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1.
J Colloid Interface Sci ; 605: 752-765, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34365311

RESUMO

One major challenge of photothermal therapy (PTT) is achieving thermal ablation of the tumor without damaging the normal cells and tissues. Here, we designed a self-regulating photothermal conversion system for selective thermotherapy based on self-assembling gold nanoparticles (S-AuNPs) and investigated the selectivity effect using a novel home-made in vitro selective photothermal transformation model and an in vivo skin damaging assessment model. In the in vitro selective photothermal transformation model, laser irradiation selectively increased the temperature of the internal microenvironment (pH 5.5) and resulted in an obvious temperature difference (ΔT ≥ 5 °C) with that of the external environment (pH 7.4). More importantly, in the in vivo skin damaging assessment model, S-AuNPs achieved good tumor inhibition without damaging the normal skin tissue compared with the conventional photothermal material. This work provides not only a novel validation protocol for tumor thermotherapy to achieve the biosafety of specifically killing tumor cells and normal tissue but also an evaluation methodology for other precise therapy for cancers.

2.
Nanoscale ; 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34643196

RESUMO

Chemotherapy has been a conventional paradigm for cancer treatment, and multifarious chemotherapeutic drugs have been widely employed for decades with significant performances in suppressing tumors. Moreover, some of the antitumor chemotherapeutic agents, such as doxorubicin (DOX), oxaliplatin (OXA), cyclophosphamide (CPA) and paclitaxel (PTX), can also tackle tumors through the induction of immunogenic cell death (ICD) in tumor cells to trigger specific antitumor immune responses of the body and improve chemotherapy efficacy. In recent years, chemo-immunotherapy has attracted increasing attention as one of the most promising combination therapies to struggle with malignant tumors. Many effective antitumor therapies have benefited from the successful induction of ICD in tumors, which could incur the release of endogenous danger signals and tumor-associated antigens (TAAs), further stimulating antigen-presenting cells (APCs) and ultimately initiating efficient antitumor immunity. In this review, several well-characterized damage-associated molecular patterns (DAMPs) were introduced and the progress of ICD induced by representative chemotherapeutic drugs for nanomedicine-based chemo-immunotherapy was highlighted. In addition, the combination strategies involving ICD cooperated with other therapies were discussed. Finally, we shared some perspectives in chemotherapeutic drug-induced ICD for future chemo-immunotherapy. It was hoped that this review would provide worthwhile presentations and enlightenments for cancer chemo-immunotherapy.

3.
Clin Oral Investig ; 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34622309

RESUMO

OBJECTIVES: To assess alveolar bone changes and treatment modality alterations after ridge preservation on maxillary molar extraction sockets with severe periodontitis, compared to natural healing. MATERIAL AND METHODS: Thirty-six maxillary infected-molar teeth either receiving ridge preservation (RG group) or undergoing natural healing (NT group) were investigated. Cone-beam computed tomography (CBCT) scanning was performed immediately after surgery (the baseline) and repeated 6 months later to measure the linear and volumetric changes of the sockets. RESULTS: Based on radiographic measurements, alveolar bone width decreased by 1.58 ± 4.61 mm in the NT group but increased by 3.74 ± 4.17 mm in the RG group (p < 0.05). Significant increases in ridge height at the center of both the NT (7.54 ± 4.54 mm) and RG (9.20 ± 3.26 mm) groups were observed. Mean sinus pneumatization was 0.19 ± 0.45 mm in the RG group and 0.59 ± 0.63 mm in the NT group (p < 0.05). The relative increase in total ridge volume was 8.0% and 35.5% in the NT and RG group, respectively (p < 0.05). Implant placement with additional sinus augmentation procedure was performed in 16.7% of the RG group cases, whereas 50% in the NT group cases. CONCLUSIONS: Ridge preservation in the maxillary molar extraction sockets with severe periodontitis can improve alveolar ridge dimensions and decrease the necessity of advanced regenerative procedures at implant placement compared to natural healing. CLINICAL RELEVANCE: Ridge preservation on maxillary molar extraction sockets with severe periodontitis maintained the vertical bone height more efficiently and resulted in less need for sinus augmentation procedures at 6 months compared to natural healing.

4.
Bioengineered ; 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34606417

RESUMO

Previous studies have demonstrated that protein tyrosine phosphatase 1B (PTP1B) can promote tumor progression in breast cancer, colon cancer and prostate cancer. Additionally, PTP1B also acts as a tumor suppressor in esophageal cancer and lymphoma. These findings suggest that PTP1B functions as a double-faceted molecule in tumors. However, the role of PTP1B in malignant melanoma (MM) is still unknown. PTP1B expression in normal and melanoma tissues was evaluated by GEO analysis and immunohistochemistry. The effects of PTP1B on cell migration and invasion were evaluated in melanoma cells with up- and downregulated PTP1B expression. In this study, we initially demonstrated that the expression of PTP1B in malignant melanoma tissue is significantly higher than its expression in benign nevus tissue and indicated poor survival of malignant melanoma patients. In vitro studies have demonstrated that inhibition of PTP1B suppresses and overexpression of PTP1B promotes migration and invasion of melanoma cells. Moreover, we found that PTP1B could interact with Src via coimmunoprecipitation and dephosphorylation of the Tyr530 site. Collectively, our study revealed that PTP1B can promote melanoma cell metastasis by interacting with Src and provides a theoretical basis for future applications of PTP1B inhibitors in the treatment of malignant melanoma.

5.
Neurobiol Aging ; 109: 22-30, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34638000

RESUMO

Elevated expression of ß-amyloid (Aß1-42) and tau are considered risk-factors for Alzheimer's disease in healthy older adults. We investigated the effect of aging and cerebrospinal fluid levels of Aß1-42 and tau on 1) frontal metabolites measured with proton magnetic resonance spectroscopy (MRS) and 2) cognition in cognitively normal older adults (n = 144; age range 50-85). Levels of frontal gamma aminobutyric acid (GABA+) and myo-inositol relative to creatine (mI/tCr) were predicted by age. Levels of GABA+ predicted cognitive performance better than mI/tCr. Additionally, we found that frontal levels of n-acetylaspartate relative to creatine (tNAA/tCr) were predicted by levels of t-tau. In cognitively normal older adults, levels of frontal GABA+ and mI/tCr are predicted by aging, with levels of GABA+ decreasing with age and the opposite for mI/tCr. These results suggest that age- and biomarker-related changes in brain metabolites are not only located in the posterior cortex as suggested by previous studies and further demonstrate that MRS is a viable tool in the study of aging and biomarkers associated with pathological aging and Alzheimer's disease.

6.
Brain Res Bull ; 176: 174-183, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34478811

RESUMO

Aryl Hydrocarbon Receptor (AHR) is a ligand-activated transcription factor expressed in various brain regions. However, little is known about the role of AHR during neuroinflammation in the 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model. Here, mice were sacrificed at day 4, day 6 and day 8 respectively after MPTP or saline treatment. Behavioral tests, Tyrosine hydroxylase (TH) expression, glial reaction, and AHR expression and activation were then assayed. As expected, mice treated with MPTP showed apparent behavioral dysfunctions and significantly reduced TH content. Immunofluorescence (IF) labeling showed an increased trend of phosphorylated AHR activation in the Substantia Nigra pars compacta (SNpc) and striatum after MPTP treatment. Western blot analysis demonstrated that MPTP treatment induced a significantly increased level of AHR at each time point tested, with the highest level observed at day 6 in the striatum. To determine exactly the AHR activation in relation to changes of glial cell reactivity, double IF labeling was performed for either IBA1 (microglia marker) and p-AHR, or GFAP (astrocyte marker) and p-AHR. The results demonstrated that MPTP treatment not only increases the number of p-AHR-positive IBA1-expressing cells in the striatum and the SNpc, but also increases that of p-AHR-positive GFAP-expressing cells in the striatum. Intriguingly, the increase of the number of cells co-expressing both p-AHR and IBA1 was highest at day 4 in response to MPTP in the striatum and at day 8 in the SNpc. The number of cells co-expressing both p-AHR and GFAP was increased at days 4, 6 and 8 in the striatum. In conclusion, our study suggests that AHR activation may facilitate PD diagnosis and serve as a target for the treatment of PD.

7.
Chem Commun (Camb) ; 57(76): 9680-9683, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34486623

RESUMO

We describe a catalytic asymmetric iminium ion cyclization reaction of simple 2-alkenylbenzaldimines using a BINOL-derived chiral N-triflyl phosphoramide. The corresponding 1-aminoindenes and tetracyclic 1-aminoindanes are formed in good yields and high enantioselectivities. Further, the chemical utility of the obtained enantiopure 1-aminoindene is demonstrated for the asymmetric synthesis of (S)-rasagiline.

8.
Nutrients ; 13(9)2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34579032

RESUMO

Green tea extracts and tea catechins have been shown to prevent or alleviate diabetes. The present study tests the hypothesis that green tea leaves in powder form (GTP), which also contain fiber and other water non-extractable materials, are more effective than the corresponding green tea extracts (GTE) in impeding the development of diabetes in db/db mice. Female db/db mice were treated with a diet containing 1% of GTE, 2% of GTE, 2% of GTP (with the same catechin content as 1% GTE) or 1% GTP. The 1% GTE group had lower food intake, water consumption, body weight and fasting blood glucose levels than the control group, while 2% GTP did not have any significant effect. Dietary 1% GTE also preserved ß-cell insulin secretion. However, 1% GTP increased food intake, water consumption and blood glucose levels. Microbiome analysis with 16S rRNA gene V4 sequencing showed that the gut microbiota was modified by GTE and GTP, and a few bacterial guilds were associated with blood glucose levels. In the Random Forest regression model, the leading predictor of metabolic outcome was food consumption, followed by changes in some bacterial guilds. The results illustrate the importance of food consumption and gut microbiota in affecting the progression of diabetes.

9.
Biosens Bioelectron ; 194: 113597, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34534951

RESUMO

DNA hydrogels have received considerable attention in various promising applications due to their excellent biocompatibility, controlled biodegradability, adjustable mechanical properties, stability against proteases, self-healing ability, and stimuli responsiveness. To obtain the specific molecular recognition capability, aptamers and many other functional motifs are utilized. Aptamers are short single-stranded DNA or RNA selected through SELEX to bind with specific target with high affinity and specificity. With advantages of broad range of targets, good stability, easy modification, and low cost, aptamer functionalized DNA hydrogels become popular in a wide range of promising applications. In this review, the recent progress on aptamer functionalized DNA hydrogels including general design principles, applications and kinetics has been summarized. Finally, the current challenges and prospects are discussed.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , DNA/genética , Hidrogéis , Cinética
10.
Genomics ; 113(6): 3735-3749, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34517091

RESUMO

Germination and seedling growth are crucial for plant development and agricultural production. While, the regulatory mechanisms during these processes in Tibetan hulless barley (Hordeum vulgare L. var. nudum) are not well understood. Given the regulatory roles of microRNAs (miRNAs) in crop plants and the irreplaceability of barley in the highland area of China, we herein presented a genome-wide survey of miRNAs to reveal a potential regulatory network in the early developmental stages of two Tibetan hulless barleys, from which a total of 156 miRNAs was identified including 35 known and 121 novel ones. Six of the identified novel miRNAs were further experimentally validated. According to the evolutionary analysis, miR156, miR166, miR168, and miR171 were conserved across Tibetan hulless barleys and eight other seed plants. Expression profiles of ten known miRNAs showed that they were involved in phytohormone signaling, carbohydrate and lipid metabolism, as well as juvenile-adult transition during barley development. Moreover, a total of 1280 genes targeted by 101 miRNAs were predicted from both barley libraries. Three genes (PLN03212, MATE eukaryotic, and GRAS) were validated via the RNA ligase-mediated 5'-rapid amplification of cDNA ends (RLM-5' RACE) to be the targets of hvu-miR159a, hvu-miR166a, and hvu-miR171-3p, respectively. Based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of putative targets, the most abundant pathways were related to "metabolism". These results revealed that miRNA-target pairs participating in the regulation of multigene expression and the embryonic development of Tibetan hulless barleys were controlled by complex mechanisms involving the concordant expression of different miRNAs and feedback loops among miRNAs as well as their targets. The study provides insight into the regulatory network of barley miRNAs for better understanding of miRNA functions during germination and seedling growth.

11.
Radiat Oncol ; 16(1): 149, 2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34391452

RESUMO

BACKGROUND: To compare the clinical outcomes of stereotactic body radiation therapy (SBRT) and fractionated radiation therapy (FRT) for primary liver cancer with portal vein tumor thrombus (PVTT). METHODS: This retrospective study included 36 patients who underwent SBRT and 36 patients who underwent FRT from August 2016 to June 2018. Patients were evaluated for short-term efficacy, long-term efficacy, AEs, and quality of life before and after treatment. RESULTS: With a median follow-up of 28.8 months (26-36 months), 27 patients survived in the SBRT group while 19 patients survived in the FRT group. The survival rate in the SBRT group was statistically higher than that of the FRT group after 6 months (80.56% vs. 58.33%; P = 0.041), 12 months (77.78% vs. 55.56%; P = 0.046) and 24 months 75.00% vs. 52.78%; P = 0.049). The median whole survival time of the SBRT group was 13.3 months (95% CI 12.83-13.97), which was statistically longer than 9.8 months in the FRT group (95% CI 8.83-10.97, P < 0.05) based on the Kaplan-Meier method. The SBRT group had better survival quality and fewer adverse events than the FRT group. CONCLUSION: SBRT had better clinical outcomes than FRT for primary liver cancer with PVTT.

12.
Fish Physiol Biochem ; 47(5): 1565-1583, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34415453

RESUMO

Pearlscale angelfish Centropyge vrolikii is a kind of protogynous hermaphrodite fish with a natural sexual reversion. Under appropriate social conditions, a female fish can transform into a male fish spontaneously. It is an important prerequisite for artificial breeding to understand the process of its gonadal development and sexual reversion. Gonadal development is regulated by many sex-related genes. In this study, we used unreferenced RNA-Seq technology to sequence the ovary at the perinucleolus stage (OII), ovary at the yolk vesicle stage (OIV),IV and testis (T), respectively; screened the gonadal differential expression genes (DEGs); and analyzed the expression of these genes in different developmental stages of ovary and different sex gonads. The results showed that a total of 142,589 all-unigene samples were assembled, and gene annotation was performed by COG, GO, KEGG, KOG, Pfam, Swissprot, eggNOG, and NR functional database. Comparative analysis revealed that there were 1919 genes that were up-regulated and 1289 genes were down-regulated in comparison to OIV vs OII, while there were 3653 genes that were up-regulated and 2874 genes were down-regulated in comparison of OIV vs T, there were 3345 genes that were up-regulated and 2995 genes were down-regulated in comparison of the OII vs the T. At the same time, the results verified by RT-qPCR were consistent with the variation trend of transcriptome data. Among the results, amh, sox9b, dmrt1, dmrt2, cyp11a, cyp17a, and cyp19a were significantly expressed in the testes, while sox3, sox4, sox11, sox17, and hsd3b7 were significantly expressed in the ovaries. And, the expression of the amh, sox9b, dmrt2, and dmrt1 were low in the OII and OIV, while significantly increased during the ovotestis in the hermaphroditic period (OT), and finally reached the highest level in pure testis after sex reversal. The expression of sox3, sox4, hsd3b7, sox11, and sox17 was significantly reduced during the hermaphroditic period (OT). These results suggested that these genes may play an important role in the process of sex reversal. This study is helpful to further understand the molecular regulation mechanism of gonadal development and sexual reversion in Pearlscale angelfish and also provide important clues for future studies.

13.
Int J Biol Sci ; 17(10): 2476-2486, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34326688

RESUMO

Extracellular vesicles (EVs), are membrane-bound vesicles that have many advantages over traditional nanocarriers for drug and gene delivery. Evidence from recent studies indicate that EVs have therapeutic capability with chemical or biological modification. Tumor-derived exosomes (TEXs) were used as a new type of antigens or tumor vaccines in anti-tumor immunotherapy. With superior characteristics, modified EVs were applied to loaded and delivered synthetic drugs, silencing RNA, and microRNA for treatment. Different surface functionalization strategies have been proposed to improve the therapeutic functions of EVs. Appropriately modified EVs for disease intervention provide new avenues for effective clinical treatment strategies. Therefore, this review aimed at elucidating the therapeutic functions of EVs to generate new ideas for treatment and to unlock their hidden potential in translational medicine.

14.
Virulence ; 12(1): 1754-1770, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34233588

RESUMO

In our previous study, a gut microbiota-targeted dietary intervention with a high-fiber diet improved the immune status of both genetically obese (Prader-Willi Syndrome, PWS) and simple obese (SO) children. However, PWS children had higher inflammation levels than SO children throughout the trial, the gut microbiota of the two cohorts was similar. As some virulence factors (VFs) produced by the gut microbiota play a role in triggering host inflammation, this study compared the characteristics and changes of gut microbial VF genes of the two cohorts before and after the intervention using a fecal metagenomic dataset. We found that in both cohorts, the high-fiber diet reduced the abundance of VF, and particularly pathogen-specific, genes. The composition of VF genes was also modulated, especially for offensive and defensive VF genes. Furthermore, genes belonging to invasion, T3SS (type III secretion system), and adherence classes were suppressed. Co-occurrence network analysis detected VF gene clusters closely related to host inflammation in each cohort. Though these cohort-specific clusters varied in VF gene combinations and cascade reactions affecting inflammation, they mainly contained VFs belonging to iron uptake, T3SS, and invasion classes. The PWS group had a lower abundance of VF genes before the trial, which suggested that other factors could also be responsible for the increased inflammation in this cohort. This study provides insight into the modulation of VF gene structure in the gut microbiota by a high-fiber diet, with respect to reduced inflammation in obese children, and differences in VF genes between these two cohorts.

15.
Int J Infect Dis ; 109: 253-260, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34216736

RESUMO

BACKGROUND: The natural resistance of rapidly growing mycobacteria (RGM) to multiple antibiotics renders the treatment of the infections caused less successful. The objective of this study was to evaluate the in vitro susceptibilities of four oxazolidinones against different RGM species. METHODS: The microplate alamarBlue assay was performed to identify the minimum inhibitory concentrations (MICs) of four oxazolidinones - delpazolid, sutezolid, tedizolid, and linezolid - for 32 reference strains and 115 clinical strains of different RGM species. The MIC breakpoint concentration was defined as 16 µg/ml for linezolid. Next, the gene fragments associated with oxazolidinone resistance were amplified and sequenced, and mutations were defined in contrast with the sequences of the reference strains. RESULTS: Tedizolid showed the strongest inhibitory activity against the Mycobacterium abscessus isolates. Delpazolid exhibited better antimicrobial activity against the Mycobacterium fortuitum isolates when compared to linezolid, with 4-fold lower MIC values. The protein alignment and structure-based analysis showed that there might be no correlation between oxazolidinone resistance and mutations in the rplC, rplD, and 23S rRNA genes in the tested RGM. CONCLUSIONS: Tedizolid had the strongest inhibitory activity against M. abscessus in vitro, while delpazolid presented the best inhibitory activity against M. fortuitum. This provides important insights into the potential clinical application of oxazolidinones to treat RGM infections.


Assuntos
Mycobacterium abscessus , Oxazolidinonas , Antibacterianos/farmacologia , Pequim , Humanos , Linezolida/farmacologia , Testes de Sensibilidade Microbiana , Oxazolidinonas/farmacologia , Tetrazóis
16.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(7): 690-693, 2021 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-34247380

RESUMO

OBJECTIVE: To explore the phenotypic and genetic characteristics of acute megakaryoblastic leukemia (AMKL) in young children accompany by WT1, MLL-PTD and EVI1, in order to improve the diagnosis level of AMKL. METHODS: EDTA-K2 anticoagulation venous blood was collected for blood routine and morphological analysis of blood cells; bone marrow was extracted for cell morphology, immunophenotype, chromosome karyotype and fusion gene analysis. RESULTS: White blood cell count was 12.3× 109/L, hemoglobin was 73 g/L, and platelet count was 13× 109/L. The morphological analysis of blood cells showed that the size of immature cells was like that of primitive immature lymphocytes, which was circular or irregular and part of them with obvious pseudopodia. The cytoplasm is basophilic with heterogeneous coloration and granules. Nuclear chromatin is fine and even, 1-3 nucleoli can be seen, these immature cells account for about 40%; the morphology of bone marrow cells was consistent with acute leukemia, negative for peroxidase staining, negative for AS-DNCE staining and alpha-NBE staining. Flow cytometry results showed that the protocells account for about 52% and significant expression of megakaryocytes related markers (cCD41+, CD61+, CD36+). Chromosome karyotype is 46, XX, der(3) add(3)(p21)add(3)(q25), add (9)(q22), -13, +mar [4]/46, XX, del(13)(q12q22) [3]/46, XX[3]. The fusion gene WT1 was overexpressed, MLL-PTD and EVI1 were positive. CONCLUSION: Acute megakaryocytic leukemia has unique and complex phenotypic and genetics characteristics.


Assuntos
Leucemia Megacarioblástica Aguda , Medula Óssea , Criança , Pré-Escolar , Aberrações Cromossômicas , Humanos , Cariotipagem , Leucemia Megacarioblástica Aguda/genética , Proteína do Locus do Complexo MDS1 e EVI1 , Megacariócitos , Proteínas de Fusão Oncogênica , Proteínas WT1
17.
Emerg Microbes Infect ; 10(1): 1530-1535, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34288833

RESUMO

More sensitive, rapid, and affordable diagnostic tools for pulmonary tuberculosis (PTB) are urgently needed. This study aimed to assess the performance of EasyNAT MTC (abbreviation: EasyNAT) (Ustar Biotechnologies, China), a novel isothermal amplification method with a turnaround time of less than two hours that requires a few manual steps to process the sputum. Sputum samples from 249 patients with suspected PTB were subjected to smear, culture, Xpert MTB/RIF (Cepheid, USA) and EasyNAT assay testing. Of the 169 PTB patients, EasyNAT detected more PTB patients than Xpert (72.19% vs. 61.54%, P < 0.05, χ2 = 4.326). Both the Xpert assay and EasyNAT assay detected almost all the culture-positive sputa successfully, but EasyNAT yielded more positive results among the smear-negative and culture-negative PTB cases (44.59% (33/74) vs. 22.97% (17/74), P < 0.01, χ2 = 7.732). Although the specificity of EasyNAT was lower in contrast to Xpert [95.00% (76/80) vs. 98.75% (79/80)], the difference was not significant (P = 0.363, χ2 = 0.826). EasyNAT could be used as an initial test for PTB diagnosis due to its simplicity, rapid turnaround time, high sensitivity, and low cost.

18.
J Clin Nurs ; 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34289524

RESUMO

AIMS AND OBJECTIVES: Quarantine during the COVID-19 pandemic resulted in longer-term sedentary behaviours and mental health problems. Our study aimed to evaluate the impact of the Otago exercise programme (OEP) on physical function and mental health among elderly with cognitive frailty during COVID-19. BACKGROUND: Lockdowns and restrictions during the COVID-19 pandemic result in longer-term sedentary behaviours related disease and mental problem. Older people with cognitive frailty are more vulnerable to be influenced. Timely intervention may achieve better outcomes, OEP exercise was designed as a balance and muscle-strengthening programme for elderly people. DESIGN: A parallel-group, assessor-blinded randomised controlled trial was performed according to CONSORT guidelines. METHODS: This study was conducted from July 2020 to October 2020 among 62 elderly people with cognitive frailty from a nursing home. Participants were randomly divided into an OEP group (n = 31) or a control group (n = 31). Both groups received sleep- and diet-related health education. The OEP group also received a 12-week group exercise programme. The Five Times Sit to Stand Test (FTSST), Berg Balance Scale (BBS), and Timed Up and Go Test (TUGT) were used to assess physical function. The Geriatric Depression Scale-15 (GDS-15) and the 12-Item Short Form Health Survey Mental Component Summary (SF-12 MCS) were used to assess mental health. Outcomes were measured at 6 and 12 weeks. RESULTS: Physical function and mental health were similar in the two groups at baseline. At 12 weeks, the OEP group (difference in change from baseline: FTSST, -2.78; TUGT, -3.73; BBS, 2.17; GDS-15, -0.72; SF-12 MCS, 2.58; all p < .001) exhibited significantly greater improvements than the control group (difference in change from baseline: FTSST, 1.55; TUGT, 1.66; BBS, -0.10; GDS-15, 1.07; SF-12 MCS, -5.95; all p < .001). CONCLUSION: Our findings showed the OEP group had better physical function and mental health outcomes than the control group. OEP can be used to improve the physical and mental function among elderly people with cognitive frailty during the COVID-19 pandemic. RELEVANCE TO CLINICAL PRACTICE: Otago exercise program intervention programmes should be implemented to improve physical function for cognitive frailty elderly to reduce the harm of longer-term sedentary behaviours, and to ruduce depression symptom and improve mental health, particularly during COVID-19 pandemic period.

19.
Cell Tissue Res ; 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34223978

RESUMO

Sensory hair cells (HCs) are highly susceptible to damage by noise, ototoxic drugs, and aging. Although HCs cannot be spontaneously regenerated in adult mammals, previous studies have shown that signaling pathways are involved in HC regeneration in the damaged mouse cochlea. Here, we used a Notch antagonist (DAPT), a Wnt agonist (QS11), and recombinant Sonic hedgehog (SHH) protein to investigate their concerted actions underlying HC regeneration in the mouse cochlea after neomycin-induced damage both in vivo and in vitro. With DAPT, the numbers of HCs increased, and supporting cell (SC) proliferation was seen in both the intact and damaged cochlear sensory epithelia, while these numbers were unchanged in the presence of QS11. When simultaneously treated with DAPT and QS11, the number of HCs increased dramatically, and much greater SC proliferation was seen in the cochlear epithelium. In transgenic mice with both Notch1 conditional knockout and ß-catenin over-expression, cochlear SC proliferation and HC regeneration were more obvious than in either Notch1 knockout or ß-catenin over-expressing mice separately. When cochleae were treated with DAPT, QS11, and SHH together, SC proliferation was even greater, and this proliferation was seen in both the HC region and the greater epithelial ridge. High-throughput RNA sequencing was used to identify the differentially expressed genes between all groups, and the results showed that the SHH and Wnt signaling pathways are involved in SC proliferation. Our study suggests that co-regulation of the Notch, Wnt, and SHH signaling pathways promotes extensive cell proliferation and regeneration in the mouse cochlea.

20.
Se Pu ; 39(7): 721-729, 2021 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-34227370

RESUMO

8-Oxoguanine DNA glycosylase (OGG1) is an important enzyme that plays a key role in oxidative DNA damage repair. OGG1 can specifically recognize and excise 8-oxoG (a product of oxidative damage found in double-stranded DNA) through base excision repair (BER). OGG1 is expressed in normal tissues, and in most tumor tissues. Oxidative cellular damage can produce an inflammatory reaction, alleviating some measure of constitutive OGG1 inhibition. OGG1 inhibition in cancer cells shows some promise as a new method of cancer treatment. Most current OGG1 research focuses on regulating OGG1 with targeted small molecules. To date, no aptamer screen for OGG1 has been reported. Aptamers are single-stranded DNA (ssDNA) or RNA oligonucleotides that can bind to a target with high affinity and specificity in vitro, that can be identified by systematic evolution of ligands by exponential enrichment (SELEX). Aptamers can be used as chemical ligands to regulate intermolecular interactions. In this study, a screen for aptamers with OGG1 affinity was performed for the first time. Capillary electrophoresis (CE) is a microanalytical technique that offers speed and high separation efficiency. In this work, two screening methods based on CE-SELEX technology were established: a one-round pressure controllable selection, and a multi-round selection. The most important criterion for successful one-round pressure controllable selection is to select a competitive target with a different CE migration time than that of the target of interest. We mixed OGG1 with a competitive target and a nucleic acid library for CE analysis. Two proteins competitively bind sequences in the library, forming independent complexes. The concentration of the competitive target is continuously increased until complexes with the target stop decreasing, indicating that the target and the ssDNA library have formed a stable complex. Complexes were collected for PCR amplification, purification, and high-throughput sequencing to obtain high affinity aptamers. This method greatly improves screening efficiency, and reduces non-specific binding to the target, which is helpful for obtaining aptamers with high affinity and specificity. One-round pressure controllable selection for high affinity OGG1 selective aptamers was performed using single strand binding protein (SSB) to competitively and tightly bind nucleic acids in the library. The competitive screening pressure was increased by increasing the SSB concentration to eliminate sequences with low affinity for OGG1 from the random oligonucleotide library. Nucleic acid sequences with high OGG1 affinity were obtainable in one step, and OGG1-ssDNA complexes were collected by creating a timed program on Beckman P/ACE MDQ capillary electrophoresis. Collection occurred from 2.2 to 2.8 min. Under identical incubation and electrophoresis conditions, multiple round selections were conducted by injecting samples of co-incubated nucleic acid library and target into the capillary. After separation under a high-voltage electric field, nucleic acid target complexes were collected, amplified by PCR, purified, and used as an enriched secondary library in the next round of screening. High affinity aptamers were generally obtained within three rounds. Comparing results of the two screening methods, the three candidate aptamer sequences found with the highest frequency were consistent, and displayed KD values ranging from 1.71 to 2.64 µmol/L. Molecular docking analysis suggests that Apt 1 may bind to the OGG1 active pocket, which functions to repair oxidative damage. Comparison of the two screening methods indicates that one-round pressure controllable selection is more rapid and efficient, providing guidance for the design of other protein aptamer screening methods. The obtained aptamer is expected to be function effectively as an OGG1-mediated DNA repair inhibitor.


Assuntos
Aptâmeros de Nucleotídeos , DNA Glicosilases , Aptâmeros de Nucleotídeos/química , DNA Glicosilases/química , DNA de Cadeia Simples , Eletroforese Capilar , Guanina/análogos & derivados , Simulação de Acoplamento Molecular , Técnica de Seleção de Aptâmeros
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