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1.
BMC Neurol ; 22(1): 16, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34996389

RESUMO

BACKGROUND: Progressive haemorrhagic injury after surgery in patients with traumatic brain injury often results in poor patient outcomes. This study aimed to develop and validate a practical predictive tool that can reliably estimate the risk of postoperative progressive haemorrhagic injury (PHI) in patients with traumatic brain injury (TBI). METHODS: Data from 645 patients who underwent surgery for TBI between March 2018 and December 2020 were collected. The outcome was postoperative intracranial PHI, which was assessed on postoperative computed tomography. The least absolute shrinkage and selection operator (LASSO) regression model, univariate analysis, and Delphi method were applied to select the most relevant prognostic predictors. We combined conventional coagulation test (CCT) data, thromboelastography (TEG) variables, and several predictors to develop a predictive model using binary logistic regression and then presented the results as a nomogram. The predictive performance of the model was assessed with calibration and discrimination. Internal validation was assessed. RESULTS: The signature, which consisted of 11 selected features, was significantly associated with intracranial PHI (p < 0.05, for both primary and validation cohorts). Predictors in the prediction nomogram included age, S-pressure, D-pressure, pulse, temperature, reaction time, PLT, prothrombin time, activated partial thromboplastin time, FIB, and kinetics values. The model showed good discrimination, with an area under the curve of 0.8694 (95% CI, 0.8083-0.9304), and good calibration. CONCLUSION: This model is based on a nomogram incorporating CCT and TEG variables, which can be conveniently derived at hospital admission. It allows determination of this individual risk for postoperative intracranial PHI and will facilitate a timely intervention to improve outcomes.


Assuntos
Lesões Encefálicas Traumáticas , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Humanos , Hemorragias Intracranianas , Modelos Logísticos , Nomogramas , Prognóstico
2.
Acta Biochim Pol ; 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-34995050

RESUMO

OBJECTIVE(S): Transient receptor potential vanilloid 4 (TRPV4) participates in malignant tumor. However, the role of TRPV4 in non-small cell lung cancer (NSCLC) remains unclear. In this study, we demonstrated TRPV4 was upregulated in NSCLC tissues and NSCLC cell lines. MATERIALS AND METHODS: TRPV4 level in the NSCLC patients and cell lines were detected, and its function was studied both in vivo and vitro. RESULTS: The level of TRPV4 showed a positive correlation with tumor size of NSCLC patients. Activation TRPV4 by agonist GSK1016790A promoted cell proliferation and decreased apoptosis in A549 cells, and these effects were enhanced when the cells have overexpressed TRPV4. Moreover, GSK1016790A induced inhibitory effects on apoptosis of A549 cells was impaired when GSK1016790A used together with TRPV4 selective antagonist HC-067047, or impaired when the cells have already downregulated TRPV4 expression by TRPV4 siRNA. In vivo study, pharmacological inhibition of TRPV4 prevented A549 cells transplanted tumor growth. It was showed Foxp3 level was significantly increased in the NSCLC tissues, and showed a positive correlation with the level of TRPV4. Deactivation of TRPV4 using TRPV4 siRNA or HC-067047 significantly reduced expression of Foxp3 in GSK1016790A treated NSCLC cells. Moreover, downregulation Foxp3 by transfection of Foxp3 siRNA significantly impaired TRPV4 induced NSCLC cells proliferations in vitro. CONCLUSIONS: Antitumor effects caused by TRPV4 inhibition in NSCLC might be attributed to the suppression of Foxp3 which induced subsequent cell apoptosis. Thus, pharmacological inhibition of TRPV4 may be a promising option for NSCLC treatment.

3.
Methods Mol Biol ; 2393: 3-14, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34837171

RESUMO

Exosomes are nanosized (50-150 nm) extracellular vesicles released by all types of cells in the body. They transport various biological molecules, such as DNAs, RNAs, proteins, and lipids from parent cells to recipient cells for intercellular communication. Exosomes, especially those from tumor cells, are actively involved in caner development, metastasis, and drug resistance. Recently, many studies have shown that exosomal proteins are promising biomarkers for cancer screening, early detection and prognosis. Among many detection techniques, surface plasmon resonance (SPR) is a highly sensitive, label-free, and real-time optical detection method. Commercial prism-based wavelength/angular-modulated SPR sensors afford high sensitivity and resolution, but their large footprint and high cost limit their adaptability for clinical settings. We have developed an intensity-modulated, compact SPR biosensor (25 cm × 10 cm × 25 cm) for the detection of exosomal proteins. We have demonstrated the potential application of the compact SPR biosensor in lung cancer diagnosis using exosomal epidermal growth factor receptor (EGFR) and programmed death-ligand 1 (PD-L1) as biomarkers. The compact SPR biosensor offers sensitive, simple, fast, user-friendly, and cost-effective detection of exosomal proteins, which may serve as an in vitro diagnostic test for cancer.

4.
J Ethnopharmacol ; 284: 114753, 2022 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-34662667

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Pteryxin is a natural coumarin compound that is found in "Qianhu", a traditional Chinese medicine, which possesses heat-clearing and detoxifying functions according to the theory of Traditional Chinese Medicine. Despite its medicinal effects, its anti-inflammatory and mechanisms of actions have not been established. AIM OF THIS STUDY: This study aims to evaluate the anti-inflammatory property and reveal the possible anti-inflammatory mechanisms of pteryxin. MATERIAL AND METHODS: LPS-induced RAW 264.7 macrophages and LPS-induced zebrafish model were used for the anti-inflammatory activity determination of pteryxin. The level of NO, PEG2, TNF-α and IL-6 were measured by ELISA. The accumulation of NO and ROS was stained and observed by a fluorescence microscopy. The nuclear translocation of NF-κB p65 and formation of NLRP3 inflammasome complex in LPS-induced RAW 264.7 macrophage cells were analyzed by immunofluorescence assay. The expression level of iNOS, IL-6, COX-2, TNF-α, p-p38, p38, ERK, JNK, p-ERK, p-JNK, IKK, IκB-α, p-IKK, p-IκB-α, p65, NLRP3, p-p65, Caspase 1 (p 20), ASC, and GAPDH were determined by Western blotting. RESULTS: Lipopolysaccharide (LPS)-induced prostaglandin E2 (PGE2) and nitric oxide (NO) secretions were found to be downregulated by pteryxin. Moreover, pteryxin significantly suppressed inflammatory factor secretion in LPS-treated RAW 264.7 cells. Mechanistically, pteryxin significantly downregulated NF-κB/MAPK activation. Moreover, pteryxin inhibited caspase-1 and NLRP3 activation and formation of ASC specks in RAW 264.7 cells, implying that pteryxin inhibits inflammasome assembly, which is a signal for NLRP3 inflammasome activation. In conclusion, pteryxin blocks NF-κB/MAPK signaling, and suppresses the initiation and activation of NLRP3 thereby preventing inflammation. CONCLUSION: Pteryxin is a potential treatment option for inflammatory-related diseases.

5.
Bioact Mater ; 9: 77-91, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34820557

RESUMO

Dry eye is a common ocular disease that results in discomfort and impaired vision, impacting an individual's quality of life. A great number of drugs administered in eye drops to treat dry eye are poorly soluble in water and are rapidly eliminated from the ocular surface, which limits their therapeutic effects. Therefore, it is imperative to design a novel drug delivery system that not only improves the water solubility of the drug but also prolongs its retention time on the ocular surface. Herein, we develop a copolymer from mono-functional POSS, PEG, and PPG (MPOSS-PEG-PPG, MPEP) that exhibits temperature-sensitive sol-gel transition behavior. This thermo-responsive hydrogel improves the water solubility of FK506 and simultaneously provides a mucoadhesive, long-acting ocular delivery system. In addition, the FK506-loaded POSS hydrogel possesses good biocompatibility and significantly improves adhesion to the ocular surface. In comparison with other FK506 formulations and the PEG-PPG-FK506 (F127-FK506) hydrogel, this novel MPOSS-PEG-PPG-FK506 (MPEP-FK506) hydrogel is a more effective treatment of dry eye in the murine dry eye model. Therefore, delivery of FK506 in this POSS hydrogel has the potential to prolong drug retention time on the ocular surface, which will improve its therapeutic efficacy in the management of dry eye.

6.
Sci Total Environ ; 804: 150147, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34509840

RESUMO

Microbial conversion of methane to electricity, fuels, and liquid chemicals has attracted much attention. However, due to the low solubility of methane, it is not considered a suitable substrate for microbial fuel cells (MFCs). In this study, a conductive fiber membrane (CFM) module was constructed as the bioanode of methane-driven MFCs, directly delivering methane. After biofilm formation on the CFM surface, a steady voltage output of 0.6 to 0.7 V was recorded, and the CFM-MFCs obtained a maximum power density of 64 ± 2 mW/m2. Moreover, methane oxidation produced a high concentration of intermediate acetate (up to 7.1 mM). High-throughput 16S rRNA gene sequencing suggests that the microbial community was significantly changed after electricity generation. Methane-related archaea formed a symbiotic consortium with characterized electroactive bacteria and fermentative bacteria, suggesting a combination of three types of microorganisms for methane conversion into acetate and electricity.


Assuntos
Fontes de Energia Bioelétrica , Acetatos , Eletricidade , Eletrodos , Metano , RNA Ribossômico 16S/genética
7.
Nucleic Acids Res ; 50(1): 458-472, 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-34904664

RESUMO

An embryo starts its life with maternal mRNA clearance, which is crucial for embryonic development. The elimination of maternal transcripts occurs by the joint action of two pathways: the maternally encoded mRNA decay pathway (M-decay) and the zygotic genome activation (ZGA)-dependent pathway (Z-decay). However, zygotic factors triggering maternal mRNA decay in early mammalian embryos remain largely unknown. In this study, we identified the zygotically encoded nuclear poly(A) binding protein 1 (PABPN1) as a factor required for maternal mRNA turnover, with a previously undescribed cytoplasmic function. Cytoplasmic PABPN1 docks on 3'-uridylated transcripts, downstream of terminal uridylyl transferases TUT4 and TUT7, and recruits 3'-5' exoribonuclease DIS3L2 to its targets, facilitating maternal mRNA decay. Pabpn1-knockout in mice resulted in preimplantation stage mortality due to early developmental arrest at the morula stage. Maternal mRNAs to be eliminated via the Z-decay pathway failed to be removed from Pabpn1-depleted embryos. Furthermore, PABPN1-mediated Z-decay is essential for major ZGA and regulates the expression of cell fate-determining factors in mouse preimplantation embryos. This study revealed an unforeseen cytoplasmic function of PABPN1 coupled with early embryonic development, characterized the presence of a zygotic destabilizer of maternal mRNA, and elucidated the Z-decay process mechanisms, which potentially contribute to human fertility.

8.
Environ Sci Technol ; 56(1): 194-207, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34935353

RESUMO

In recent years, dozens of halogenated disinfection byproducts (DBPs) with cyclic structures were identified and detected in drinking water globally. Previous in vivo toxicity studies have shown that a few new cyclic DBPs possessed higher developmental toxicity and growth inhibition rate than common aliphatic DBPs; however, in vitro toxicity studies have proved that the latter exhibited higher cytotoxicity and genotoxicity than the former. Thus, to provide a more comprehensive toxicity comparison of DBPs from different endpoints, 11 groups of cyclic DBPs and nine groups of aliphatic DBPs were evaluated for their comparative in vitro and in vivo toxicity using human hepatoma cells (Hep G2) and zebrafish embryos. Notably, results showed that the in vitro Hep G2 cytotoxicity index of the aliphatic DBPs was nearly eight times higher than that of the cyclic DBPs, whereas the in vivo zebrafish embryo developmental/acute toxicity indexes of the cyclic DBPs were roughly 48-50 times higher than those of the aliphatic DBPs, indicating that the toxicity rank order differed when different endpoints were applied. For a broader comparison, a Pearson correlation analysis of DBP toxicity data from nine different endpoints was conducted. It was found that the observed Hep G2 cytotoxicity and zebrafish embryo developmental/acute toxicity in this study were highly correlated with the previously reported in vitro CHO cytotoxicity and in vivo toxicity in aquatic organisms (P < 0.01), respectively. However, the observed in vitro toxicity had no correlation with the in vivo toxicity (P > 0.05), suggesting that the toxicity rank orders obtained from in vitro and in vivo bioassays had large discrepancies. According to the observed toxicity data in this study and the candidate descriptors, two quantitative structure-activity relationship (QSAR) models were established, which help to further interpret the toxicity mechanisms of DBPs from different endpoints.

9.
J Ethnopharmacol ; 286: 114924, 2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-34942323

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Peucedanum praeruptorum seed root is a common medicinal herb with antipyretic, expectorant, antitussive, and therapeutic effects against bronchitis and furuncle. The roots of this herb contain many coumarin compounds, including pteryxin. AIM OF THIS STUDY: To investigate whether pteryxin can alleviate the LPS-induced lung injury and the mechanism involved. MATERIAL AND METHODS: Male BALB/C mice were orally given sodium carboxymethylcellulose (CMC-Na) (0.5%, 1mL/100g) and pteryxin (suspended in CMC-Na; 0.5%) at 5, 10, 25 mg/kg once daily for 7 days. Subsequently, the mice received a single intratracheal instillation of 5 mg/kg LPS or saline as the control. After 8 hours, the mice were sacrificed to collect bronchoalveolar lavage fluid (BALF) and lung tissues. These samples were used to determine the lung W/D (wet/dry) weight ratio, total protein (TP) levels, inflammatory cytokines (IL-6, TNF-α, and IL-1ß) and expression of protein involved in MAPK/NF-κB pathway and NLRP3 inflammasome. H&E staining was carried out on tissue sections to explore the pathological alterations induced by LPS. The protein expression of F4/80 and NLRP3 in lung tissues was analyzed using immunohistochemical staining. The binding of pteryxin to target proteins (MAPK, NF-κB and NLRP3) was determined based on molecular docking tests. RESULTS: Treatment with pteryxin reduced the lung W/D weight ratio, total protein (TP) level and levels of inflammatory cytokines (TNFα, IL-6 and IL-1 ß) significantly. Therefore, it ameliorated LPS-induced inflammatory response in BALB/C mice. Moreover, pteryxin suppressed LPS-induced upregulation of proteins involved in MAPK/NF-κB signaling pathway and NLRP3 inflammasome activation. The expression level of F4/80 and NLRP3 was also downregulated by pteryxin pretreatment in lung tissues. Docking analysis revealed that pteryxin bound to target proteins (MAPK, NF- κB and NLRP3) with a fit-well pattern . CONCLUSION: Pteryxin may attenuate LPS-induced acute lung injury by dampening MAPK/NF-κB signaling and NLRP 3 inflammasome activation.

10.
Nat Commun ; 12(1): 7169, 2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34887396

RESUMO

Electrons navigate more easily in a background of ordered magnetic moments than around randomly oriented ones. This fundamental quantum mechanical principle is due to their Bloch wave nature and also underlies ballistic electronic motion in a perfect crystal. As a result, a paramagnetic metal that develops ferromagnetic order often experiences a sharp drop in the resistivity. Despite the universality of this phenomenon, a direct observation of the impact of ferromagnetic order on the electronic quasiparticles in a magnetic metal is still lacking. Here we demonstrate that quasiparticles experience a significant enhancement of their lifetime in the ferromagnetic state of the low-density magnetic semimetal EuCd2As2, but this occurs only in selected bands and specific energy ranges. This is a direct consequence of the magnetically induced band splitting and the multi-orbital nature of the material. Our detailed study allows to disentangle different electronic scattering mechanisms due to non-magnetic disorder and magnon exchange. Such high momentum and energy dependence quasiparticle lifetime enhancement can lead to spin selective transport and potential spintronic applications.

11.
ACS Appl Nano Mater ; 4(3): 2806-2819, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-34849458

RESUMO

Exosomes are cell-derived, nanosized extracellular vesicles for intercellular communication. Exosomal RNAs have been shown as one type of promising cancer liquid biopsy biomarkers. Conventional methods to characterize exosomal RNAs such as quantitative reverse transcription polymerase chain reaction (qRT-PCR) are limited by low sensitivity, large sample consumption, time-consuming process, and high cost. Many technologies have been developed to overcome these challenges; however, many hours are still required to complete the assays, especially when exosome lysis and RNA extraction are required. We have developed a microfluidic cationic lipoplex nanoparticles (mCLN) assay that utilizes a micromixer biochip to allow for the effective capture of exosomes by cationic lipoplex nanoparticles and thus enables ultrafast and sensitive exosomal RNA detection for cancer diagnosis. The sensing performance and diagnostic performance of the mCLN assay were investigated using non-small cell lung cancer (NSCLC) as the disease model and exosomal microRNA-21 and TTF-1 mRNA as the biomarkers. The limits of detection of the mCLN assay were 2.06 × 109 and 3.71 × 109 exosomes/mL for microRNA-21 and TTF-1 mRNA, respectively, indicating that the mCLN assay may require as low as 1 µL of serum for exosomal RNA detection. The mCLN assay successfully distinguished NSCLC from normal controls by detecting significantly higher microRNA-21 and TTF-1 mRNA levels in exosomes from both NSCLC patient serum samples and A549 NSCLC cells than those from normal controls and BEAS-2B normal bronchial epithelial cells. Compared with conventional qRT-PCR assay, the mCLN assay showed a higher diagnostic accuracy in lung cancer, required less sample volume (30 vs 100 µL), and consumed much less time (10 min vs 4 h).

12.
Front Plant Sci ; 12: 727957, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34868113

RESUMO

Quantifying the relations between plant-antagonistic interactions and natural selection among populations is important for predicting how spatial variation in ecological interactions drive adaptive differentiation. Here, we investigate the relations between the opportunity for selection, herbivore-mediated selection, and the intensity of plant-herbivore interaction among 11 populations of the insect-pollinated plant Primula florindae over 2 years. We experimentally quantified herbivore-mediated directional selection on three floral traits (two display and one phenological) within populations and found evidence for herbivore-mediated selection for a later flowering start date and a greater number of flowers per plant. The opportunity for selection and strength of herbivore-mediated selection on number of flowers varied nonlinearly with the intensity of herbivory among populations. These parameters increased and then decreased with increasing intensity of plant-herbivore interactions, defined as an increase in the ratio of herbivore-damaged flowers per individual. Our results provide novel insights into how plant-antagonistic interactions can shape spatial variation in selection on floral traits and contribute toward understanding the mechanistic basis of geographic variation in angiosperm flowers.

13.
J Clin Med ; 10(23)2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34884235

RESUMO

Adjacent segment disease (ASD) is troublesome condition that has proved to be highly related to spinal malalignment after spinal surgery. Hence, we aimed to evaluate the morphological changes after anterior lumbar interbody fusion (ALIF) and oblique LIF (OLIF) to establish the differences between the two surgical methods in terms of possible ASD avoidance. Fifty patients, half of whom received ALIF while the other half received OLIF, were analyzed with image studies and functional outcomes during the pre-operative and post-operative periods, and 2 years after surgery. Image measurements obtained included spinal-pelvic parameters, index lordosis (IL), segmental lordosis (SL), anterior disc height (ADH), posterior disc height (PDH) and adjacent segment disc angle (ASDA). The ADH and PDH in the adjacent segment decreased in the two groups while OLIF showed greater decrease without radiological ASD noted at 2-year follow-up. Both groups showed an increase in IL after surgery while ALIF showed greater improvement. No statistical difference was identified in functional outcomes between LIFs. We suggest that both ALIF and OLIF can restore adequate lordosis and prevent ASD after surgery. However, it should be noted that patient selection remains crucial when making any decision involving which of the two methods to use.

14.
Small ; : e2105362, 2021 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-34862741

RESUMO

Fluorophores with emission in the second near-infrared (NIR-II) window have displayed salient advantages for biomedical applications. However, exploration of new luminogens with high NIR-II fluorescent brightness is still challenging. Herein, based on the "ring-fusion" strategy, a series of heteroatom-inserted rigid-planar cores is proposed to achieve the bathochromic NIR-II fluorophores with aggregation-induced emission (AIE) performance. Interestingly, one of the representative fluorophores, 4,4'-(5,5'-([1,2,5]thiadiazolo[3,4-i]dithieno[2,3-a:3',2'-c]phenazine-8,12-diyl)bis(4-octylthiophene-5,2-diyl))bis(N,N-diphenylaniline) (TTQiT), enjoys a maximum emission beyond 1100 nm because of the efficiently narrowed energy bandgap by electron-rich sulfur-atom-inserted core, which is verified by theoretical calculation. Taking advantage of the bright NIR-II emission of TTQiT nanoparticles, the desirable in vivo NIR-II imaging with high signal-to-background ratios is successfully performed and a long-term stem cell tracking in the detection of acute lung injury is further realized. Therefore, it is anticipated that this work will provide a promising molecular engineering strategy to enrich the scope of NIR-II fluorophores for catering to diverse demands in biomedical applications.

15.
Dalton Trans ; 2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-34939636

RESUMO

The nitrogen reduction reaction (NRR) has great potential as a method to replace the industrial Haber-Bosch process for ammonia synthesis. Nevertheless, the efficiency of the NRR is mainly dependent on the rational design of highly efficient and active electrocatalysts on account of the high energy of N2 and HER as a competitive reaction. Herein, a simple solid-phase synthesis method is adopted to design and synthesize a LiNb3O8 (LNO) electrocatalyst, which proves that the synergistic effect of electron-rich Nb and Li elements can effectively improve the NRR activity of commercial Nb2O5 and Li2CO3. The resultant LNO electrocatalyst presents an ammonia yield rate of 7.85 µg h-1 mgcat.-1 with a faradaic efficiency of 82.83% at -0.4 V vs. RHE under ambient conditions, which are much higher than those of commercial Nb2O5 (1.67 µg h-1 mgcat.-1, 13.51%) and Li2CO3 (1.93 µg h-1 mgcat.-1, 8.41%). Detailed characterizations demonstrate that the obtained LNO electrocatalyst has a larger specific surface area of electrochemical activity and more active sites to promote the activity of the NRR. Moreover, the synergistic effect of Li and Nb elements greatly improves the hydrophobicity of the material, which is more conducive to the occurrence of the NRR. This work highlights the enormous potential of the LNO electrocatalyst with a hydrophobic surface and easy activation of NN for highly efficient ammonia synthesis under ambient conditions.

16.
Small Methods ; 5(7): e2100347, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34927997

RESUMO

The constant feeding of oxygen and nutrients through the blood vasculature has a vital role in maintaining tumor growth. Interestingly, recent endeavors have shown that nanotherapeutics with the strategy to block tumor blood vessels feeding nutrients and oxygen for starvation therapy can be helpful in cancer treatment. However, this field has not been detailed. Hence, this review will present an exhaustive summary of the existing biomaterial based strategies to disrupt tumor vascular function for effective cancer treatment, including hydrogel or nanogel-mediated local arterial embolism, thrombosis activator loaded nano-material-mediated vascular occlusion and anti-vascular drugs that block tumor vascular function, which may be beneficial to the design of anti-cancer nanomedicine by targeting the tumor vascular system.

17.
Front Cell Dev Biol ; 9: 714320, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34900982

RESUMO

Precise regulation of cell cycle is essential for tissue homeostasis and development, while cell cycle dysregulation is associated with many human diseases including renal fibrosis, a common process of various chronic kidney diseases progressing to end-stage renal disease. Under normal physiological conditions, most of the renal cells are post-mitotic quiescent cells arrested in the G0 phase of cell cycle and renal cells turnover is very low. Injuries induced by toxins, hypoxia, and metabolic disorders can stimulate renal cells to enter the cell cycle, which is essential for kidney regeneration and renal function restoration. However, more severe or repeated injuries will lead to maladaptive repair, manifesting as cell cycle arrest or overproliferation of renal cells, both of which are closely related to renal fibrosis. Thus, cell cycle dysregulation of renal cells is a potential therapeutic target for the treatment of renal fibrosis. In this review, we focus on cell cycle regulation of renal cells in healthy and diseased kidney, discussing the role of cell cycle dysregulation of renal cells in renal fibrosis. Better understanding of the function of cell cycle dysregulation in renal fibrosis is essential for the development of therapeutics to halt renal fibrosis progression or promote regression.

18.
PLoS One ; 16(12): e0261749, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34965263

RESUMO

There is increasing interest in the effect that food environments may have on obesity, particularly through mechanisms related to the marketing and consumption of calorie-dense, nutrient-poor foods and sugary beverages. Price promotions, such as temporary price discounts, have been particularly effective in the marketing of carbonated soft drinks (CSDs) among consumers. Research has also suggested that the purchasing behavior of consumer groups may be differentially sensitive to price discounts on CSDs, with obese women particularly sensitive. In addition, the intensity of price discount in a person's food environment may also vary across geography and over time. This study examines whether the weight change of obese women, compared to overweight or normal BMI women, is more sensitive to the intensity of price discounts on CSDs in the food environment. This study used longitudinal survey data from 1622 women in the Montreal Neighborhood Networks and Health Aging (MoNNET-HA) Panel. Women were asked to report their height and weight in 2008, 2010 and 2013 in order to calculate women's BMI in 2008 and their change of weight between 2008 and 2013. Women's exposure to an unhealthy food environment was based on the frequency in which their neighborhood food stores placed price discounts on CSDs in 2008. The price discount frequency on CSDs within women's neighborhoods was calculated from Nielsen point-of sales transaction data in 2008 and geocoded to participant's forward sortation area. The prevalence of obesity and overweight among MoNNET-HA female participants was 18.3% in 2008, 19.9% in 2010 and 20.7% in 2013 respectively. Results showed that among obese women, exposure to unhealthy food environments was associated with a 3.25 kilogram (SE = 1.35, p-value = 0.02) weight gain over the five-year study period. Exposure to price discounts on CSDs may disproportionately affect and reinforce weight gain in women who are already obese.

19.
J Psychiatr Res ; 146: 125-134, 2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-34971910

RESUMO

BACKGROUND: Obsessive-compulsive disorder (OCD) is a heterogeneous psychiatric illness with a complex array of symptoms and potentially distinct neural underpinnings. We employed meta-analysis and connectivity modeling of symptom dimensions to delineate the circuit mechanisms of OCD. METHODS: With the activation likelihood estimation (ALE) algorithm we performed meta-analysis of whole-brain functional magnetic resonance imaging (fMRI) studies of symptom provocation. We contrasted all OCD patients and controls in a primary analysis and divided the studies according to clinical symptoms in secondary meta-analyses. Finally, we employed meta-analytic connectivity modeling analyses (MACMs) to examine co-activation patterns of the brain regions revealed in the primary meta-analysis. RESULTS: A total of 14 experiments from 12 eligible studies with a total of 238 OCD patients (124 men) and 219 healthy controls (120 men) were included in the primary analysis. OCD patients showed higher activation in the right caudate body/putamen/insula and lower activation in the left orbitofrontal cortex (OFC), left inferior frontal gyrus (IFG), left caudate body/middle cingulate cortex (MCC), right middle temporal gyrus (MTG), middle occipital gyrus (MOG) and right lateral occipital gyrus (LOG). MACMs revealed significant co-activation between left IFG and left caudate body/MCC, left MOG and right LOG, right LOG and MTG. In the secondary meta-analyses, the washing subgroup showed higher activation in the right OFC, bilateral ACC, left MOG and right caudate body. CONCLUSION: OCD patients showed elevated dorsal striatal activation during symptom provocation. In contrast, the washing subgroup engaged higher activation in frontal, temporal and posterior cortical structures as well as right caudate body. Broadly consistent with the proposition of cortico-striatal-thalamic-cortical circuit dysfunction, these findings highlight potentially distinct neural circuits that may underlie the symptoms and potentially etiological subtypes of OCD.

20.
PLoS Negl Trop Dis ; 15(12): e0010025, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34919557

RESUMO

Pneumocystis pneumonia (PCP) and pulmonary toxoplasmosis (PT) are caused by Pneumocystis jirovecii and Toxoplasma gondii. The clinical symptoms and imaging of PCP and PT are indistinguishable. A duplex qPCR was developed to differentiate between these two pathogens. In testing 92 clinical samples to validate the performance of this method for P. jirovecii detection, it identified 31 positive samples for P. jirovecii infection, consistent with clinical diagnosis. Among the remainder of the 61 clinical samples with suspected PCP, yet showing as negative by the conventional PCR diagnosis approach, 6 of them proved positive using our new assay. Our new approach also produced similar results in identification of T. gondii infections, giving a result of 2 positive and 20 negative in clinical samples. An investigation was undertaken on the prevalence of P. jirovecii and T. gondii infections using 113 samples from lung infection patients. 9% (10/113) were shown to be positive with infections of P. jirovecii, 2% with T. gondii (2/113) and 5% (6/113) were co-infected with both pathogens. Although this duplex qPCR can detect individual P. jirovecii and T. gondii infection, and co-infection of both pathogens, further large-scale investigations are needed to validate its performance, especially in T. gondii detection. Our assay provides a rapid and accurate tool for PCP and PT diagnosis in immunocompromised population and clinical surveillance of these infections in patients with no immune defects.

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