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1.
J Affect Disord ; 296: 428-433, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34606806

RESUMO

BACKGROUND: Heart failure is the leading cause of mortality in older people with bipolar disorder (BD). Studies examining cardiac structure and function in middle-aged patients with BD by using echocardiography and cardiac strain imaging are scant. METHODS: We recruited 48 patients with bipolar I disorder (BD-I) older than 45 years to undergo conventional and tissue speckle tracking echocardiography. Data of 31 mentally healthy adults older than 45 years were randomly retrieved from the echocardiographic dataset and compared with the data of BD patients. RESULTS: Patients with BD-I had significantly higher mean values of interventricular septal thickness (Cohen's d = 0.83, p = 0.001) and left ventricular internal diameter (Cohen's d = 0.90, p = 0.001) at end-diastole relative to controls. Additionally, BD-I patients exhibited significantly lower mean values of mitral valve E/A ratio (Cohen's d = 0.67, p = 0.007) and a more reduced global longitudinal strain (Cohen's d = 0.72, p = 0.029) than controls. Multiple linear regression revealed that body mass index was negatively correlated with the mitral valve E/A ratio (adjustment R2 = 0.363, p = 0.043) in patients with BD-I. LIMITATIONS: A relatively small sample size may limit generalization. CONCLUSIONS: After midlife, BD patients exhibit cardiac diastolic (low mitral valve E/A ratio) and systolic (reduced global longitudinal strain) dysfunction. High body mass index may play a role in the unfavorable cardiac function in aging patients with BD.

2.
Chemosphere ; 286(Pt 3): 131866, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34391112

RESUMO

Tralopyril (TP), an antifouling biocide, is widely used to prevent heavy biofouling, and can have potential risks to aquatic organisms. In this study, the effect of TP on locomotor activity and related mechanisms were evaluated in zebrafish (Danio rerio) larvae. TP significantly reduced locomotor activity after 168 -h exposure. Adverse modifications in tail muscle tissue, the nervous system, and energy metabolism were also observed in larvae. TP caused thinning of the muscle bundle in the tail of larvae. In conjunction with the metabolomics results, changes in dopamine (DA) and acetylcholine (ACh), acetylcholinesterase (AChE) activity, and the expression of genes involved in neurodevelopment, indicate that TP may disrupt the nervous system in zebrafish larvae. The change in metabolites (e.g., glucose 6-phosphate, cis-Aconitic acid, acetoacetyl-CoA, coenzyme-A and 3-Oxohexanoyl-CoA) involved in carbohydrate and lipid metabolism indicates that TP may disrupt energy metabolism. TP exposure may inhibit the locomotor activity of zebrafish larvae by impairing tail muscle tissue, the nervous system, and energy metabolism.


Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Acetilcolinesterase , Animais , Metabolismo Energético , Larva , Locomoção , Músculos , Sistema Nervoso , Pirróis , Poluentes Químicos da Água/toxicidade
3.
Talanta ; 238(Pt 2): 123030, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34801893

RESUMO

The development of analytical method for selective and sensitive detection of gossypol (Gsp), an extraction from the cotton plants, is important but still challenging in food safety and medical field. Herein, we reported a turn-on near infrared (NIR) fluorescence detection strategy for Gsp based on a metal-organic framework (MOF), QBA-Yb, which was prepared from 4,4'-(quinolone-5, 8-diyl) benzoate with Yb(NO3)3·5H2O by solvothermal synthesis. The Gsp acted as another "antenna" to sensitize the luminescence of Yb3+, leading to the turn-on NIR emission upon 467 nm excitation. As Gsp concentration increased, the NIR emission at 973 nm enhanced gradually, thus enabling highly sensitive Gsp detection in a turn-on way. The experiment and theoretical calculation results revealed the presence of strong hydrogen bonds between Gsp molecules and the MOF skeleton. The developed QBA-Yb probe showed excellent characteristics for detection of Gsp molecules, accompanied by wide linear range (5-160 µg/mL), low detection limit (0.65 µg/mL) and short response time (within 10 min). We have further demonstrated that the QBA-Yb probe was successfully applied for the determination of Gsp in real samples of cottonseeds.

4.
Int J Mol Sci ; 22(21)2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34769032

RESUMO

BACKGROUND: Fluoroquinolones (FQs) are potent antimicrobials with multiple effects on host cells and tissues. Although FQs can attenuate cancer invasion and metastasis, the underlying molecular mechanisms remain unclear. Matrix metalloproteinase-9 (MMP-9) has functional roles in tumor angiogenesis, invasion, and metastasis, and is associated with cancer progression and poor prognosis, suggesting that inhibitors of MMP-9 activity and transcription are prime candidates for cancer therapy. Despite numerous preclinical data supporting the use of MMP-9 inhibitors as anticancer drugs, the few available examples are not therapeutically useful due to low specificity and off-target effects. We examined the effects of FQs on MMP-9 production in cancer cells following transforming growth factor beta (TGF-ß) and phorbol 12-myristate 13-acetate (PMA) stimulation. EXPERIMENTAL APPROACHES: Using confluent cultures of HepG2 and A549 cells, the effects of FQs (ciprofloxacin, levofloxacin, clinafloxacin, gatifloxacin, and enrofloxacin) on TGF-ß and PMA-induced MMP-9 mRNA expression and production were studied in RNA extracts and culture supernatants, respectively. FQs specifically abrogated TGF-ß and PMA-induced MMP-9 levels and activity in a concentration and time-dependent manner, without affecting other MMPs or proteins involved in epithelial-mesenchymal transition. Additionally, FQs inhibited TGF-ß and PMA-induced cell migration via p38 and cyclic AMP signaling pathways. CONCLUSIONS AND IMPLICATIONS: Overall, we demonstrated that FQs inhibit cancer cell migration and invasion by downregulating MMP-9 expression and revealed the cellular mechanisms underlying their potential value in cancer treatment.

5.
Cancers (Basel) ; 13(21)2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34771525

RESUMO

Liver cancer is the leading cause of cancer-related mortality in the world. This mainly reflects the lack of early diagnosis tools and effective treatment methods. MicroRNAs (miRNAs) are a class of non-transcribed RNAs, some of which play important regulatory roles in liver cancer. Here, we discuss microRNAs with key impacts on liver cancer, such as miR-122, miR-21, miR-214, and miR-199. These microRNAs participate in various physiological regulatory pathways of liver cancer cells, and their modulation can have non-negligible effects in the treatment of liver cancer. We discuss whether these microRNAs can be used for better clinical diagnosis and/or drug development. With the advent of novel technologies, fast, inexpensive, and non-invasive RNA-based biomarker research has become a new mainstream approach. However, the clinical application of microRNA-based markers has been limited by the high sequence similarity among them and the potential for off-target problems. Therefore, researchers particularly value microRNAs that are specific to or have special functions in liver cancer. These include miR-122, which is specifically expressed in the liver, and miR-34, which is necessary for the replication of the hepatitis C virus in liver cancer. Clinical treatment drugs have been developed based on miR-34 and miR-122 (MRX34 and Miravirsen, respectively), but their side effects have not yet been overcome. Future research is needed to address these weaknesses and establish a feasible microRNA-based treatment strategy for liver cancer.

6.
Bioresour Technol ; : 126259, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34775050

RESUMO

To explore an effective approach for accelerating cornstalk decomposition and return under low temperature, nine psychrotrophic cellulose-, hemicellulose-, and lignin-degrading bacterial strains were used with biochar as the carrier to prepare a novel psychrotrophic stalk-degrading bacterial consortium (PSBC). With PSBC, the maximum cornstalk degradation rate reached 59.3% after 50 d at 10-15 °C, which accelerated cornstalk decomposition, resulting in increases in organic matter, phosphorus, and potassium in the soil. Microbial community analysis demonstrated that PSBC enhanced microbial community diversity and altered specific selection. Genera Arthrobacter, Pseudomonas, and Pantoea in PSBC became dominant in the soil microbiota, which benefited cornstalk degradation. Therefore, this work provides a promising strategy to facilitate the degradation of cornstalks in cold regions, which has potential application value for carbon neutrality.

7.
Chem Sci ; 12(42): 14254-14259, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34760211

RESUMO

Controlled synthesis of hydrogen-bonded organic frameworks (HOFs) remains challenging, because the self-assembly of ligands is not only directed by weak hydrogen bonds, but also affected by other competing van der Waals forces. Herein, we demonstrate the coordination-bond-directed synthesis of HOFs using a preformed metal-organic framework (MOF) as the template. A MOF (CuI-TTFTB) based on two-coordinated CuI centers and tetrathiafulvalene-tetrabenzoate (TTFTB) ligands was initially synthesized. CuI-TTFTB was subsequently oxidized to the intermediate (CuII-TTFTB) and hydrated to the HOF product (TTFTB-HOF). Single-crystal-to-single-crystal (SC-SC) transformation was realized throughout the MOF-to-HOF transformation so that the evolution of structures was directly observed by single-crystal X-ray diffraction. The oxidation and hydration of the CuI center are critical to breaking the Cu-carboxylate bonds, while the synergic corbelled S⋯S and π⋯π interactions in the framework ensured stability of materials during post-synthetic modification. This work not only provided a strategy to guide the design and discovery of new HOFs, but also linked the research of MOFs and HOFs.

8.
Tzu Chi Med J ; 33(4): 412-418, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34760640

RESUMO

Objectives: During perioperative, lung cancer (LC) patients are often left to experience debilitating disease-related symptoms, impaired physical activity and health-related quality of life (HRQoL), and social difficulties, despite the progress achieved in terms of treatment efficacy. Nonpharmacological intervention, such as exercise, has been identified as an effective strategy in LC patients before and after lung resection. Therefore, we aimed to assess evidence of the effect of perioperative exercise among patients with LC. Materials and Methods: Seven databases were searched from January 1998 to September 2020. All randomized controlled trials (RCTs) that evaluated the effect of exercise on the physical and psychological status of patients with LC during the perioperative period were reviewed. Two reviewers independently assessed the quality of all studies included here using the revised Cochrane risk of bias tool for RCTs. Results: Seventeen RCTs (1199 participants) published between 2011 and 2019 met for this literature review. The outcome measures that emerged from these studies included subjective outcomes, such as HRQoL, pain score, fatigue, and objective effects, such as cardiorespiratory fitness, pulmonary function, physical activity, and biological markers. Overall, these studies suggest that exercise should be an optimal option for LC; however, its efficacy and effectiveness regarding HRQoL should be investigated further. Conclusion: Perioperative exercise could be included in the rehabilitation program of patients with LC. More extensive, high-quality RCTs evidence is needed on the ideal exercise type, duration, intensity, and timing across the LC perioperative care.

9.
Br J Haematol ; 2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34741461

RESUMO

Haploidentical allogeneic haematopoietic stem cell transplantation (haplo-HSCT) is a significant alternative treatment for severe aplastic anaemia (SAA). To improve this process by modifying the risk stratification system, we conducted a retrospective study using our database. 432 SAA patients who received haplo-HSCT between 2006 and 2020 were enrolled. These patients were divided into a training (n = 288) and a validation (n = 144) subset randomly. In the training cohort, longer time from diagnosis to transplantation, poorer Eastern Cooperative Oncology Group (ECOG) status and higher haematopoietic cell transplantation-specific comorbidity index (HCT-CI) score were independent risk factors for worse treatment-related mortality (TRM) in the final multivariable model. The haplo-HSCT scoring system was developed by these three parameters. Three-year TRM after haplo-HSCT were 6% [95% confidence interval (CI), 1-21%], 21% (95% CI, 7-40%), and 47% (95% CI, 20-70%) for the low-, intermediate-, and high-risk group, respectively (P < 0·0001). In the validation cohort, the haplo-HSCT scoring system also separated patients into three risk groups with increasing risk of TRM: intermediate-risk [hazard ratio (HR) 2·45, 95% CI, 0·92-6·53] and high-risk (HR 11·74, 95% CI, 3·07-44·89) compared with the low-risk group (P = 0·001). In conclusion, the haplo-HSCT scoring system could effectively predict TRM after transplantation.

10.
Front Cell Infect Microbiol ; 11: 759435, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34737978

RESUMO

Autism spectrum disorder (ASD) is a severe brain development disorder that is characterized by deficits in social communication and restricted, repetitive and stereotyped behaviors. Accumulating evidence has suggested that gut microbiota disorders play important roles in gastrointestinal symptoms and neurodevelopmental dysfunction in ASD patients. Manipulation of the gut microbiota by fecal microbiota transplantation (FMT) was recently shown to be a promising therapy for the treatment of various diseases. Here, we performed a clinical trial to evaluate the effect of FMT on gastrointestinal (GI) and ASD symptoms and gut microbiota alterations in children with ASD. We found that there was a large difference in baseline characteristics of behavior, GI symptoms, and gut microbiota between children with ASD and typically developing (TD) control children. FMT could improve GI symptoms and ASD symptoms without inducing any severe complications. Similarly, FMT significantly changed the serum levels of neurotransmitters. We further observed that FMT could promote the colonization of donor microbes and shift the bacterial community of children with ASD toward that of TD controls. The abundance of Eubacterium coprostanoligenes pre-FMT was positively correlated with high GSRS scores, whereas a decrease in Eubacterium coprostanoligenes abundance induced by FMT was associated with the FMT response. Our data suggest that FMT might be a promising therapeutic strategy to improve the GI and behavioral symptoms of patients with ASD, possibly due to its ability to alter gut microbiota and highlight a specific microbiota intervention that targets Eubacterium coprostanoligenes that can enhance the FMT response. This trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn) (trial registration number ChiCTR1800014745).


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Microbioma Gastrointestinal , Transtorno do Espectro Autista/terapia , Criança , Eubacterium , Transplante de Microbiota Fecal , Humanos
11.
Small ; : e2104401, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34825486

RESUMO

2D van der Waals (vdW) semiconductors hold great potentials for more-than-Moore field-effect transistors (FETs), and the efficient utilization of their theoretical performance requires compatible high-k dielectrics to guarantee the high gate coupling efficiency. The deposition of traditional high-k dielectric oxide films on 2D materials usually generates interface concerns, thereby causing the carrier scattering and degeneration of device performance. Here, utilizing a space-confined epitaxy growth approach, the authors successfully obtained air-stable ultrathin indium phosphorus sulfide (In2 P3 S9 ) nanosheets, the thickness of which can be scaled down to monolayer limit (≈0.69 nm) due to its layered structure. 2D In2 P3 S9 exhibits excellent insulating properties, with a high dielectric constant (≈24) and large breakdown voltage (≈8.1 MV cm-1 ) at room temperature. Serving as gate insulator, ultrathin In2 P3 S9 nanosheet can be integrated into MoS2 FETs with high-quality dielectric/semiconductor interface, thus providing a competitive electrical performance of device with subthreshold swings (SS) down to 88 mV dec-1 and a high ON/OFF ratio of 105 . This study proves an important strategy to prepare 2D vdW high-k dielectrics, and greatly facilitates the ongoing research of 2D materials for functional electronics.

12.
Neoplasia ; 23(12): 1289-1299, 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34785448

RESUMO

Most low-grade oral epithelial dysplasia remains static or regress, but a significant minority of them (4-11%) advances to oral squamous cell carcinoma (OSCC) within a few years. To monitor the progression of epithelial dysplasia for early cancer detection, we investigated the expression profiles of nucleostemin (NS) and phospho-STAT3 (p-STAT3) in rodent and human samples of dysplasia and OSCCs. In a 4NQO-induced rat oral carcinogenesis model, the number and distribution of NS and p-STAT3-positive cells increased in hyperplastic, dysplastic, and neoplastic lesions compared to normal epithelium. In human samples, the NS signal significantly increased in high-grade dysplasia and poorly differentiated OSCC, whereas p-STAT3 was more ubiquitously expressed than NS and showed increased intensity in high-grade dysplasia and both well and poorly differentiated OSCC. Analyses of human dysplastic samples with longitudinally followed outcomes revealed that cells with prominent nucleolar NS signals were more abundant in low-grade dysplasia that advanced to OSCC in 2 or 3 years than those remaining static for 7-14 years. These results suggest that NS upregulation and STAT3 activation are early events in the progression of low-grade dysplasia to OSCC.

13.
Adv Sci (Weinh) ; : e2104272, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34816629

RESUMO

Porous particles have found widespread applications in therapeutic diagnosis, drug delivery, and tissue engineering due to their typical properties of large surface area, extensive loading capacity, and hierarchical microstructures. Attempts in this aspect are focusing on the development of effective methods to generate functional porous particles. Herein, a simple droplet microfluidics for continuously and directly generating porous particles by introducing bubble-propelled nanomotors into the system is presented. As the nanomotors can continuously generate gas bubbles in the unsolidified droplet templates, the desirable porous microparticles can be obtained after droplet polymerization. It is demonstrated that the generation process is highly controlled and the resultant microparticles show excellent porosity and monodispersity. In addition, the obtained porous microparticles can serve as microcarriers for 3D cell culture, because of their characteristic porous structures and favorable biocompatibility. Moreover, owing to the existence of oxygen in these microparticles, they can be used to improve the healing effects of wounds in the type I diabetes rat models. These remarkable features of the generation strategy and the porous microparticles point to their potential values in various biomedical fields.

14.
Biochem Biophys Res Commun ; 584: 32-38, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34763165

RESUMO

Melatonin is a hormone majorly secreted by the pineal gland and contributes to a various type of physiological functions in mammals. The melatonin production is tightly limited to the AANAT level, yet the most known molecular mechanisms underlying AANAT gene transcription is limited in the pinealocyte. Here, we find that c-Fos and cAMP-response element-binding protein (CREB) decreases and increases the AANAT transcriptional activity in renal tubular epithelial cell, respectively. Notably, c-Fos knockdown significantly upregulates melatonin levels in renal tubular cells. Functional results indicate that AANAT expression is decreased by c-Fos and resulted in enhancement of cell damage in albumin-injury cell model. We further find an inverse correlation between c-Fos and AANAT levels in renal tubular cells from experimental membranous nephropathy (MN) samples and clinical MN specimens. Our finding provides the molecular basis of c-Fos in transcriptionally downregulating expression of AANAT and melatonin, and elucidate the protective role of AANAT in preventing renal tubular cells death in albumin-injury cell model and MN progression.

16.
Anim Biosci ; 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34727641

RESUMO

Objective: The objective was to evaluate the efficacy of increasing supplementation of Yarrowia lipolytica (YL) up to 3.0% replacing 1.6% poultry fat and 0.9% blood plasma for growth performance, intestinal health and nutrient digestibility of diets fed to nursery pigs. Methods: Twenty-four pigs weaned at 24 d of age (initial body weight at 7.2 ± 0.6 kg) were allotted to three dietary treatments (n = 8) based on the randomized complete block. The diets with supplementation of YL (0.0, 1.5 and 3.0%, replacing poultry fat and blood plasma up to 1.6 and 0.9%, respectively) were fed for 21 d. Feed intake and body weight were recorded at d 0, 10 and 21. Fecal score was recorded at every odd day from d 3 to 19. Pigs were euthanized on d 21 to collect proximal and distal jejunal mucosa to measure intestinal health markers including tumor necrosis factor-alpha, interleukin-8, immunoglobulin A and immunoglobulin G. Ileal digesta was collected for AID of nutrients in diets. Data were analyzed using Proc Mixed of SAS. Results: Supplementation of YL (1.5 and 3.0%) replacing poultry fat and blood plasma did not affect growth performance, fecal score and intestinal health. Supplementation of YL at 1.5% did not affect nutrient digestibility, whereas supplementation of YL at 3.0% reduced AID of dry matter (40.2 to 55.0%), gross energy (44.0 to 57.5%), crude protein (52.1 to 66.1%) and ether extract (50.8 to 66.9%) compared to diets without supplementation. Conclusion: Yarrowia lipolytica can be supplemented at 1.5% in nursery diet, replacing 0.8% poultry fat and 0.45% blood plasma without affecting growth performance, intestinal health and nutrient digestibility. Supplementation of YL at 3.0% replacing 1.6% poultry fat and 0.9% blood plasma did not affect growth performance and intestinal health, whereas nutrient digestibility was reduced.

17.
J Pers Med ; 11(11)2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34834409

RESUMO

Schizophrenia and bipolar disorder are severe mental disorders with a major component of genetic factors in their etiology. Rare mutations play a significant role in these two disorders, and they are highly heterogeneous and personalized. Identification of personalized mutations is essential for the establishment of molecular diagnosis, providing insight into pathogenesis and guiding the personalized treatment for each affected patient. We conducted whole-genome sequencing analysis of families with schizophrenia and bipolar disorder to search for their genetic underpinnings. This report identified a rare missense mutation Arg1087Gln of BSN (bassoon presynaptic cytomatrix protein) co-segregating with schizophrenia in a family with multiple affected members. Furthermore, we identified the rare missense mutation Ser1535Leu of PCLO (piccolo presynaptic cytomatrix protein) in two sisters with bipolar disorder and another rare missense mutation, His5142Arg in PCLO, in a patient with schizophrenia. These three missense mutations were very rare and were predicted to be pathogenic. The BSN and PCLO genes encode two structurally related proteins of the presynaptic cytomatrix at the active zone that regulates neurotransmission at the presynaptic neuronal terminal. Our findings suggest the involvement of the presynaptic matrix in the pathogenesis of schizophrenia and bipolar disorder, and BSN and PCLO are the risk genes for schizophrenia and bipolar disorder.

18.
J Multidiscip Healthc ; 14: 3213-3223, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34824535

RESUMO

Objective: This study aimed to develop an appropriate scale accessing healthcare students' and providers' humanistic professional awareness (HPAS-HSP). Methods: Following a literature review, stakeholder interviews, and panel discussions for item generation, 65 items for the HPAS-HSP scale were created based on a nine-point Likert scale, with 9 indicating "strongly agree" and 1 indicating "strongly disagree." A pilot study using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA), with seven hundred twenty-five medical care students and providers in Taiwan as the total sample number of the study, was administered to examine the practicability of the HPAS-HSP scale. The statistics software SPSS and AMOS 24.0 were used to examine the psychometric properties of the scale, including internal consistency, convergent validities, discriminant validities, and exploratory and confirmatory factor analysis. Results: The EFA resulted in 21 items in three factors, with 66.221% of the total variance explained: "personal integrity and accountability" (9 items; 51.763% of the variance explained), "sensitivity to others" (6 items; 8.667% of the variance explained), and "medical professional competence" (6 items; 5.791% of the variance explained). The Cronbach's alphas for the three subscales and the entire questionnaire ranged from 0.892 to 0.949. The CFA results yielded 20 items, with the same three factors, and demonstrated good model fit in the χ 2/df ratio (1.130; p = 0.140), CFI (0.998), TFI (0.998), and RMSEA (0.013). The composite alphas ranged between 0.900 and 0.969. Convergent and discriminant validity also confirmed the stability and consistency of the scale. Conclusion: The statistical results demonstrated that the HPAS-HSP scale can be a measure to assess healthcare students' and providers' humanistic professional awareness.

19.
Biomater Sci ; 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34826322

RESUMO

The therapeutic efficacy of methoxypolyethylene glycol (mPEG)-coated nanomedicines in solid tumor treatment is hindered by tumor-associated fibroblasts (TAFs), which promote tumor progression and form physical barriers. We developed an anti-HER2/anti-FAP/anti-mPEG tri-specific antibody (TsAb) for one-step conversion of mPEG-coated liposomal doxorubicin (Lipo-Dox) to immunoliposomes, which simultaneously target HER2+ breast cancer cells and FAP+ TAFs. The non-covalent modification did not adversely alter the physical characteristics and stability of Lipo-Dox. The TsAb-Lipo-Dox exhibited specific targeting and enhanced cytotoxicity against mono- and co-cultured HER2+ breast cancer cells and FAP+ TAFs, compared to bi-specific antibody (BsAb) modified or unmodified Lipo-Dox. An in vivo model of human breast tumor containing TAFs also revealed the improved tumor accumulation and therapeutic efficacy of TsAb-modified mPEGylated liposomes without signs of toxicity. Our data indicate that arming clinical mPEGylated nanomedicines with the TsAb is a feasible and applicable approach for overcoming the difficulties caused by TAFs in solid tumor treatment.

20.
J Clin Med ; 10(22)2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34830523

RESUMO

BACKGROUND: Anti-melanoma differentiation-associated gene 5 (MDA-5) antibody is associated with respiratory failure and death in patients with idiopathic inflammatory myositis (IIM) and interstitial lung disease (ILD). This study aimed to investigate clinical parameters associated with mortality in anti-MDA-5 antibody-positive patients. METHODS: We retrospectively reviewed the clinical and laboratory data, and pulmonary function test results in 55 anti-MDA-5 antibody-positive patients. A comparison was made between the survivors and non-survivors at the 12-month follow-up. RESULTS: A total of 13 patients (23.6%) died within 12 months. Non-survivors had higher GAP scores (gender, age, and physiology score for idiopathic pulmonary fibrosis) (1 vs. 6, p < 0.01) and CA-153 (16.4 vs. 72.9, p < 0.01). In addition, rapid progressive ILD, fever, peak ferritin, leukocyte count, lactate dehydrogenase, CT score, intravenous immunoglobulin, mycophenolic acid, CMV infections, pneumocystis pneumonia, and pneumothorax were significantly associated with increased risks of 1-year mortality, while forced vital capacity, forced expiratory volume in one second, and diffusion capacity for carbon monoxide were correlated with decreased risk of 1-year mortality. CONCLUSIONS: Our study results suggest that GAP scores and CA-153 could be prognostic factors for 1-year mortality in anti-MDA-5 antibody-positive patients. A prompt pulmonary function test and CA-153 are essential for these patients to guide further management.

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