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1.
Med Sci Monit ; 27: e929884, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33967266

RESUMO

BACKGROUND Hepatocellular carcinoma (HCC) is one of the most common tumors. Transarterial chemoembolization (TACE) is the first choice of treatment for intermediate HCC and an important treatment option for advanced HCC. This retrospective study compared the prognosis between patients showing coagulative necrosis and patients showing liquefactive necrosis after the first TACE procedure. MATERIAL AND METHODS We divided 171 patients with Barcelona Clinic Liver Cancer (BCLC) Stage B or C HCC into 2 groups; a coagulative necrosis group (79 patients) and a liquefactive necrosis group (92 patients). The coagulative and liquefactive necroses were identified by computed tomography after the first TACE procedure. Kaplan-Meier analysis was used to identify the differences in the overall survival (OS) and progression-free survival (PFS) between the 2 groups, and the associated risk factors and safety of TACE were analyzed. RESULTS The median OS durations were 23.27±1.40 months and 8.83±2.15 months (P=0.004) and the median PFS durations were 9.33±0.96 months and 3.70±0.44 months (P=0.002) in the coagulative necrosis and liquefactive necrosis groups, respectively. Intrahepatic in situ progression, new intrahepatic metastasis, and extrahepatic progression occurred significantly earlier in the liquefactive necrosis group (P<0.05). Univariate analysis and multivariate analyses showed liquefactive necrosis was the main risk factor for OS. There was no significant difference in the hepatic function impairment or post-embolism syndrome after TACE. CONCLUSIONS After the first TACE procedure, the patients with liquefactive necrosis experienced recurrence and metastasis earlier and had a worse prognosis. Therefore, these patients should be considered for earlier administration of targeted therapies or immunotherapies after TACE.

2.
Breast Cancer ; 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33942253

RESUMO

AIMS: Metaplastic breast cancer (MBC) comprises a heterogeneous group of tumors, of which MBC with osseous differentiation (MBC-OD) is extremely rare that only few cases have been reported. This study aimed to present the clinicopathologic and molecular features of MBC-OD. METHODS: We collected 6 cases of MBC-OD from five different centers and described its clinicopathologic and molecular characteristics based on the next-generation sequencing. Another 11 cases from the literature were also reviewed to better characterize the tumor. RESULTS: The tumor primarily showed an osteosarcoma-like appearance, which composed of high cellularity with spindle cells and osteoblast-like cells producing coarse lace-like neoplastic bone (4/6) or osteoid matrix (6/6). 55 somatic mutations including 39 missenses (70.9%), 9 frameshifts (16.4%), 3 splice sites (5.5%), 3 in-frame InDels (5.5%) and 1 nonsense (1.8%) were identified. TP53 was the most frequently mutated genes (5/6, 83.3%), followed by RB1 (3/6, 50.0%), BCOR (2/6, 33.3%), MED12 (2/6, 33.3%), PIK3CA (2/6, 33.3%), and TET2 (2/6, 33.3%). Genetic alterations suggesting therapies with clinical benefit, including mTOR inhibitors, tyrosine kinase inhibitors (TKI), and poly-ADP ribose polymerase inhibitor (PARPi), were observed in five cases. The median follow-up was 21 months (range, 3-80 months). Local recurrence was observed in two cases and three patients displayed distant metastasis. Two patients died of the disease at 3 months and 7 months, respectively. CONCLUSIONS: Based on this series, MBC-OD is a highly aggressive breast tumor with osteosarcoma-like morphology and a high incidence of recurrent disease showing specific genetic profiles.

3.
Comput Math Methods Med ; 2021: 8072126, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33953794

RESUMO

Thyroid cancer is a relatively common endocrine gland malignant tumor; if improper treatment, there will be a high risk of recurrence or metastasis, and abnormal sugar chain glycoprotein (TAP) has a close relationship with the development of the disease; therefore, the purpose of this article is to discuss abnormal sugar chain glycoprotein (TAP) as thyroid cancer curative effect evaluation and radiation and chemotherapy after surgery clinical significance. In this paper, 95 patients with thyroid cancer diagnosed in a hospital were selected as the study objects and treated as the observation group. The clinical and follow-up data of the observation group were retrospectively analyzed. Meanwhile, 55 healthy patients were randomly selected as the control group. TAP, squamous cell carcinoma antigen (SCC) level, and carcinoembryonic antigen (CEA) level were detected in peripheral blood of 95 patients with thyroid cancer before and after treatment. The short-term efficacy was evaluated by chest CT examination, and the changes of the three markers before and after treatment and the correlation with the short-term efficacy of the patients were compared. According to the results of testing, the TAP positive expression in patients before radiotherapy can better predict the recent curative effect has certain clinical value; before radiotherapy TAP positive expression rate was significantly higher than that of healthy people, TAP positive expression quantity decreased obviously after radiation treatment, and patients with a recent radiotherapy curative effect is good or bad and negatively correlated with the degree of TAP protein positive expression; TAP high protein in patients with recent poor radiation effects, prompt the factor can be predicted in the near future curative effect of the molecular markers, and can TAP level for clinicians provide certain reference for targeted therapy.

4.
Psychol Health Med ; : 1-6, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33971765

RESUMO

This study aimed to explore which age group out of the patients in quarantine wards with novel coronavirus pneumonia is the most susceptible to anxiety. The data of 32 Covid-19 patients isolated in the quarantine wards of the second Infectious Diseases Department of Baoding Hospital and 71 Covid-19 patients in Tangshan City Infectious Disease Hospital from January 24th to March 5th, 2020, a total of 103 patients, were analyzed. Among these patients, 97 isolated patients were scored with a self-rating anxiety scale (SAS) score seven days after quarantine, and the correlation between age and score was analyzed. These 97 isolated patients were then divided into three groups according to age: group A (up to 35 years old), group B (36-60 years), and group C (over 60 years). One-way analysis of variance was used to compare the scores among groups. The Q-test was used for pairwise comparison.P < 0.05 was considered statistically significant.There was a negative correlation between age and SAS score in isolated Covid-19 patients, and the differences in the score among groups were statistically significant. Patients under 35 years old were more prone to anxiety when they were isolated for seven days. Isolated patients aged up to 35 years old need more attention from quarantine medical staff, communication should be strengthened, and psychological intervention from psychotherapists should be given if necessary.

5.
Aging (Albany NY) ; 13(8): 12113-12128, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33848262

RESUMO

Long non-coding RNAs are key regulators of tumor development and progression, with the potential to be biomarkers of tumors. This study aimed to explore the role of PlncRNA-1 in the progression of prostate cancer (PCa). We found that PlncRNA-1 was up-regulated in 85.29% of PCa tissues and could predict the T stage of PCa patients to a certain extent. Results showed that inhibition of PlncRNA-1 expression potentially promoted cell apoptosis, suppressed the proliferation, migration, and invasion of cells, and triggered G2/M cycle arrest in vitro and in vivo. PlncRNA-1 was mainly localized in the nucleus and PlncRNA-1 expression and phosphatase and tensin homologue (PTEN) expression were negatively correlated. Mechanistically, knockdown of PlncRNA-1 increased expression levels of PTEN protein and phosphorylated PTEN protein, and decreased expression levels of Akt protein and phosphorylated Akt protein. Rescue experiments demonstrated that PTEN inhibitors abolished the changes in PTEN/Akt pathway caused by PlncRNA-1 interference. PlncRNA-1 can promote the occurrence and development of PCa via the PTEN/Akt pathway. PlncRNA-1 may, therefore, be a new candidate target for the treatment of PCa.

6.
Nanotechnology ; 32(29)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33827054

RESUMO

Tremendous attention has been paid to high-performance flexible tactile sensors owing to their potential applications in bionic skin, wearable electronics, the Internet of Things, etc.However, the majority of pressure sensors require an intricately designed nanostructure requiring a high-cost complex manufacturing process. Therefore, the high-throughput and low-cost technology to produce high-sensitivity, flexible, pressure-sensitive materials with a large responding range is urgently needed. Herein, a novel flexible piezoresistive tactile sensor is fabricated based on the Ti2C-PDMS sponge as the conductive elastomer. The sensor exhibits a high sensitivity of 279 kPa-1in a wide pressure range (0-34.4 kPa). The response time is as fast as 0.45 s with excellent durability over 4,000 cycles. Moreover, a 16-pixel wireless sensor system is fabricated and a series of applications have been demonstrated, including real-time force perception and pressure morphology feedback, which promote the potential applications in the visualizing of pressure distribution, human-machine communication and wearable devices.

7.
BMC Public Health ; 21(1): 776, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33892657

RESUMO

BACKGROUND: To investigate the combined effect of hypertension and hyperuricemia to the risk of ischemic stroke in a rural Chinese population. METHODS: The cross-sectional study was conducted from 2012 to 2013 in a rural area of China. After exclusion for missing data, we finally included 11,731 participants into analysis. RESULTS: After adjusting for age, current smoking, current drinking, BMI, TG, HDL-C and eGFR, hypertension was significantly associated with ischemic stroke in men (OR: 2.783, 95% CI: 1.793, 4.320) and in women (OR: 4.800, 95% CI: 2.945, 7.822). However, hyperuricemia was significantly associated with ischemic stroke only in women (OR: 1.888, 95% CI: 1.244, 2.864). After full adjustment, participants with both hypertension and hyperuricemia had 8.9 times higher risk than those without them. Finally, the interaction between hypertension and hyperuricemia was statistically significant only in women rather than in men after full adjustment. CONCLUSIONS: This study demonstrated the positive correlations between hypertension, hyperuricemia and ischemic stroke. Our study also demonstrated the joint effect between hypertension and hyperuricemia towards ischemic stroke only in women, not in men.

8.
J Chromatogr Sci ; 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33860296

RESUMO

In this study, a method was developed for determination of three organophosphorus pesticides (OPPs) using graphene aerogel solid-phase extraction (SPE) combined with gas chromatography-mass spectrometry (GC-MS). The experimental results showed that the target analytes could be extracted on packed SPE cartridges and then eluted with tetrahydrofuran. The final sample solution was analyzed by GC-MS, which demonstrated good linearity between 0.5 and 500 µg L-1 with a correlation coefficient (r) of 0.9991-0.9998. The limits of detection (S/N = 3) and the limits of quantification (S/N = 10) for the three OPPs ranged from 0.38 to 0.82 µg L-1 and 1.32 to 2.75 µg L-1, respectively. The accuracy of the proposed method was evaluated by measuring the recovery of the spiked samples, which ranged from 91.2 to 103.7%, with relative standard deviations of 2.1-7.2%. This method was successfully applied for the determination of the target analytes in water samples taken from tap, wetlands and canal water.

9.
Molecules ; 26(7)2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33804930

RESUMO

Fungi fibrinolytic compound 1 (FGFC1) is a rare marine-derived compound that can enhance fibrinolysis both in vitro and in vivo. The fibrinolytic activity characterization of FGFC1 mediated by plasminogen (Glu-/Lys-) and a single-chain urokinase-type plasminogen activator (pro-uPA) was further evaluated. The binding sites and mode of binding between FGFC1 and plasminogen were investigated by means of a combination of in vitro experiments and molecular docking. A 2.2-fold enhancement of fibrinolytic activity was achieved at 0.096 mM FGFC1, whereas the inhibition of fibrinolytic activity occurred when the FGFC1 concentration was above 0.24 mM. The inhibition of fibrinolytic activity of FGFC1 by 6-aminohexanoic acid (EACA) and tranexamic acid (TXA) together with the docking results revealed that the lysine-binding sites (LBSs) play a crucial role in the process of FGFC1 binding to plasminogen. The action mechanism of FGFC1 binding to plasminogen was inferred, and FGFC1 was able to induce plasminogen to exhibit an open conformation by binding through the LBSs. The molecular docking results showed that docking of ligands (EACA, FGFC1) with receptors (KR1-KR5) mainly occurred through hydrophilic and hydrophobic interactions. In addition, the binding affinity values of EACA to KR1-KR5 were -5.2, -4.3, -3.7, -4.5, and -4.3 kcal/moL, respectively, and those of FGFC1 to KR1-KR5 were -7.4, -9.0, -6.3, -8.3, and -6.7 kcal/moL, respectively. The findings demonstrate that both EACA and FGFC1 bound to KR1-KR5 with moderately high affinity. This study could provide a theoretical basis for the clinical pharmacology of FGFC1 and establish a foundation for practical applications of FGFC1.

10.
BMC Surg ; 21(1): 182, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33827518

RESUMO

BACKGROUND: Misdiagnosis or failure to intraoperatively detect occult hernia in the inguinal region can lead to the recurrence of postoperative hernia and the appearance of local pain symptoms, which affect the patient's quality of life and make it difficult to reperform hernia repair. METHODS: This study included 1066 inguinal hernia patients who underwent surgical treatment at Shanghai Tongren Hospital between January 2016 and October 2018 to investigate ipsilateral occult hernia epidemiology, to analyze the characteristics of ipsilateral occult hernias with regards to patient age, gender, classification and anatomical site, and to explore the superiority and inferiority of the expert hernia surgeons/ non-expert hernia surgeons group and of operation methods in finding occult inguinal hernias. RESULTS: The incidence of ipsilateral occult hernia in the surgical population was 8.26%. Ipsilateral occult hernia included indirect inguinal hernia, direct inguinal hernia, femoral hernia, obturator hernia, and spigelian hernia, among which the highest incidence was direct inguinal hernia (4.11%), followed by indirect inguinal hernia (2.45%). There was no difference in the incidence of ipsilateral occult hernia between males and females, but there were significant differences in the incidence of ipsilateral occult hernia, which decreased gradually with increasing age in patients younger than 70 years-old; there was no difference in incidence in patients over 70 years-old. There were significant differences in the incidence of ipsilateral occult hernia in the bilateral inguinal region between direct and femoral hernia, with the higher incidence found on the right side; in contrast, there was no difference in the incidence of indirect inguinal hernia in the bilateral inguinal region. There was no difference in the ability of experienced physicians to detect ipsilateral occult inguinal hernias, either professionally or by surgery. CONCLUSIONS: Ipsilateral occult inguinal hernia has a higher incidence in patients with inguinal hernia, especially older patients; therefore, it is necessary for experienced surgeons to carefully detect for possible occult hernia during the operation and in elderly patients.


Assuntos
Hérnia Inguinal , Herniorrafia , Idoso , China/epidemiologia , Feminino , Hérnia Inguinal/epidemiologia , Hérnia Inguinal/cirurgia , Herniorrafia/efeitos adversos , Humanos , Incidência , Masculino , Recidiva , Estudos Retrospectivos
11.
Cell Mol Biol Lett ; 26(1): 12, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33794762

RESUMO

BACKGROUND: The purpose of this study was to explore the clinical value of miR-378c and its target gene YY1 in gastric cancer. METHODS: The TCGA database was employed to analyse miR-378c expression in gastric cancer. qRT-PCR was applied to identify miR-378c and YY1 in tissues and serum of patients suffering from gastric cancer. The association of miR-378c with the clinical data of patients with gastric cancer was analysed. Receiver operating characteristics (ROC) curve analysis was used to determine the diagnostic value of miR-378c and YY1 in gastric cancer, and analyse the relationship between miR-378c and YY1 and patients' survival. Pearson's test was applied to determine the association between miR-378c and YY1 in tissue and serum of patients. Dual-Luciferase Reporter assay was employed to examine the targeting association between miR-378c and YY1. Finally, independent prognostic factors was determined in patients with gastric cancer using Cox regression analysis. RESULTS: In the TCGA database, miR-378c was weakly expressed in gastric cancer. Overall, patients with low expression had a lower survival rate. The expression of miR-378c decreased and the expression of YY1 increased in cancer tissues and serum of tumour patients. In patients with low expression of miR-378c the tumour size was ≥ 5 cm. Low differentiation, high TNM staging and lymph node invasion rate increased significantly, but the 5-year survival rate decreased in the patients. miR-378c and YY1 had better diagnostic value in gastric cancer. TargetScan, miRDB, starBase and miRTarBase predicted that YY1 was a potential gene of miR-378c, and the Dual-Luciferase Reporter assay revealed that there was a targeting relationship between the two, which was proved by correlation analysis. Multivariate Cox analysis revealed that differentiation, TNM staging and miR-378c were independent prognostic factors for patients. CONCLUSIONS: MiR-378c is weakly expressed in gastric cancer patients and may be considered as a promising diagnostic and prognostic indicator for gastric cancer.

12.
Surg Innov ; : 1553350620983640, 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33830818

RESUMO

Purpose. The purpose of this study was to explore the feasibility of left central lymph node dissection (CLND) in endoscopic thyroidectomy via chest-breast approach (ETCB). Methods. Retrospective analysis of 57 cases of left CLND (group A) via ETCB, 35 cases of open left CLND (group B), and 90 cases of right CLND via ETCB (Group C) were performed from October 2014 to October 2019. Surgical data, complications, and follow-up data were compared among group A and group B, group A and group C, respectively. Results. There were no significant differences between group A and group B in intraoperative blood loss, tumor size, lymph node (LN) metastasis rate, dissected LN number, metastatic LN number, serum thyroglobulin (sTg), radioactive iodine uptake (RAIU), radioactive technetium uptake (RATU), radionuclide imaging of the residual area (RITRA), and radionuclide imaging of suspicious lymph node metastasis (RISLNM). There were no significant differences between group A and group C in age, operation time, intraoperative blood loss, postoperative hospital stay, tumor size, LN metastasis rate, dissected LN number, metastatic LN number, hypoparathyroidism, sTg, RAIU, RATU, RITRA, and RISLNM. There were 5 cases of temporary recurrent laryngeal nerve (RLN) palsy and 1 case of recurrence in group C. Besides, 1 case of lymphatic leakage was in group A. Conclusion. For selected cases, endoscopic left CLND is safe, feasible, efficient, and more easier than endoscopic right CLND.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33798334

RESUMO

Nanofiltration (NF) with high water flux and precise separation performance with high Li+/Mg2+ selectivity is ideal for lithium brine recovery. However, conventional polyamide-based commercial NF membranes are ineffective in lithium recovery processes due to their undesired Li+/Mg2+ selectivity. In addition, they are constrained by the water permeance selectivity trade-off, which means that a highly permeable membrane often has lower selectivity. In this study, we developed a novel nonpolyamide NF membrane based on metal-coordinated structure, which exhibits simultaneously improved water permeance and Li+/Mg2+ selectivity. Specifically, the optimized Cu-m-phenylenediamine (MPD) membrane demonstrated a high water permeance of 16.2 ± 2.7 LMH/bar and a high Li+/Mg2+ selectivity of 8.0 ± 1.0, which surpassed the trade-off of permeance selectivity. Meanwhile, the existence of copper in the Cu-MPD membrane further enhanced anti-biofouling property and the metal-coordinated nanofiltration membrane possesses a pH-responsive property. Finally, a transport model based on the Nernst-Planck equations has been developed to fit the water flux and rejection of uncharged solutes to the experiments conducted. The model had a deviation below 2% for all experiments performed and suggested an average pore radius of 1.25 nm with a porosity of 21% for the Cu-MPD membrane. Overall, our study provides an exciting approach for fabricating a nonpolyamide high-performance nanofiltration membrane in the context of lithium recovery.

14.
Acta Biomater ; 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33894348

RESUMO

INTRODUCTION: Incomplete hemostasis after vascular cannulation can cause a hematoma or pseudoaneurysm. We hypothesized that a hydrogel-coated needle would effectively and rapidly stop bleeding after vascular cannulation. METHODS: A hydrogel composed of sodium alginate, hyaluronic acid, and calcium carbonate was coated onto the surface of suture needles. Needles were observed using scanning electronic microscopy (SEM) and immunofluorescence. Cannulation was performed in both mouse and rat models; the liver, kidney, jugular vein, inferior vena cava and aorta were punctured using uncoated and hydrogel-coated needles. Needles coated with a hydrogel with and without CD34 antibody were used to puncture the rat jugular vein and aorta. Tissues were examined by histology and immunofluorescence. RESULTS: The hydrogel was successfully coated onto the surface of 22G and 30G needles and confirmed by SEM. Hydrogel-coated needles rapidly stopped bleeding after cannulation of the liver, kidney, jugular vein, inferior vena cava and aorta. Hydrogel-coated needles that contained CD34 antibody attracted vascular progenitor cells near the puncture site; there were fewer M1-type macrophages and more M2-type macrophages. CONCLUSION: Hydrogel-coated needles can effectively and rapidly stop puncture-site bleeding. The hydrogel that contains CD34 antibody attracted vascular progenitor cells, potentially promoting healing of the site after cannulation. STATEMENT OF SIGNIFICANCE: Incomplete hemostasis after vascular cannulation can cause a hematoma or pseudoaneurysm and remains a significant clinical problem. We developed a hydrogel composed of sodium alginate, hyaluronic acid, and calcium carbonate; hydrogel-coated needles effectively and rapidly stopped bleeding after vascular cannulation. Interestingly, the hydrogel can also serve as a carrier for drugs that are delivered to the puncture site during the short time of cannulation that could additionally promote puncture site healing. Hydrogel-coated needles may be a new method for rapid hemostasis with application to patients especially at risk for bleeding.

15.
Medicine (Baltimore) ; 100(14): e25344, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33832110

RESUMO

ABSTRACT: Excision repair cross complementing 1 (ERCC1), ribonucleotide reductase M1 (RRM1), ß-tubulin III (TUBB3), thymidylate synthetase (TYMS), and topoisomerase IIα (TOP2A) genes have been shown to be associated with the pathogenesis and prognosis of various types of carcinomas; however, their roles in breast cancer have not been fully validated. In this study, we evaluated the correlations among these biomarkers and the associations between their expression intensity and the clinicopathological characteristics to investigate whether the above genes are underlying biomarkers for patients with breast cancer.Ninety-seven tissue specimens collected from breast cancer patients. The expression levels of these biomarkers were measured by the multiplex branched DNA liquidchip (MBL) technology and clinicopathological characteristics were collected simultaneously.The expression levels of ERCC1, TUBB3, TYMS, and TOP2A were significantly associated with the characteristics of menopausal status, tumor size, lymph node metastasis, hormone receptor status, triple-negative status, Ki-67 index, and epidermal growth factor receptor. The expression intensity of ERCC1 negatively associated with that of TUBB3 and TYMS, and positively associated with that of RRM1. The expression intensity of TOP2A positively associated with that of TYMS. Hierarchical clustering analysis and difference test indicated that breast cancer with higher levels of TUBB3, TYMS, and TOP2A, as well as lower levels of ERCC1 and RRM1 tended to have higher histological grade and Ki-67 index.Our studies showed that ERCC1, TYMS, TUBB3, and TOP2A may be potential biomarkers for prognosis and individualized chemotherapy guidance, while there may be interactions between ERCC1 and RRM1, or TUBB3, or TYMS, as well as between TOP2A and TYMS in pathogenesis and development of breast cancer.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Adulto , Idoso , Biomarcadores Tumorais , DNA Topoisomerases Tipo II/genética , Proteínas de Ligação a DNA/genética , Receptores ErbB/biossíntese , Feminino , Expressão Gênica , Humanos , Antígeno Ki-67/biossíntese , Metástase Linfática/patologia , Menopausa/fisiologia , Pessoa de Meia-Idade , Ribonucleotídeo Redutases/genética , Timidilato Sintase/genética , Neoplasias de Mama Triplo Negativas/patologia , Carga Tumoral
16.
Neurol Sci ; 2021 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-33837876

RESUMO

Glucocerebrosidase (GBA) gene has been proved to be a risk factor for the development of Parkinson's disease (PD). However, the gender effect in the prevalence of GBA-associated PD (GBA-PD) is still controversial. And there is no conclusion whether the age at onset (AAO) of PD is different between carriers and non-carriers of GBA. To clarify the association between gender and AAO in GBA-PD, we conducted a systematic review and meta-analysis. PubMed, Web of Science, and Embase were retrieved to obtain potentially related studies. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to determine the association between gender and GBA-PD. And the weighted mean difference (WMD) with 95% CIs was employed to assess the difference of AAO between carriers and non-carriers of GBA. A total of twenty-eight studies involving 16,488 PD patients were included in this meta-analysis. The results showed the prevalence of female patients was higher in GBA-PD [OR: 1.19, (95% CI, 1.07-1.32), P = 0.001]. Meanwhile, GBA carriers had younger age at PD onset than GBA non-carriers [WMD: 2.87, (95% CI, 2.48-3.27), P < 0.001]. Results of subgroup analysis showed the prevalence of women in GBA-PD was higher than men in North American and European PD patients, while the gender difference was not significant in other areas around the world, suggesting an ethnic specificity of gender effect for GBA-PD. Our results indicate the higher female prevalence with ethnic specificity and younger AAO of GBA carriers in GBA-PD.

17.
Int Immunopharmacol ; 96: 107619, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33831806

RESUMO

Osteoporosis is a metabolic bone-loss disease characterized by abnormally excessive osteoclast formation and bone resorption. Identification of natural medicines that can inhibit osteoclastogenesis, bone resorption, and receptor activator of nuclear factor-κB ligand (RANKL)-induced signaling is necessary for improved treatment of osteoporosis. In this study, hinokitiol, a tropolone-related compound extracted from the heart wood of several cupressaceous plants, was found to inhibit RANKL-induced osteoclast formation and bone resorption in vitro. Hinokitiol inhibited early activation of the ERK, p38, and JNK-MAPK pathways, thereby suppressing the activity and expression of downstream factors (c-Jun, c-Fos, and NFATC1). Consistent with the above in vitro findings, hinokitiol treatment protected against ovariectomy-induced bone loss in vivo. Collectively, our results imply that hinokitiol can potentially serve as an effective agent for treating osteoclast-induced osteoporosis.

18.
BMC Endocr Disord ; 21(1): 47, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33711989

RESUMO

BACKGROUND: NKX6.1 is a transcription factor for insulin, as well as a marker for ß cell maturity. Abnormal NKX6.1 expression in ß cells, such as translocation from the nucleus to cytoplasm or lost expression, has been shown as a marker for ß cell dedifferentiation. METHODS: We obtained pancreatic sections from organ donors and immunofluorescence staining with NKX6.1 and insulin was performed to characterize NKX6.1 expression in subjects with or without type 2 diabetes mellitus (T2DM). RESULTS: Our results showed that cells with insulin expression but no nucleic NKX6.1 expression (NKX6.1Nuc-Ins+), and cells with cytoplasmic NKX6.1 expression but no insulin expression (NKX6.1cytIns-) were significantly increased in T2DM subjects and positively correlated with glycated hemoglobin (HbA1c), indicating the elevated ß cell dedifferentiation with NKX6.1 inactivation in T2DM. To investigate whether ß cell dedifferentiation has initiated in subjects with higher risks for T2DM, we next analyzed the association between ß-cell dedifferentiation level in ND subjects with different ages, body mass index, and HbA1c. The results showed the absolute number and percentage of dedifferentiated ß cells with NKX6.1 inactivation did not significantly change in subjects with advanced aging, obesity, or modest hyperglycemia, indicating that the ß cell dedifferentiation might mainly occur after T2DM was diagnosed. CONCLUSION: Our results suggested that NKX6.1 expression in ß cells was changed in type 2 diabetic subjects, evidenced by significantly increased NKX6.1Nuc-Ins+ and NKX6.1cytIns- cells. This abnormality did not occur more frequently in subjects with a higher risk for T2DM, suggesting that ß cell dedifferentiation might be secondary to the pathological changes in T2DM.

19.
Diabetes ; 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33722839

RESUMO

Downregulation of mitochondrial function in adipose tissue is considered as one important driver for the development of obesity-associated metabolic disorders. Inorganic Pyrophosphatase 1 (PPA1) is an enzyme catalyzes the hydrolysis of PPi to Pi, and is required for anabolism to take place in cells. Although alternation of PPA1 has been related to some diseases, the importance of PPA1 in metabolic syndromes has never been discussed before. In this study, we found that global PPA1 knockout mice (PPA1+/-) showed impaired glucose tolerance and severe insulin resistance under HFD feeding. In addition, impaired adipose tissue development and ectopic lipid accumulation were also observed. Conversely, overexpression of PPA1 in adipose tissue by AAV injection can partly reverse the metabolic disorders in PPA1+/- mice, suggesting that impaired adipose tissue function is responsible for the metabolic disorders observed in PPA1+/- mice. Mechanistic studies revealed that PPA1 acted as a PPARγ target gene to maintain mitochondrial function in adipocytes. Furthermore, specific knockdown of PPA1 in fat body of Drosophila led to impaired mitochondria morphology, decreased lipid storage, and made Drosophila more sensitive to starvation. In conclusion, for the first time, our findings demonstrated the importance of PPA1 in maintaining adipose tissue function and whole body metabolic homeostasis.

20.
Microb Biotechnol ; 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33755314

RESUMO

Acinetobacter baumannii poses a serious threat to human health, mainly because of its widespread distribution and severe drug resistance. However, no licensed vaccines exist for this pathogen. In this study, we created a conjugate vaccine against A. baumannii by introducing an O-linked glycosylation system into the host strain. After demonstrating the ability of the vaccine to elicit Th1 and Th2 immune responses and observing its good safety in mouse a model, the strong in vitro bactericidal activity and prophylactic effects of the conjugate vaccine against infection were further demonstrated by evaluating post-infection tissue bacterial loads, observing suppressed serum pro-inflammatory cytokine levels. Additionally, the broad protection from the vaccine was further proved via lethal challenge with A. baumannii. Overall, these results indicated that the conjugate vaccine could elicit an efficient immune response and provide good protection against A. baumannii infection in murine sepsis models. Thus, the conjugate vaccine can be considered as a promising candidate vaccine for preventing A. baumannii infection.

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