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1.
Anesthesiology ; 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35503999

RESUMO

BACKGROUND: Intraoperative isoelectric electroencephalography (EEG) has been associated with hypotension and postoperative delirium in adults. This international prospective observational study sought to determine the prevalence of isoelectric EEG in young children during anesthesia. We hypothesized that the prevalence of isoelectric events would be common worldwide and associated with certain anesthetic practices and intraoperative hypotension. METHODS.: Fifteen hospitals enrolled patients age ≤ 36 months for surgery using sevoflurane or propofol anesthetic. Frontal 4-channel EEG was recorded for isoelectric events. Demographics, anesthetic, emergence behavior, and Pediatric Quality of Life (PedsQL) variables were analyzed for association with isoelectric events. RESULTS.: Isoelectric events occurred in 32% (206/648) of patients, varied significantly among sites (9-88%), and were most prevalent during pre-incision (117/628, 19%) and surgical maintenance (117/643, 18%). Isoelectric events were more likely with [odds ratio-OR (95% confidence interval-CI)] infants < 3 months [4.4 (2.57-7.4) p<0.001], endotracheal tube use [1.78 (1.16-2.73) p=0.008], propofol bolus for airway placement after sevoflurane induction [2.92 (1.78-4.8) p<0.001], and less likely with use of muscle relaxant for intubation [0.67 (0.46-0.99) p=0.046]. Expired sevoflurane was higher in patients with isoelectric events [mean difference (95% CI)] during pre-incision [0.2% (0.1, 0.4) p=0.005] and surgical maintenance [0.2% (0.1, 0.3) p=0.002]. Isoelectric events were associated with moderate (8/12, 67%) and severe hypotension (11/18, 61%) during pre-incision [OR: 4.6 (1.30-16.1) p=0.018; 3.54 (1.27, 9.9) p=0.015] and surgical maintenance [OR: 3.64 (1.71-7.8) p=0.001; 7.1 (1.78- 28.1) p=0.005], and lower PedsQL scores [median of differences (95% CI)] at baseline in patients 0-12 [-3.5 (-6.2, -0.7) p=0.008] and 25-36 months [-6.3 (-10.4, -2.1) p=0.003] and 30-day follow-up in 0-12 months [-2.8 (-4.9, 0) p=0.036]. Isoelectric events were not associated with emergence behavior or anesthetic (sevoflurane vs propofol). CONCLUSIONS.: Isoelectric events were common worldwide in young children during anesthesia and associated with age, specific anesthetic practices, and intraoperative hypotension.

2.
Eur J Immunol ; 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35524548

RESUMO

Human nasal mucosa is susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and serves as a reservoir for viral replication before spreading to other organs (e.g. the lung and brain) and transmission to other individuals. Chronic rhinosinusitis (CRS) is a common respiratory tract disease and there is evidence suggesting that susceptibility to SARS-CoV-2 infection differs between the two known subtypes, eosinophilic CRS and non-ECRS (NECRS). However, the mechanism of SARS-CoV-2 infection in the human nasal mucosa and its association with CRS has not been experimentally validated. In this study, we investigated whether the human nasal mucosa is susceptible to SARS-CoV-2 infection and how different endotypes of CRS impact on viral infection and progression. Primary human nasal mucosa tissue culture revealed highly efficient SARS-CoV-2 viral infection and production, with particularly high susceptibility in the NECRS group. The gene expression differences suggested that human nasal mucosa is highly susceptible to SARS-CoV-2 infection, presumably due to an increase in ACE2-expressing cells and a deficiency in antiviral immune response, especially for NECRS. Importantly, patients with NECRS may be at a particularly high risk of viral infection and transmission, and therefore, close monitoring should be considered.

3.
Ying Yong Sheng Tai Xue Bao ; 33(3): 793-800, 2022 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-35524533

RESUMO

Soil microorganism is an important indicator of soil health and plays a critical role in biogeochemical processes. We collected soil samples from a multi-year in-situ field experiment with two cropping modes (maize monocropping and maize-potato intercropping) subjected to four nitrogen (N) levels (N0, 0 kg·hm-2; N125, 125 kg·hm-2; N250, 250 kg·hm-2; N375, 375 kg·hm-2). By using the Biolog-ECO microplate method, soil microbial metabolic activity, diversity and utilization of six carbon groups were analyzed. The results showed that N application significantly increased the average well color development (AWCD) values, Simpson and Shannon indices, with the highest value at N250 in mono- and inter-cropped soils. Moreover, N application promoted the utilization of amino acids, amines and phenolic compounds, but decreased the utilization of polymers. Compared with monocropping at the same N level, intercropping improved the AWCD values, Simpson and Shannon indices, with a maximal improvement at N250. Intercropping and nitrogen application significantly affected the metabolic activities of the six carbon-source groups. In addition, intercropping improved the utilization of labile carbon sources, such as amino acids and carbohydrates. Results of the redundancy analysis and linear regression showed that intercropping and N application elevated AWCD values by increasing soil temperature, water content, and soil organic carbon content. Therefore, the changes in soil physicochemical properties after intercropping were the main reason for the enhancement of microbial metabolic activity under N application.


Assuntos
Nitrogênio , Solo , Agricultura/métodos , Aminoácidos/metabolismo , Carbono/metabolismo , Nitrogênio/análise , Solo/química , Microbiologia do Solo , Zea mays
4.
J Viral Hepat ; 2022 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-35567395

RESUMO

The study aimed to investigate the role of AR/CCRK signaling pathway in chronic hepatitis B virus (HBV) infection and gender differences, and the contribution of AR regulatory factor STAT3 in it. AR, CCRK, and phosphorylated STAT3 expressions in liver tissues of chronic HBV-infected patients and non-HBV controls were determined by western blot and compared between genders. The relationships of expression levels with serum HBV DNA levels, liver inflammation activity and fibrosis score were analyzed in chronic HBV-infected patients. The relationships between expression levels of three proteins were also analyzed. HBV-infected patients had significantly higher expression levels of AR, CCRK, and p-STAT3Tyr705 compared with controls (P<0.01). The expression levels of AR, CCRK, and p-STAT3Tyr705 in chronic HBV-infected patients with severe inflammation were significantly higher than those with mild inflammation (P<0.05). Expression levels in patients with heavier fibrosis (stage F4) were higher than those with less fibrosis (stage F0-3) (P<0.01). No gender differences were observed in AR, CCRK and p-STAT3Tyr705 levels in non-HBV controls; higher levels were observed in HBV-infected males than in HBV-infected females (P<0.05). AR, CCRK, and p-STAT3Tyr705 levels in liver tissues positively correlated with each other (P<0.0001) and with serum HBV DNA levels (P<0.0001). In conclusion, in this study, we first found concordant over-expression of AR, CCRK and STAT3 in liver tissues of chronic HBV-infected patients who have not yet developed HCC, significantly correlated with the severity of the disease and showed gender differences. STAT3 may be a potential therapeutic co-target for chronic HBV infection.

5.
Bioact Mater ; 15: 29-43, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35386360

RESUMO

Low back pain, mainly caused by intervertebral disc degeneration (IVDD), is a common health problem; however, current surgical treatments are less than satisfactory. Thus, it is essential to develop novel non-invasive surgical methods for IVDD treatment. Here, we describe a therapeutic strategy to inhibit IVDD by injecting hydrogels modified with the extracellular matrix of costal cartilage (ECM-Gels) that are loaded with cartilage endplate stem cells (CESCs). After loaded with CESCs overexpressing Sphk2 (Lenti-Sphk2-CESCs) and injected near the cartilage endplate (CEP) of rats in vivo, ECM-Gels produced Sphk2-engineered exosomes (Lenti-Sphk2-Exos). These exosomes penetrated the annulus fibrosus (AF) and transported Sphk2 into the nucleus pulposus cells (NPCs). Sphk2 activated the phosphatidylinositol 3-kinase (PI3K)/p-AKT pathway as well as the intracellular autophagy of NPCs, ultimately ameliorating IVDD. This study provides a novel and efficient non-invasive combinational strategy for IVDD treatment using injectable ECM-Gels loaded with CESCs that express Sphk2 with sustained release of functional exosomes.

6.
Plant Cell Rep ; 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35381869

RESUMO

KEY MESSAGE: Overexpression of miR171 restored SE competence in the recalcitrant citrus callus, and inhibition of miR171 function weakened SE competence in the strongly embryogenic citrus callus. Somatic embryogenesis (SE) is an important way of in vitro regeneration for plants. For perennial woody crops such as citrus, embryogenic callus is usually induced from unfertilized aborted ovules and widely used in biotechnology aided breeding. However, SE capacity always declines in callus during subculture, which makes regeneration difficult and hinders the application of biotechnology. We previously found that miR171 may be a regulator of SE in citrus, based on the abundant expression of csi-miR171c in the embryogenic callus and during SE of citrus. Here, we report that miR171 promotes SE and is required for SE in citrus. Overexpression of miR171 restored SE competence in the recalcitrant callus of 'Guoqing No.1' Satsuma mandarin (G1), whereas inhibition of miR171 function by Short Tandem Target Mimic (STTM) weakened SE competence in the strongly embryogenic callus of 'Valencia' sweet orange (V). The comparative transcriptomic analysis in miR171 overexpressed callus line (OE) and the wild type callus (WT) indicated that overexpression of miR171 decreased the expression level of its SCARECROW-LIKE (CsSCL) targets, and activated stress response related biological processes and metabolic processes that are required for cell differentiation. However, CsSCLs were up-regulated in the OE callus during SE induction process, which activated the cell division and developmental processes that are required for embryogenesis progress. Our results validate the function of miR171 in regulation of SE and reveal the biological responses provoked by miR171 in citrus that may promote SE.

7.
J Biomater Appl ; : 8853282221087412, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35428411

RESUMO

Most drug-delivery systems (DDS) suffer from poor selectivity to cancer/normal cells or the complicated synthetic process. Herein, we employed a novel facile method to develop an oligodeoxy nucleotides based DDS composed with adenosine-5'- triphosphate (ATP) aptamer and a pH responsive cytosine (C) DNA fragment for specific daunomycine (DNM) delivery. The DDS has ATP/pH dual-responsive drug release, can selectively internalize into tumor cell lines and thus has ultrahigh cancer/normal cell selectivity over the individual drug. The non-chemical synthesis, controllable dual-responsive intracellular drug release, and high cancer/normal cell selectivity endowed the DDS high biocompatibility and significant tumor suppression.

9.
Acta Biomater ; 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35364319

RESUMO

Chitin is found in the exoskeleton and peritrophic matrix of arthropods, but recent studies have also identified chitin in the spinning duct of silk-spinning arthropods. Here, we report the presence and function of chitin and cuticle proteins ASSCP1 and ASSCP2 in the spinning duct of silkworm. We show that chitin and these proteins are co-located in the cuticular layer of the spinning duct. Ultrastructural analysis indicates that the cuticular layer has a multilayer structure by layered stacking of the chitin laminae. After knocking down ASSCP1 and ASSCP2, the fine structure of this layer was disrupted, which had negative impacts on the mechanical properties of silk. This work clarifies the function of chitin in the spinning duct of silkworm. Chitin and cuticle proteins are the main components of the cuticular layer, providing the shearing stress during silk fibrillogenesis and regulating the final mechanical properties of silk. STATEMENT OF SIGNIFICANCE: Recent studies have identified chitin in the spinning duct of silk-spinning arthropods. However, the role of chitin in this specific organ remains unclear. This study reports that chitin and cuticle proteins form the cuticular layer, a unique structure of the spinning duct of silkworm. This layer with a precise laminate structure gives the spinning duct flexible properties, provides shearing forces for silk fibrillogenesis, and contributes to silk final mechanical properties. Our work clarifies the component, ultrastructure, and biological significance of the silkworm cuticular layer, describes the specific process of silk fiber formation, and proposes new molecular targets (chitin and cuticle proteins) for the improvement of animal silks.

10.
Food Chem ; 387: 132823, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35398680

RESUMO

The current study analysed concentrations of furan and its derivatives in coffee products commercially available in China based on an improved headspace gas chromatography-mass spectrometry (HS-GC-MS) method and estimated health risks. A total of 101 samples of coffee products on the Chinese market was analysed. Furan (98%, ND-6569 µg/kg) and 2-methylfuran (100%, 2-29639 µg/kg) were the compounds with the highest concentrations and detection rates in coffee products. The mean dietary exposure of Chinese consumers to furan and the sum of furan, 2-methylfuran and 3-methylfuran in coffee products was 0.09 and 0.46 µg/kg bw/day, respectively. For the neoplastic effects of furan, the margin of exposure (MOE) was 14,556 for the mean dietary exposure of consumers. For the non-neoplastic effects of furan, MOEs were 711 and 139 for furan and the sum of furan, 2-methylfuran and 3-methylfuran, respectively. Overall, a health concern is indicated for coffee consumers with MOEs below 10000.


Assuntos
Café , Furanos , China , Café/química , Furanos/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos
11.
Food Chem ; 386: 132683, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-35364490

RESUMO

Pectins obtained from citrus peel of different cultivars and growth regions were compared based on physicochemical properties and antioxidant activity in vitro. The physicochemical features were elucidated using Fourier transform infrared (FT-IR), molecular weight distribution, monosaccharide composition, thermal behaviors and flow behaviors. Results showed that the different cultivars and growing areas have significant effects on the properties of citrus peel pectins (CPPs). Citrus peel pectins extracted by acetic acid were highly heterogeneous polysaccharides with broad molecular weight distributions and had high proportions of the RG-I domain. Among the 10 kinds of citrus peel pectins, Shatangju (CPP-6) and Xuecheng (CPP-7) own superior antioxidant biological activity and Dahongpao (CPP-3) and Buzhihuo (CPP-9) had excellent functional properties (thermal stability and viscosity). According to the correlation analysis, molecular weight, galacturonic acid content and degree of methyl-esterification were beneficial to increase the thermal stability and viscosity of citrus peel pectins, while the rhamnose content, rhamnogalacturonan I region and lower molecular weight can improve citrus peel pectins antioxidant activity. Our findings suggest that CPP-6 and CPP-7 may be useful as a potential natural antioxidant in pharmaceutical and cosmetic industries. Meanwhile, CPP-3 has great application potential in high temperature food and CPP-9 can be used as a thickener or stabilizer in the food industry.


Assuntos
Antioxidantes , Citrus , Antioxidantes/química , Citrus/química , Esterificação , Pectinas/química , Espectroscopia de Infravermelho com Transformada de Fourier
12.
Front Pharmacol ; 13: 865524, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35392559

RESUMO

Metformin is a widely accepted first-line hypoglycemic agent in current clinical practice, and it has been applied to the clinic for more than 60 years. Recently, researchers have identified that metformin not only has an efficient capacity to lower glucose but also exerts anti-aging effects by regulating intracellular signaling molecules. With the accelerating aging process and mankind's desire for a long and healthy life, studies on aging have witnessed an unprecedented boom. Osteoporosis, sarcopenia, degenerative osteoarthropathy, and frailty are age-related diseases of the musculoskeletal system. The decline in motor function is a problem that many elderly people have to face, and in serious cases, they may even fail to self-care, and their quality of life will be seriously reduced. Therefore, exploring potential treatments to effectively prevent or delay the progression of aging-related diseases is essential to promote healthy aging. In this review, we first briefly describe the origin of metformin and the aging of the movement system, and next review the evidence associated with its ability to extend lifespan. Furthermore, we discuss the mechanisms related to the modulation of aging in the musculoskeletal system by metformin, mainly its contribution to bone homeostasis, muscle aging, and joint degeneration. Finally, we analyze the protective benefits of metformin in aging-related diseases of the musculoskeletal system.

13.
Open Biol ; 12(4): 220031, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35382568

RESUMO

Juvenile hormone (JH) plays a key role in preventing larval precocious metamorphosis, maintaining larval state, controlling adult sexual development and promoting insect egg maturation. Genetic studies have shown that POU factor ventral veins lacking regulates JH synthesis to control the timing of insect metamorphosis. However, how POU factor regulates JH synthesis is largely unknown. Here, we found POU-M2 was highly expressed in corpora allata (CA) and specifically localized in the nucleus of CA. The overexpression of POU-M2 promoted the expression of JH synthase genes and kr-h1 and enhanced the activity of JH synthase genes promoter. Further, POU-M2 promoted the transcription of JH acid O-methyltransferase (JHAMT) by directly binding to the key cis-regulatory elements -207, -249 and -453 within the proximal regions of JHAMT promoter. Both the POU domain and homeodomain were vital for the activation of POU-M2 on JHAMT transcription. Our study reveals the mechanism by which POU-M2 regulates JHAMT transcription.


Assuntos
Bombyx , Animais , Bombyx/genética , Bombyx/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Insetos/metabolismo , Hormônios Juvenis/metabolismo , Larva/genética , Larva/metabolismo , Metamorfose Biológica/genética
14.
Dis Markers ; 2022: 1291996, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35242240

RESUMO

OBJECTIVE: To investigate the effect and safety of 3D printing technology in proximal femoral osteotomy in children with developmental dysplasia of the hip. METHODS: 40 cases of children with developmental dysplasia of the hip treated by pelvic osteotomy combined with proximal femoral osteotomy at Ningbo No. 6 Hospital from January 2017 to December 2019 were retrieved and retrospectively analyzed. Among them, 20 cases received preoperative measurement and design assisted by 3D printing technology (the 3D printing group), and 20 cases received conventional preoperative measurement and design (the conventional group). RESULTS: All patients were followed up for an average of 25 (12~36) months. During the follow-up, there were no complications such as infection, fracture of internal fixation, or malunion of osteotomy. Compared with the conventional group, the 3D printing group had a shorter operation time, less intraoperative blood loss, and fewer intraoperative X-ray fluoroscopies (all p < 0.05). In the last follow-up, the clinical efficacy was evaluated by the McKay standard: in the 3D printing group, 14 cases were excellent, 5 cases were good, and 1 case was fair. In the conventional group, 10 cases were excellent, 9 cases were good, and 1 case was fair (Z = -0.382, p > 0.05). CONCLUSION: Preoperative 3D printing of bilateral femur and other large physical models is accurate, which is ideal for the development of individual preoperative planning. Proximal femoral osteotomy using preoperative measurements and simulated surgical data improves the safety of the operation.


Assuntos
Displasia do Desenvolvimento do Quadril/reabilitação , Fêmur/anormalidades , Osteotomia/reabilitação , Impressão Tridimensional/instrumentação , Criança , China , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
15.
Contracept X ; 4: 100072, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35243326

RESUMO

Developing new long-acting products of well-characterized contraceptive drugs is one way to address some of the reasons for unmet need for modern methods of family planning among women in low- and middle-income countries. Development and approval of such products traditionally follow a conventional paradigm that includes large Phase 3 clinical trials to evaluate efficacy (pregnancy prevention) and safety of the investigational product. Exposure-bracketing is a concept that applies known pharmacokinetics and pharmacodynamics of a drug substance to inform its safe and efficacious use in humans. Several therapeutic areas have applied this concept by leveraging established drug concentration-response relationships for approved products to expedite development and shorten the timeline for the approval of an investigational product containing the same drug substance. Based on discussions at a workshop hosted by the Bill & Melinda Gates Foundation in December 2020, it appears feasible to apply exposure-bracketing to develop novel contraceptive products using well-characterized drugs.

16.
Emerg Microbes Infect ; 11(1): 873-884, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35249454

RESUMO

Yellow fever virus (YFV) infection is a major public concern that threatens a large population in South America and Africa. No specific anti-YFV drugs are available till now. Here, we report that rifapentine is a potent YFV inhibitor in various cell lines by high-throughput drugs screening, acting at both cell entry and replication steps. Kinetic test and binding assay suggest that rifapentine interferes the viral attachment to the target cells. The application of YFV replicon and surface plasmon resonance assay indicates that rifapentine suppresses viral replication by binding to the RNA-dependent RNA polymerase (RdRp) domain of viral nonstructural protein NS5. Further molecular docking suggests that it might interact with the active centre of RdRp. Rifapentine significantly improves the survival rate, alleviates clinical signs, and reduces virus load and injury in targeted organs both in YFV-infected type I interferon receptor knockout A129-/- and wild-type C57 mice. The antiviral effect in vivo is robust during both prophylactic intervention and therapeutic treatment, and the activity is superior to sofosbuvir, a previously reported YFV inhibitor in mice. Our data show that rifapentine may serve as an effective anti-YFV agent, providing promising prospects in the development of YFV pharmacotherapy.


Assuntos
Febre Amarela , Vírus da Febre Amarela , Animais , Camundongos , Simulação de Acoplamento Molecular , Rifampina/análogos & derivados , Proteínas não Estruturais Virais/metabolismo , Replicação Viral , Febre Amarela/tratamento farmacológico , Vírus da Febre Amarela/genética
17.
Am J Chin Med ; 50(3): 639-652, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35282807

RESUMO

Autoimmune diseases (AIDs) are conditions arising from abnormal immune reactions to autoantigens, which can be defined as the loss of immune tolerance to autoantigens, causing the production of autoantibodies and subsequent inflammation and tissue injury. The etiology of AIDs remains elusive, which may involve both genetic and environmental factors, such as diet, drugs, and infections. Despite rapid progress in the treatment of autoimmune diseases over the past few decades, there is still no approach that can cure AIDs. As an alternative approach, traditional Chinese medicine (TCM) such as acupuncture has been used in an attempt to treat AIDs including multiple sclerosis (MS), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD), and the results have proven to be quite promising, despite the fact that its mechanism is still not fully understood. In this review, the present knowledge regarding mechanisms of acupuncture in the treatment of AIDs has been summarized, and deeper insights will be provided in order to better understand how acupuncture may regulate immune responses during AIDs.


Assuntos
Síndrome de Imunodeficiência Adquirida , Terapia por Acupuntura , Artrite Reumatoide , Doenças Autoimunes , Síndrome de Imunodeficiência Adquirida/complicações , Terapia por Acupuntura/métodos , Artrite Reumatoide/terapia , Autoantígenos , Doenças Autoimunes/terapia , Humanos
18.
Cancer Lett ; 534: 215618, 2022 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-35259457

RESUMO

Basal-like breast cancer (BLBC) is the most aggressive subtype of breast cancer with a poor prognosis. Long noncoding RNAs (lncRNAs) play critical roles in human cancers. Krüppel-like Factor 5 (KLF5) is a key oncogenic transcription factor in BLBC. However, the underlying mechanism of mutual regulation between KLF5 and lncRNA remains largely unknown. Here, we demonstrate that lncRNA KPRT4 promotes BLBC cell proliferation in vitro and in vivo. Mechanistically, KLF5 directly binds to the promoter of KPRT4 to promote KPRT4 transcription. Reciprocally, KPRT4 recruits the YB-1 transcription factor to the KLF5 promoter by interacting with YB-1 at its 5' domain and forming an RNA-DNA-DNA triplex structure at its 3' domain, resulting in enhanced transcription of KLF5 and ultimately establishing a feedforward circuit to promote cell proliferation. Moreover, the antisense oligonucleotide (ASO)-based therapy targeting KPRT4 substantially attenuated tumor growth in vivo. Clinically, the expression levels of YB-1, KLF5 and KPRT4 are positively correlated in clinical breast specimens. Together, our data suggest that KPRT4 is a major molecule for BLBC progression and that the feedforward circuit between KLF5 and KPRT4 may represent a potential therapeutic target in BLBC.


Assuntos
Neoplasias da Mama , Fatores de Transcrição Kruppel-Like , RNA Longo não Codificante , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , RNA Longo não Codificante/genética , Fatores de Transcrição/genética
19.
Acta Biomater ; 144: 81-95, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35288310

RESUMO

Ulcerative colitis (UC) is one type of inflammatory bowel disease (IBD) and lactoferrin (LF) is a promising protein drug to treat UC. However, targeted LF delivery to optimize bioavailability, targeting and effectiveness remains a challenge. Here, we report an effective strategy to fabricate silk sericin nanospheres systems for the delivery of recombinant human lactoferrin (SS-NS-rhLF). The system is based on the use of optimized transgenic silkworms to generate genetically engineered silk fibers (rhLF-silks). The rhLF silks were used for fabricating SS-NS-rhLF by ethanol precipitation. The SS-NS-rhLF were stable with a spherical morphology with an average diameter of 123 nm. The negatively charged sericins in a pH ≥ 5.5 environment achieved specific targeting of the SS-NS-rhLF to positively charged colonic sites. The SS-NS-rhLF achieved efficient uptake by cells in the inflamed colon of mice when compared to free lactoferrin in solution (SOL-rhLF). Furthermore, oral administration of the SS-NS-rhLF with low dose of rhLF significantly relived symptoms of UC in mice and achieved comparable therapeutic effect to the high dose of SOL-rhLF by supporting the reformation of cell structure and length of colon tissue, reducing the release of inflammatory factors, inhibiting the activation of the NF-κB inflammatory pathway, and maintaining a stable intestinal microbial population in mice. These results showed that the SS-NS-rhLF is a promising system for colitis treatment. STATEMENT OF SIGNIFICANCE: Targeting and effective delivery of multiple biological functional protein human lactoferrin (rhLF) is a promising strategy to treat ulcerative colitis in the clinic. Here, rhLF-transgenic silk cocoons were used to fabricate a rhLF-sericin nanosphere delivery system (SS-NS-rhLF). The fabricated SS-NS-rhLF showed identical spherical morphology, stable structure, sustainable rhLF release, efficient cell uptake and negative charge in an environment of pH above 5.5, thus realized the specific targeting to the positively charged colonic sites to treat UC mice through oral administration. The therapeutic effect of SS-NS-rhLF with a low rhLF dose in the UC mice was comparable to the high dose of free rhLF treatment in solution form, suggesting that the SS-NS-rhLF is a promising system for colitis treatment.


Assuntos
Colite Ulcerativa , Nanosferas , Sericinas , Animais , Animais Geneticamente Modificados , Colite Ulcerativa/tratamento farmacológico , Concentração de Íons de Hidrogênio , Lactoferrina/metabolismo , Lactoferrina/farmacologia , Camundongos , Nanosferas/uso terapêutico , Sericinas/química , Sericinas/farmacologia , Seda
20.
Int Ophthalmol ; 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35353294

RESUMO

PURPOSE: The proliferation and angiogenesis of human retinal endothelial cells (HRECs) are critical for the pathophysiology of diabetic retinopathy (DR). C-terminal binding protein 2 (CtBP2) has multiple biologic functions, but its effect on HRECs under high-glucose (HG) conditions is unclear. METHODS: The cell viability, angiogenesis, cellular adhesion and CtBP2 expression levels of HRECs were measured following treatment with different concentrations of glucose. Small interfering CtBP2-targeting RNA, wide-type and function mutant plasmid of CtBP2 were constructed and then were transfected into HRECs to evaluate the effects of CtBP2 on cell functions of HRECs. RESULTS: The expression of CtBP2 in HRECs was increased after HG treatment. HG treatment significantly increased cell proliferation, angiogenesis, and decreased relative gene expressions in gap junctions, tight junctions and adherens junctions. After CtBP2 was inhibited via siRNA, the changes induced by HG were partially restored. Conversely, only wild-type CtBP2 could increase cell proliferation and angiogenesis under HG condition. Mechanistically, we also found that CtBP2 exerted its functions to effect HG-induced changes via Akt signaling pathway. CONCLUSION: This study implicates that CtBP2 promotes HG-induced cell proliferation, angiogenesis and cellular adhesion, and CtBP2 might be a potential target in the prevention of DR.

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