This cross-sectional study explored the prevalence of posttraumatic growth (PTG) and posttraumatic stress disorder (PTSD) in Tibetan adolescent survivors (98% Tibetan and 2% Han) 6 years after the ...2010 Yushu earthquake to identify the PTG predictors. In 2016, 850 high school students (from 11 to 20 years) in Yushu (
N
= 850) completed the self-rating depression scale, the PTSD Check List-Civilian version, the exposure degree scale, and the posttraumatic growth inventory. It was found that the PTG and probable PTSD prevalence rates were 49.7% and 8.9% 6 years after the earthquake, and that exposure level, depression level, and PTSD symptoms were all significant negative predictors for PTG in both the junior high school and senior high school students. Specifically, having a lower degree of exposure, a lower PTSD level, and no depression symptoms were associated with higher PTG. There was a significant PTG difference found between males and females; however, this gender difference was not found in the senior high school students. No significant PTG differences were found for the different ethnicities. The implications of the results and the limitations of this study are discussed.
Magnolol, a lignin compound extracted from
Magnolia officinalis
Cortex, has been found to have prominent antifungal effects against
Candida albicans
. However, the specific mechanism still remains ...unclear. Therefore, this study aimed to further explore the inhibition mechanism of magnolol against
Candida albicans
virulence factors and the related signaling pathways. By an XTT reduction assay, a hyphal formation assay, confocal laser scanning microscopy, transmission electron microscopy, a calcofluor white staining assay, and a cell wall β-glucan quantitative detection assay, we evaluated the inhibitory effects of magnolol against the adhesion, hyphal formation, biofilm viability, biofilm spatial structure, and cell wall ultrastructure of
Candida albicans
. Moreover, by RNA sequencing and qRT-PCR, we confirmed the effects of magnolol in inhibiting the gene expression of
Candida albicans
virulence factors and the related signaling pathways. The results revealed that the adhesion and hyphal formation of
Candida albicans
were inhibited significantly by magnolol. The viability and spatial structures of
Candida albicans
biofilms were further weakened.
Candida albicans
ultrastructure showed partial thinning of cell walls and even rupture, with cytoplasmic leakage. The cell wall intergrity and β-glucan content were also radically reduced. Moreover, magnolol caused significant inhibition of the expression of
Candida albicans
adhesion, invasion, hyphal formation, biofilm formation, β-1,3-glucan synthesis, and hydrolase secretion-related genes, including
ALS1
,
ALS3
,
EFG1
,
EAP1
,
FKS1
,
FKS2
,
PLB2
, and
SAP2
. Furthermore, the PKC pathway-related genes (
RHO1
,
PKC1
,
BCK1
,
MKK2
,
MKC1
) and Cek1 pathway-related genes (
CDC42
,
CST20
,
STE11, HST7
,
CEK1
) were also significantly downregulated, indicating that the inhibition of magnolol against
Candida albicans
virulence factors might be related to PKC and Cek1 MAPK signaling pathways. In conclusion, the findings of this study confirmed the inhibition mechanism of magnolol against
Candida albicans
virulence factors, which might be related to PKC and Cek1 MAPK pathways, thus laying the theoretical foundation for its clinical antifungal applications.
Current liver fibrosis scoring by computer-assisted image analytics is not fully automated as it requires manual preprocessing (segmentation and feature extraction) typically based on domain ...knowledge in liver pathology. Deep learning-based algorithms can potentially classify these images without the need for preprocessing through learning from a large dataset of images. We investigated the performance of classification models built using a deep learning-based algorithm pre-trained using multiple sources of images to score liver fibrosis and compared them against conventional non-deep learning-based algorithms - artificial neural networks (ANN), multinomial logistic regression (MLR), support vector machines (SVM) and random forests (RF). Automated feature classification and fibrosis scoring were achieved by using a transfer learning-based deep learning network, AlexNet-Convolutional Neural Networks (CNN), with balanced area under receiver operating characteristic (AUROC) values of up to 0.85-0.95 versus ANN (AUROC of up to 0.87-1.00), MLR (AUROC of up to 0.73-1.00), SVM (AUROC of up to 0.69-0.99) and RF (AUROC of up to 0.94-0.99). Results indicate that a deep learning-based algorithm with transfer learning enables the construction of a fully automated and accurate prediction model for scoring liver fibrosis stages that is comparable to other conventional non-deep learning-based algorithms that are not fully automated.
Radiotherapy and chemotherapy-induced oral mucositis can affect cancer patients' quality of life, even necessitate cancer therapy and influence prognosis. Chinese patent medicines (CPMs) have been ...widely used as complementary alternative medicines for the prevention and treatment of oral mucositis, and their efficacy and safety require further evaluation. Therefore, this study was conducted to provide references for clinical practice.
Ten databases were searched electronically and manually to identify randomized controlled trials (RCTs) from their inception to August 2021, concerning the prevention and treatment of radiotherapy and chemotherapy-induced oral mucositis with CPMs. The prevalence, pain level, and the severity of radiotherapy and chemotherapy-induced oral mucositis, as well as the effectiveness rate and adverse effects of CPMs, were set as the outcome criteria. The assessment criteria of the Cochrane Handbook were used to determine study quality and bias, and meta-analysis was conducted using Review Manager 5.4.1 software.
A total of 2,312 cases from 27 RCTs were included. Most studies were considered to have a low or unclear risk of bias. More research is available on the use of CPMs in the prevention of radiotherapy and chemotherapy-induced oral mucositis than in its treatment. As for the prevention, it was proved that CPMs could significantly reduce the prevalence of radiotherapy and chemotherapy-induced oral mucositis, especially for the severe types, and decrease pain levels (
< 0.05). For treatment, CPMs could alleviate the symptoms, promote the healing of ulceration in radiotherapy and chemotherapy-induced oral mucositis, and thus improve the efficiency of clinical treatment (
< 0.05). The results of subgroup analyses were mainly consistent with the above results. The adverse effects of CPMs mainly included gastrointestinal reactions and bitter taste, and no serious adverse events were reported.
This systematic review and meta-analysis indicated CPMs might be effective for the prevention and treatment of radiotherapy and chemotherapy-induced oral mucositis through reducing the prevalence, decreasing the occurrence of severe types, alleviating the symptoms, and promoting the healing of ulceration. However, due to the limited number of eligible studies and the publication bias, more high-quality, double-blinded, placebo-controlled RCTs are still needed in future research.
: https://inplasy.com/, identifier INPLASY2021100100.
Cardiovascular disease (CVD) is a group of systemic disorders threatening human health with complex pathogenesis, among which mitochondrial energy metabolism reprogramming has a critical role. ...Mitochondria are cell organelles that fuel the energy essential for biochemical reactions and maintain normal physiological functions of the body. Mitochondrial metabolic disorders are extensively involved in the progression of CVD, especially for energy-demanding organs such as the heart. Therefore, elucidating the role of mitochondrial metabolism in the progression of CVD is of great significance to further understand the pathogenesis of CVD and explore preventive and therapeutic methods. In this review, we discuss the major factors of mitochondrial metabolism and their potential roles in the prevention and treatment of CVD. The current application of mitochondria-targeted therapeutic agents in the treatment of CVD and advances in mitochondria-targeted gene therapy technologies are also overviewed.
Glucocorticoid drugs are widely used to treat immune-related diseases, but their use is limited by side effects and by resistance, which especially occurs in macrophage-dominated diseases. In order ...to improve glucocorticoid therapies, more research is required into the mechanisms of glucocorticoid action. In the present study, we have used a zebrafish model for inflammation to study glucocorticoid effects on the innate immune response. In zebrafish larvae, the migration of neutrophils towards a site of injury is inhibited upon glucocorticoid treatment, whereas migration of macrophages is glucocorticoid resistant. We show that wounding-induced increases in the expression of genes that encode neutrophil-specific chemoattractants (Il8 and Cxcl18b) are attenuated by the synthetic glucocorticoid beclomethasone, but that beclomethasone does not attenuate the induction of the genes encoding Ccl2 and Cxcl11aa, which are required for macrophage recruitment. RNA sequencing on FACS-sorted macrophages shows that the vast majority of the wounding-induced transcriptional changes in these cells are inhibited by beclomethasone, whereas only a small subset is glucocorticoid-insensitive. As a result, beclomethasone decreases the number of macrophages that differentiate towards a pro-inflammatory (M1) phenotype, which we demonstrated using a
reporter line and analysis of macrophage morphology. We conclude that differentiation and migration of macrophages are regulated independently, and that glucocorticoids leave the chemotactic migration of macrophages unaffected, but exert their anti-inflammatory effect on these cells by inhibiting their differentiation to an M1 phenotype. The resistance of macrophage-dominated diseases to glucocorticoid therapy can therefore not be attributed to an intrinsic insensitivity of macrophages to glucocorticoids.
Dysregulation of the inflammatory response in humans can lead to various inflammatory diseases, like asthma and rheumatoid arthritis. The innate branch of the immune system, including macrophage and ...neutrophil functions, plays a critical role in all inflammatory diseases. This part of the immune system is well-conserved between humans and the zebrafish, which has emerged as a powerful animal model for inflammation, because it offers the possibility to image and study inflammatory responses
at the early life stages. This review focuses on different inflammation models established in zebrafish, and how they are being used for the development of novel anti-inflammatory drugs. The most commonly used model is the tail fin amputation model, in which part of the tail fin of a zebrafish larva is clipped. This model has been used to study fundamental aspects of the inflammatory response, like the role of specific signaling pathways, the migration of leukocytes, and the interaction between different immune cells, and has also been used to screen libraries of natural compounds, approved drugs, and well-characterized pathway inhibitors. In other models the inflammation is induced by chemical treatment, such as lipopolysaccharide (LPS), leukotriene B4 (LTB4), and copper, and some chemical-induced models, such as treatment with trinitrobenzene sulfonic acid (TNBS), specifically model inflammation in the gastro-intestinal tract. Two mutant zebrafish lines, carrying a mutation in the hepatocyte growth factor activator inhibitor 1a gene (
) and the cdp-diacylglycerolinositol 3-phosphatidyltransferase (
) gene, show an inflammatory phenotype, and they provide interesting model systems for studying inflammation. These zebrafish inflammation models are often used to study the anti-inflammatory effects of glucocorticoids, to increase our understanding of the mechanism of action of this class of drugs and to develop novel glucocorticoid drugs. In this review, an overview is provided of the available inflammation models in zebrafish, and how they are used to unravel molecular mechanisms underlying the inflammatory response and to screen for novel anti-inflammatory drugs.
Glucocorticoids are effective drugs for treating immune-related diseases, but prolonged therapy is associated with an increased risk of various infectious diseases, including tuberculosis. In this ...study, we have used a larval zebrafish model for tuberculosis, based on
Mycobacterium marinum
(
Mm
) infection, to study the effect of glucocorticoids. Our results show that the synthetic glucocorticoid beclomethasone increases the bacterial burden and the dissemination of a systemic
Mm
infection. The exacerbated
Mm
infection was associated with a decreased phagocytic activity of macrophages, higher percentages of extracellular bacteria, and a reduced rate of infected cell death, whereas the bactericidal capacity of the macrophages was not affected. The inhibited phagocytic capacity of macrophages was associated with suppression of the transcription of genes involved in phagocytosis in these cells. The decreased bacterial phagocytosis by macrophages was not specific for
Mm
, since it was also observed upon infection with
Salmonella
Typhimurium. In conclusion, our results show that glucocorticoids inhibit the phagocytic activity of macrophages, which may increase the severity of bacterial infections like tuberculosis.
Mineral elements (copper (Cu), zinc (Zn), calcium (Ca), magnesium (Mg), iron (Fe)) play important biological roles in enzymes, hormones, vitamins, and normal metabolism. The deficiency of mineral ...elements can lead to abnormal physiological functions. And some elements (such as lead (Pb)) are harmful to the body. We aim to identify genetic loci which can influence the serum levels of mineral elements (Cu, Zn, Ca, Mg, Fe, and Pb). Genotyping was performed using Applied Biosystems Axiom™ PMDA in 587 individuals, and 6,423,076 single-nucleotide polymorphisms (SNPs) were available for the genome-wide association study (GWAS) analysis. The association between genotype and phenotype was analyzed using mixed linear regression (additive genetic model) adjusting by age and gender combined with identical by descent (IBD) matrix. Genetic loci in
BCHE-LOC105374194
,
DTX2P1-UPK3BP1-PMS2P11
,
VAT1L
,
LINC00908-LINC00683
,
LINC01310-NONE
, and rs6747410 in
VWA3B
were identified to be associated with serum Cu element concentration (
p
< 5 × 10
−6
).
ADAMTSL1
rs17229526 (
p
= 4.96 × 10
−6
) was significantly associated with serum Zn element levels. Genetic loci in
LRP1B
,
PIGZ-MELTF
,
LINC01365-LINC02502
, and
HAPLN3
were related to serum Ca element levels (
p
< 5 ×1 0
−6
). Three SNPs in
ALPK1
,
ASAP1-ADCY8
and
IER3IP1-SKOR2
also achieved a significant association with Mg element levels (
p
< 5 × 10
−6
).
TACSTD2-MYSM1
,
LRP1B
, and
ASAP1-ADCY8
showed suggestive associations with serum Fe element levels (
p
< 5 × 10
−6
). Moreover, the two most significant SNPs associated with Pb were rs304234 in
CADPS-LINC00698
(
p
= 2.47 × 10
−6
) and rs12666460 in
LOC101928211-GPR37
(
p
= 1.81 × 10
−6
). In summary, we reported 19 suggestive loci associated with serum mineral elements in the Chinese Han population. These findings provided new insights into the potential mechanisms regulating serum mineral elements levels.
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