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1.
Molecules ; 26(19)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34641409

RESUMO

The online preconcentration technique, cyclodextrin-assisted sweeping (CD-sweeping), coupled with micellar electrokinetic chromatography (MEKC) was established to determine 13-cis-retinoic acid (13-cis-RA), all-trans-retinoic acid (all-trans-RA) and 4-oxo-13-cis-retinoic acid (4-oxo-13-cis-RA) in human plasma. A CD-sweeping buffer (45 mM borate (pH 9.2), containing 80 mM sodium dodecyl sulfate (SDS) and 22 mM hydroxypropyl ß-CD (HP-ß-CD) was introduced into the capillary and, then, the sample dissolved in 70 mM borate (pH 9.2): methanol = 9:1 (v/v) was injected into capillary by pressure. The separation voltage was 23 kV. Compared to the conventional cyclodextrin-micellar electrokinetic chromatography (CD-MEKC) method, the new technique achieved 224-257-fold sensitivity enrichment of analytes. The limits of detection of 13-cis-RA, all-trans-RA were 1 ng/mL, whereas that of 4-oxo-13-cis-RA was 25 ng/mL in plasma. The linear ranges of 13-cis-RA, all-trans-RA were between 15 and 1000 ng/mL, whereas that of 4-oxo-13-cis-RA was between 75 and 1500 ng/mL. The coefficient of correlation between the concentration of analytes and peak area ratio of analytes and internal standard (2, 4-dihydroxy-benzophenone) for intra-day (n = 3) and inter-day (n = 5) analyses were both greater than 0.999. The optimized experimental conditions were successfully applied to determine 13-cis-retinoic acid and its metabolites in plasma samples from a patient during the administration of 13-cis-RA for treating acne.

2.
Indian Heart J ; 73(5): 653-655, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34627588

RESUMO

Real-world data regarding the efficacy and safety of coronary intravascular lithotripsy (IVL) are lacking. We conducted a study of 50 consecutive patients (64 lesions) who underwent IVL. 3 patients suffered in-hospital mortality unrelated to the IVL; there was no other occurrence of MACE up to 30 days. Angiographic success was nearly universal (98% of patients with residual stenosis <50%, 96% of patients with TIMI 3 flow) and complication was rare, including among patients undergoing IVL for in-stent restenosis or left main coronary artery lesions. In a high-risk real-world cohort, IVL was a safe and effective treatment for highly-calcified coronary lesions.

3.
J Med Chem ; 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34619959

RESUMO

The development of novel drugs against Gram-negative bacteria represents an urgent medical need. To overcome their outer cell membrane, we synthesized conjugates of antibiotics and artificial siderophores based on the MECAM core, which are imported by bacterial iron uptake systems. Structures, spin states, and iron binding properties were predicted in silico using density functional theory. The capability of MECAM to function as an effective artificial siderophore in Escherichia coli was proven in microbiological growth recovery and bioanalytical assays. Following a linker optimization focused on transport efficiency, five ß-lactam and one daptomycin conjugates were prepared. The most potent conjugate 27 showed growth inhibition of Gram-positive and Gram-negative multidrug-resistant pathogens at nanomolar concentrations. The uptake pathway of MECAMs was deciphered by knockout mutants and highlighted the relevance of FepA, CirA, and Fiu. Resistance against 27 was mediated by a mutation in the gene encoding ExbB, which is involved in siderophore transport.

4.
Biomed Res Int ; 2021: 4535349, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34608437

RESUMO

Hermansky-Pudlak syndrome (HPS) is a rare genetic disorder with an autosomal recessive inherited pattern. It is mainly characterized by deficiencies in lysosome-related organelles, such as melanosomes and platelet-dense granules, and leads to albinism, visual impairment, nystagmus, and bleeding diathesis. A small number of patients will present with granulomatous colitis or fatal pulmonary fibrosis. At present, mutations in ten known genetic loci (HPS1-11) have been identified to be the genetic cause of HPS. In this study, we enrolled a consanguineous family who presented with typical HPS phenotypes, such as albinism, visual impairment, nystagmus, and bleeding diathesis. Whole-exome sequencing and Sanger sequencing were applied to explore the genetic lesions of the patient. A novel homozygous frameshift mutation (NM_032383.5, c.1231dupG/p.Aps411GlyfsTer32) of HPS3 was identified and cosegregated in the family members. Furthermore, real-time PCR confirmed that the mutation decreased the expression of HPS3, which has been identified as the disease-causing gene of HPS type 3. According to ACMG guidelines, the novel mutation, resulting in a premature stop codon at amino acid 442, is a pathogenic variant. In summary, we identified a novel mutation (NM_032383.5, c.1231dupG/p.Aps411GlyfsTer32) of HPS3 in a family with HPS. Our study expanded the variant spectrum of the HPS3 gene and contributed to genetic counseling and prenatal genetic diagnosis of the family.

5.
Cancer Lett ; 523: 121-134, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34626691

RESUMO

Sunitinib resistance is a major challenge in systemic therapy for renal cell carcinoma (RCC). The role of circular RNAs (circRNAs) in regulating sunitinib resistance of RCC is largely unknown. We established sunitinib-resistant RCC cell lines in vivo. Through RNA-sequencing, we identified circSNX6, whose expression is upregulated in sunitinib-resistant cells compared with their parental cells. High circSNX6 expression was correlated with sunitinib resistance and worse oncologic outcomes in a cohort of 81 RCC patients. In vitro and in vivo experiments confirmed that circSNX6 could promote sunitinib resistance in RCC. circSNX6 acts as a molecular "sponge" to relieve the suppressive effect of microRNA (miR)-1184 on its target gene, glycerophosphocholine phosphodiesterase 1 (GPCPD1), which increases intracellular lysophosphatidic acid (LPA) levels and, ultimately, promotes sunitinib resistance in RCC cells. Our findings demonstrated that the circSNX6/miR-1184/GPCPD1 axis had a critical role in regulation of intracellular LPA levels and sunitinib resistance in RCC; they also provide a novel prognostic indicator and promising therapeutic targets.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34549541

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of blood flow restriction training (BFRT) in the treatment of patients with knee osteoarthritis (KOA). METHOD: Seven electronic databases were searched to identify trials comparing BFRT and conventional resistance training (RT) in a population with KOA. Studies were selected according to the inclusion and exclusion criteria. Standardized mean differences (SMDs) or risk ratio (RR) with 95% confidence intervals (CIs) was calculated to compare outcome measures of the groups. The methodological quality of selected studies and the quality of evidence were evaluated for included studies. RESULTS: A total of five studies were included in this meta-analysis, with very low to moderate risk of bias. The pooled results showed no significant difference between BFRT and conventional RT for KOA, including pain (SMD = -0.04 [95%CI: -0.31, 0.24], P = 0.79), physical function performance (SMD = 0.12 [95%CI: -0.55, 0.78], P = 0.73), self-reported function (SMD = 0.14 [95%CI: -0.24, 0.52], P = 0.48), and AEs (RR = 0.45 [95%CI: 0.20, 1.01], P = 0.05). In subgroup analysis, BFRT had a lower incidence of adverse events when compared with high-load resistance training (HLRT). CONCLUSION: Data from pooled studies showed BFRT may not have greater efficacy for treating patients with KOA and it is less likely to have a higher risk of adverse events. However, limited evidence supports that BFRT is likely safer than the HLRT. More evidence with high quality is needed in further research for its efficacy and safety.

7.
Ann Plast Surg ; 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34510079

RESUMO

BACKGROUND: Extensive cervicofacial reconstruction is challenging for plastic surgeons. Because of the location of the adjacent scalp flap nourished by the superficial temporal artery (STA), it can be a candidate for cervicofacial reconstruction. OBJECTIVES: This article aims to report a combined treatment of an expanded island STA flap and an 810-nm diode laser hair removal technique for extensive cervicofacial defects. METHODS: Between January 2015 and December 2018, 10 patients with lower face and neck scar contraction were reconstructed with a bilateral or unilateral expanded STA island flap and an 810-nm diode laser for hair removal in this retrospective study. Hair removal via the 810-nm laser was started when the injected volume reached the volume of the expander, with a fluence of 35 to 40 J/cm2 and a 1 to 2 Hz repetition rate. Before second-stage surgery, the hair reduction rate was assessed. Twelve months after surgery, the degree of epilation efficacy according to the satisfaction scale and Global Aesthetic Improvement Scale was evaluated. RESULTS: This study included 2 single-pedicle flaps and 8 double-pedicle flaps. The average size of the implanted expanders was 600 mL. The average injected volume was 1405 mL. Before second surgery, there was a 67.4% hair reduction rate. Twelve months after surgery, the results of Global Aesthetic Improvement Scale were very good (3), good (6), average (1), and poor (0). CONCLUSIONS: The expanded island STA flap and 810-nm diode laser technique may be a novel treatment option for severe face and neck aesthetic reconstruction.

8.
J Invest Dermatol ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34534577

RESUMO

MAPK/extracellular signal-regulated kinase kinase (MEK) 1/2 inhibitors (MEKis) have recently achieved surprising success in treating unresectable plexiform neurofibromas (PNFs). However, few studies have investigated the mechanisms of MEKi resistance in patients with PNF. We determined the efficacy of six different MEKis for treating PNFs, explored drug resistance mechanisms, and identified potential combination therapies to overcome resistance. By screening drug efficacy among six MEKis in human NF1-deficient PNF cell lines, TAK-733 was found to reduce PNF cell viability the most. We then cultured the TAK-733‒resistant cells and explored the potential targets for further treatment. Both high-throughput drug screening and RNA sequencing analyses of MEKi-resistant PNF cells identified cyclin-dependent kinase inhibitors as potential agents for PNFs. Dinaciclib, a cyclin-dependent kinase inhibitor, showed synergistic effects on MEKi-resistant cells. Coadministration of dinaciclib and TAK-733 significantly reduced cell viability and inhibited sphere formation and colony formation. Dinaciclib did not affect MEK signaling but decreased the expression of several prosurvival proteins, including survivin and cyclin-dependent kinase 1, to induce apoptosis and inhibit mitosis. TAK-733/dinaciclib combination therapy induced tumor reduction in PNF patient‒derived xenografts mouse models. Therefore, the combination of MEKi and cyclin-dependent kinase inhibitor may be promising for treating inoperable PNFs, especially when drug resistance exists. Our findings provide evidence for future clinical trials with MEKi-resistant patients with PNF.

9.
Clin Nutr ; 40(8): 4980-4987, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34364237

RESUMO

BACKGROUND: Body composition profiles influence the prognosis of several types of cancer; however, the role of body composition in patients with locally advanced gastric cancer (LAGC) after neoadjuvant treatment (NT) has not been well characterized. PATIENTS AND METHODS: A total of 213 patients with LAGC who underwent gastrectomy after NT at a high-volume institution from southern China were comprehensively evaluated for primary analysis. Additionally, 170 and 77 patients from Western China and Italy, respectively, were reviewed for external validation. The skeletal muscle index (SMI), skeletal muscle radiodensity (SMD), and the subcutaneous as well as the visceral adiposity index were assessed from clinically acquired CT scans at diagnosis and preoperatively. RESULTS: Overall, none of the body composition parameters significantly changed after NT. The pre-NT skeletal muscle radiodensity (SMD) and change in SMI (ΔSMI) were both significantly lower in the patients with poor response (tumor regression <50%; mean SMD: 43.5 vs 46.5, P = 0.003; mean ΔSMI: -1.0 vs 2.2, P < 0.001), and the cutoff values were calculated according to the Youden index as 43.7 and 1.2, respectively. Based on these 2 parameters, a novel model, the Skeletal Muscle Score (SMS), was proposed to predict the pathological response (AUC = 0.764 alone and = 0.822 in combination with the radiological response). Moreover, patients with an SMI loss >1.2 had a significantly prolonged drainage tube removal time (mean: 10.0 vs 8.2, P = 0.003) and postoperative hospital stay (mean: 11.1 vs 9.8, P = 0.048), as well as a significantly higher rate of postoperative complications (30.9% vs 16.7%, P = 0.015). In the multivariate analysis, SMI loss >1.2 independently predicted poor overall survival (HR: 1.677, 95% CI 1.040-2.704, P = 0.034) and recurrence-free survival (HR: 1.924, 95% CI 1.165-3.175, P = 0.011). ΔSMI was also significantly associated with pathological response, surgical outcomes, and survival in the 2 external cohorts (P all < 0.05). CONCLUSIONS: For LAGC, the pre-NT SMD and ΔSMI could accurately predict the pathological response after NT. An SMI loss >1.2 is closely associated with poorer outcomes and may indicate the need more supportive treatment.

10.
Int J Mol Sci ; 22(16)2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34445521

RESUMO

Poly(aspartamide) derivatives, one kind of amino acid-based polymers with excellent biocompatibility and biodegradability, meet the key requirements for application in various areas of biomedicine. Poly(aspartamide) derivatives with stimuli-responsiveness can usually respond to external stimuli to change their chemical or physical properties. Using external stimuli such as temperature and pH as switches, these smart poly(aspartamide) derivatives can be used for convenient drug loading and controlled release. Here, we review the synthesis strategies for preparing these stimuli-responsive poly(aspartamide) derivatives and the latest developments in their applications as drug carriers.


Assuntos
Ácido Aspártico/análogos & derivados , Portadores de Fármacos/síntese química , Polímeros/síntese química , Ácido Aspártico/síntese química , Ácido Aspártico/química , Preparações de Ação Retardada , Portadores de Fármacos/química , Concentração de Íons de Hidrogênio , Polímeros/química , Temperatura
11.
Front Immunol ; 12: 643282, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34421886

RESUMO

Background: Only a proportion of patients with bladder cancer may benefit from durable response to immune checkpoint inhibitor (ICI) therapy. More precise indicators of response to immunotherapy are warranted. Our study aimed to construct a more precise classifier for predicting the benefit of immune checkpoint inhibitor therapy. Methods: This multi-cohort study examined the top 20 frequently mutated genes in five cohorts of patients with bladder cancer and developed the TP53/PIK3CA/ATM mutation classifier based on the MSKCC ICI cohort. The classifier was then validated in a validation set consisting of IMvigor210 cohort and Broad/Dana-Farber cohort. The molecular profile and immune infiltration characteristics in each subgroup as defined by this classifier were explored. Results: Among all 881 patients with bladder cancer, the mutation frequency of TP53, PIK3CA, and ATM ranked in the top 20 mutated genes. The TP53/PIK3CA/ATM mutation classifier was constructed based on the Memorial Sloan Kettering Cancer Center (MSKCC) ICI cohort and only showed predictive value for patients with bladder cancer who received ICI therapy (median overall survival: low-risk group, not reached; moderate-risk group, 13.0 months; high-risk group, 8.0 months; P<0.0001). Similar results were found in subgroups of MSKCC ICI cohort defined by tumor mutation burden. Multivariate Cox analysis revealed that the risk group defined by the classifier served as an independent prognostic factor for overall survival in patients with bladder cancer. Efficacy of the classifier was verified in a validation set consisting of IMvigor210 cohort and Broad/Dana-Farber cohort. Lower expression of PD-1/PD-L1 and less tumor immune infiltration were observed in the high-risk group than the other two groups of the TCGA cohort and the IMvigor210 cohort. Conclusion: Our study constructed a TP53/PIK3CA/ATM mutation classifier to predict the benefit of immune checkpoint inhibitor therapy for patients with bladder cancer. This classifier can potentially complement the tumor mutation burden and guide clinical ICI treatment decisions according to distinct risk levels.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia , Classe I de Fosfatidilinositol 3-Quinases , Inibidores de Checkpoint Imunológico/administração & dosagem , Mutação , Proteína Supressora de Tumor p53 , Neoplasias da Bexiga Urinária , Adulto , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/imunologia , Classe I de Fosfatidilinositol 3-Quinases/genética , Classe I de Fosfatidilinositol 3-Quinases/imunologia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Taxa de Sobrevida , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/imunologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/mortalidade
12.
Disabil Rehabil ; : 1-25, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34448416

RESUMO

PURPOSE: Participation is a key outcome of rehabilitation. However, no reviews have investigated the impact of low vision on the activities, participation, and goals of older adults. This paper aims to review and synthesize available literature on how low vision impacts the activity and participation of older adults. METHOD: A scoping review was conducted. The key findings were extracted from 30 full-text articles that met the selection criteria. The International Classification of Functioning, Disability and Health was used to frame the findings at the activity and participation levels. RESULTS: At the activity level, the categories of Walking, Moving around in different locations, and Reading were commonly impacted by low vision. The main domains impacted at the participation level were Community, social and civic life and Interpersonal interaction and relationships. Only one study addressed the goals of older adults with low vision. CONCLUSION: Low vision impacts reading, walking, and moving around in different locations. Rehabilitation therapists should be aware of and consider assessing these activities. Further research is needed on the impact of low vision on other functional activities, participation, and self-identified goals of older adults to guide clinical practice.Implications for rehabilitationLow vision has an impact on the activity level of older adults, consistently identified in the areas of walking and moving around in different locations and reading for knowledge and leisure.At the participation level, the impact of low vision is less frequently identified compared to the areas identified at the activity level, in the areas of leisure, social interactions and basic and instrumental ADL.Rehabilitation therapists working with older adults with low vision should assess clients' performance of moving around in different locations, in addition to walking, and include screening questions on the impact of low vision on driving.Rehabilitation therapists working with older adults with low vision should determine clients' reading needs and acquire competence in assessing clients' reading ability and providing intervention for different types of reading to enable them to continue participating in various life situations that require the performance of reading.

13.
Bioorg Chem ; 115: 105251, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34390969

RESUMO

Thirteen previously undescribed guaiane-type sesquiterpenoids based on [5,7] bicyclic system, stelleranoids A-M (1-13), along with six known analogues (14-20), were isolated from the roots of Stellera chamaejasme with chromatographic techniques. Their structures including absolute configurations were determined by HRESIMS and spectroscopic data, quantum chemical calculations, as well as X-ray crystallographic analysis. Cytotoxicity test in three cell lines indicated that compound 14 had relatively stronger cytotoxic effect against MKN-45, SKOV3, and Du145 cell lines with IC50 of 9.8, 17.4 and 7.3 µM, respectively; compounds 3 and 8 displayed moderate cytotoxic effect against MKN-45 and Du145 cell lines with IC50 ranged from 14.5 to 18.8 µM, comparable to those of the positive control. As determined by fluorescent microscopy and flow cytometry in Du145 cell line, compound 14 could promote cell apoptosis and cause cell cycle arrest at the G0/G1 phase, leading to the inhibition of cell proliferation. Further Western blot analysis revealed that this inhibitory effect was accompanied by upregulating pro-apoptosis proteins cleaved-PARP, cleaved-Caspase-9 and tumor suppressor protein p53 while downregulating anti-apoptotic protein Bcl-2 in 14-treated Du145 cells.

14.
Viruses ; 13(8)2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34452299

RESUMO

Tomato (Solanum lycopersicum) is an important economic crop worldwide. However, tomato production is jeopardized by the devastating tomato yellow leaf curl disease caused by whitefly-transmitted begomoviruses (WTBs). In this study, we evaluated the efficacy of our previously developed plant antiviral immunity inducer, fungal F8-culture filtrate, on tomato to combat tomato yellow leaf curl Thailand virus (TYLCTHV), the predominant WTB in Taiwan. Our results indicated that F8-culture filtrate treatment induced strong resistance, did not reduce the growth of tomato, and induced prominent resistance against TYLCTHV both in the greenhouse and in the field. Among TYLCTHV-inoculated Yu-Nu tomato grown in the greenhouse, a greater percentage of plants treated with F8-culture filtrate (43-100%) were healthy-looking compared to the H2O control (0-14%). We found that TYLCTHV cannot move systemically only on the F8-culture filtrate pretreated healthy-looking plants. Tracking the expression of phytohormone-mediated immune maker genes revealed that F8-culture filtrate mainly induced salicylic acid-mediated plant immunity. Furthermore, callose depositions and the expression of the pathogen-induced callose synthase gene, POWDERY MILDEW RESISTANT 4 were only strongly induced by TYLCTHV on tomato pretreated with F8-culture filtrate. This study provides an effective way to induce tomato resistance against TYLCTHV.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34431114

RESUMO

BACKGROUND: For initial respiratory management, continuous positive airway pressure (CPAP) is increasingly used for preterm infants, especially for gestational age less than 32 weeks. However, neonatologists are concerned about the potential risks of CPAP support failure. OBJECTIVES: To examine the association between different initial respiratory support modalities and the outcomes of preterm infants at <32 weeks of gestation across multiple neonatal intensive care units (NICU) in China. METHODS: This study was carried out over a period of 12 months in 2018. Unadjusted relative risks (RR) for demographic and clinical characteristics were calculated for CPAP failure and CPAP success in the total cohort using log-linear model based on generalised estimating equations for clustered observations. RESULTS: Among 1560 preterm infants delivered at <32 weeks, the incidence of CPAP failure was 10.3%. After adjustment for demographic and clinical factors, the relative risk of mortality (RR 7.54, 95% CI 5.56, 10.44), pneumothorax (RR 9.85, 95% CI 2.89, 61.53), pulmonary haemorrhage (RR 7.78, 95% CI 4.51, 14.64) and BPD (RR 3.65, 95% CI 3.65, 4.51) were considerably higher for infants in the CPAP failure group than those in the CPAP-S group. However, the risk of poor outcomes in CPAP failure infants was similar to that of those in the initial mechanical ventilation (MV) group. CONCLUSIONS: Continuous positive airway pressure failure was associated with an increased risk of mortality and major morbidities, including BPD, pulmonary haemorrhage and pneumothorax, and was comparable to the risk associated with initial MV.

16.
J Cyst Fibros ; 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34393091

RESUMO

Chronic Pseudomonas aeruginosa (Pa) infection is associated with increased morbidity and mortality in people with cystic fibrosis (CF). There is no gold standard definition of chronic Pa infection in CF. We compared chronic Pa definitions using encounter-based versus annualized data in the Early Pseudomonas Infection Control (EPIC) Observational study cohort, and subsequently compared annualized chronic Pa definitions across a range of U.S. cohorts spanning decades of CF care. We found that an annualized chronic Pa definition requiring at least 1 Pa+ culture in 3 of 4 consecutive years ("Green 3/4") resulted in chronic Pa metrics similar to established encounter-based modified Leeds criteria definitions, including a similar age at and proportion who fulfilled chronic Pa criteria, and a similar proportion with sustained Pa infection after meeting the chronic Pa definition. The Green 3/4 chronic Pa definition will be valuable for longitudinal analyses in cohorts with limited culture frequency.

17.
Cancer Lett ; 520: 307-320, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34390764

RESUMO

Multiple myeloma (MM) is incurable and the second most common hematologic malignancy in plasma cells. Multiple myeloma stem cell-like cells (MMSCs), a rare population of MM cells, are believed to be the major cause of drug resistance and high recurrence rates in patients with MM. Therefore, developing novel strategies to eradicate MMSCs may favor myeloma treatment. In this study, based on the drug repositioning strategy, we found that albendazole (ABZ), a broad-spectrum antiparasitic drug, selectively suppresses the proliferation of multiple myeloma cells in vitro and in vivo and decreases number of aldehyde dehydrogenase (ALDH)-positive MMSCs in MM. Furthermore, RNA-seq of MM cells after ABZ treatment revealed that inhibition of the nuclear factor kappa-B (NF-κB) pathway is a key mediator of ABZ against MM. Moreover, we demonstrated that ABZ can resensitize cells resistant to bortezomib and overcome MMSCs-induced bortezomib resistance by decreasing ALDH1+ MMSCs numbers. Our findings provide preclinical evidence for utilizing the previously known pharmacologically active drug albendazole for the treatment of multiple myeloma.

18.
Clin Nurs Res ; : 10547738211041692, 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34423684

RESUMO

This qualitative descriptive study aimed to explore expectations of patients and healthcare experts for an online self-management program for rheumatoid arthritis. Participants were recruited from rheumatology clinics, medical centers, and universities in Taiwan. Individual face-to-face, semi-structured interviews were conducted with patients (n = 16) and healthcare experts (n = 7). Content analysis of the interview data resulted in five subthemes for expectations of an online self-management program: information about how the disease trajectory would impact future health status, availability of opportunities for self-monitoring, opportunities to interact with fellow patients and healthcare providers, simplicity and ease-of-use of the program, and methods to facilitate patient-motivation. These subthemes formulated two overarching themes: content and format. An online self-management program for patients with rheumatoid arthritis should provide evidence-based information about disease variables and behaviors aligned with the specific needs of the individual and adopt strategies that encourage and increase motivation and confidence.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34444121

RESUMO

Interventions engaging community health workers (CHW) for diabetes management aim to improve diabetes care and self-management behaviors among patients. We evaluated the effects of nonsurgical periodontal treatment (NSPT) with the CHW strategy on oral self-care behaviors, periodontal status and oral health-related quality of life (OHQoL) in patients with type 2 diabetes mellitus (T2DM). The participants were randomly assigned to experimental (EG; n = 35) and control (CG; n = 33) groups. All participants received NSPT, whereas the patients in the EG also received one-on-one 30 min lessons from a CHW over 4 weeks. The EG exhibited greater improvement in the probing pocket depth (ß = -0.2, effect size [ES] = 0.61) and clinical attachment level (ß = -0.2, ES = 0.59) at 1-month follow-up than the CG did. The ES increased over the 1-, 3- and 6-month follow-ups, indicating an increase in OHQoL (ES = 0.19, 0.60, and 0.62, respectively) in the EG. The patients in the EG were more likely to change their oral self-care behaviors than patients in the CG were. The NSPT with CHW strategy had a positive effect on 1-month periodontal treatment outcomes, long-term OHQoL and oral self-care behaviors in patients with T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Autogestão , Agentes Comunitários de Saúde , Diabetes Mellitus Tipo 2/terapia , Humanos , Qualidade de Vida , Resultado do Tratamento
20.
Gastroenterology ; 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34391772

RESUMO

BACKGROUND & AIMS: Metaplasia and dysplasia in the corpus are reportedly derived from de-differentiation of chief cells. However, the cellular origin of metaplasia and cancer remained uncertain. Therefore, we investigated whether pepsinogen C (PGC) transcript-expressing cells represent the cellular origin of metaplasia and cancer using a novel Pgc-specific CreERT2 recombinase mouse model. METHODS: We generated a Pgc-mCherry-IRES-CreERT2 (Pgc-CreERT2) knock-in mouse model. Pgc-CreERT2/+ and Rosa-EYFP mice were crossed to generate Pgc-CreERT2/Rosa-EYFP (Pgc-CreERT2/YFP) mice. Gastric tissues were collected, followed by lineage-tracing experiments and histologic and immunofluorescence staining. We further established Pgc-CreERT2;KrasG12D/+ mice and investigated whether PGC transcript-expressing cells are responsible for the precancerous state in gastric glands. To investigate cancer development from PGC transcript-expressing cells with activated Kras, inactivated Apc, and Trp53 signaling pathways, we crossed Pgc-CreERT2/+ mice with conditional KrasG12D, Apcflox, Trp53flox mice. RESULTS: Expectedly, mCherry mainly labeled chief cells in the Pgc-CreERT2 mice. However, mCherry was also detected throughout the neck cell and isthmal stem/progenitor regions, albeit at lower levels. In the Pgc-CreERT2;KrasG12D/+ mice, PGC transcript-expressing cells with KrasG12D/+ mutation presented pseudopyloric metaplasia. The early induction of proliferation at the isthmus may reflect the ability of isthmal progenitors to react rapidly to Pgc-driven KrasG12D/+ oncogenic mutation. Furthermore, Pgc-CreERT2;KrasG12D/+;Apcflox/flox mice presented intramucosal dysplasia/carcinoma and Pgc-CreERT2;KrasG12D/+;Apcflox/flox;Trp53flox/flox mice presented invasive and metastatic gastric carcinoma. CONCLUSIONS: The Pgc-CreERT2 knock-in mouse is an invaluable tool to study the effects of successive oncogenic activation in the mouse corpus. Time-course observations can be made regarding the responses of isthmal and chief cells to oncogenic insults. We can observe stomach-specific tumorigenesis from the beginning to metastatic development.

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