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1.
BMC Pregnancy Childbirth ; 21(1): 689, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627190

RESUMO

BACKGROUND: Pseudoaneurysms are formed when a local arterial wall ruptures, leading to hemorrhage and hematoma adjacent to the artery. Continuous perfusion of the injured artery increases the pressure in the lumen of the pseudoaneurysm. It may rupture and lead to massive hemorrhage that could be life-threatening. Cesarean scar pregnancy (CSP) is an ectopic pregnancy where the gestational sac is implanted in the cesarean scar. Uterine artery pseudoaneurysm (UAP) after CSP treatment is rare. CASE PRESENTATION: We report the case of a 36-year-old Chinese woman who presented with acute massive vaginal bleeding 53 days after transabdominal scar pregnancy excision. Doppler ultrasound confirmed UAP. Selective uterine artery embolization (UAE) failed because of the thin and curved blood vessels. The lesion decreased in size after transvaginal ultrasound-guided direct thrombin injection (UGTI); however, massive vaginal bleeding recurred and endangered the patient's life. The uterus was removed thereafter. CONCLUSIONS: UAP is a rare complication after CSP treatment that can lead to fatal massive hemorrhage. Ultrasound should be reexamined regularly after treatment of CSP. In case of unexplained vaginal bleeding, we should be alert to the existence of UAP and the possibility of rupture and take effective diagnosis and treatment measures promptly.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34593304

RESUMO

The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling system regulates a variety of biological processes, including embryogenesis, angiogenesis, wound repair, tissue homeostasis, and cancer. It exerts these regulatory functions by controlling proliferation, differentiation, migration, survival, and metabolism of target cells. The morphological structure of the lung is a complex tree-like network for effective oxygen exchange, and the airway terminates in the middle and distal ends of many alveoli. FGF/FGFR signaling plays an important role in the pathophysiology of lung development and pathogenesis of various human respiratory diseases. Here, we mainly review recent advances in FGF/FGFR signaling during human lung development and respiratory diseases, including lung cancer, acute lung injury (ALI), pulmonary arterial hypertension (PAH), chronic obstructive pulmonary disease (COPD), asthma, and pulmonary fibrosis.

3.
J Affect Disord ; 296: 400-407, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34606812

RESUMO

BACKGROUND: The anterior cingulate cortex (ACC) is a crucial region in the pathophysiology of major depressive disorder (MDD). However, the relationship between functional alterations of the ACC subregions, anhedonia and sleep quality remains unclear in MDD patients. METHODS: The resting-state functional connectivity (rsFC) of ACC subregions was measured in 41 first-episode medication-naïve MDD patients and 63 healthy controls who underwent functional magnetic resonance imaging. Between-group differences were examined using two-sample t-test. Furthermore, correlation and mediation analyses were carried out to investigate the relationships between the aberrant rsFC of ACC subregions, anhedonia and sleep quality in the patients and controls. RESULTS: Compared to healthy controls, the MDD patients exhibited increased rsFC of ACC subregions to areas of the anterior default mode network (DMN) and showed decreased rsFC of the right subgenual ACC to left precuneus (PCUN), which belongs to the posterior DMN. In MDD group, the sleep quality and consummatory anhedonia are correlated with some rsFC, which involves the angular gyrus (ANG) and superior frontal gyrus (SFG). More importantly, the rsFC between the right perigenual ACC and left SPG mediates the association between anhedonia and sleep quality in MDD. LIMITATIONS: The cross-sectional design and the subjective questionaries for assessment. CONCLUSION: These findings confirm the functional alterations of the ACC subregions and reveal the mediating role of ACC subregions in sleep and reward dysfunction in MDD.

4.
Technol Cancer Res Treat ; 20: 15330338211043975, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34632869

RESUMO

Objective: To investigate the features of helical tomotherapy and co-planar dual Arcs volumetric-modulated arc therapy during prophylactic cranial irradiation associated with bilateral hippocampal tissue sparing. Materials and methods: Helical tomotherapy and co-planar dual arcs volumetric-modulated arc therapy treatment plans were generated with a dose of 30 Gy/10 fractions in 16 patients treated with prophylactic cranial irradiation. The dose to the bilateral hippocampal tissues, organs at risk, and planning target volume were determined when the average dose of bilateral hippocampal tissues was reduced by approximately 4 Gy as an observation point. Changes in dosimetry when sparing the bilateral hippocampal tissues were determined for both modalities. Results: When bilateral hippocampal tissues were restricted to 8 Gy, D40%mean-bilateral hippocampal tissues = 7.64 ± 0.41 Gy in helical tomotherapy, while D40%mean-bilateral hippocampal tissues = 10.96 ± 0.38 Gy in co-planar dual arcs volumetric-modulated arc therapy volumetric-modulated arc therapy. Helical tomotherapy was associated with significantly lower doses to organs at risk, including Dmean-bilateral hippocampal tissues (P = .03), D98%-bilateral hippocampal tissues (P = .01), D2%-bilateral hippocampal tissues (P = .01), Dmean-inner ear (P = .02), Dmean-parotid glands (P = .02), Dmax-lens (P = .02), and Dmax-brainstem (P = .02), but not Dmax-optic nerves (P = .87). Helical tomotherapy provided better target coverage, with lower average D2%-PTV (P = .02), higher average D98%-PTV (P = .02), and better conformal index (0.87 vs 0.84, P = .02) and homogeneity index (0.15 vs 0.21, P = .05). With smaller bilateral hippocampal tissues doses, the planning target volume dose changed across 3 dosimetry regions for both modalities; the plateau region (>20.0 Gy for helical tomotherapy versus >16.0 Gy for co-planar dual arcs volumetric-modulated arc therapy), gradient region (20.0-12.0 Gy vs 16.0-11.0 Gy), and falling region (<12.0 Gy vs <11.0 Gy). The average delivery duration of helical tomotherapy was almost 7.7 times longer than that of co-planar dual arcs volumetric-modulated arc therapy. Conclusions: Helical tomotherapy was better at sparing the bilateral hippocampal tissues and organs at risk and had better target coverage but a significantly longer treatment duration than co-planar dual arcs volumetric-modulated arc therapy. Further dose decreases in the bilateral hippocampal tissues would yield worse target dose coverage.

5.
Nurs Open ; 8(3): 1098-1107, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-34482653

RESUMO

AIM: Cancer patients have long been found to have multiple types of unmet needs during their survivorship. Composite psychological instruments are essential for measuring the unmet needs of cancer patients. The objective of this study was to evaluate the psychometric properties of the Short-Form Survivor Unmet Needs Survey (SF-SUNS)-Chinese version. DESIGN: A cross-sectional survey. METHODS: The Chinese version was developed using the standard Functional Assessment of Chronic Illness Therapy (FACIT) translation methodology and 428 Chinese cancer patients participated in the survey between 2016-2017. Inter-rater reliability, exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were calculated. RESULTS: Confirmatory factor analysis supported the four-factor structure with good model fit. Cronbach's alpha of 0.894 for the overall scale and intra-class correlation coefficients (0.869-0.884) indicated that reliability was satisfactory. The EFA extracted four factors with eigenvalues greater than 1 and these factors explained 50.68% of the total variance. The Chinese version of SF-SUNS was confirmed to have the potential to become a useful and valid instrument. It could contribute to the assessment of unmet needs among Chinese cancer patients with accuracy and with respect to Chinese culture and context. This measurement of unmet needs may help promote cancer management and nursing quality. Clinical nurses and researchers could use the simple assessment tool to target the individual needs of Chinese cancer patients and then provide more personalized care efficiently.


Assuntos
Neoplasias , Sobreviventes , China/epidemiologia , Estudos Transversais , Humanos , Neoplasias/epidemiologia , Reprodutibilidade dos Testes
6.
Neurol Res ; : 1-6, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34559025

RESUMO

BACKGROUND: Intracerebral hemorrhage (ICH) has a high mortality and morbidity in the world. C-Reaction Protein (CRP) has been demonstrated to be an independent risk factor and could predict the severity and outcome of ischemic stroke. In our study, we aimed to find out the relationship between CRP levels and the severity and outcome of patients with ICH. METHODS: This study comes from the Chinese Stroke Center Alliance (CSCA). Patients' basic characteristics and laboratory examination results, including the concentration of CRP were taken from August 2015 to July 2019. Chi-square test and Logistic regression were used to analyze the relationship between different CRP levels and clinical outcome. RESULTS: A total of 9589 patients with acute ICH were enrolled in our study. In the logistic regression analysis, we found out that high CRP level is an independent risk factor for the prevalence of severe ICH and in-hospital death. After adjusting sex, age and other relevant stroke risk factors, the difference still exists (Severe ICH: odd ratio (OR) (95% confidence interval (CI) = 1.14 (1.04-1.26), P = 0.0076 for CRP between 3-10mg/l group and 1.64 (1.46-1.84), P<0.0001 for CRP>10mg/l group. In-hospital death: OR(95%CI)= 2.03(1.39-2.95), P=0.0002 for CRP>10mg/l group). CONCLUSIONS: High CRP level was independently associated with poorer clinical outcome and higher in-hospital death in patients with ICH.

7.
J Clin Lab Anal ; : e23971, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34569664

RESUMO

BACKGROUND: Corpus callosum abnormality (CCA) can lead to epilepsy, moderate severe neurologic or mental retardation. The prognosis of CCA is closely related to genetic etiology. However, copy number variations (CNVs) associated with fetal CCA are still limited and need to be further identified. Only a few scattered cases have been reported to diagnose CCA by whole exome sequencing (WES). METHODS: Karyotyping analysis, copy number variation sequencing (CNV-seq), chromosomal microarray analysis (CMA) and WES were parallelly performed for prenatal diagnosis of 19 CCA cases. RESULTS: The total detection rate of karyotyping analysis, CMA (or CNV-seq) and WES were 15.79% (3/19), 21.05% (4/19) and 40.00% (2/5), respectively. Two cases (case 11 and case 15) were diagnosed as aneuploidy (47, XY, + 13 and 47, XX, + 21) by karyotyping analysis and CNV-seq. Karyotyping analysis revealed an unknown origin fragment (46,XY,add(13)(p11.2)) in case 3, which was further confirmed to originate from p13.3p11.2 of chromosome 17 by CNV-seq. CMA revealed arr1q43q44 (238923617-246964774) × 1(8.04 Mb) in case 8 with a negative result of chromosome karyotype. WES revealed that 2 of 5 cases with negative results of karyotyping and CNV-seq or CMA carried pathogenic genes ALDH7A1 and ARID1B. CONCLUSION: Parallel genetic tests showed that CNV-seq and CMA are able to identify additional, clinically significant cytogenetic information of CCA compared to karyotyping; WES significantly improves the detection rate of genetic etiology of CCA. For the patients with a negative results of CNV-seq or CMA, further WES test is recommended.

8.
Analyst ; 146(19): 5866-5872, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34570847

RESUMO

DNA-tuned dye assemblies have received considerable attention toward developing various devices. Owing to easy conformation implementation, G-quadruplexes (G4s) have been extensively used as initiators to grow dye assemblies with controllable chiralities. However, programmed chirality regulation of dye assemblies for a given G4 sequence has not been realized in a straightforward manner. In this work, we replaced a middle guanine in the G-tracts of a human telomeric G4 with an apurinic site (AP site) to meet the programmed dye assemblies. Although all of the AP site replacements altered the G4 conformation from the hybrid to the antiparallel folding, the handedness of pinacyanol (PIN) assemblies grown on the AP site-containing G4 was programmably regulated. The G4 with the AP site at the 5'-most G-tract grew right-handed assemblies, while that with the AP site at the 3'-most G-tract grew left-handed assemblies. The handedness of assemblies almost totally mirrored each other within 450-700 nm. Interestingly, we found that the AP site provided a specific binding site for guanosine and guanine, and this binding event sensitively broke the chiral assemblies. Thus, dye assembly-based sensors can be easily established based on the chiral responses with a high selectivity and sensitivity. Our work first demonstrates the AP site programmed chirality regulation of G4-grown dye assemblies and will find wide application in chiral devices.


Assuntos
Quadruplex G , DNA , Guanina , Guanosina , Humanos , Telômero
9.
Small ; : e2103557, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34590427

RESUMO

Mesocarbon microbeads (MCMB) are highly desirable as anode materials for rechargeable potassium ion batteries (PIBs) due to their commercially availability, high stability and low-cost. However, their charge storage and interfacial mechanisms are still unclear. In this work, the intercalation mechanisms and the solid-electrolyte-interphase (SEI) formation of the MCMB in four different electrolytes is comprehensively studied. The MCMB anodes exhibit superior rate and cycle performances via a naked K-ions sequentially staging intercalation mechanism, realizing the complete transformation from graphite to KC8 . Whereas a solvated K-ions co-intercalation mechanism of the MCMB occurs in ether-based electrolytes, which might induce graphite exfoliation and result in unsatisfied specific capacity and capacity decay. Nevertheless, this co-intercalation behavior could be effectively suppressed by a highly concentrated electrolytes. Interfacial analyses unveil the distinct SEI components, which vary with the electrolyte chemistries. These SEI components also varies from surface to bulk and especially attention should be paid to the accurate control of the concentration of the fluoroethylene carbonate additives. This work provides a panoramic understanding of the intercalation and interfacial mechanisms on the MCMB anodes for PIBs.

10.
Cell Signal ; 87: 110145, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34517087

RESUMO

Endometriosis is a debilitating gynecological disease affecting millions of women worldwide, but its exact pathogenesis remains unclear. Circular RNAs (circRNAs) have been demonstrated to be important regulators in multiple diseases. Nonetheless, the potential regulatory mechanism of aberrant circRNA expression in endometriosis has been elusive. The up-regulated circZFPM2 in ectopic endometrial tissues was previously screened by circRNA high-throughput sequencing and was furtherly validated by quantitative real time reverse transcriptase polymerase chain reaction (RT-qPCR). Overexpression of circZFPM2 promoted the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in Ishikawa and End1/E6E7 cells, whereas silencing circZFPM2 produced the opposite effect. Luciferase reporter assays validated that circZFPM2 could directly target miR-205-5p and miR-205-5p target ZEB1. RT-qPCR results showed that miR-205-5p was underexpressed while ZEB1 was overexpressed in ectopic endometrial tissues compared with their expression in eutopic endometria and non-endometriosis control endometria. The expression level of miR-205-5p was inversely proportional and that of ZEB1 was directly proportional with the proliferative, migrative, and invasive ability of endometrial cells. Further in vitro investigation indicated that miR-205-5p could inhibit EMT by targeting ZEB1. Subsequent rescue experiments confirmed that circZFPM2 could induce EMT and promote cell proliferation, migration, and invasion cascades through the miR-205-5p /ZEB1 signaling pathway. Conclusively, circZFPM2 may present a promising biomarker in the diagnosis and treatment of endometriosis.

11.
Int J Med Mushrooms ; 23(9): 63-71, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34591399

RESUMO

Three major polysaccharides (wHEP-1, wHEP-2, and wHEP-3) were isolated from the mycelium of Hericium erinaceus. This study assessed their chemical and physical properties, molecular weight, monosaccharide compositions, and anti-ulcerative colitis ability to protect Caco-2 cells from lipopolysaccharide (LPS)-induced inflammation. The results showed that the average molecular weight of wHEP-1, wHEP-2, and wHEP-3 was 5010, 1812, and 1118 Da, respectively. wHEP-1 was composed of mannose, glucose, and galactose in a molar ratio of 1.2:16.9:1:1, whereas wHEP-2 and wHEP-3 were composed of glucose and galactose in different molar ratios. Anti-inflammatory activity was compared using LPS-induced Caco-2 cells and a rat model. wHEP-1 exhibited the best anti-inflammatory activity. Thus, the polysaccharide from H. erinaceus as a natural material shows potential for the development of alternative therapies.

12.
Hum Mol Genet ; 2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34508586

RESUMO

GNAO1 encephalopathy is a neurodevelopmental disorder with a spectrum of symptoms that include dystonic movements, seizures and developmental delay. While numerous GNAO1 mutations are associated with this disorder, the functional consequences of pathological variants are not completely understood. Here, we deployed the invertebrate C. elegans as a whole-animal behavioral model to study the functional effects of GNAO1 disorder-associated mutations. We tested several pathological GNAO1 mutations for effects on locomotor behaviors using a combination of CRISPR/Cas9 gene editing and transgenic overexpression in vivo. We report that all three mutations tested (G42R, G203R and R209C) result in strong loss of function defects when evaluated as homozygous CRISPR alleles. In addition, mutations produced dominant negative effects assessed using both heterozygous CRISPR alleles and transgenic overexpression. Experiments in mice confirmed dominant negative effects of GNAO1 G42R, which impaired numerous motor behaviors. Thus, GNAO1 pathological mutations result in conserved functional outcomes across animal models. Our study further establishes the molecular genetic basis of GNAO1 encephalopathy, and develops a CRISPR-based pipeline for functionally evaluating mutations associated with neurodevelopmental disorders.

13.
Lipids Health Dis ; 20(1): 121, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34587966

RESUMO

BACKGROUND: Current studies support lipid ratios [the total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio; the triglyceride (TG)/HDL-C ratio; the low-density lipoprotein cholesterol (LDL -C)/HDL-C ratio; and non-HDL-C] as reliable indicators of cardiovascular disease, stroke, and diabetes. However, whether lipid ratios could serve as markers for hyperuricemia (HUA) remains unclear due to limited research. This study aimed to explore the association between lipid ratios and HUA in hypertensive patients. METHODS: The data from 14,227 Chinese hypertensive individuals in the study were analyzed. Multiple logistic regression analysis and smooth curve fitting models examined the relationship between lipid ratios and HUA. RESULTS: The results showed positive associations between the lipid ratios and HUA (all P < 0.001). Furthermore, lipid ratios were converted from continuous variables to tertiles. Compared to the lowest tertile, the fully adjusted ORs (95 % CI) of the TC/HDL-C ratio, the TG/HDL-C ratio, the LDL-C/HDL-C ratio, and non-HDL-C in the highest tertile were 1.79 (1.62, 1.99), 2.09 (1.88, 2.32), 1.67 (1.51, 1.86), and 1.93 (1.74, 2.13), respectively (all P < 0.001). CONCLUSIONS: The study suggested that high lipid ratios (TC/HDL-C ratio, TG/HDL-C ratio, LDL-C/HDL-C ratio, and non-HDL-C) are associated with HUA in a Chinese hypertensive population. This study's findings further expand the scope of the application of lipid ratios. These novel and essential results suggest that lipid ratio profiles might be potential and valuable markers for HUA. TRIAL REGISTRATION: No. ChiCTR1800017274. Registered July 20, 2018.

14.
World J Pediatr ; 17(5): 467-475, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34476758

RESUMO

BACKGROUND: Allergic diseases are one of the most common and important diseases that can exert hazardous effects on children's health. The prevalence of allergic diseases in childhood is gradually increasing all over the world in recent decades. Known causes of these diseases include anomalous immune responses and allergic inflammatory reactions, but the causes of allergic diseases in childhood are complex. DATA SOURCES: PubMed, Cochrane Library, Embase and Web of Science were searched for articles focusing on environmental exposure during pregnancy and the risk of childhood allergic diseases, including asthma and atopic dermatitis, and the possible underlying mechanism. RESULTS: In terms of environmental factors, allergic diseases in childhood are closely related to environmental chemical exposure during pregnancy, including bisphenols, phthalates acid esters, perfluorochemicals, polybrominated diphenyl ethers, and polychlorinated biphenyls. However, allergic diseases in childhood are also closely associated with maternal dietary nutrition, maternal intake of drugs, such as acetylsalicylic acid (aspirin), paracetamol and antibiotics, and maternal lifestyle. CONCLUSIONS: Several harmful environmental factors during pregnancy can result in the interruption of the function of helper T cells (Th1/Th2), cytokines and immunoglobulins and may activate allergic reactions, which can lead to allergic diseases during childhood.

15.
BMC Genomics ; 22(1): 593, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34348644

RESUMO

BACKGROUND: The mutation of insulin-like growth factor 2 (IGF2 mutation) that a single-nucleotide substitution (G→A) in the third intron of IGF2 abrogates the interaction with zinc finger BED-type containing 6 (ZBED6) and leads to increased muscle mass in pigs. IGF2 mutation knock-in (IGF2 KI) and ZBED6 knockout (ZBED6 KO) lead to changes in IGF2 expression and increase muscle mass in mice and pigs. Long noncoding RNAs (lncRNAs) may participate in numerous biological processes, including skeletal muscle development. However, the role of the ZBED6-lncRNA axis in skeletal muscle development is poorly characterized. RESULTS: In this study, we assembled transcriptomes using RNA-seq data published in previous studies by our group and identified 11,408 known lncRNAs and 2269 potential lncRNAs in seven tissues, heart, longissimus dorsi, gastrocnemius muscle, liver, spleen, lung and kidney, of ZBED6 KO (lean mass model) and WT Bama pigs. ZBED6 affected the expression of 1570 lncRNAs (differentially expressed lncRNAs [DE-lncRNAs]; log2-fold change ≥ 1, nominal p-value ≤ 0.05) in the seven examined tissues. The expressed lncRNAs (FPKM > 0.1) exhibited tissue-specific patterns in WT pigs. Specifically, 3410 lncRNAs were expressed exclusively in only one tissue. Potential functions of lncRNAs were indirectly predicted by searching their target cis- and trans-regulated protein-coding genes. LncRNAs with tissue-specific expression influence numerous genes related to tissue functions. Weighted gene coexpression network analysis (WGCNA) of 1570 DE-lncRNAs between WT and ZBED6 KO pigs was used to define the following six lncRNA modules specific to different tissues: skeletal muscle, heart, lung, spleen, kidney and liver modules. Furthermore, by conjoint analysis of longissimus dorsi data (tissue-specific expression, muscle module and DE-lncRNAs) and ChIP-PCR revealed NONSUSG002145.1 (adjusted p-values = 0.044), which is coexpressed with the IGF2 gene and binding with ZBED6, may play important roles in ZBED6 KO pig skeletal muscle development. CONCLUSIONS: These findings indicate that the identified lncRNAs may play essential roles in tissue function and regulate the mechanism of ZBED6 action in skeletal muscle development in pigs. To our knowledge, this is the first study describing lncRNAs in ZBED6 KO pigs. These results may open new research directions leading to a better understanding of the global functions of ZBED6 and of lncRNA functions in skeletal muscle development in pigs.


Assuntos
RNA Longo não Codificante , Animais , Íntrons , Camundongos , Desenvolvimento Muscular , Músculo Esquelético/metabolismo , RNA Longo não Codificante/genética , Proteínas Repressoras/genética , Suínos/genética , Transcriptoma
16.
Brain Imaging Behav ; 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34449034

RESUMO

Cognitive impairments are core aspects of schizophrenia and are highly related to poor outcomes. However, the effect of therapy on cognitive impairments remains unsatisfactory as its biological mechanisms are not fully understood. The purpose of this study was to investigate the disrupted intrinsic neural activity of the frontal areas and to further examine the functional connectivity of frontal areas related to cognitive impairments in schizophrenia. We collected brain imaging data using a 3T Siemens Prisma MRI system in 32 patients with schizophrenia and 34 age- and sex-matched healthy controls. The mean fractional amplitude of low-frequency fluctuation (mfALFF) in the frontal regions was calculated and analyzed to evaluate regional neural activity alterations in schizophrenia. Seed regions were generated from clusters showing significant changes in mfALFF in schizophrenia, and its resting-state functional connectivity (rs-FC) with other brain regions were estimated to detect possible aberrant rs-FC indicating cognitive impairments in schizophrenia. We found that mfALFF in the bilateral frontal cortices was increased in schizophrenia. mfALFF-based rs-FC revealed that decreased rs-FC between left middle frontal gyrus (MFG) and left medial superior frontal gyrus (MFSG) was associated with poor delayed memory (r = 0.566, Bonferroni-corrected p = 0.012). These findings demonstrate increased neural activity in the frontal cortices in schizophrenia. FC analysis revealed a diminished rs-FC pattern between the left MFG and left MSFG that was associated with cognitive impairments. These findings have provided deeper insight into the alterations in brain function related to specific domains of cognitive impairment and may provide evidence for precise interventions for cognitive deficits in schizophrenia.

17.
J Biomed Nanotechnol ; 17(7): 1404-1416, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34446143

RESUMO

The development of multidrug resistance (MDR) is a commonly observed phenomenon in many cancer types. It contributed significantly to the poor outcome of many currently available chemotherapies. Considering autophagy as one of the most important physiological process in cancer progression, we thereby proposed an anti-autophagy siRNA and doxorubicin (Dox) co-delivery system (MC/D-siR) to combat MDR breast cancer using sequential construction. Our results demonstrated the potential of MC/D-siR to effectively transfect the loaded siRNA to result in significant downregulation of intracellular autophagy level in MCF-7/Adr (Dox resistance MCF-7 cell line) cells, which in turn cut off the ATP supply and to reverse the MDR and potentiated accumulated drug retention in cells. As a result, MC/D-siR showed much elevated anticancer benefits than single loaded platforms (MC/Dox or MC/siRNA), indicating the ability for effective MDR cancer treatment through the combination of autophagy regulation and chemotherapy.


Assuntos
Neoplasias da Mama , Nanopartículas , Autofagia , Neoplasias da Mama/tratamento farmacológico , Membrana Celular , Doxorrubicina/farmacologia , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Células MCF-7
18.
Neurol Res ; : 1-10, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34431446

RESUMO

To systematically compare 27 ICH models with regard to mortality and functional outcome at 1-month, 3-month and 1-year after ICH. The validation cohort was derived from the Beijing Registration of Intracerebral Hemorrhage. Poor functional outcome was defined as modified Rankin Scale score (mRS) ≥3 at 1-month, 3-month and 1-year after ICH, respectively. The area under the receiver operating characteristic curve (AUROC) and Hosmer-Lemeshow goodness-of-fit test were used to assess model discrimination and calibration. A total number of 1575 patients were included. The mean age was 57.2 ± 14.3 and 67.2% were male. The median NIHSS score on admission was 11 (IQR: 3-21). For predicting mortality at 3-month after ICH, AUROC of 27 ICH models ranged from 0.604 to 0.856. In pairwise comparison, the ICH-FOS (0.856, 95%CI = 0.835-0.878, P < 0.001) showed statistically better discrimination than other models for mortality at 3-month after ICH (all P < 0.05). For predicting poor functional outcome (mRS≥3) at 3-month after ICH, AUROC of 27 ICH models ranged from 0.602 to 0.880. In pairwise comparison with other prediction models, the ICH-FOS was superior in predicting poor functional outcome at 3-month after ICH (all P < 0.001). The ICH-FOS showed the largest Cox and Snell R-square. Similar results were verified for mortality and poor functional outcome at 1-month and 1-year after ICH. Several risk models are externally validated to be effective for risk stratification and outcome prediction after ICH, especially the ICH-FOS, which would be useful tools for personalized care and clinical trial in ICH.

19.
Clin Transl Med ; 11(8): e509, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34459137

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive scarring disease with unknown etiology. The evidence of a pathogenic role for transforming growth factor-beta (TGF-ß) in the development and progression of IPF is overwhelming. In the present study, we investigated the role of interleukin-22 (IL-22) in the pathogenesis of IPF by regulating the TGF-ß pathway. We measured parameters and tissue samples from a clinical cohort of IPF. IL-22R knock out (IL-22RA1-/- ) and IL-22 supplementation mouse models were used to determine if IL-22 is protective in vivo. For the mechanistic study, we tested A549, primary mouse type II alveolar epithelial cell, human embryonic lung fibroblast, and primary fibroblast for their responses to IL-22 and/or TGF-ß1. In a clinical cohort, the expression level of IL-22 in the peripheral blood and lung tissues of IPF patients was lower than healthy controls, and the lower IL-22 expression was associated with poorer pulmonary function. IL-22R-/- mice demonstrated exacerbated inflammation and fibrosis. Reciprocally, IL-22 augmentation by intranasal instillation of recombinant IL-22 repressed inflammation and fibrotic phenotype. In vitro, IL-22 treatment repressed TGF-ß1 induced gene markers representing epithelial-mesenchymal-transition and fibroblast-myofibroblast-transition, likely via the inhibition of TGF-ß receptor expression and subsequent Smad2/3 activation. IL-22 appears to be protective against pulmonary fibrosis by inhibiting TGF-ß1 signaling, and IL-22 augmentation may be a promising approach to treat IPF.

20.
Cells ; 10(8)2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34440725

RESUMO

Innate and adaptive immune systems are evolutionarily divergent. Primary signaling in T and B cells depends on somatically rearranged clonotypic receptors. In contrast, NK cells use germline-encoded non-clonotypic receptors such as NCRs, NKG2D, and Ly49H. Proliferation and effector functions of T and B cells are dictated by unique peptide epitopes presented on MHC or soluble humoral antigens. However, in NK cells, the primary signals are mediated by self or viral proteins. Secondary signaling mediated by various cytokines is involved in metabolic reprogramming, proliferation, terminal maturation, or memory formation in both innate and adaptive lymphocytes. The family of common gamma (γc) cytokine receptors, including IL-2Rα/ß/γ, IL-7Rα/γ, IL-15Rα/ß/γ, and IL-21Rα/γ are the prime examples of these secondary signals. A distinct set of cytokine receptors mediate a 'third' set of signaling. These include IL-12Rß1/ß2, IL-18Rα/ß, IL-23R, IL-27R (WSX-1/gp130), IL-35R (IL-12Rß2/gp130), and IL-39R (IL-23Rα/gp130) that can prime, activate, and mediate effector functions in lymphocytes. The existence of the 'third' signal is known in both innate and adaptive lymphocytes. However, the necessity, context, and functional relevance of this 'third signal' in NK cells are elusive. Here, we define the current paradigm of the 'third' signal in NK cells and enumerate its clinical implications.

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