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1.
Transl Oncol ; 14(7): 101107, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33946033

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, partly due to the dense desmoplasia and a lack of suitable model systems to study. In the present work, we developed a 3D heterospecies spheroid model to study the microenvironmental interactions between tumor cells and stellate cells which can also be employed to test therapeutic regimens. We set up monospheroids and heterospheroids made up from murine pancreatic stellate cells (mPSCs) and human PDAC cells (Panc1), which allowed for direct isolation of mRNA from a mixed cell population followed by an in silico separation of the RNA-seq reads. Global transcript level changes for cells in heterospheroids versus monospheroids were calculated, followed by gene set enrichment analysis and molecular subtype analysis. We observed an apparent shift of Panc1 from the classical to the squamous/basal-like phenotype upon co-culture with mPSCs. Moreover, mPSCs acquired a different cancer-associated fibroblast-related phenotype upon co-culture with Panc1. We analyzed the tumor cell-specific chemosensitivities towards gemcitabine, paclitaxel and SN38 and compared these to published pharmacotranscriptomic signatures. In conclusion, our heterospecies spheroid model reflected key aspects of PDAC and facilitated the study of intercellular interactions between tumor and stroma while additionally proving to be a good model for studying therapeutic responses.

2.
Endocrinology ; 2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-33963396

RESUMO

OBJECTIVE: Healthy hyperplasic (many but smaller fat cells) white adipose tissue (WAT) expansion is mediated by recruitment, proliferation and/or differentiation of new fat cells. This process (adipogenesis) is controlled by transcriptional programs mostly identified in rodents. A systemic investigation of adipogenic human transcription factors (TFs) that are relevant for metabolic conditions has not been revealed previously. METHODS: TFs regulated in WAT by obesity, adipose morphology, cancer cachexia and insulin resistance were selected from microarrays. Their role in differentiation of human adipose tissue-derived stem cells (hASC) was investigated by RNA interference (RNAi) screen. Lipid accumulation, cell number and lipolysis were measured for all screened factors (148 TFs). RNA (RNAseq), protein (western blot) expression, insulin and catecholamine responsiveness were examined in hASC following siRNA treatment of selected target TFs. RESULTS: Analysis of TFs regulated by metabolic conditions in human WAT revealed that many of them belong to adipogenesis-regulating pathways. The RNAi screen identified 39 genes that affected fat cell differentiation in vitro, where 11 genes were novel. Of the latter JARID2 stood out as being necessary for formation of healthy fat cell metabolic phenotype by regulating expression of multiple fat-cell phenotype-specific genes. CONCLUSIONS: This comprehensive RNAi screening in hASC suggests that a large proportion of WAT TFs that are impacted by metabolic conditions might be important for hyperplastic adipose tissue expansion. The screen also identified JARID2 as a novel TF essential for the development of functional adipocytes.

3.
AAPS PharmSciTech ; 22(4): 139, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33880664

RESUMO

Chemical enhancers (CEs) decreased the barrier of the stratum corneum (SC) to enhance drug permeation. This was a "dynamic" behavior, which involved three processes including passing in, acting on, and passing out of the SC. However, compared with mature "static" researches about acting on the SC, the other two processes were poorly understood. This work aimed to probe the dynamic behavior of CEs and modulate it for satisfactory effectiveness. The investigating method of CEs' dynamic behavior was established to obtain the rate of CEs passing in and out of the SC. An analysis attribution was conducted to obtain the possible reasons for the quite different dynamic behavior of CEs based on log P, solubility parameter, and minimum binging energy. It demonstrated the rate of CEs passing in and out of the SC was dependent on CE affinity with the SC and the interaction between CEs and the SC, respectively. The relevance between CEs' dynamic behavior and the extent of decreasing SC barrier was confirmed by transepidermal water loss (TEWL). The higher rate of CE passing in the SC and a lower rate of passing out of the SC may contribute to an increased concentration of CEs in the SC, leading to a stronger ability to decrease the SC barrier. More importantly, two biodegradable CEs (Leu-Dod and Ser-Dod) of dodecanol were synthesized and achieved a modulation of its dynamic behavior to obtain more satisfactory effectiveness of enhancing drug permeation. This work was meaningful for the guidance of rationally promoting CEs' effectiveness from a dynamic perspective, which was an unprecedented attempt in this field.

4.
Pol J Microbiol ; 70(1): 33-43, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33815525

RESUMO

Short-term or acute temperature stress affect the immune responses and alters the gut microbiota of broilers, but the influences of long-term temperature stress on stress biomarkers and the intestinal microbiota remains largely unknown. Therefore, we examined the effect of three long-term ambient temperatures (high (HC), medium (MC), and low (LC) temperature groups) on the gene expression of broilers' heat shock proteins (Hsps) and inflammation - related genes, as well as the caecal microbial composition. The results revealed that Hsp70 and Hsp90 levels in HC group significantly increased, and levels of Hsp70, Hsp90, IL-6, TNF-α, and NFKB1 in LC group were significantly higher than in MC group (p < 0.05). In comparison with the MC group, the proportion of Firmicutes increased in HC and LC groups, while that of Bacteroidetes decreased in LC group at phylum level (p < 0.05). At genus level, the proportion of Escherichia/Shigella, Phascolarctobacterium, Parabacteroides,and Enterococcus increased in HC group; the fraction of Faecalibacterium was higher in LC group; and the percentage of Barnesiella and Alistipes decreased in both HC and LC groups (p < 0.05). Functional analysis based on communities' phylogenetic investigation revealed that the pathways involved in environmental information processing and metabolism were enriched in the HC group. Those involved in cellular processes and signaling, metabolism, and gene regulation were enriched in LC group. Hence, we conclude that the long-term temperature stress can greatly alter the intestinal microbial communities in broilers and may further affect the host's immunity and health.

5.
Biomed Pharmacother ; 139: 111625, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33895524

RESUMO

OBJECTIVE: The current study was to evaluate the association of Etoricoxib treatment and incident hypoxia among type-B aortic dissection (AD) patients undergoing endovascular aortic repair (EVAR). METHODS: Patients undergoing EVAR were retrospectively recruited. Based on Etoricoxib use, patients were divided into the non-treated and Etoricoxib-treated groups. Baseline characteristics including demographics, laboratory parameters, characteristics of aortic computer tomography and echocardiography, medications used, and procedural characteristics were collected from the electronic health record. RESULTS: Compared to non-treated group (n = 36), prevalence of obesity and fever at baseline was higher in Etoricoxib-treated group (n = 24; P < 0.05). Mean number of neutrophils, and mean serum CRP and D-dimer levels were higher in Etoricoxib-treated group (P < 0.05). The overall incidence of hypoxia was lower in Etoricoxib-treated group (44.4% vs 33.4%, P < 0.05). Increase in neutrophils count, serum CRP and D-dimer levels was associated with incident hypoxia, with an odds ratio (OR) of 1.36 (95% confidence interval [CI] 1.07-1.65), 1.44 (95% CI 1.12-1.78) and 1.25 (95% CI 1.01-1.47) respectively. In unadjusted model, Etoricoxib use was associated with a 44% lower odds of incident hypoxia. After adjustment for inflammatory markers, the association between Etoricoxib and incident hypoxia was non-significant, with OR of 0.95% and 95% CI of 0.78-1.06. CONCLUSION: Compared to patients who did not receive Etoricoxib during hospitalization, those treated with Etoricoxib had lower incidence of hypoxia, which might be attributed to its anti-inflammatory effects.

6.
Exp Cell Res ; 402(2): 112576, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33798592

RESUMO

The brain vasculature has several specific features, one of them being the blood-brain barrier (BBB), which supports and protects the brain by allowing for the passage of oxygen and nutrients, while at the same time preventing passage of pathogens and toxins. The BBB also prevents efficient delivery of drugs to the brain, e.g. for treatment of brain tumors. In the murine brain, perivascular fibroblasts were recently identified as a novel potential constituent of the BBB. Here we present the existence of human cells that could be the equivalent to the murine brain perivascular fibroblasts. Using RNA sequencing, we show a similar transcriptomic profile of cultured human brain cells and murine perivascular fibroblasts. These data open up a window for new hypotheses on cell types involved in human CNS diseases.

7.
Mol Pharm ; 18(5): 2039-2052, 2021 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-33769816

RESUMO

Up to now, insufficient drug accumulation in tumor remains a major challenge for nanochemotherapy. However, the spherical nanocarriers with large diameter, which are beneficial for blood circulation and tumor extravasation, cannot travel deep in a tumor. Additionally, high tumor interstitial fluid pressure (IFP) in the tumor microenvironment may promote the efflux of the penetrable nanodrugs. Therefore, the size and shape of nanocarriers as well as the tumoral IFP can be regulated synchronously for improved tumor penetration and combined chemotherapy. Herein, a novel dual-functional polymer-polypeptide (Biotin-PEG2000-GKGPRQITITK) for both verified tumor targeting and responsiveness was synthesized to construct the "peel" of nanopomegranate-like nanovectors (DI-MPL), in which docetaxel-loaded micelles was encapsulated as "seeds". Interestingly, DI-MPL was endowed multi-abilities of tunable size/shape switch and controlled release of IFP alleviator imatinib (IM), which were developed with one and the same strategy-alteration of membrane fluidity under the cleavage of polymer-polypeptide and PEGylation. As a result, the peel of DI-MPL could turn into small pieces with the seed scattered out in response to matrix metalloproteinase-9 (MMP-9), making nanopomegranate (180 nm) switch into spheres/disks (40 nm), during which IM is released to reduce IFP synchronously. With prominent tumor penetration ability in both multicellular tumor spheroids (MCTS) and tumor tissue, DI-MPL exhibited optimal inhibition of MCTS growth and the enhanced chemotherapy in comparison to other preparations. Meanwhile, the improved penetrability of DI-MPL in tumor tissue was found to be related to the reduced IFP, which is achieved via inhibiting expression of phosphorylated platelet-derived growth factor receptor-ß (p-PDGFR-ß) by IM. Altogether, the bilateral adjusting strategies from nanocarrier size/shape and tumoral IFP with a single enzyme-responsive material could provide a potential combined chemotherapy to improve tumor penetration.

8.
Org Biomol Chem ; 19(12): 2767-2772, 2021 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-33751014

RESUMO

Lycorine-type alkaloids are privileged structures in drug development due to their attractive biological activities. In this paper, the carbonyl on the C ring was proved to have played a critical role in stereoselectivity during the synthesis process, and the galanthan skeleton with a cis-B/C ring is more thermodynamically stable in its presence. Furthermore, the total synthesis of (±)-ß-lycorane was successfully completed by employing the Michael addition reaction to construct the galanthan skeleton with a trans-B/C ring. This system might be applied to other structural types with similar stereochemistry setting.

9.
Vet Microbiol ; 255: 109016, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33677370

RESUMO

Porcine Reproductive and Respiratory Syndrome (PRRS) is a devastating disease among the most notorious threats to the swine industry worldwide and is characterized by respiratory distress and reproductive failure. Highly evolving porcine reproductive and respiratory syndrome virus (PRRSV) strains with complicated genetic diversity make the current vaccination strategy far from cost-effective and thus urge identification of potent lead candidates to provide prevention and treatment approaches. From an in vitro small molecule screening with the TargetMol Natural Compound Library comprising 623 small molecules, cytopathic effect (CPE) observations and RT-qPCR analysis of viral ORF7 gene expression identified cepharanthine (CEP) to be one of the most protent inhibitors of PRRSV infection in Marc-145 cells. When compared with tilmicosin, which is one of the most commonly used antibiotics in swine industry to inhibit infections, CEP more prominently inhibited PRRSV infection represented by both RNA and protein levels, further reduced the TCID50 by 5.6 times, and thus more remarkably protected Marc-145 cells against PRRSV infection. Mechanistically, western blot analyses of the Marc-145 cells and the porcine alveolar macrophages (PAMs) with or without CEP treatment and PRRSV infection at various time points revealed that CEP can inhibit the expression of integrins ß1 and ß3, integrin-linked kinase (ILK), RACK1 and PKCα, leading to NF-κB suppression and consequent alleviation of PRRSV infection. Collectively, our small molecule screening identified cepharanthine as an inhibitor of PRRSV infection in vitro by suppressing Integrins/ILK/RACK1/PKCα/NF-κB signalling axis, which may enlighten the deeper understanding of the molecular pathogenesis of PRRSV infection and more importantly, suggested CEP as a potential promising drug for PRRS control in veterinary clinics.

10.
Nat Commun ; 12(1): 1570, 2021 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-33692357

RESUMO

The ULK complex initiates the autophagosome formation, and has recently been implicated in selective autophagy by interacting with autophagy receptors through its FIP200 subunit. However, the structural mechanism underlying the interactions of autophagy receptors with FIP200 and the relevant regulatory mechanism remain elusive. Here, we discover that the interactions of FIP200 Claw domain with autophagy receptors CCPG1 and Optineurin can be regulated by the phosphorylation in their respective FIP200-binding regions. We determine the crystal structures of FIP200 Claw in complex with the phosphorylated CCPG1 and Optineurin, and elucidate the detailed molecular mechanism governing the interactions of FIP200 Claw with CCPG1 and Optineurin as well as their potential regulations by kinase-mediated phosphorylation. In addition, we define the consensus FIP200 Claw-binding motif, and find other autophagy receptors that contain this motif within their conventional LC3-interacting regions. In all, our findings uncover a general and phosphoregulatable binding mode shared by many autophagy receptors to interact with FIP200 Claw for autophagosome biogenesis, and are valuable for further understanding the molecular mechanism of selective autophagy.


Assuntos
Proteínas Relacionadas à Autofagia/química , Proteínas Relacionadas à Autofagia/metabolismo , Autofagia/fisiologia , Motivos de Aminoácidos , Animais , Cromatografia em Gel , Cristalografia por Raios X , Espectroscopia de Ressonância Magnética , Fosforilação , Ligação Proteica , Células Sf9
11.
Neurosci Res ; 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33744332

RESUMO

Neonatal hypoxic-ischemia encephalopathy (HIE) refers to hypoxic-ischemic brain damage caused by perinatal asphyxia. Increasing evidence has revealed the crucial roles of microRNAs (miRNAs) in neonatal HIE. In the current research, we aimed to explore the biological role of miR-363-3p in neonatal HIE. For this purpose, we established in vitro models of PC-12 and SH-SY5Y cells subjected to oxygen-glucose deprivation and reperfusion (OGD/R) and an in vivo rat model subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) treatment. First, using H&E staining, TTC staining, and western blot analysis, we observed that DUSP5 knockdown suppressed HIE in vivo. Then, by performing flow cytometric analysis, western blotting, RT-qPCR, and MTT assays, we observed that DUSP5 silencing suppressed OGD/R-induced cell injury in vitro. Subsequently, we explored the potential regulatory mechanism of DUSP5 in OGD/R-treated cells with luciferase reporter assays and RT-qPCR analysis. The results demonstrated that DUSP5 was targeted by miR-363-3p. Next, functional assays, including flow cytometric analysis, MTT assays, western blotting and RT-qPCR, were conducted to explore the biological functions of miR-363-3p in SH-SY5Y and PC-12 cells. Our data showed that miR-363-3p overexpression suppressed OGD/R-induced cell injury. Finally, the results from rescue experiments showed that enhanced DUSP5 expression counteracted the effect of miR-363-3p overexpression. In conclusion, our data suggested that miR-363-3p attenuates neonatal HIE by targeting DUSP5.

12.
BMC Biol ; 19(1): 57, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33761951

RESUMO

BACKGROUND: Mitochondrial dysfunction is a common feature of aging, neurodegeneration, and metabolic diseases. Hence, mitotherapeutics may be valuable disease modifiers for a large number of conditions. In this study, we have set up a large-scale screening platform for mitochondrial-based modulators with promising therapeutic potential. RESULTS: Using differentiated human neuroblastoma cells, we screened 1200 FDA-approved compounds and identified 61 molecules that significantly increased cellular ATP without any cytotoxic effect. Following dose response curve-dependent selection, we identified the flavonoid luteolin as a primary hit. Further validation in neuronal models indicated that luteolin increased mitochondrial respiration in primary neurons, despite not affecting mitochondrial mass, structure, or mitochondria-derived reactive oxygen species. However, we found that luteolin increased contacts between mitochondria and endoplasmic reticulum (ER), contributing to increased mitochondrial calcium (Ca2+) and Ca2+-dependent pyruvate dehydrogenase activity. This signaling pathway likely contributed to the observed effect of luteolin on enhanced mitochondrial complexes I and II activities. Importantly, we observed that increased mitochondrial functions were dependent on the activity of ER Ca2+-releasing channels inositol 1,4,5-trisphosphate receptors (IP3Rs) both in neurons and in isolated synaptosomes. Additionally, luteolin treatment improved mitochondrial and locomotory activities in primary neurons and Caenorhabditis elegans expressing an expanded polyglutamine tract of the huntingtin protein. CONCLUSION: We provide a new screening platform for drug discovery validated in vitro and ex vivo. In addition, we describe a novel mechanism through which luteolin modulates mitochondrial activity in neuronal models with potential therapeutic validity for treatment of a variety of human diseases.

13.
BMC Complement Med Ther ; 21(1): 101, 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33757500

RESUMO

BACKGROUND: Chinese eye acupuncture, focuses on treating different diseases by applying needle stimulation around the orbit of the eye. Since 1970, it has been used in China for the management of pain-related disorders. This scoping review systematically collected clinical studies on the use of eye acupuncture to treat pain conditions and identify any adverse events. METHODS: Six databases including PubMed, the Cochrane Library, CNKI, VIP, Wan Fang Data and SinoMed were searched from 1970 to March 2019. Randomized controlled trials (RCTs), clinical controlled trials (CCTs) and case series on eye-acupuncture for pain conditions meeting the inclusion criteria were identified. Data were extracted on patients, interventions, details of eye acupuncture, control treatments and outcomes. RESULTS: Searches identified 81 clinical studies and a trend demonstrating an increasing number of published studies. All studies were conducted in China and published in Chinese. These included, 45 (55.6%) RCTs, 5 (6.2%) CCTs, and 31 (38.3%) case series, treating 7113 patients with 44 different pain-related diseases or symptoms. The most frequently reported conditions were headache (18, 16.2%), acute lumbar pain (7, 6.3%) and lumbar disc herniation (7, 6.3%). Treatment using small needles (φ0.25 × 13 mm), retained ≤30 min, needling the horizontal outer orbital edge and the avoidance of manipulation during treatment were the most frequent descriptions of the interventions used. Eye acupuncture was used alone in about half of the studies and of the remaining studies it was combined with other treatment. All studies suggested some beneficial effects including: pain relief, improved quality of life and mental health, and 18 (22.2%) adverse events. CONCLUSION: Eye acupuncture, predominantly studied in China, may be a promising intervention for managing diverse pain conditions. However, given the variety of study designs and reported treatment outcomes, conclusions about the evidence for eye acupuncture for specific conditions are not possible at this stage.

14.
EPMA J ; 12(1): 67-89, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33786091

RESUMO

Relevance: Human growth hormone (hGH) is synthesized, stored, and secreted by somatotroph cells in the pituitary gland, and promotes human growth and metabolism. Compared to a normal pituitary, a GH-secreting pituitary adenoma can secrete excessive GH to cause pathological changes in body tissues. GH proteoform changes would be associated with GH-related disease pathogenesis. Purpose: This study aimed to elucidate changes in GH proteoforms between GH-secreting pituitary adenomas and control pituitaries for the predictive diagnostics, targeted prevention, and personalization of medical services. Methods: The isoelectric point (pI) and relative molecular mass (Mr) are two basic features of a proteoform that can be used to effectively array and detect proteoforms with two-dimensional gel electrophoresis (2DGE) and 2DGE-based western blot. GH proteoforms were characterized with liquid chromatography (LC) and mass spectrometry (MS). Phosphoproteomics, ubiquitinomics, acetylomics, and bioinformatics were used to analyze post-translational modifications (PTMs) of GH proteoforms in GH-secreting pituitary adenoma tissues and control pituitaries. Results: Sixty-six 2D gel spots were found to contain hGH, including 46 spots (46 GH proteoforms) in GH-secreting pituitary adenomas and 35 spots (35 GH proteoforms) in control pituitaries. Further, 35 GH proteoforms in control pituitary tissues were matched with 35 of 46 GH proteoforms in GH-secreting pituitary adenoma tissues; and 11 GH proteoforms were presented in only GH-secreting pituitary adenoma tissues but not in control pituitary tissues. The matched 35 GH proteoforms showed quantitative changes in GH-secreting pituitary adenomas compared to the controls. The quantitative levels of those 46 GH proteoforms in GH-secreting pituitary adenomas were significantly different from those 35 GH proteoforms in control pituitaries. Meanwhile, different types of PTMs were identified among those GH proteoforms. Phosphoproteomics identified phosphorylation at residues Ser77, Ser132, Ser134, Thr174, and Ser176 in hGH. Ubiquitinomics identified ubiquitination at residue Lys96 in hGH. Acetylomics identified acetylation at reside Lys171 in hGH. Deamination was identified at residue Asn178 in hGH. Conclusion: These findings provide the first hGH proteoform pattern changes in GH-secreting pituitary adenoma tissues compared to control pituitary tissues, and the status of partial PTMs in hGH proteoforms. Those data provide in-depth insights into biological roles of hGH in GH-related diseases, and identify hGH proteoform pattern biomarkers for treatment of a GH-secreting pituitary adenoma in the context of 3P medicine -predictive diagnostics, targeted prevention, and personalization of medical services. Supplementary information: The online version contains supplementary material available at 10.1007/s13167-021-00232-7.

15.
ACS Appl Mater Interfaces ; 13(6): 7115-7126, 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33543935

RESUMO

The success of cancer therapy is always accompanied by severe side effects due to the high amount of toxic antitumor drugs that off-target normal organs/tissues. Herein, we report the development of a trifunctional layered double hydroxide (LDH) nanosystem for combined photochemotherapy of skin cancer at very low therapeutic doses. This nanosystem (ICG/Cu-LDH@BSA-DOX) is composed of acid-responsive bovine serum albumin-doxorubicin prodrug (BSA-DOX) and indocyanine green (ICG)-intercalated Cu-doped LDH nanoparticle. ICG/Cu-LDH@BSA-DOX is able to release DOX in an acid-triggered manner, efficiently and simultaneously generates heating and reactive oxygen species (ROS) upon 808 nm laser irradiation, and synergistically induces apoptosis of skin cancer cells. In vivo therapeutic evaluations demonstrate that ICG/Cu-LDH@BSA-DOX nearly eradicated the tumor tissues upon one-course treatment using very low doses of therapeutic agents (0.175 mg/kg DOX, 0.5 mg/kg Cu, and 0.25 mg/kg ICG) upon very mild 808 nm laser irradiation (0.3 W/cm2 for 2 min). This work thus provides a novel strategy to design anticancer nanomedicine for efficient combination cancer treatment with minimal side effects in clinical applications.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Hidróxidos/farmacologia , Melanoma/terapia , Fotoquimioterapia , Neoplasias Cutâneas/terapia , Animais , Antibióticos Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cobre/química , Cobre/farmacologia , Relação Dose-Resposta a Droga , Doxorrubicina/química , Ensaios de Seleção de Medicamentos Antitumorais , Hidróxidos/química , Verde de Indocianina/química , Verde de Indocianina/farmacologia , Lasers , Melanoma/metabolismo , Melanoma/patologia , Camundongos , Estrutura Molecular , Tamanho da Partícula , Espécies Reativas de Oxigênio/metabolismo , Soroalbumina Bovina/química , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Propriedades de Superfície
16.
Plant J ; 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33570751

RESUMO

Phosphorus is a crucial macronutrient for plant growth and development. The mechanisms for maintaining inorganic phosphate (Pi) homeostasis in rice are not well understood. The ubiquitin-conjugating enzyme variant protein OsUEV1B was previously found to interact with OsUbc13 and mediate lysine63-linked polyubiquitination. In the present study, we found OsUEV1B was specifically inhibited by Pi deficiency, and was localized in the nucleus and cytoplasm. Both osuev1b mutant and OsUEV1B-RNA interference (RNAi) lines displayed serious symptoms of toxicity due to Pi overaccumulation. Some Pi starvation inducible and phosphate transporter genes were upregulated in osuev1b mutant and OsUEV1B-RNAi plants in association with enhanced Pi acquisition, and representative Pi starvation responses, including stimulation of acid phosphatase activity and root hair growth, were also activated in the presence of sufficient Pi. A yeast two-hybrid screen revealed an interaction between OsUEV1B and OsVDAC1, which was confirmed by bimolecular fluorescence complementation and firefly split-luciferase complementation assays. OsVDAC1 encoded a voltage-dependent anion channel protein localized in the mitochondria, and OsUbc13 was shown to interact with OsVDAC1 via yeast two-hybrid and bimolecular fluorescence complementation assays. Under sufficient Pi conditions, similar to osuev1b, a mutation in OsVDAC1 resulted in significantly greater Pi concentrations in the roots and second leaves, improved acid phosphatase activity, and enhanced expression of the Pi starvation inducible and phosphate transporter genes compared with wild-type DongJin, whereas overexpression of OsVDAC1 had the opposite effects. OsUEV1B or OsVDAC1 knockout reduced the mitochondrial membrane potential and adenosine triphosphate levels. Moreover, overexpression of OsVDAC1 in osuev1b partially restored its high Pi concentration to a level between those of osuev1b and DongJin. Our results indicate that OsUEV1B is required for rice phosphate homeostasis.

17.
Phytother Res ; 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33533107

RESUMO

Chinese herbal medicine (CHM) has long been used for allergic rhinitis (AR). This systematic review aimed to investigate the clinical effects and safety of oral CHM for AR by comparing it to Western medications (WM). Nineteen databases were searched up to May 27, 2020. Randomized controlled trials (RCTs) assessing the effects of CHM on the primary or secondary outcomes comparing to WM, in any age of the patients, were included. The pooled results were expressed as mean difference, standardized mean difference, or odds ratio with 95% confidence intervals. Eighteen RCTs were included and 17 of them were evaluated in the meta-analysis. CHM may improve total nasal symptom scores, individual symptom scores (rhinorrhea, nasal congestion, sneezing, and nasal itching), quality of life, and recurrence rate, compared to antihistamines (loratadine and chlorpheniramine). Only mild and transient adverse events of CHM were reported. However, there were no significant differences in some subgroup analyses in total nasal symptom scores, rhinorrhea, nasal obstruction, sneezing, nasal itching, and SF-36. Due to the small number of included studies, poor quality of trial design, and substantial heterogeneities, the potential of CHM for AR should be validated in large, multicenter, and well-designed RCTs in the future.

18.
Anal Chim Acta ; 1145: 114-123, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33453872

RESUMO

The development of reliable bioanalytical probes for sensitive and specific detection of hydrogen sulfide (H2S) plays important role for better understanding the roles of this biomolecule in living cells and organisms. Taking advantages of unique photophysical properties of ruthenium(II) (Ru(II)) complex, this work presents the development of a responsive Ru(II) complex probe, Ru-PNBD, for colorimetric and luminescent analysis of H2S in living cells and organisms. In aqueous solution, Ru-PNBD is yellow color and non-luminescent because of the photoinduced electron transfer (PET) process from Ru(II) complex luminophore to NBD moiety. The H2S-triggered specific nucleophilic substitution reaction with Ru-PNBD cleaves the NBD moiety to form pink NBD-SH and highly luminescent Ru-PH. The color of the solution thus changes from yellow to pink for colorimetric analysis and the emission intensity is about 65-fold increased for luminescent analysis. Ru-PNBD has high sensitivity and selectivity for H2S detection, low cytotoxicity and good permeability to cell membrane, which allow the application of this probe for H2S imaging in living cells, Daphnia magna, and larval zebrafish. Collectively, this work provides a useful tool for H2S analysis and expands the scope of transition metal complex probes.

19.
Artigo em Inglês | MEDLINE | ID: mdl-33486687

RESUMO

Transdermal drug delivery is limited by the stratum corneum of skin, which blocks most molecules, and thus, only few molecules with specific physicochemical properties (molecular weight < 500 Da, adequate lipophilicity, and low melting point) are able to penetrate the skin. Recently, various technologies have been developed to overcome the strong barrier properties of stratum corneum. Iontophoresis technology, which uses a small current to improve drug permeation through skin, is one of the effective ways to circumvent the stratum corneum. This approach not only provides a more efficient, noninvasive, and patient-friendly method of drug delivery but also widens the scope of drugs for transdermal delivery. In this review, the mechanisms underlying iontophoresis and affecting factors are outlined. The focus will be on the latest advancements in iontophoretic transdermal drug delivery and application of iontophoresis with other enhancing technologies. The challenges of this technology for drug administration have also been highlighted, and some iontophoretic systems approved for clinical use are described.

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