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1.
Sci Rep ; 11(1): 7520, 2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33824394

RESUMO

Chronic Fatigue Syndrome (CFS) has been defined as unexplained relapsing or persistent fatigue for at least 6 consecutive months. Immuno-inflammatory pathway, bacterial infection, and other causes play essential roles in CFS. Helicobacter pylori infection is one of the most common causes of foregut inflammation, leading to peptic ulcer disease (PUD). This study aimed to analyze the risk of CFS development between patients with and without PUD. Other related factors were also analyzed. We performed a retrospective, nationwide cohort study identifying patients with or without PUD respectively by analyzing the Longitudinal Health Insurance Database 2000 (LHID2000), Taiwan. The overall incidence of CFS was higher in the PUD cohort than in the non- PUD cohort (HR = 2.01, 95% CI = 1.75-2.30), with the same adjusted HR (aHR) when adjusting for age, sex, and comorbidities. The sex-specific PUD cohort to the non-PUD cohort relative risk of CFS was significant in both genders. The age-specific incidence of CFS showed incidence density increasing with age in both cohorts. There is an increased risk of developing CFS following PUD, especially in females and the aging population. Hopefully, these findings can prevent common infections from progressing to debilitating, chronic conditions such as CFS.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33808092

RESUMO

The Stereotype Content Model (SCM) has been validated in multiple countries and regions. However, previous validation studies in China have been limited by small sample size. The current research increased the sample size (n = 184 in the pilot study; n1 = 1315 and n2 = 268 in the formal study) to validate the SCM in mainland China in study 1. Supporting the SCM, 41 social groups were clustered into four quadrants based on warmth and competence dimensions. 35 of the 41 target groups (85.37%) receive ambivalent stereotype. Perceived warmth and competence were positively correlated (r = 0.585, p < 0.001). Status and competence were positively related (r = 0.81, p < 0.001), and competition and warmth were negatively related (r = -0.77, p < 0.001). In addition, 24 typical social groups were selected and a list of stereotype words for these groups was developed in study 2 (n1 = 48, n2 = 52). The implications of the emerging social groups and the applications of this stereotype word list are discussed.

3.
Poult Sci ; 100(5): 101051, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33756249

RESUMO

Preserved eggs without adding heavy metals in the pickling solution (heavy metals-free preserved eggs) have been developed, but it was found that the undesirable phenomenon such as dry shrinkage and fading occurred when they were not packaged and stored at room temperature. In this study, the effects of 5 packaging methods on the quality of heavy metals-free preserved eggs during storage were systematically studied. These methods included storage at room temperature and 4°C without packaging, wrapping with plastic bags, paraffin coating, and vacuum package. Through adopting these 5 packaging methods, the results showed that the moisture content and pH of the albumen decreased continuously, the mass loss rate increased continuously, the content of total volatile basic nitrogen increased firstly and then decreased, and the albumen hardness increased continuously. No microorganisms were detected in all samples with the 5 packaging methods during storage. Among them, the uncoated preserved eggs suffered the most serious moisture loss and mass loss, and the pH dropped at the fastest rate, followed by the preserved eggs wrapped in plastic bags. Preserved eggs stored at low temperature tended to turn yellow during storage, and the albumen showed higher hardness. The packaging method of paraffin coating performed the best in preventing the moisture loss of the albumen and the weight loss, which only decreased by 0.34 and 1.24%, respectively, after 3 mo. The best springiness, the darkest color, and the highest sensory score were found in the vacuum-packed preserved eggs after 3 mo of storage. It was concluded that paraffin coating and vacuum packing had better effect, while plastic bag packing showed the worst preservation performance for heavy metals-free preserved eggs.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33761079

RESUMO

In the present work, the Fe-MIL(100) was encapsulated on the outer surface of magnetic g-C3N4 through a simple method to synthesize a novel adsorbent. The as-prepared g-C3N4/MnFe2O4/Fe-MIL(100) was characterized with scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), BET specific surface area (BET), vibrating sample magnetometry (VSM), and plasma emission spectrometry (PES). The g-C3N4/MnFe2O4/Fe-MIL(100) possessed rough surface, large surface area (303.68 m2/g), mesoporous structure and magnetic properties, which exhibited excellent adsorption performance for ciprofloxacin (CIP), oxytetracycline (OTC) and indomethacin (IDM) with the maximum adsorption capacities reaching up to 45.51, 64.34 and 103.91 mg/g, respectively. The adsorption processes of all three PPCPs could be described by different kinds of isotherms and kinetic models. Additionally, the adsorption capacity of the resulting adsorbent could maintain 73.43% of the first adsorption capacity even after ten cycles. Finally, the possible adsorption mechanisms of g-C3N4/MnFe2O4/Fe-MIL(100) for CIP/OTC/IDM were proposed. Thus, g-C3N4/MnFe2O4/Fe-MIL(100) possessed excellent features of high adsorption capacity, fast removal rate, easy synthesis, salt resistance and magnetic separation, which showed great potential application to be used as an effective adsorbent for adsorptive removal of PPCPs in wastewater.

5.
Chemosphere ; 275: 130034, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33652285

RESUMO

Polybrominated diphenyl ethers (PBDEs), a kind of flame retardants, were widely used in the furniture, textile and electronics industries. Because of their lipophilic, persistent and bio-accumulative properties, PBDEs were listed on the Stockholm Convention as typical persistent organic pollutants (POPs). We have previously reported that a highly active, quinone-type metabolite of PBDEs (PBDEQ) causes DNA damage and subsequently triggers apoptosis. However, it is remaining unclear whether PBDEQ provokes protein damage and stimulates corresponding signaling cascade. Using human normal liver (LO2) cells as an in vitro model, we demonstrated that PBDEQ causes oxidative protein damage through excess reactive oxygen species (ROS). Consistently, we found PBDEQ exposure causes the depletion of protein thiol group, the appearance of carbonyl group and the accumulation of protein aggregates. Endoplasmic reticulum (ER) stress was involved in the repair of oxidized proteins. Under the scenario of severe damage, LO2 cells degrade oxidized proteins through ubiquitin-proteasome system (UPS) and autophagy. The blockage of these protein degradation pathways aggravates PBDEQ-induced cytotoxicity in LO2 cells, whilst antioxidant N-acetyl-cysteine (NAC) rescues PBDEQ-induced oxidative protein damage conversely. In summary, our current study first demonstrated PBDEQ-induced protein oxidative damage in LO2 cells, which offer a better understanding of the cytotoxicity of PBDEs and corresponding metabolites.

6.
Sleep Breath ; 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33709192

RESUMO

STUDY OBJECTIVE: Bilateral endoscopic nasal surgery is usually associated with pain and sleep disturbance. The aim of this study was to evaluate the effects of dexmedetomidine-soaked nasal packing on analgesia and improvement of sleep quality in patients undergoing this surgery. METHOD: Eighty patients were enrolled and randomly allocated into 4 groups. At the end of surgery, dexmedetomidine-soaked nasal packings were applied to three groups with a dosage of 1 µg kg-1 (D1), 2µg kg-1 (D2), 4 µg kg-1 (D4) and normal saline-soaked nasal packing (NS) was applied to a fourth group. The primary outcome was postoperative pain scores using a visual analog scale (VAS) recorded at six time points: before the surgery (T1); 2 h (T2), 8 h (T3), 24 h (T4), 48 h (T5) after surgery; and at the moment of nasal packing removal (T6). Secondary outcomes were postoperative sleep status evaluated by the Pittsburgh sleep quality index (PSQI) and subjective sleep quality value (SSQV). Factors affecting sleep, hemodynamic changes, and adverse events were also recorded. RESULTS: Compared with the NS group, dexmedetomidine-soaked nasal packing significantly relieved postoperative pain and improved sleep quality. The effect was similar between D2 and D4, which was greater than in D1. However, D2 was associated with fewer adverse events. CONCLUSIONS: Dexmedetomidine-soaked nasal packing not only offers effective analgesia but also improves postoperative sleep quality in patients undergoing bilateral endoscopic nasal surgery. Taking effect and adverse events into consideration, a dosage of 2µg kg-1 may be optimal. TRIAL REGISTRATION: www.chictr.org.cn/index.aspx (ChiCTR1900025692) Retrospectively registered 5 September 2019.

7.
BMC Neurol ; 21(1): 120, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33731000

RESUMO

BACKGROUND: Anti-IgLON5 antibody-related encephalopathy is a recently discovered and rare autoimmune disease, and its diagnosis and treatment are more challenging than for other autoimmune encephalopathic diseases. Sleep disorder is the most prominent symptom of the disease. It can also present with gait instability, dysarthria, dysphagia, dementia, ataxia, autonomic nervous system dysfunction, chorea, vertical gaze paralysis, and other symptoms. Immunotherapy remains the primary treatment for this disease; however, there is no definitive conclusion regarding the effect of immunotherapy. The clinical symptoms of the reported cases of anti-IgLON5 antibody-related encephalopathy were generally severe. However, the symptoms in our patient were mild and relieved without immunotherapy, unlike the previously reported cases. CASE PRESENTATION: A 62-year-old man presented with behavioural abnormalities and involuntary movements after nearly 2 months of fever and headache. He also had symptoms of mild sleep disorder. Due to the abnormal levels of infection-related indicators, antiviral treatment was started on the day of admission. The serum analysis confirmed the presence of IgLON5 antibody, and the patient was found to be genetically susceptible. The patient's symptoms resolved rapidly without immunotherapy and did not recur. CONCLUSIONS: This case demonstrated that IgLON5 antibody-related encephalopathy might have mild manifestations. Infection and a genetic predisposition may be important causes for the disease. Patients with a mild disease may have a better prognosis.

8.
Hepatol Int ; 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33751394

RESUMO

BACKGROUND: Among elder children/young adults who received hepatitis B virus (HBV) vaccination during infancy, the serological status of HBsAg-negative and anti-HBc-positive [HBsAg(-)/anti-HBc(+)] was frequently reported, indicating potential occult HBV infection (OBI). It is required to define the long-term protection of neonatal vaccination against OBI in their mature adulthood. METHODS: Building upon the 1983-1990 established Qidong Hepatitis B Intervention Study, we sampled 10% of the 28-35-year-old participants, who remained in the cohort by 2012. Each participant was tested for serological markers of HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc. HBV-DNA and relaxed circular DNA (rcDNA) were determined in some HBsAg(-)/anti-HBc(+) individuals. RESULTS: Totally, 3615 individuals from the neonatal vaccination group and 3100 individuals from the control group donated blood samples, respectively. In the vaccination group, the prevalence of HBsAg was 1.58% (57/3615), HBsAg(-)/anti-HBc(+) was 4.70% (170/3615), significantly lower than in the control group, which was 7.45% (231/3100) and 19.48% (640/3100) respectively (all p < 0.001). With aging, HBsAg(-)/anti-HBc(+) prevalence increased in the sampled participants from the control group (pfor trend < 0.001), but uncertain from the vaccination group. Of HBsAg(-)/anti-HBc(+), HBV-DNA was detected in 13.08% (17/130) from the vaccination group, and in 4.18% (12/287) from the control group. HBV rcDNA was detected in most sera that were tested positive for HBV-DNA. CONCLUSIONS: OBI occurred in some vaccinated adults. However, neonatal HBV vaccination kept the effective protection against OBI in mature adults.

9.
Dalton Trans ; 50(13): 4651-4662, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33725060

RESUMO

Dual-emitting manganese ion doped LaM1-xAl11-yO19 (M = Mg, Zn) phosphors were prepared by substituting Zn2+/Mg2+ with Mn2+ and replacing Al3+ with Mn4+. The LaM1-xAl11-yO19:xMn2+,yMn4+ phosphors show a narrow green emission band of the Mn2+ ions at 514 nm and a red emission band of the Mn4+ ions at 677 nm. In addition, the thermal stability of luminescence shows that the response of Mn2+ and Mn4+ to the temperature is obviously different in LaMAl11O19, implying the potential of the prepared phosphors as optical thermometers. The decay lifetime of Mn4+ was changed with temperature due to the different fluorescence intensity ratios of Mn2+ and Mn4+, and a dual-mode optical temperature-sensing mechanism was studied in the temperature range of -50-200 °C. The maximum relative sensitivities (Sr) are calculated as 3.22 and 3.13% K-1, respectively. The unique optical thermometric features demonstrate the application potential of LaMAl11O19:Mn2+,Mn4+ in optical thermometry.

10.
Clin Cancer Res ; 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33558426

RESUMO

PURPOSE: Fluzoparib (PARP inhibitor) showed promising antitumor activity for advanced ovarian cancer in a phase I study. This study aimed to assess the efficacy and safety of fluzoparib in patients with germline BRCA1/2-mutated recurrent ovarian cancer. PATIENTS AND METHODS: This open-label, multicenter, single-arm, phase II study enrolled patients with platinum-sensitive recurrent ovarian cancer and germline BRCA1/2 mutation who had previously received two to four lines of platinum-based chemotherapy. Fluzoparib 150 mg was administered orally twice daily. The primary endpoint was independent review committee (IRC)-assessed objective response rate per RECIST v1.1. RESULTS: A total of 113 patients were enrolled and received at least one dose of fluzoparib. As of data cutoff on March 21, 2020, the median follow-up period was 15.9 months (interquartile range, 13.5-18.5). The IRC- and investigator-assessed objective response rates were 69.9% [95% confidence interval (CI), 60.6-78.2] and 70.8% (95% CI, 61.5-79.0), respectively. The objective response rates were similar across all prespecified subgroups. The median IRC- and investigator-assessed progression-free survival was 12.0 months (95% CI, 9.3-13.9) and 10.3 months (95% CI, 9.2-12.0), respectively. The 12-month survival rate was 93.7% (95% CI, 87.2-96.9). Grade ≥3 adverse events occurred in 63.7% (72/113) of the patients, with the most common one being anemia/decreased hemoglobin. Adverse events that led to treatment interruption, dose reduction, and discontinuation occurred in 39.8%, 34.5%, and 0.9% of patients, respectively. One treatment-related death occurred. CONCLUSIONS: Fluzoparib demonstrated promising antitumor activity and acceptable safety profile in germline BRCA1/2-mutated, platinum-sensitive relapsed ovarian cancer. Thus, fluzoparib might be a novel treatment option for this population.

11.
Int J Biol Sci ; 17(2): 549-561, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33613112

RESUMO

Comprehensive reviews and large population-based cohort studies have played an important role in the diagnosis and treatment of pancreatitis and its sequelae. The incidence and mortality of pancreatitis have been reduced significantly due to substantial advancements in the pathophysiological mechanisms and clinically effective treatments. The study of extracellular vesicles (EVs) has the potential to identify cell-to-cell communication in diseases such as pancreatitis. Exosomes are a subset of EVs with an average diameter of 50~150 nm. Their diverse and unique constituents include nucleic acids, proteins, and lipids, which can be transferred to trigger phenotypic changes of recipient cells. In recent years, many reports have indicated the role of EVs in pancreatitis, including acute pancreatitis, chronic pancreatitis and autoimmune pancreatitis, suggesting their potential influence on the development and progression of pancreatitis. Plasma exosomes of acute pancreatitis can effectively reach the alveolar cavity and activate alveolar macrophages to cause acute lung injury. Furthermore, upregulated exosomal miRNAs can be used as biomarkers for acute pancreatitis. Here, we summarized the current understanding of EVs in pancreatitis with an emphasis on their biological roles and their potential use as diagnostic biomarkers and therapeutic agents for this disease.

13.
Eur Radiol ; 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33569616

RESUMO

OBJECTIVES: To summarise the CT findings of gastric poorly cohesive carcinoma (PCC) in the 40 s late arterial phase and differentiate it from tubular adenocarcinoma (TAC) using an integrative nomogram. METHODS: A total of 241 patients including 59 PCCs, 109 TACs, and 73 other type gastric cancers were enrolled. Thirteen CT morphological characteristics of each lesion in the late arterial phase were evaluated. In addition, CT value-related parameters were extracted from ROIs encompassing the area of greatest enhancement on four-phase CT images. Nomograms based on regression models were built to discriminate PCCs from TACs and from non-PCCs. ROC curve analysis was performed to assess the diagnostic efficiency. RESULTS: Six morphological characteristics, 10 CT value-related parameters, and the enhanced curve types differed significantly among the above three groups in the primary cohort (all p < 0.05). The paired comparison revealed that 10 CT value-related parameters differed significantly between PCCs and TACs (all p < 0.05). The AUC of the nomogram based on the multivariate model for discriminating PCCs from TACs was 0.954, which was confirmed in the validation cohort (AUC = 0.895). The AUC of another nomogram for discriminating PCCs from non-PCCs was 0.938, which was confirmed in the validation cohort (AUC = 0.880). CONCLUSIONS: In the 40 s late arterial phase, the morphological characteristics and CT value-related parameters were significantly different among PCCs, TACs, and other types. PCCs were prone to manifest mucosal line interruption, diffuse thickening, infiltrative growth, and slow-rising enhanced curve (Type A). Furthermore, multivariate models were useful in discriminating PCCs from TACs and other types. KEY POINTS: • Multiple morphological characteristics and CT value-related parameters differed significantly between gastric PCCs and TACs in the 40 s late arterial phase. • The nomogram integrating morphological characteristics and CT value-related parameters in the 40 s late arterial phase had favourable performance in discriminating PCCs from TACs. • More useful information can be derived from 40 s late arterial phase CT images; thus, a more accurate evaluation can be made in clinical practice.

14.
J Colloid Interface Sci ; 592: 51-65, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33639538

RESUMO

Pharmaceutical and personal care products (PPCPs) as emerging organic pollutants have received widespread attention. A novel composite adsorbent was successfully prepared through the modification of polypyrrole (PPy) onto the surface of magnetic Bi2MoO6 (MnFe2O4/Bi2MoO6/PPy) and acted as excellent adsorbent to remove organic compounds from aqueous solution. The adsorbent was characterized by SEM, TEM, FT-IR, XRD, BET, VSM, XPS and PES. The resulting composites combined the advantages of all three parts and possessed porous structure and magnetic properties, which showed excellent adsorption performance for ketoprofen (KET) and indomethacin (IDM), as evidenced by 87.03% and 86.24% of removal in just 120 min at initial concentration of 10 mg/L, respectively. The adsorption processes of MnFe2O4/Bi2MoO6/PPy for PPCPs were well fitted with the pseudo-second order kinetic model and described better by Langmuir isotherm model. The possible adsorption mechanisms of KET and IDM by MnFe2O4/Bi2MoO6/PPy were provided. Additionally, the effect of other coexisting substances was also explored using Cu2+ as a model. Moreover, the adsorption performances were further studied to remove several dyes, in which showed superior affinity for anionic dyes. In practical application, it had almost equal removal capacity for KET both in the Yellow River water and sewage treatment plant inlet water.

15.
Pain Ther ; 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33629263

RESUMO

INTRODUCTION: Adding adjuvants to local wound infiltration (LWI) provides long analgesic duration with fewer adverse effects. We aimed to compare the clinical effects of nalbuphine and ketorolac as an adjuvant to LWI in patients undergoing open colorectal cancer surgery. METHOD: A total of 126 ASA I-III patients aged ≥ 18 years who were scheduled for open colorectal cancer surgery were included. Patients were randomly assigned to receive LWI using 10 mL 0.75% ropivacaine, with 20 mL normal saline (group R), 10 mg nalbuphine in 1 mL (group RN), or 25 mg ketorolac in 0.8 mL (group RK). Analgesia duration was the primary outcome. The total 48-h postoperative morphine-equivalent consumption and additional rescue analgesia rates were recorded as key secondary outcomes. RESULTS: Among 126 patients randomized, 124 completed the trial. The duration until the first press of the analgesia pump was significantly shorter in group R (median: 320.0 min) compared with group RN (median: 829.5 min) and group RK (median: 820.0 min) (P < 0.001). The median difference in morphine consumption was 113.0 mg for group R vs. group RN (P < 0.001), and 115.5 mg for group R vs. group RK (P < 0.001). The proportion of patients using additional morphine within the first day after surgery in group R showed a higher relative risk (RR) compared with group RN (RR, 3.89; P = 0.001) and group RK (RR, 3.17; P = 0.001). There were no apparent differences between the RN and RK groups in any outcomes, whether in adjusted or unadjusted analysis. CONCLUSIONS: Among patients undergoing open colorectal cancer surgery, both nalbuphine and ketorolac infiltration achieved equally prolonged duration of analgesia and reduced morphine consumption compared with ropivacaine alone after surgery, suggesting that the equivalent analgesic dose of nalbuphine and ketorolac as local anesthetic adjuvants in LWI could have a similar analgesic effect. TRIAL REGISTRATION: ChiCTR1800019209.

16.
Hum Vaccin Immunother ; : 1-10, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33449866

RESUMO

Cervical cancer is a leading cause of high mortality in women in developing countries and has a serious impact on women's health. Human papilloma virus (HPV) prophylactic vaccines have been produced and may hold promise for reducing the incidence of cervical cancer. However, the limitations of current HPV vaccine strategies make the development of HPV therapeutic vaccines particularly important for the treatment of HPV related lesions. Our previous work has demonstrated that LM4Δhly::E7 was safe and effective in inducing antitumor effect by antigen-specific cellular immune responses and direct killing of tumor cell on a cervical cancer model. In this study, the codon usage effect of a novel Listeria-based cervical cancer vaccine LM4Δhly::E7-1, was evaluated for effects of codon-optimized E7 expression, cellular immune response and therapeutic efficacy in a tumor-bearing murine model. Our data demonstrated that up-regulated expression of E7 was strikingly elevated by codon usage optimization, and thus induced significantly higher Th1-biased immunity, lymphocyte proliferation, and strong specific CTL activity ex-vivo compared with LM4Δhly::E7-treated mice. Furthermore, LM4Δhly::E7-1 enhanced a remarkable therapeutic effect in establishing tumors. Taken together, our results suggest that codon usage optimization is an important consideration in constructing live bacterial-vectored vaccines and is required for promoting effective T cell responses.

17.
Chem Commun (Camb) ; 57(14): 1794-1797, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33475634

RESUMO

Preferred-handed propeller conformation was induced by circularly polarized light irradiation to three amorphous molecules with trigonal symmetry, and the molecules with induced chirality efficiently exhibited blue circularly polarized luminescence. In both chirality induction and luminescence, chirality appeared to be amplified due to intermolecular interactions through π-stacking.

18.
Neurochem Res ; 46(3): 523-534, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33394222

RESUMO

Voltage-gated sodium channels (VGSCs) are fundamental to the initiation and propagation of action potentials in excitable cells. Ca2+/calmodulin (CaM) binds to VGSC type II (NaV1.2) isoleucine and glutamine (IQ) motif. An autism-associated mutation in NaV1.2 IQ motif, Arg1902Cys (R1902C), has been reported to affect the combination between CaM and the IQ motif compared to that of the wild type IQ motif. However, the detailed properties for the Ca2+-regulated binding of CaM to NaV1.2 IQ (1901Lys-1927Lys, IQwt) and mutant IQ motif (IQR1902C) remains unclear. Here, the binding ability of CaM and CaM's constituent proteins including N- and C lobe to the IQ motif of NaV1.2 and its mutant was investigated by protein pull-down experiments. We discovered that the combination between CaM and the IQ motif was U-shaped with the highest at [Ca2+] ≈ free and the lowest at 100 nM [Ca2+]. In the IQR1902C mutant, Ca2+-dependence of CaM binding was nearly lost. Consequently, the binding of CaM to IQR1902C at 100 and 500 nM [Ca2+] was increased compared to that of IQwt. Both N- and C lobe of CaM could bind with NaV1.2 IQ motif and IQR1902C mutant, with the major effect of C lobe. Furthermore, CaMKII had no impact on the binding between CaM and NaV1.2 IQ motif. This research offers novel insight to the regulation of NaV1.2 IQwt and IQR1902C motif, an autism-associated mutation, by CaM.

19.
J Clin Lab Anal ; 35(3): e23664, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33332661

RESUMO

BACKGROUND: The incidence of thyroid cancer has been on a rise. Papillary thyroid cancer (PTC) is the most common type of malignant thyroid tumor and accounts for approximately 85% of thyroid cancer cases. Although the genetic background of PTC has been studied extensively, relatively little is known about the role of small noncoding RNAs (sncRNAs) in PTC. tRNA-derived fragments (tRFs) represent a newly discovered class of sncRNAs that exist in many species and play key roles in various biological processes. METHODS: In this study, we used high-throughput next-generation sequencing technology to analyze the expression of tRFs in samples from PTC tissues and normal tissues. We selected four tRFs to perform qPCR to determine the expression levels of these molecules and make bioinformatic predictions. RESULTS: We identified 53 unique tRFs and transfer RNA halves (tsRNAs). The 10 most upregulated tRFs and tsRNAs were tRF-39-I6D3887S1RMH5MI2, tRF-21-2E489B3RB, tRF-18-JMRPFQDY, tRF-17-202L2YF, tRF-17-VBY9PYJ, tRF-18-YRRHQFD2, tRF-21-WE884U1DD, tRF-41-EX2Z10I9BZBZOS4YB, tRF-39-HPDEXK7S1RNS9MI2, and tRF-20-1SS2P46I. The 10 most downregulated tRFs and tsRNAs were tRF-31-HQ9M739P8WQ0B, tRF-43-5YXENDBP1IUUK7VZV, tRF-38-RZYQHQ9M739P8WD8, tRF-25-9M739P8WQ0, tRF-33-V6Z3M8ZLSSXUD6, tRF-27-MY73H3RXPLM, tRF-26-DBNIB9I1KQ0, tRF-38-Z9HMI8W47W1R7HX, tRF-40-Z6V6Z3M8ZLSSXUOL, and tRF-39-YQHQ9M739P8WQ0EB. qPCR verification of cell lines and tissue samples yielded results consistent with the sequencing analysis. As tRF-39 expression showed the maximum difference between PTC cells and normal cells, we chose this tRF to predict targets and perform functional tRF and tsRNA enrichment analysis. CONCLUSION: In this study, we provided a comprehensive catalog of tRFs involved in PTC and assessed the abnormal expression of these fragments. Through qPCR verification, tRF-39-0VL8K87SIRMM12E2 was found to be the most significantly upregulated tRF. Further tRF and enrichment analysis revealed that tRF-39 was mostly enriched in the "metabolic pathways." These preliminary findings can be used as the basis for further research studies based on the functional role of tRFs in patients with PTC.

20.
Bioengineered ; 12(1): 117-126, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33315500

RESUMO

The successful treatment of keloids is a great challenge in the plastic surgery field. Activating transcription factor 3 (ATF3) is discovered as an adaptive responsive gene, which plays a critical role in fibroblast activation. This study aimed to investigate the expression and biological role of ATF3 in the pathogenesis of keloids. ATF3 expression in normal skins and keloids was evaluated by real-time PCR, western blot and immunohistochemistry. Effects of ATF3 on cell growth, apoptosis, invasion and collagen production were evaluated in keloid fibroblast cells overexpressing or downregulating ATF3. ATF3 expression was significantly elevated in keloid tissues when compared with that of normal skins and parakeloidal skin tissues. Moreover, ATF3 promoted cell proliferation and collagen production in keloid fibroblast cells. Conversely, transfection with siRNA targeting ATF3 led to decreased cell viability and collagen synthesis via inhibiting transforming growth factor-ß1 (TGF-ß1) and fibroblast growth factor 2/8 (FGF2/8) production in keloid fibroblasts. ATF3 could reduce the apoptosis rate of keloid fibroblast cells. Molecularly, we found that ATF3 promoted BCL2 level and inhibit the expression of BCL2 associated agonist of cell death (Bad), Caspase3 and Caspase9 in keloid fibroblast cells. ATF3 also enhanced the invasive potential via upregulating the expression of Matrix Metalloproteinases (MMP) family members (MMP1, MMP2, MMP9 and MMP13). ATF3 could induce activation of TGF-ß/Smad signaling pathway in fibroblasts. Collectively, ATF3 could promote growth and invasion, and inhibit apoptosis via TGF-ß/Smad pathway in keloid fibroblast cells, suggesting that ATF3 might be considered as a novel therapeutic target for the management of keloid.

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