inhibitors before these drugs are used in China.The baseline susceptibility of 14 representative HIV-1 isolates (5 CRF07_BC, 4 CRF01_AE, and 5 B'), most of which were R5 viruses, obtained from drug-naïve patients to HIV entry inhibitors, including two fusion inhibitors (enfuvirtide and C34), two CCR5 antagonists (maraviroc and TAK779) and one CXCR4 antagonist (AMD3100), were determined by virus inhibition assay. The sequences of their env genes were amplified and analyzed. These isolates possessed similar susceptibility to C34, but they exhibited different sensitivity to enfuvirtide, maraviroc or TAK779. CRF07_BC isolates, which carried polymorphisms of A578T and V583I in the N-terminal heptad repeat and E630Q, E662A, K665S, A667K and S668N in the C-terminal heptad repeat of gp41, were about 5-fold less sensitive than B' and CRF01_AE isolates to enfuvirtide. Subtype B' isolates with a unique polymorphism site of F317W in V3 loop, were about 4- to 5-fold more sensitive than CRF07_BC and CRF01_AE isolates to maraviroc and TAK779. AMD3100 at the concentration as high as 5 µM exhibited no significant inhibitory activity against any of the isolates tested.Our results suggest that there are significant differences in baseline susceptibility to HIV entry inhibitors among the predominant HIV-1 subtypes in China and the differences may partly result from the naturally occurring polymorphisms in these subtypes. This study provides useful information for rational design of optimal therapeutic regimens for HIV-1-infected patients in China

Molecular genetic epidemiological studies of smoking behaviour and growth promoting genes

Objectives: 1. Smoking is a major cause of death and often initiates in adolescence. Raploinsufficiency of CYP2A6 in adults is associated with lower cigarette consumption, lower cotinine level and higher quit rates. Other genes are also implicated in smoking behaviour. I explored genotypes of CYP2A6 and other genes in relation to smoking behaviour and cotinine levels in the UK-wide School Heart and Health Study (SHHS). 2. The associations between low birthweight and adult disorders have been widely investigated. Environmental factors have been widely investigated but there has been less focus on genetic factors. There is however evidence that GH-CSH influences adult OR level, one year weight, metabolic syndrome traits and bone loss. I focused on major growth genes in relation to birthweight and other metabolic traits in the SHHS cohort. 3. Results from previous studies led to the hypothesis that some ACE D allele phenotypic associations may represent proxy marking of causal factors located in the GH-CSHgene cluster. I tested this hypothesis for cardiac muscle growth response to exercise and ACE level in a British army heart study cohort. Methods: 1. 1,520 subjects from the SHHS were genotyped for CYP2A6 alleles *lA, *IB, *2, *4, *5, *9 and *12 to classify predicted nicotine metabolism rate. DBB, MAOA, DRD4 and 5HT2A markers were also studied. 2. Microsatellites CSHI.OI and IGFI(CA)n were genotyped and analysed in relation to birthweight and other metabolic traits in the SHHS cohort. 3. Combined analyses ofACEYD and GH-CSHBgl IlB in relation to exercise induced left ventricular mass (LVM) change and serum ACE activity were investigated in a group of Caucasian males in the UK. Linkage disequilibrium (LD) analysis and other genetic statistical analysis were carried out. Results: 1. Those predicted to be half normal metabolisers due to haploinsufficiency ofCYP2A6 (carriers of one fully inactive allele, i.e. *2, *4, or *5) were more likely to be a current smoker at age 18 years. Current versus ever odds ratio was 1.95 (95% C.I. 1.03-3.68). Salivary cotinine levels in current smokers were significantly lower in the 'normal' group compared with 'slow' or 'very slow' group. 2. The CSHI.OI IT genotype in the SHHS boys showed a higher birthweight compared with those DIDI or D2D2 genotype. There was no evidence for association ofthe IGFI(CA)n genotype with birthweight in the SHHS, but boys of 1921192bp genotype did show a leg length 0.65cm greater (p=0.05) than those not homozygous for allele I92bp. 3. A significant association between GH-CSHBgl lIB and ACE activity was detected but only through its LD with ACEYD. No association between GH-CSHBgl lIB and LVM change was found. Conclusions: 1. CYP2A6 haploinsufficiency increases likelihood of continuing smoking in teenagers. 2. My study provides evidence for effects ofGH-CSHon birthweight in males. Complexities ofmy data relative to previous data are discussed. 3. Cardiac muscle growth response to exercise and ACE levels both appear to be attributable to ACE polymorphism and not to nearby GH-CSHpolymorphism, although this does not exclude otherACE attributed phenotypes being due to GH-CSHvariation.EThOS - Electronic Theses Online ServiceGBUnited Kingdo