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1.
J Cell Biochem ; 121(1): 231-243, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31190401

RESUMO

The significance of actin-related protein 2/3 complex subunit 4 (ARPC4) expression in bladder cancer, and its potential role in the invasion and migration of bladder cancer cells, has yet to be determined. This study was to identify the correlation between ARPC4 and lymph node metastasis, and to determine the role of ARPC4 in the invasive migration of T24 bladder cancer cells. One hundred and ninety-eight bladder cancer tissues and 40 normal bladder and lymph node tissues were examined. Tissue microarrays were constructed and subjected to immunohistochemical stating for ARPC4. Multiple logistic analysis was used to determine risk factors associated with bladder cancer metastasis. ARPC4 expression in T24 bladder cancer cells was suppressed using small interfering RNA and changes in protein levels were determined by Western blot analysis. The proliferation of bladder cancer cells after knocking down of ARPC4 was determined by cell counting kit-8. The effects of ARPC4 knockdown on T24 cell invasion and migration was determined using transwell and wound healing assays. Immunofluorescence analysis was performed to examine changes in pseudopodia formation and actin cytoskeleton structure. The expression of ARPC4 was elevated in bladder cancer tissues than normal tissues (84.3% vs 27.5%, P < 0.001). The multivariate logistic analysis demonstrated that the level of ARPC4, as a risk factor, was correlated with lymphatic metastasis (P < 0.05). ARPC4 knockdown attenuated proliferation, migration, invasion, and pseudopodia formation in T24 cells. ARPC4 expression, as a risk factor, is associated with lymphatic metastasis and is upregulated in bladder cancer tissues in comparison with normal tissues. Inhibition of ARPC4 expression significantly attenuates the proliferation, migration, and invasion of bladder cancer cell, possibly due to defects in pseudopodia formation.

2.
BMC Evol Biol ; 19(1): 212, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31747896

RESUMO

Following publication of the original article [1], we have been notified that Additional file 3 was published with track changes.

3.
Curr Mol Med ; 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31749427

RESUMO

Butyric acid (BT), a short-chain fatty acid, is the preferred colonocyte energy source. The effects of BT on the differentiation, proliferation, and apoptosis of small intestinal epithelial cells of piglets and its underlying mechanisms are not yet fully elucidated. In this study, we found that 0.2-0.4 mM BT promoted the procine jejuna epitheial cell line (IPEC-J2) cells differentiation. BT at 0.5 mM or higher concentrations significantly impaired cell viability in a dose- and time- dependent manner. In addition, BT at high concentrations inhibited the IPEC-J2 cells proliferation and induced cell cycle arrest in the G2/M phase. Our results demonstrate that BT triggered IPEC-J2 cell apoptosis via the caspase8- caspase3 pathway and was accompanied by excess reactive oxygen species (ROS) and TNF-α production. BT at high concentrations inhibited cell autophagy associated with increased lysosome formation. We found that BT-reduced IPEC-J2 cell viability can be attenuated by p38 MAPK inhibitor SB202190. And SB202190 attenuated BT-increased p38 MAPK target DDIT3 mRNA level and V-ATPase mRNA level that responsible for normal acidy lyososomes. In conclusion, 1) at 0.2-0.4 mM, BT promotes the IPEC-J2 cells differentiation; 2) BT at 0.5 mM or higher concentrations induce cell apoptosis via the p38 MAPK pathway; 3) BT inhibits cells autophagy and promote lysosome formation at high concentrations.

4.
Prep Biochem Biotechnol ; : 1-7, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31738649

RESUMO

Gellan gum, produced by Sphingomonas paucimobilis, is increasingly used in food and pharmaceutical industries as stabilizing, emulsifying, texturing and gelling agents. However, its high production costs may limit its full commercial potential. Therefore, in this study, we investigated ways to reduce gellan gum production costs and improve yields. We first revealed corn steep liquor (CSL) as a cost-effective nutrient source that can improve gellan gum yields. We then systematically optimized culture conditions even further, and revealed that the addition of Triton X-100 surfactant and selected inorganic nitrogen sources improved gellan gum production. Under our optimized conditions (glucose 33.75 g/L, CSL 10 g/L, urea 2.5 g/L, MgSO4 1.08 g/L, KH2PO4 3.24 g/L, K2SO4 1 g/L and Triton X-100 0.75 g/L), we yielded a maximum concentration of 14.41 g/L, which was about 1.5-fold higher than non-optimized CSL-based medium. Our findings highlight the use of CSL as a cost effective and promising nutrient source for industrial production of gellan gum.

5.
BMC Infect Dis ; 19(1): 925, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666015

RESUMO

BACKGROUND: Ruili is a border city in southwest China along the heroin trafficking route. In recent decades, the city has witnessed increased in HIV transmission. The current study aims to explore the spatiotemporal trends in HIV prevalence identify and map the spatial variation and clustering of factors associated with HIV transmission through drug use and heterosexual contact transmissions at the village level from 1989 through 2016. METHODS: Geographic information system-based spatiotemporal analyses, including global and local spatial autocorrelation analyses and space-time scanning statistics, were applied to detect the location and extent of HIV/AIDS high-risk areas. RESULTS: Drug use and heterosexual contact were identified as the major transmission routes causing infection in Ruili. Results of global spatial analysis showed significant clustering throughout the city caused by transmission via drug use in the early phase of the epidemic and transmission via heterosexual contact in the late phase of the epidemic during the study period. Hotspots of transmission from drug use were randomly distributed throughout the city. However, the hotspots of transmission by heterosexual contact were located in the central area only around the Jiegao China-Myanmar land port. Space-time scanning showed that transmission from drug use clustered in the southwest area between 1989 and 1990, while transmission by heterosexual contact clustered in the central area between 2004 and 2014. CONCLUSIONS: Heterosexual contact has become the dominant mode of transmission. Interventions should focus on highly clustered area where is around the Jiegao land port.

6.
J Gene Med ; : e3144, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31742830

RESUMO

BACKGROUND: The hepatobiliary tract may be a valuable administration site for gene delivery. We demonstrated the role of temporary biliary obstruction for gene transfection by retrograde intrabiliary infusion. METHODS: Male Sprague-Dawley rats received intrabiliary infusion of luciferase plasmid via an artificial common bile duct, with temporary biliary obstruction for 0 minute (NO group), 30 minutes (30min group) and 24 hours (24h group), respectively (n=4 for each group). Gene expression levels were evaluated by luciferase bioluminescence on postoperative days (POD) 1, 2, and 7. Serum and livers were collected on POD 1 and 14 for liver biochemistry, hematoxylin-eosin staining and immunohistochemistry. RESULTS: On POD 1, luciferase chemoluminescence was significantly higher in the 24h group than in the NO group (p=0.002) and the 30min group (p=0.002). But it decreased rapidly after reversal of the obstruction in the 24h group (POD 1 vs POD 2, p=0.002; POD 1 vs POD 7, p=0.002). Liver biochemistry was changed on POD 1, but no significant differences were detected after 14-day recovery (p>0.05). Similar histological changes were found in the three groups, with no unwanted proliferation of biliary epithelial cells. The obstruction did not cause serious liver damage. CONCLUSIONS: Temporary biliary obstruction for 24 hours facilitated safe, feasible and effective transfection of plasmid DNA into liver via hepatobiliary tract. In the future, ERCP and its dilation balloon could be used to create biliary obstruction and allow direct gene delivery into liver. More researches are necessary for achieving stable gene expression, and weighing its benefits against potential complications.

7.
Drug Des Devel Ther ; 13: 3717-3726, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31754297

RESUMO

Background: Melanoma is known as the most aggressive and lethal type of cutaneous cancer due to its rapid development of drug resistance to chemotherapy drugs. Methods: In our study, we conducted a variety of studies, including quantitative PCR, Western blot, and autophagy and apoptosis assays to investigate the involvement of miR-26a and HMGB1 in modulation of dabrafenib sensitivity in human melanoma cell lines. Results: Our studies revealed that the expressions of miR-26a and HMGB1 were altered in two melanoma cell lines after dabrafenib treatment. Additionally, dabrafenib caused autophagy in melanoma and this autophagic process was regulated by miR-26a via modifying HMGB1 expression. Furthermore, silencing HMGB1-inhibited autophagy induced by dabrafenib in melanoma cells. Last, we verified that treatment with a miR-26a mimic and HMGB1 shRNA could increase the efficacy of dabrafenib in melanoma cells. Conclusion: Taken together, we showed that miR-26a is involved in the regulation of dabrafenib efficacy via a HMGB1-dependent autophagy pathway in melanoma cells. These results shed light on a novel treatment for conventional dabrafenib-based chemotherapy for melanoma.

8.
ChemSusChem ; 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31769174

RESUMO

The copolymerization of CO 2 /EP offers an efficient approach to sustainable polycarbonates and has accordingly drawn a great deal of attention in recent decades. Industrial scale processes have been applied for these copolymerisations as a result of better catalysts enabling the process to become more economically viable. In turn, this could facilitate the production of a diverse array of polycarbonates with tuneable thermomechanical properties under increasingly mild conditions. Nevertheless, the current portfolio of non-degradable plastics still remains comparatively inexpensive, but environmental concerns associated with their irresponsible use are drastically increasing. Therefore, it is imperative to continue the development of more sustainable polymers (those from renewable sources and/or possessing biodegradability) and lower the cost of such materials. As it stands, renewable plastics from bio-based monomers and CO 2 are poised to compete with petroleum-derived products. For example, poly (limonene carbonate) and 2,5-furandicarboxylic acid (FDCA) (a monomer from biomass waste/CO 2 ) have led to various methodologies of CO 2 utilisation and shown great promise as robust plastics. The issue of replacing petroleum commodity plastics remains a great challenge for the chemistry community, but producing polycarbonates from CO 2 , and sustainable polymers in general, are still nascent and further improvements will certainly be gained from more efficient organometallic catalysts and the maturation of organocatalysts. Organocatalyzed methods could provide a breakthrough and further drive the production price down while offering an even greener approach. Although both metal- and organic-based catalysts present several respective advantages and viable options for CO 2 -based polymer synthesis, overcoming the sensitivity against contamination ( e.g. oxygen, moisture), and using air as a CO 2 resource, could allow CO 2 -based fabrication to be carried out on a global industrial scale.

9.
Aging (Albany NY) ; 11(21): 9478-9491, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672930

RESUMO

BACKGROUND: Numerous patients with clear cell renal cell carcinoma (ccRCC) experience drug resistance after immunotherapy. Regulatory T (Treg) cells may work as a suppressor for anti-tumor immune response. PURPOSE: We performed bioinformatics analysis to better understand the role of Treg cells in ccRCC. RESULTS: Module 10 revealed the most relevance with Treg cells. Functional annotation showed that biological processes and pathways were mainly related to activation of the immune system and the processes of immunoreaction. Four hub genes were selected: LCK, MAP4K1, SLAMF6, and RHOH. Further validation showed that the four hub genes well-distinguished tumor and normal tissues and were good prognostic biomarkers for ccRCC. CONCLUSION: The identified hub genes facilitate our knowledge of the underlying molecular mechanism of how Treg cells affect ccRCC in anti-tumor immune therapy. METHODS: The CIBERSORT algorithm was performed to evaluate tumor-infiltrating immune cells based on the Cancer Genome Atlas cohort. Weighted gene co-expression network analysis was conducted to explore the modules related to Treg cells. Gene Ontology analysis and pathway enrichment analysis were performed for functional annotation and a protein-protein interaction network was built. Samples from the International Cancer Genomics Consortium database was used as a validation set.

10.
Anal Chem ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31691558

RESUMO

It has been reported that PIWI-interacting RNAs (piRNAs) play critical roles in activating invasion and metastasis, evading growth suppressors, and sustaining proliferative signaling of cancer and can be regarded as a novel biomarker candidate. Thus, it is necessary to develop an effective method for imaging and regulating cancer-related piRNAs to diagnose and treat cancers. Herein, we designed aptamer-functionalized activatable DNA tetrahedron nanoprobes (apt-ADTNs) to image and regulate endogenous piRNAs in cancer cells. As proof of concept, overexpressed piRNA-36026 in MCF-7 cells was used for this study. In brief, aptamer AS1411 and piRNA-36026 antisequence with Cy5 fluorescent dye are appended from the DNA tetrahedron; then, a short oligonucleotide with black hole quencher 2 (Q-oligo) is complementary with piRNA-36026 antisequence to quench the fluorescence of Cy5. The apt-ADTNs can recognize the MCF-7 cells through aptamer AS1411, and then enter the cells. Q-oligo is detached from the apt-ADTNs because of the binding between apt-ADTNs and piRNA-36026, leading to the recovery of the Cy5 fluorescence signal. Meanwhile, the hybridization of apt-ADTNs and piRNA-36026 results in down-regulating of dissociative piRNA-36026 in cytoplasm and the subsequent apoptosis of MCF-7 cells. As the achievement of synchronously imaging and regulating piRNA-36026 in MCF-7 cells, we believe that this design holds great promise in application of diagnosis and therapy for cancer.

11.
Medicine (Baltimore) ; 98(44): e17548, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689756

RESUMO

BACKGROUND: The incidence of atrial fibrillation (AF) varies from 5.4% to 47.1% in patients with mitral annulus calcification (MAC). We conducted a systematic review and meta-analysis on the association between MAC and AF, as well as the relation between MAC and major cardiac adverse events (MACEs) in AF patients. METHODS: We conducted comprehensive search for literature on associations between MAC and AF using the following databases: MEDLINE, PubMed, Embase, and the Web of Science. The pooled odds ratio (OR) or relative risk and the corresponding 95% confidence intervals (CIs) were calculated to assess the relationship between MAC and AF, as well as the rates of MACEs in AF patients with or without MAC. RESULTS: Thirteen studies met our eligibility criteria on associations between MAC and AF, including 6232 patients with MAC and 15,199 patients without MAC. Moreover, 5 studies met our eligibility criteria on the rates of MACEs in AF patients with or without MAC. The pooled analysis demonstrated a statistically significant increased risk of development of incident AF in patients with MAC than those without MAC (random effects OR: 2.34; 95% CI: 1.91, 2.85; P = .000). And the pooled analysis demonstrated a statistically significant increased risk of development of MACEs in AF patients with MAC (random effects OR: 2.34; 95% CI: 1.24, 4.41; P = .009). CONCLUSION: MAC was independently associated with AF and AF patients with MAC were at greater risk for cardiovascular and cerebrovascular events.

12.
Diabetes Metab Res Rev ; : e3226, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31655001

RESUMO

BACKGROUND: The impact of hypoglycaemic episode (HE) on the risk of ventricular arrhythmia (VA) and sudden cardiac arrest (SCA) remains unclear. We hypothesized that HE increases the risk of both VA and SCA and that glucose-lowering agents causing HE also increase the risk of VA/SCA in patients with type 2 diabetes (T2D). METHODS: Patients aged 20 years or older with newly diagnosed T2D were identified using the Taiwan National Health Insurance Database. HE was defined as the presentation of hypoglycaemic coma or specified/unspecified hypoglycaemia. The control group consisted of T2D patients without HE. The primary outcome was the occurrence of VA (including ventricular tachycardia and fibrillation) and SCA during the defined follow-up periods. A multivariate Cox hazards regression model was used to evaluate the hazard ratio (HR) for VA or SCA. RESULTS: A total of 54 303 patients were screened, with 1037 patients with HE assigned to the HE group and 4148 frequency-matched patients without HE constituting the control group. During a mean follow-up period of 3.3 ± 2.5 years, 29 VA/SCA events occurred. Compared with the control group, HE group had a higher incidence of VA/SCA (adjusted HR: 2.42, P = .04). Patients who had used insulin for glycaemic control showed an increased risk of VA/SCA compared with patients who did not receive insulin (adjusted HR: 3.05, P = .01). CONCLUSIONS: The HEs in patients with T2D increased the risk of VA/SCA, compared with those who did not experience HEs. Use of insulin also independently increased the risk of VA/SCA.

14.
Cells ; 8(10)2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31614673

RESUMO

: Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide. Reactive oxygen species (ROS), as potent oxidants in cells, have been shown to promote the development of NAFLD. Previous studies reported that for ROS-induced cellular oxidative stress, promoting lipid droplet (LD) accumulation is associated with the cellular antioxidation process. However, the regulatory role of LDs in relieving cellular oxidative stress is poorly understood. Here, we showed that Perilipin 5 (PLIN5), a key LD protein related to mitochondria-LD contact, reduced ROS levels and improved mitochondrial function in HepG2 cells. Both mRNA and protein levels of PLIN5 were significantly increased in cells with hydrogen peroxide or lipopolysaccharide (LPS) treatment (p < 0.05). Additionally, the overexpression of PLIN5 promoted LD formation and mitochondria-LD contact, reduced cellular ROS levels and up-regulated mitochondrial function-related genes such as COX and CS. Knockdown PLIN5, meanwhile, showed opposite effects. Furthermore, we identified that cellular oxidative stress up-regulated PLIN5 expression via the JNK-p38-ATF pathway. This study shows that the up-regulation of PLIN5 is a kind of survival strategy for cells in response to stress. PLIN5 can be a potential therapeutic target in NAFLD.

15.
Curr Pharm Des ; 2019 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-31663471

RESUMO

Traumatic brain injury (TBI) can cause disorders of consciousness (DOC) by impairing the neuronal circuits of the ascending reticular activating system (ARAS) structures, including the hypothalamus, which are responsible for the maintenance of the wakefulness and awareness. Current awakening therapies for TBI-induced DOC comprise, among others, the regulation of excitatory and inhibitory neurotransmitters and the stimulation of the peripheral or central nervous system (CNS). However, the effects of these awakening therapies are still not satisfactory. Hypothalamus has been identified as a sleep/wake center, and its anterior and posterior regions have diverse roles in the regulation of the sleep/wake function. In particular, posterior hypothalamus (PH) possesses several types of neurons, including the orexin neurons in the lateral hypothalamus (LH) with widespread projections to other wakefulness-related regions of the brain. Orexins have been known to affect feeding and appetite, and recently their profound effect on sleep disorders and DOC has been identified. Orexin antagonists are used for the treatment of insomnia, and orexin agonists can be used for narcolepsy. Additionally, several studies demonstrated that the agonists of orexin might be effective in the treatment of DOC, providing novel therapeutic opportunities in this field.

16.
Molecules ; 24(19)2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31591309

RESUMO

Ralstonia solanacearum (R. solanacearum)-induced bacterial wilt of the nightshade family causes a great loss in agricultural production annually. Although there has been some efficient pesticides against R. solanacearum, inaccurate pesticide releasing according to the onset time of bacterial wilt during the use of pesticides still hinders the disease management efficiency. Herein, on the basis of the soil pH change during R. solanacearum growth, and pH sensitivity of the Schiff base structure, a pH-sensitive oxidized alginate-based double-crosslinked gel was fabricated as a pesticide carrier. The gel was prepared by crosslinking oxidized sodium alginate (OSA) via adipic dihydrazide (ADH) and Ca2+. After loading tetramycin into the gel, it showed a pH-dependent pesticide releasing behavior and anti-bacterial activity against R. solanacearum. Further study also showed that the inhibition rate of the tetramycin-loaded gel was higher than that of industrial pesticide difenoconazole. This work aimed to reduce the difficulty of pesticide administration in the high incidence period of bacterial wilt and we believe it has a great application potential in nightshade production.

17.
Lung Cancer ; 138: 88-94, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31655368

RESUMO

OBJECTIVE: The purpose of this study was to estimate the cost-effectiveness analysis of pembrolizumab versus chemotherapy as first-line treatment in locally advance or metastatic non-small cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) tumor proportion score (TPS) 1% or greater from the United States (US) payer perspective. MATERIALS AND METHODS: This Markov structure was developed to estimate cost and effectiveness of pembrolizumab vs chemotherapy in the first-line treatment of locally advance or metastatic NSCLC based on the data from KEYNOTE-042. Cost and health outcomes were estimated at a willingness-to-pay (WTP) threshold of $150,000 per quality adjusted life year (QALY) in three PD-L1 TPS populations (≥50%, ≥20% and ≥1%). One-way, two-way and probabilistic sensitivity analysis were to test the model stability. Subgroup analysis were performed in three PD-L1 TPS populations (≥50%, ≥20% and ≥1%). RESULTS: The incremental costs and QALYs that pembrolizumab yielded, compared with chemotherapy, were $86164.87 and 0.63, $74562.25 and 0.46 and $70886.65 and 0.39 for the populations with a PD-L1 TPS ≥ 50%, TPS ≥ 20% and TPS ≥ 1%, leading an incremental cost-effective ratio (ICER) of $136,228.82, $160,625.98 and $179,530.17 per QALY, respectively. CONCLUSION: First-line treatment with pembrolizumab is a cost-effective strategy compared with platinum-based chemotherapy when the value of WTP was $150,000 per QALY in locally advanced or metastatic NSCLC patients with PD-L1 TPS ≥ 50% and without epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations, but not in the TPS ≥ 20% and 1% populations.

18.
PLoS Med ; 16(10): e1002953, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31652273

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with increased metabolic risk, though data on long-term follow-up of cardiometabolic traits are limited. We postulated that Chinese women with PCOS would have higher risk of incident diabetes and cardiometabolic abnormalities than those without PCOS during long-term follow-up. METHODS AND FINDINGS: One hundred ninety-nine Chinese women with PCOS diagnosed by the Rotterdam criteria and with a mean age of 41.2 years (SD = 6.4) completed a follow-up evaluation after an average of 10.6 ± 1.3 years. Two hundred twenty-five women without PCOS (mean age: 54.1 ± 6.7 years) who underwent baseline and follow-up evaluation over the same period were used for comparison. Progression of glycaemic status of women both with and without PCOS was assessed by using 75-g oral glucose tolerance test (OGTT) screening with the adoption of 2009 American Diabetes Association diagnostic criteria. The frequency of impaired glucose regulation, hypertension, and hyperlipidaemia of women with PCOS at follow-up has increased from 31.7% (95% CI 25.2%-38.1%) to 47.2% (95% CI 40.3%-54.2%), 16.1% (95% CI 11.0%-21.2%) to 34.7% (95% CI 28.1%-41.3%), and 52.3% (95% CI 45.3%-59.2%) to 64.3% (95% CI 57.7%-71.0%), respectively. The cumulative incidence of diabetes mellitus (DM) in follow-up women with PCOS is 26.1% (95% CI 20.0%-32.2%), almost double that in the cohort of women without PCOS (p < 0.001). Age-standardised incidence of diabetes among women with PCOS was 22.12 per 1,000 person-years (95% CI 10.86-33.37) compared with the local female population incidence rate of 8.76 per 1,000 person-years (95% CI 8.72-8.80) and 10.09 per 1,000 person-years (95% CI 4.92-15.26, p < 0.001) for women without PCOS in our study. Incidence rate for women with PCOS aged 30-39 years was 20.56 per 1,000 person-years (95% CI 12.57-31.87), which is approximately 10-fold higher than that of the age-matched general female population in Hong Kong (1.88 per 1,000 person-years, [95% CI 1.85-1.92]). The incidence rate of type 2 DM (T2DM) of both normal-weight and overweight women with PCOS was around double that of corresponding control groups (normal weight: 8.96 [95% CI 3.92-17.72] versus 4.86 per 1,000 person-years [95% CI 2.13-9.62], p > 0.05; overweight/obese: 28.64 [95% CI 19.55-40.60] versus 14.1 per 1,000 person-years [95% CI 8.20-22.76], p < 0.05). Logistic regression analysis identified that baseline waist-to-hip ratio (odds ratio [OR] = 1.71 [95% CI 1.08-2.69], p < 0.05) and elevated triglyceride (OR = 6.63 [95% CI 1.23-35.69], p < 0.05) are associated with the progression to T2DM in PCOS. Limitations of this study include moderate sample size with limited number of incident diabetes during follow-up period and potential selection bias. CONCLUSIONS: High risk of diabetes and increased cardiovascular disease risk factors among Chinese women with PCOS are highlighted in this long-term follow-up study. Diabetes onset was, on average, 10 years earlier among women with PCOS than in women without PCOS.

19.
Proc Natl Acad Sci U S A ; 116(46): 23264-23273, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31662475

RESUMO

Glycolytic enzyme phosphoglycerate mutase 1 (PGAM1) plays a critical role in cancer metabolism by coordinating glycolysis and biosynthesis. A well-validated PGAM1 inhibitor, however, has not been reported for treating pancreatic ductal adenocarcinoma (PDAC), which is one of the deadliest malignancies worldwide. By uncovering the elevated PGAM1 expressions were statistically related to worse prognosis of PDAC in a cohort of 50 patients, we developed a series of allosteric PGAM1 inhibitors by structure-guided optimization. The compound KH3 significantly suppressed proliferation of various PDAC cells by down-regulating the levels of glycolysis and mitochondrial respiration in correlation with PGAM1 expression. Similar to PGAM1 depletion, KH3 dramatically hampered the canonic pathways highly involved in cancer metabolism and development. Additionally, we observed the shared expression profiles of several signature pathways at 12 h after treatment in multiple PDAC primary cells of which the matched patient-derived xenograft (PDX) models responded similarly to KH3 in the 2 wk treatment. The better responses to KH3 in PDXs were associated with higher expression of PGAM1 and longer/stronger suppressions of cancer metabolic pathways. Taken together, our findings demonstrate a strategy of targeting cancer metabolism by PGAM1 inhibition in PDAC. Also, this work provided "proof of concept" for the potential application of metabolic treatment in clinical practice.

20.
Bioresour Technol ; 294: 122218, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31606600

RESUMO

Fermentation slurry from food waste (FSFW) generated by acidogenic fermentation at mesophilic temperature was utilized to improve the nutrients removal from wastewater. Organic acids (such as lactate and volatile fatty acids) in the FSFW behaved as readily biodegradable carbon sources, while the particulate and macromolecular organics acted as slowly biodegradable carbon sources during denitrification processes. The FSFW dosage significantly influenced the nitrogen removal performance, and a C/N ratio (in terms of chemical oxygen demand to nitrogen ratio) of 8 could achieve complete denitrification in the batch tests. In a sequencing batch reactor (SBR) using FSFW for long-term wastewater treatment, extracellular polymeric substances (EPS) gradually accumulated, sludge particle size significantly increased, and microbial communities were selectively enriched, which contributed to promoting the nitrogen (>80%) and phosphate (90.1%) removal efficiencies. Overall, the FSFW produced by acidogenic fermentation under mesophilic temperature served as an excellent intermediary between FW valorization and wastewater treatment.


Assuntos
Eliminação de Resíduos , Águas Residuárias , Reatores Biológicos , Carbono , Desnitrificação , Fermentação , Alimentos , Nitrogênio , Nutrientes , Esgotos , Eliminação de Resíduos Líquidos
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