ABSTRACT
BACKGROUND: Protein kinase C delta (PRKCD) and caspase recruitment domain family member 9 (CARD9) are genes involved in B and T cell activation, and cytokine production, which are vital mechanisms underlying autoimmune disease development. This study aimed to explore the association of the PRKCD and CARD9 genes with Vogt-Koyanagi-Harada disease (VKH) disease. The case-control study was performed to in 912 patients with VKH and 878 normal controls. MassARRAY system, SHEsis online platform, real-time PCR, and enzyme-linked immunosorbent assay were used to detect genotyping, haplotyping, mRNA expression, and cytokine levels, respectively. RESULTS: We found that rs74437127 C allele of PRKCD, rs3812555 CC genotype, and C allele of CARD9 were associated with increased susceptibility of VKH (Pc = 0.020, OR = 1.624; Pc = 2.04 × 10-5, OR = 1.810; Pc = 2.76 × 10-5, OR = 1.698, respectively). However, the rs74437127 T allele, and rs3812555 TC genotype and T allele were linked with decreased susceptibility to VKH (Pc = 0.020, OR = 0.616; Pc = 7.85 × 10-5, OR = 0.559; Pc = 2.76 × 10-5, OR = 0.589, respectively). PRKCD ATG and CARD9 GCTTA haplotypes decreased susceptibility to VKH (Pc = 3.11 × 10-3, OR = 0.594; Pc = 5.00 × 10-3, OR = 0.639, respectively). Functional studies on rs3812555 genotyped individuals revealed that CC carriers had significantly higher CARD9 mRNA expression and tumour necrosis factor-α production than TC/TT carriers (P = 1.00 × 10-4; P = 2.00 × 10-3, respectively). CONCLUSIONS: We found an association between PRKCD rs74437127 and CARD9 rs3812555 polymorphisms and VKH susceptibility and revealed that the increased susceptibility of rs3812555 for VKH may be mediated by regulating CARD9 gene expression and the production of pro-inflammatory cytokines, such as TNF-α.
Subject(s)
Protein Kinase C-delta , Uveomeningoencephalitic Syndrome , Humans , Protein Kinase C-delta/genetics , Protein Kinase C-delta/metabolism , Gene Frequency , Uveomeningoencephalitic Syndrome/genetics , Uveomeningoencephalitic Syndrome/metabolism , Case-Control Studies , East Asian People , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide/genetics , Cytokines/genetics , Cytokines/metabolism , RNA, Messenger , CARD Signaling Adaptor Proteins/genetics , CARD Signaling Adaptor Proteins/metabolismABSTRACT
Contemporary approaches for facial rejuvenation encompass the utilization of both ablative and nonablative laser techniques. Extensive research has elucidated the adverse consequences associated with ablative laser treatment, such as the emergence of infectious, follicular, scarring, and pigmentary alterations. Nonablative fractional lasers exhibit commendable cosmetic outcomes, characterized by a diminished incidence of complications owing to their photomechanical mechanisms, in contrast to ablative laser modalities. Nonetheless, it is imperative to acknowledge that untoward effects may still manifest. In this report, we present two cases of herpes simplex virus (HSV) reactivation subsequent to nonablative fractional resurfacing. Timely identification and the appropriate administration of antiviral agents are important, which serve as imperative measures to mitigate the long-term consequences that may arise in the event of complications.
Subject(s)
Skin Aging , Humans , Female , Skin Aging/radiation effects , Middle Aged , Low-Level Light Therapy/methods , Low-Level Light Therapy/adverse effects , Herpes Simplex/etiology , Virus Activation/radiation effects , Simplexvirus , Antiviral Agents/therapeutic use , Rejuvenation , Cosmetic Techniques/adverse effects , Cosmetic Techniques/instrumentation , Face , Laser Therapy/adverse effects , Laser Therapy/methodsABSTRACT
Peutz-Jeghers Syndromeis a rare autosomal dominant genetic disease characterized by gastrointestinal hamartomatous polyps and skin and mucous membrane pigmentation. The pathogenesis of PJS remains unclear; however, it may be associated with mutations in the STK11 gene, and there is currently no effective treatment available. The gut microbiota plays an important role in maintaining intestinal homeostasis in the human body, and an increasing number of studies have reported a relationship between gut microbiota and human health and disease. However, relatively few studies have been conducted on the gut microbiota characteristics of patients with PJS. In this study, we analyzed the characteristics of the gut microbiota of 79 patients with PJS using 16 S sequencing and measured the levels of short-chain fatty acids in the intestines. The results showed dysbiosis in the gut microbiota of patients with PJS, and decreased synthesis of short-chain fatty acids. Bacteroides was positively correlated with maximum polyp length, while Agathobacter was negatively correlated with age of onset. In addition, acetic acid, propionic acid, and butyric acid were positively correlated with the age of onset but negatively correlated with the number of polyps. Furthermore, the butyric acid level was negatively correlated with the frequency of endoscopic surgeries. In contrast, we compared the gut microbiota of STK11-positive and STK11-negative patients with PJS for the first time, but 16 S sequencing analysis revealed no significant differences. Finally, we established a random forest prediction model based on the gut microbiota characteristics of patients to provide a basis for the targeted diagnosis and treatment of PJS in the future.
Subject(s)
Gastrointestinal Microbiome , Peutz-Jeghers Syndrome , Humans , Peutz-Jeghers Syndrome/genetics , Peutz-Jeghers Syndrome/pathology , Germ-Line Mutation , Fatty Acids, Volatile , ButyratesABSTRACT
In this paper, nine strains of salt-tolerant petroleum-degrading bacteria were applied to an biological aerated filter. Simulating the degradation of high-salinity petroleum wastewater with n-hexadecane and 2,4-ditert-butylphenol as the primary pollutants and analyzing the structure of the biofilm at various salt concentrations. According to the results, when the salinity was 4%, the COD removal efficiency reached 74.34%. Various halotolerant microorganisms have adapted to various salt concentrations. At a salinity of 3%, n-hexadecane exhibited the best degradation effect, with a rate of 83.21%. Shewanella, Acinetobacter, and Marinobacter were the predominant bacterial groups at the time. At 4% salinity, Acinetobacter and Pseudomonas were the predominant bacteria, and the average 2,4-ditert-butylphenol degradation rate was the highest at 63.02%. This study provided an experimental basis for further studying the biological treatment of high-salinity petroleum wastewater.
Subject(s)
Environmental Pollutants , Petroleum , Petroleum/analysis , Environmental Pollutants/metabolism , Wastewater , Biodegradation, Environmental , Environmental Monitoring , Bacteria/metabolismABSTRACT
Avian influenza viruses, such as A(H5N1) and A(H7N9), are primary public health concerns due to their pandemic potential. Influenza vaccines represent the most effective response to this threat especially with timely provision. The current pandemic response timelines require a substantial period for strain-specific reference antigen and sera preparation for use with single-radial immunodiffusion (SRID), the accepted vaccine potency assay. To address this time lag, the isotope dilution mass spectrometry (IDMS) method was developed to quantify the absolute hemagglutinin (HA, the main influenza antigen) amount in the vaccine without the need for purified, inactivated, and calibrated virus reference antigens. However, an additional challenge in determining potency is to differentiate between vaccine antigens in their most potent form from other less potent, stressed antigen forms. The limited trypsin digestion (LTD) method has been developed and does not require strain-specific full-length reference antigens or antibodies; instead, stressed HA is selectively degraded, leaving the more potent form to be measured. LTD, followed by precipitation and IDMS, allows for efficient differentiation between potent and significantly less potent HA for vaccine release and potency testing across the vaccine's shelf life. In this study, we tested the LTD-IDMS assay on A(H5N1) vaccine material that had been stressed by low pH, heat, and multiple freeze-thaw cycles. The results showed that the LTD-IDMS method effectively quantified the potent HA in A(H5N1) vaccine material with results comparable to SRID. As such, it shows great promise to complement and potentially replace SRID in a pandemic when strain-specific reagents may not be readily available.
Subject(s)
Hemagglutinins/metabolism , Influenza A Virus, H5N1 Subtype/pathogenicity , Influenza A Virus, H7N9 Subtype/pathogenicity , Influenza Vaccines/immunology , Mass Spectrometry/methods , HumansABSTRACT
BACKGROUND: Growing evidence has shown that the gut-renal connection and gut microbiota dysbiosis play a critical role in immunoglobulin A nephropathy (IgAN). However, the fecal microbiome profile in Chinese patients with IgAN remains unknown. A cross-sectional study was designed for the first time to investigate the fecal microbiota compositions in patients with primary IgAN in China and to evaluate the relationship between the fecal microbiome and IgAN clinical presentation. METHODS: Fecal samples were collected from 17 IgAN patients and 18 age-, sex-, and body mass index-matched healthy controls, and bacterial DNA was extracted for 16S ribosomal RNA gene sequencing targeting the V3-V4 region. RESULTS: Fecal samples from the IgAN patients and healthy controls showed differences in gut microbiota community richness and compositions. Compared to the healthy controls, IgAN patients at the phylum level had an increased abundance of Fusobacteria, but a decreased abundance of Synergistetes. The significantly increased genera in the IgAN group were Escherichia-Shigella, Hungatella, and Eggerthella, all of which possess pathogenic potential. Furthermore, the genus Escherichia-Shigella was negatively associated with the estimated glomerular filtration rate (eGFR) but was positively associated with the urinary albumin-to-creatinine ratio (uACR). However, the genus rectale_group was present in the IgAN group with a low abundance and was negatively associated with the uACR. Functional analysis disclosed that infection-related pathways were enriched in the IgAN group. CONCLUSIONS: We demonstrate that gut microbiota dysbiosis occurs in patients with IgAN, and that changes in gut bacterial populations are closely related to IgAN clinical features, suggesting that certain specific gut microbiota may be a potential therapeutic target for IgAN.
Subject(s)
Asian People , Feces/microbiology , Gastrointestinal Microbiome , Glomerulonephritis, IGA/ethnology , Glomerulonephritis, IGA/microbiology , Adult , Albuminuria/urine , Bacteria/genetics , Bacteria/isolation & purification , Creatinine/urine , Cross-Sectional Studies , Female , Gastrointestinal Microbiome/genetics , Glomerular Filtration Rate , Glomerulonephritis, IGA/physiopathology , Humans , Male , Middle Aged , RNA, Ribosomal, 16S/genetics , Sequence Analysis, RNAABSTRACT
Respiratory syncytial virus (RSV) is the leading infectious cause of severe respiratory disease in infants and a major cause of respiratory illness in the elderly. There remains an unmet vaccine need despite decades of research. Insufficient potency, homogeneity, and stability of previous RSV fusion protein (F) subunit vaccine candidates have hampered vaccine development. RSV F and related parainfluenza virus (PIV) F proteins are cleaved by furin during intracellular maturation, producing disulfide-linked F1 and F2 fragments. During cell entry, the cleaved Fs rearrange from prefusion trimers to postfusion trimers. Using RSV F constructs with mutated furin cleavage sites, we isolated an uncleaved RSV F ectodomain that is predominantly monomeric and requires specific cleavage between F1 and F2 for self-association and rearrangement into stable postfusion trimers. The uncleaved RSV F monomer is folded and homogenous and displays at least two key RSV-neutralizing epitopes shared between the prefusion and postfusion conformations. Unlike the cleaved trimer, the uncleaved monomer binds the prefusion-specific monoclonal antibody D25 and human neutralizing immunoglobulins that do not bind to postfusion F. These observations suggest that the uncleaved RSV F monomer has a prefusion-like conformation and is a potential prefusion subunit vaccine candidate. Importance: RSV is the leading infectious cause of severe respiratory disease in infants and a major cause of respiratory illness in the elderly. Development of an RSV vaccine was stymied when a clinical trial using a formalin-inactivated RSV virus made disease, following RSV infection, more severe. Recent studies have defined the structures that the RSV F envelope glycoprotein adopts before and after virus entry (prefusion and postfusion conformations, respectively). Key neutralization epitopes of prefusion and postfusion RSV F have been identified, and a number of current vaccine development efforts are focused on generating easily produced subunit antigens that retain these epitopes. Here we show that a simple modification in the F ectodomain results in a homogeneous protein that retains critical prefusion neutralizing epitopes. These results improve our understanding of RSV F protein folding and structure and can guide further vaccine design efforts.
Subject(s)
Antibodies, Neutralizing/immunology , Antigens, Viral/immunology , Epitopes/immunology , Respiratory Syncytial Viruses/immunology , Humans , ProteolysisABSTRACT
OBJECTIVES: To investigate the relationship of pre-treatment MR image features (including breast density) and clinical-pathologic characteristics with overall survival (OS) in breast cancer patients receiving neoadjuvant chemotherapy (NAC). METHODS: This retrospective study obtained an approval of the institutional review board and the written informed consents of patients were waived. From October 2013 to April 2019, 130 patients (mean age, 47.6 ± 9.4 years) were included. The univariable and multivariable Cox proportional hazards regression models were applied to analyze factors associated with OS, including MR image parameters and clinical-pathologic characteristics. RESULTS: Among the 130 included patients, 11 (8.5%) patients (mean age, 48.4 ± 11.8 years) died of breast cancer recurrence or distant metastasis. The median follow-up length was 70 months (interquartile range of 60-85 months). According to the Cox regression analysis, older age (hazard ratio [HR] = 1.769, 95% confidence interval [CI]): 1.330, 2.535), higher T stage (HR = 2.490, 95%CI:2.047, 3.029), higher N stage (HR = 1.869, 95%CI:1.507, 2.317), low breast density (HR = 1.693, 95%CI:1.391, 2.060), peritumoral edema (HR = 1.408, 95%CI:1.078, 1.840), axillary lymph nodes invasion (HR = 3.118, 95%CI:2.505, 3.881) on MR were associated with worse OS (all p < 0.05). CONCLUSIONS: Pre-treatment MR features and clinical-pathologic parameters are valuable for predicting long-time OS of breast cancer patients after NAC followed by surgery. Low breast density, peritumoral edema and axillary lymph nodes invasion on pre-treatment MR images were associated with worse prognosis.
Subject(s)
Breast Neoplasms , Humans , Adult , Middle Aged , Female , Breast Neoplasms/pathology , Neoadjuvant Therapy , Retrospective Studies , Breast Density , Neoplasm Recurrence, Local , Prognosis , EdemaABSTRACT
BACKGROUND: Several treatment modalities are used for the treatment of periorbital rejuvenation with variable results. Recent studies showed that fractional radiofrequency may be an effective treatment modality for periorbital aging. This study aims to determine the efficacy and safety of negative pressure fractional microneedle radiofrequency (NPFMR) as a treatment for periorbital aging. METHODS: Twenty-five patients with periorbital aging were involved in this study. They were treated two times with an interval of 1 month. The patients were evaluated before treatment and 1, 3, and 6 months after the final treatment. RESULTS: The research findings suggest that periorbital wrinkles of the patients were significantly improved by VISIA system (p < 0.05). Physiological indicators detected by MPA10 system showed that compared with before treatment, the hydration increased (p < 0.05) and trans epidermal water loss (TEWL) decreased (p < 0.05) at 3 and 6 months after treatment. The glossiness increased at 1 month after treatment compared to pre-treatment (p < 0.05) and returned to the baseline level at 3 and 6 months after treatment. There was no significant change in melanin content (p > 0.05). Periorbital dermal thickness of the patients significantly increased at 1, 3, and 6 months after treatment according to skin ultrasound (p < 0.05). A periorbital skin biopsy revealed that the collagen fibers in the dermis were significantly thicker and more orderly after treatment, and the expression of type I collagen fibers and elastic fibers was increased compared with that before treatment. One patient developed post-inflammatory hyperpigmentation (PIH) at 1 month after the first treatment, which improved after active treatment. No other adverse reactions were observed. CONCLUSIONS: NPMFR could be an effective and safe treatment modality for the treatment of periorbital aging.
Subject(s)
Patient Satisfaction , Skin Aging , Humans , Treatment Outcome , Skin/diagnostic imaging , Rejuvenation , AgingABSTRACT
Ulcerative colitis (UC) is a chronic aspecific gut inflammatory disorder that primarily involves the recta and colons. It mostly presents as a long course of repeated attacks. This disease, characterized by intermittent diarrhoea, fecal blood, stomachache, and tenesmus, severely decreases the living quality of sick persons. UC is difficult to heal, has a high recurrence rate, and is tightly related to the incidence of colon cancer. Although there are a number of drugs available for the suppression of colitis, the conventional therapy possesses certain limitations and severe adverse reactions. Thus, it is extremely required for safe and effective medicines for colitis, and naturally derived flavones exhibited huge prospects. This study focused on the advancement of naturally derived flavones from edible and pharmaceutical plants for treating colitis. The underlying mechanisms of natural-derived flavones in treating UC were closely linked to the regulation of enteric barrier function, immune-inflammatory responses, oxidative stress, gut microflora, and SCFAs production. The prominent effects and safety of natural-derived flavones make them promising candidate drugs for colitis treatment.
ABSTRACT
There is an increasing evidence suggesting that myo-inositol (MI) may be a renoprotective factor. Our previous study revealed that decreased MI concentrations and increased excretion are often observed in animal models of renal injury and in patients with nephropathy. However, the role of MI supplementation in renal injury remains unclear. In this study, we aimed to explore the role of MI in cisplatin-induced acute kidney injury (AKI). We established a model of acute kidney injury caused by cisplatin (CDDP). Male Kunming mice were randomly divided into six groups: Sham (normal saline), CDDP (15 mg/kg), + MI (150 mg/kg), + MI (300 mg/kg), + MI (600 mg/kg) and MI (600 mg/kg). Human renal tubular epithelial cell line HK-2 cells were likewise separated into six groups at random: Control (normal saline), CDDP (20 µM), + MI (200 µM), + MI (400 µM), + MI (800 µM) and MI (800 µM). After the model was established, renal function indexes were subsequently detected, and experiments such as pathological staining analysis and protein expression analysis were performed. Our results showed that cisplatin administration led to AKI and apoptosis in mice and HK-2 cells, accompanied by markedly increased levels of MIOX, kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL), whereas exogenous MI significantly attenuated kidney injury and HK-2 cell damage induced by cisplatin both in vivo and in vitro by inhibiting excessive apoptosis. Overall, our findings demonstrate that exogenous MI can reduce excessive apoptosis, thus playing a protective role in cisplatin-induced AKI, indicating that exogenous MI may be used as an adjunctive treatment modality in cisplatin-induced AKI.
Subject(s)
Acute Kidney Injury , Cisplatin , Mice , Humans , Male , Animals , Cisplatin/toxicity , Saline Solution/toxicity , Saline Solution/metabolism , Acute Kidney Injury/chemically induced , Acute Kidney Injury/prevention & control , Acute Kidney Injury/metabolism , Kidney , ApoptosisABSTRACT
Anaerobic landfills have long been the primary means of municipal solid waste (MSW) disposal in China. Landfills are the third largest emission source of methane (CH4), which is the second most abundant greenhouse gas in the atmosphere and has a high greenhouse effect. To date, there have been no reliable model predictions of long-term CH4 emissions from landfills in China. In this study, two general models, IPCC and LandGEM, were introduced to simulate CH4 emissions from all landfills in China. By comparing the results of the Shuangkou landfill in Tianjin with the default and local parameters, the local parameters were fixed to simulate landfill CH4 emissions in 31 regions over 40 years (2003-2042). The MSW landfills were obtained from statistical data for 18 years (2003-2020). The total emissions in China predicted by LandGEM and IPCC were 2.42 E+07 Mg and 2.36 E+07 Mg, respectively. These data provide a reliable reference for determining the long-term CH4 emissions from landfills in China.
ABSTRACT
Depression is a psychological disorder that affects the general public worldwide. It is particularly important to make an objective and accurate diagnosis of depression, and the measurement methods of brain activity have gradually received increasing attention. Resting electroencephalogram (EEG) alpha asymmetry in patients with depression shows changes in activation of the alpha frequency band of the left and right frontal cortices. In this paper, we review the findings of the relationship between frontal EEG alpha asymmetry in the resting state and depression. Based on worldwide studies, we found the following: (1) Compared with individuals without depression, those with depression showed greater right frontal EEG alpha asymmetry in the resting state. However, the pattern of frontal EEG alpha asymmetry in the resting state in depressive individuals seemed to disappear with age; (2) Compared with individuals without maternal depression, those with maternal depression showed greater right frontal EEG alpha asymmetry in the resting state, which indicated that genetic or experience-based influences have an impact on frontal EEG alpha asymmetry at rest; and (3) Frontal EEG alpha asymmetry in the resting state was stable, and little or no change occurred after antidepressant treatment. Finally, we concluded that the contrasting results may be due to differences in methodology, clinical characteristics, and participant characteristics.
ABSTRACT
In this work, the ß-cyclodextrin (ß-CD) was modified by a phosphazene compound to prepare a novel amorphous derivate (ß-CDCP), which was combined with the ammonium polyphosphate (APP) as a synergistic flame retardant (FR) of the bio-based poly(L-lactic acid) (PLA). The effects of the APP/ß-CDCP on the thermal stability, combustion behavior, pyrolysis process, fire resistance performance and crystallizability of the PLA were investigated comprehensively and in depth by thermogravimetric (TG) analysis, limited oxygen index (LOI) analysis, UL-94 test, cone calorimetry measurement, TG-infrared (TG-IR), scanning electron microscopy-energy dispersive spectrometer, Raman spectroscopy, pyrolysis-gas chromatography/mass spectrometry and differential scanning calorimetry. The PLA/5%APP/10%ß-CDCP showed a highest LOI of 33.2 %, passed V-0 rating and exhibited self-extinguish phenomenon in the UL-94 test. Also, it presented a lowest peak of heat release rate, total heat release, peak of smoke production rate and total smoke release, and a highest char yield treated by cone calorimetry analysis. In addition, the 5%APP/10%ß-CDCP shortened significantly crystallization time and enhanced crystallization rate of the PLA. Gas phase and intumescent condensed phase fire proofing mechanisms are proposed to elucidate enhanced fire resistance in this system in detail.
Subject(s)
Oxygen , Smoke , Microspheres , Calorimetry , PolyestersABSTRACT
AIM: To investigate the myopia awareness level, knowledge, attitude, and skills at baseline and to implement and evaluate the efficacy of myopia prevention health education among Chinese students. METHODS: A total of 1000 middle school students from 2 middle schools were invited to participate in the study, and myopia prevention health education was conducted. The students were assessed at baseline, followed by a survey. The efficacy of health education was evaluated using the self-comparison method pre- and post-health education. RESULTS: The study included 957 and 850 pre- and post-health education participants, respectively. The baseline knowledge of all respondents on myopic symptoms (87.5%), myopia is a risk of eyes (72.9%), myopia prevention (91.3%), myopia increases with age (86.7%), performing periodic eye examinations (92.8%), and one first, one foot, and one inch (84.8%) significantly increased after health education (P<0.001 for all). However, the percentage of students who still did not think it necessary to take breaks after 30-40min of continuous near work was 27.0%. The opinion that "myopia can be cured" was still present in 38.3%. CONCLUSION: Implementing school-based myopia prevention health education improves knowledge, attitudes, and skills regarding myopia among Chinese middle school students.
ABSTRACT
CTRP6, a newly identified adiponectin analogue, has been shown to be involved in inflammation, diabetes and cardiovascular diseases. Recently, increasing evidence has shown that CTRP6 plays a critical role in fibrotic diseases, such as myocardial fibrosis and skin fibrosis. FAO, an important energy source for kidney proximal tubular cells, also participates in the process of fibrosis. Therefore, our study aimed to investigate the effect of CTRP6 on mediating FAO in kidney fibrosis and the underlying associated mechanism. Firstly, the activity of CTRP6 and the key enzymes of FAO (CPT1A, ACOX1) were tested in vivo and vitro. Next, the regulatory effect of CTRP6/AMPK on FAO was accessed in animal models and in cell lines. Additionally, we explored the effect of exogenous recombinant CTRP6 on renal tubular epithelial cell differentiation. Decreased CTRP6 and p-AMPK were detected in UUO-induced kidney fibrosis and in TGF-ß1-treated HK-2 cells. We also observed that defective FAO occurred during kidney fibrosis. Moreover, the human CTRP6 peptide could inhibit the ECM deposition and promote the phosphorylation of AMPK by promoting FAO. However, the inhibitory effects of CTRP6 on TGF-ß1-induced ECM deposition and the protective effects of CTRP6 on FAO could be abolished by compound C, a selective inhibitor of AMPK. Compound C also reversed the CTRP6-mediated upregulation of p-AMPK. The mediation of FAO by CTRP6 plays a key role in kidney fibrosis by regulating TGF-ß1-induced renal tubular epithelial cell differentiation by promoting FAO, which is mediated via AMPK activation.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Adipokines/metabolism , Collagen/metabolism , Fatty Acids/metabolism , Kidney Diseases/enzymology , Kidney Tubules, Proximal/enzymology , Acyl-CoA Oxidase/genetics , Acyl-CoA Oxidase/metabolism , Adipokines/genetics , Animals , Carnitine O-Palmitoyltransferase/genetics , Carnitine O-Palmitoyltransferase/metabolism , Cell Line , Collagen/genetics , Disease Models, Animal , Fibrosis , Humans , Kidney Diseases/etiology , Kidney Diseases/genetics , Kidney Diseases/pathology , Kidney Tubules, Proximal/drug effects , Kidney Tubules, Proximal/pathology , Male , Mice , Oxidation-Reduction , Phosphorylation , Signal Transduction , Transforming Growth Factor beta1/pharmacology , Ureteral Obstruction/complicationsABSTRACT
Objectives: Emerging evidence suggests that gut microbiota dysbiosis plays a critical role in chronic kidney disease (CKD). However, the relationship between altered gut microbiome profiles and disease severity remains unclear. In this study, we sought to characterize the gut microbiota in CKD patients compared to healthy controls, and to explore potential relationships between gut microbiota composition and disease severity. Methods: Fecal samples were collected from 95 patients at different stages of CKD (non-dialysis patients from stage 1 to 5) and 20 healthy controls. Bacterial DNA was extracted for 16S ribosomal DNA sequencing targeting the V3-V4 region. The diversity and relative abundance of gut microbiota were analyzed as outcome indicators. Results: Differences were observed in the microbial composition and diversity of fecal samples from CKD patients and healthy controls. Specifically, disease severity was found to alter gut microbiota composition. Compared to that in healthy controls, CKD patients showed an increased abundance of Proteobacteria and decreased Synergistetes, most notably in disease stage 5. Lower levels of butyrate-producing bacteria and higher levels of potential pathogens were also detected in CKD patients. Further, Pyramidobacter and Prevotellaceae_UCG-001 were significantly decreased in the CKD1 group compared with healthy controls. Notably, nine microbial genera, including Escherichia-Shigella, Parabacteroides, Roseburia, rectale_group, Ruminococcaceae_NK4A214_group, Prevotellaceae_UCG.001, Hungatella, Intestinimonas, and Pyramidobacter, identified using a random forest model, distinguished between patients with CKD and healthy controls with high accuracy. Functional analysis also revealed that fatty acid and inositol phosphate metabolism were enriched in the CKD group, while aminoacyl-tRNA biosynthesis, oxidative phosphorylation, phenylalanine, tyrosine, and tryptophan biosynthesis, thiamine metabolism, pantothenate, and CoA biosynthesis, as well as valine, leucine, and isoleucine biosynthesis were enriched in healthy controls. Conclusion: Gut microbiota composition and function are associated with CKD severity. And, specific gut microbes are potentially helpful for CKD early diagnosis and prognosis monitoring.
Subject(s)
Bacteria , Dysbiosis/microbiology , Feces/microbiology , Gastrointestinal Microbiome/physiology , Renal Insufficiency, Chronic , Bacteria/genetics , Bacteria/isolation & purification , Bacteria/metabolism , Correlation of Data , DNA, Bacterial/analysis , Early Diagnosis , Female , Humans , Male , Middle Aged , Prognosis , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/physiopathology , Severity of Illness IndexABSTRACT
Renal fibrosis is a major pathological process in the progression of various chronic kidney diseases to end-stage renal disease (ESRD). Growing evidence has suggested that gut microbiota dysbiosis is closely related to ESRD. However, the interplay between altered fecal microbiome and metabolome during the renal fibrotic process remains unclear. Herein, an integrated approach of 16S ribosomal DNA sequencing combined with an ultra-high performance liquid chromatography-mass spectrometry-based metabolomics platform was applied to investigate the dynamic changes of fecal microbiota and metabolites throughout renal fibrosis progression in a mouse model of unilateral ureteral obstruction (UUO). The composition of gut microbiota changed markedly before and after UUO surgery. UUO mice showed a decrease in short-chain fatty acids-producing genera, including Bacteroides, Prevotellaceae_UCG-001, Roseburia, and Lachnospiraceae_NK4A136_group, as well as an increase in the genera Parasutterella and Alistipes, which changed dynamically over time. Additionally, 41 differential metabolites, mainly involved in 12 metabolic pathways, including inositol phosphate metabolism, primary bile acid biosynthesis, biosynthesis of unsaturated fatty acids, taurine and hypotaurine metabolism, purine metabolism, were identified in the UUO mice before and after surgery. Four fecal metabolites, myo-inositol, dodecanoic acid, N-acetylputrescine, and anthranilic acid, were positively associated with the progression of renal fibrosis. Moreover, by using multi-omics analyses, we found the alteration in UUO-related gut microbiota was correlated with a change in fecal metabolites. Therefore, our results provide insights into disturbances of the microbiome-metabolome interface in the progression of UUO-related renal fibrosis.
Subject(s)
Feces/microbiology , Gastrointestinal Microbiome , Kidney Diseases/pathology , Metabolome , Ureteral Obstruction/complications , Animals , Bile Acids and Salts/biosynthesis , Disease Progression , Fibrosis , Kidney/pathology , Kidney Diseases/etiology , Male , Metabolomics , Mice , Mice, Inbred C57BL , RNA, Ribosomal, 16S/analysis , Ureteral Obstruction/pathologyABSTRACT
BACKGROUND: Major depressive disorder (MDD) is a severe mental illness with high prevalence and recurrence rates. Cognitive impairments are found in most depressed patients, but systematic assessment of sex differences in cognitive deficits remains to be investigated. METHODS: A total of 69 first-diagnosed, drug-naïve depressed outpatients (males/females = 28/41; average age: 27.51±8.82 years) and 57 healthy controls (HCs) (males/females = 26/31; average age: 29.05±8.69 years) were recruited. Cognitive function, measured by repeatable battery for the assessment of neuropsychological status [RBANS] scores, was compared between depressed patients and healthy controls in males and females. RESULTS: Immediate memory, delayed memory and RBANS total score were significantly decreased in depressed patients compared with healthy controls. Moreover, among patients with first-diagnosed, drug-naïve depression, females had lower visuospatial and constructional scores than males, whereas among controls, females had higher language scores than males. Interestingly, impaired attention was negatively associated with the Beck Depression Inventory-II (BDI-II) score in female patients, but not in male patients. CONCLUSION: Female patients with first-diagnosed, drug-naïve depression had more serious cognitive impairment than male patients in the visuospatial and constructional categories. Cognitive impairment was associated with depression severity only in female patients. These observations build the basis for future investigation of sex differences in cognitive impairment of depressed patients.
Subject(s)
Cognitive Dysfunction , Depressive Disorder, Major , Pharmaceutical Preparations , Adolescent , Adult , Case-Control Studies , Cognition , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/epidemiology , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/epidemiology , Female , Humans , Male , Neuropsychological Tests , Sex Characteristics , Young AdultABSTRACT
Existing enhancement methods are empirically expected to help the high-level end computer vision task: however, that is observed to not always be the case in practice. We focus on object or face detection in poor visibility enhancements caused by bad weathers (haze, rain) and low light conditions. To provide a more thorough examination and fair comparison, we introduce three benchmark sets collected in real-world hazy, rainy, and low-light conditions, respectively, with annotated objects/faces. We launched the UG2+ challenge Track 2 competition in IEEE CVPR 2019, aiming to evoke a comprehensive discussion and exploration about whether and how low-level vision techniques can benefit the high-level automatic visual recognition in various scenarios. To our best knowledge, this is the first and currently largest effort of its kind. Baseline results by cascading existing enhancement and detection models are reported, indicating the highly challenging nature of our new data as well as the large room for further technical innovations. Thanks to a large participation from the research community, we are able to analyze representative team solutions, striving to better identify the strengths and limitations of existing mindsets as well as the future directions.