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1.
Nano Lett ; 2024 Oct 01.
Article in English | MEDLINE | ID: mdl-39352718

ABSTRACT

The design and synthesis of nanomedicines capable of regulating programmed cell death patterns to enhance antitumor efficacy remain significant challenges in cancer therapy. In this study, we developed intelligent DNA nanospheres (NS) capable of distinguishing tiny pH changes between different endosomal compartments to regulate pyroptosis or apoptosis. These NS are self-assembled from two multifunctional DNA modules, enabling tumor targeting, acid-responsive disassembly, and photodynamic therapy (PDT) activation. By modifying the embedded i-motif sequence, the NS can be activated in early endosomes (EE) or lysosomes (Ly), producing singlet oxygen (1O2) at specific locations under laser irradiation. Our results demonstrate that EE-activated PDT induces gasdermin-E-mediated pyroptosis in tumor cells, enhancing antitumor efficacy and reducing systemic toxicity compared to Ly-activated apoptosis. This study offers new insights into the design of endosome-activated nanomedicines, advancing the biomedical applications of targeted cancer therapy.

2.
Nano Lett ; 24(37): 11590-11598, 2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39225632

ABSTRACT

As a nonenzymatic DNA signal amplification technique, localized hybridization chain reaction (LHCR) was designed to improve the limitations in response speed and low sensitivity of conventional free diffusional HCR (hybridization chain reaction). However, it is still confronted with the challenges of complicated DNA scaffolds with low loading capacity and a time-consuming process of diffusion. Herein, we introduced modular assembly of a DNA minimal scaffold for coassembly of DNA hairpins for amplified fluorescence imaging of mRNA in situ. DNA hairpins were spatially bound to two Y-shaped modules to form H-shaped DNA modules, and then multiple H-shaped DNA modules can further assemble into an H-module-based hairpin scaffold (HHS). Benefiting from highly spatial localization and high loading capacity, the HHS system showed higher sensitivity and faster speed. It has also been proven to work perfectly in vitro and in vivo, which could provide a promising bioanalysis system for low abundance biomolecule detection.


Subject(s)
DNA , Nucleic Acid Hybridization , RNA, Messenger , RNA, Messenger/genetics , RNA, Messenger/analysis , DNA/chemistry , DNA/genetics , Humans , Nucleic Acid Amplification Techniques/methods , Optical Imaging/methods
3.
Nucleic Acids Res ; 50(7): e40, 2022 04 22.
Article in English | MEDLINE | ID: mdl-34935962

ABSTRACT

There is considerable interest in creating a precise and sensitive strategy for in situ visualizing and profiling intracellular miRNA. Present here is a novel photocaged amplified FRET nanoflare (PAFN), which spatiotemporal controls of mRNA-powered nanomachine for precise and sensitive miRNA imaging in live cells. The PAFN could be activated remotely by light, be triggered by specific low-abundance miRNA and fueled by high-abundance mRNA. It offers high spatiotemporal control over the initial activity of nanomachine at desirable time and site, and a 'one-to-more' ratiometric signal amplification model. The PAFN, an unprecedented design, is quiescent during the delivery process. However, upon reaching the interest tumor site, it can be selectively activated by light, and then be triggered by specific miRNA, avoiding undesirable early activation and reducing nonspecific signals, allowing precise and sensitive detection of specific miRNA in live cells. This strategy may open new avenues for creating spatiotemporally controllable and endogenous molecule-powered nanomachine, facilitating application at biological and medical imaging.


Subject(s)
Biosensing Techniques , MicroRNAs , Diagnostic Imaging , Fluorescence Resonance Energy Transfer , MicroRNAs/genetics , RNA, Messenger/genetics
4.
Small ; 19(12): e2205903, 2023 03.
Article in English | MEDLINE | ID: mdl-36638250

ABSTRACT

DNA cascaded circuits have great potential in detecting low abundance molecules in complex biological environment due to their powerful signal amplification capability and nonenzymatic feature. However, the problem of the cascaded circuits is that the design is relatively complex and the kinetics is slow. Herein, a new design paradigm called catalyst-accelerated circular cascaded circuits is proposed, where the catalyst inlet is implanted and the reaction speed can be adjusted by the catalyst concentration. This new design is very simple and only requires three hairpin probes. Meanwhile, the results of a series of studies demonstrate that the reaction speed can be accelerated and the sensitivity can be also improved. Moreover, endogenous mRNA can also be used as a catalyst to drive the circuits to amplify the detection of target miRNA in live cells and in mice. These catalyst-accelerated circular cascaded circuits can substantially expand the toolbox for intracellular low abundance molecular detection.


Subject(s)
Biosensing Techniques , MicroRNAs , Animals , Mice , DNA, Circular , DNA , MicroRNAs/genetics , RNA, Messenger , Kinetics , Biosensing Techniques/methods , Nucleic Acid Amplification Techniques/methods
5.
Nano Lett ; 22(20): 8216-8223, 2022 10 26.
Article in English | MEDLINE | ID: mdl-36194690

ABSTRACT

Visualizing intracellular microRNA (miRNA) is of great importance for revealing its roles in the development of disease. However, cell membrane barrier, complex intracellular environment and low abundance of target miRNA are three main challenges for efficient imaging of intracellular miRNA. Here, we report a size-controllable and self-assembled DNA nanosphere with ATP-fueled dissociation property for amplified miRNA imaging in live cells and mice. The DNA nanosphere was self-assembled from Y-shaped DNA (Y-DNA) monomers through predesigned base pair hybridization, and the size could be easily controlled by varying the concentration of Y-DNA. Once the nanosphere was internalized into cells, the intracellular specific target miRNA would trigger the cyclic dissociation of the DNA nanosphere driven by ATP, resulting in amplified FRET signal. The programmable DNA nanosphere has been proven to work well for detecting the expression of miRNA in cancer cells and in mice, which demonstrates its fairish cell penetration, stability and sensitivity.


Subject(s)
Biosensing Techniques , MicroRNAs , Nanospheres , Mice , Animals , DNA/genetics , Nucleic Acid Hybridization , Adenosine Triphosphate
6.
Pharmacol Res ; 166: 105459, 2021 04.
Article in English | MEDLINE | ID: mdl-33545313

ABSTRACT

Schisandrin B (Sch B) is the major active constituent of the traditional Chinese medicine Schisandra chinensis and has anti-inflammatory activity, but the target of Sch B remains unclear. T helper 17 (TH17) cells have been involved in the pathogenesis of many autoimmune and inflammatory diseases. Here, we showed that Sch B could decrease IL-17A production of CD4+ T cells by targeting STAT3 in vitro. Importantly, Sch B has therapeutic effects on DSS-induced acute and chronic colitis, CD4+CD45RBhigh T cell-induced colitis. Furthermore, we identified TH17 cells as the direct target of Sch B for mediating its anti-inflammatory activity. Sch B could serve as a lead for developing new therapeutics against TH17 cells or IL-17A cytokine-driven diseases.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Lignans/therapeutic use , Polycyclic Compounds/therapeutic use , Th17 Cells/drug effects , Animals , Anti-Inflammatory Agents/pharmacology , Cell Differentiation/drug effects , Cells, Cultured , Cyclooctanes/pharmacology , Cyclooctanes/therapeutic use , Female , Humans , Inflammatory Bowel Diseases/pathology , Lignans/pharmacology , Mice, Inbred C57BL , Polycyclic Compounds/pharmacology , Th17 Cells/pathology
7.
Angew Chem Int Ed Engl ; 59(45): 20104-20111, 2020 11 02.
Article in English | MEDLINE | ID: mdl-32725743

ABSTRACT

It is of great value to detect biological molecules in live cells. However, probes for imaging low-abundance targets in live cells are limited by the one-to-one signal-triggered model. Here, we introduce the concept of the amplified FRET nanoflare, which employs high-abundance endogenous mRNA as fuel strands to amplify the detection of low abundance intracellular miRNA. As far as we know, this is the first report of an endogenous mRNA-powered nanomachine for intracellular molecular detection. We experimentally prove the mechanism of the nanomachine and demonstrate its specificity and sensitivity. The proposed amplified FRET nanoflare can act as an excellent intracellular molecular detection strategy that is promising for biological and medical applications.


Subject(s)
Fluorescence Resonance Energy Transfer/methods , Metal Nanoparticles/chemistry , MicroRNAs/metabolism , RNA, Messenger/metabolism , Gold/chemistry , Humans , MCF-7 Cells
8.
Immunology ; 148(1): 56-69, 2016 May.
Article in English | MEDLINE | ID: mdl-26800655

ABSTRACT

Autophagy can mediate antiviral immunity. However, it remains unknown whether autophagy regulates the immune response of dendritic cells (DCs) to influenza A (H1N1) pdm09 infection. In this study, we found that infection with the H1N1 virus induced DC autophagy in an endocytosis-dependent manner. Compared with autophagy-deficient Beclin-1(+/-) mice, we found that bone-marrow-derived DCs from wild-type mice (WT BMDCs) presented a more mature phenotype on H1N1 infection. Wild-type BMDCs secreted higher levels of interleukin-6 (IL-6), tumour necrosis factor- α (TNF-α), interferon-ß (IFN-ß), IL-12p70 and IFN-γ than did Beclin-1(+/-) BMDCs. In contrast to Beclin-1(+/-) BMDCs, H1N1-infected WT BMDCs exhibited increased activation of extracellular signal-regulated kinase, Jun N-terminal kinase, p38, and nuclear factor-κB as well as IFN regulatory factor 7 nuclear translocation. Blockade of autophagosomal and lysosomal fusion by bafilomycin A1 decreased the co-localization of H1N1 viruses, autophagosomes and lysosomes as well as the secretion of IL-6, TNF-α and IFN-ß in H1N1-infected BMDCs. In contrast to Beclin-1(+/-) BMDCs, H1N1-infected WT BMDCs were more efficient in inducing allogeneic CD4(+) T-cell proliferation and driving T helper type 1, 2 and 17 cell differentiation while inhibiting CD4(+) Foxp3(+) regulatory T-cell differentiation. Moreover, WT BMDCs were more efficient at cross-presenting the ovalbumin antigen to CD8(+) T cells. We consistently found that Beclin-1(+/-) BMDCs were inferior in their inhibition of H1N1 virus replication and their induction of H1N1-specific CD4(+) and CD8(+) T-cell responses, which produced lower levels of IL-6, TNF-α and IFN-ß in vivo. Our data indicate that autophagy is important in the regulation of the DC immune response to H1N1 infection, thereby extending our understanding of host immune responses to the virus.


Subject(s)
Autophagy , Dendritic Cells/immunology , Influenza A Virus, H1N1 Subtype/immunology , Orthomyxoviridae Infections/immunology , Animals , Antigen Presentation , Apoptosis Regulatory Proteins/analysis , Beclin-1 , Cytokines/biosynthesis , Female , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Signal Transduction , Toll-Like Receptors/physiology
9.
Zhonghua Yi Xue Za Zhi ; 94(4): 301-5, 2014 Jan 28.
Article in Zh | MEDLINE | ID: mdl-24731500

ABSTRACT

OBJECTIVE: To explore the effect of Xuebijing plus methylprednisolone in a rat model of pulmonary fibrosis induced by bleomycin. METHODS: Eighty Wistar rats were randomly divided into 5 groups of control, model control, Xuebijing, methylprednisolone and combined treatment (Xuebijing plus methylprednisolone). Pulmonary fibrosis model was induced by an intra-tracheal injection of bleomycin. The treatment groups were administrated with 4.5 ml · kg(-1) · d(-1) Xuebijing and 4.5 ml · kg(-1) · d(-1) physiologic saline, 4.5 ml · kg(-1) · d(-1) methylprednisolone and 4.5 ml · kg(-1) · d(-1) physiologic saline, or 4.5 ml · kg(-1) · d(-1) methylprednisolone and 4.5 ml · kg(-1) · d(-1) Xuebijing respectively by intraperitoneal injection. And the control and model control groups received 9 ml · kg(-1) · d(-1) physiological saline. The animals were sacrificed at Days 14 and 28 respectively. The degrees of lung inflammation and pulmonary fibrosis were detected by hematoxylin & eosin and Masson staining. The serum levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were assessed by enzyme-linked immunosorbent assay (ELISA). The expression of transforming growth factor-ß1 (TGF-ß1) in lung tissue was evaluated by immunohistochemical staining. RESULTS: Compared between the combined treatment and model control groups, at Days 14 and 28, the degree of alveolitis ((1.09 ± 0.30) vs (2.03 ± 0.25) and (0.75 ± 0.27) vs (1.78 ± 0.36) ng/L) , the degree of pulmonary fibrosis ((0.91 ± 0.19 )vs (1.34 ± 0.23) and (0.75 ± 0.27) vs (1.78 ± 0.36)) . The expression of TGF-ß1 in lung tissue ((12.11 ± 3.06)% vs (17.70 ± 2.70)% & (10.96 ± 2.53)% vs (16.72 ± 2.20)%). And the serum level of TNF-α ((68.39 ± 9.28) vs (90.94 ± 11.16) ng/L & (67.14 ± 10.88) vs (81.73 ± 7.23) ng/L) all significantly decreased (all P < 0.05). At Day 14, the serum level of IL-6 in the combined treatment group significantly decreased as compared with the model control group ((199 ± 31) vs (250 ± 43)ng/L, P = 0.036). At Day 28, no statistic difference was found ( (192 ± 25) vs (227 ± 24)ng/L, P = 0.058). CONCLUSIONS: The combined treatment of methylprednisolone and Xuebijing is more effective in a rat model of pulmonary fibrosis. And its mechanism is associated with the reduced levels of IL-6 and TNF-α and TGF-ß1 expression in lung tissue.


Subject(s)
Drugs, Chinese Herbal/therapeutic use , Methylprednisolone/therapeutic use , Pulmonary Fibrosis/prevention & control , Animals , Bleomycin/adverse effects , Disease Models, Animal , Interleukin-6/metabolism , Male , Pulmonary Fibrosis/chemically induced , Rats , Rats, Wistar , Transforming Growth Factor beta1/metabolism , Tumor Necrosis Factor-alpha/metabolism
10.
Theranostics ; 14(3): 1010-1028, 2024.
Article in English | MEDLINE | ID: mdl-38250037

ABSTRACT

Background: CD93 reportedly facilitates tumor angiogenesis. However, whether CD93 regulates antitumor immunity remains undeciphered. Methods: Lung tumor tissues, malignant pleural effusions (MPEs) were obtained from lung cancer patients. Blood was obtained from healthy volunteers and lung cancer patients with anti-PD-1 therapy. Furthermore, p53fl/flLSL-KrasG12D, Ccr7-/-, Cd93-/- mice and CD11c-DTR mice were generated. Specifically, EM, NTA and western blotting were utilized to identify Tumor extracellular vesicles (TEVs). EV labeling, detection of EV uptake in vitro and in vivo, degradation of EV proteins and RNAs were performed to detect the role of TEVs in tumor progression. Pleural mesothelial cells (pMCs) were isolated to investigate related signaling pathways. Recombinant proteins and antibodies were generated to test which antibody was the most effective one to increase CCL21a in p-pMCs. RNA-Seq, MiRNA array, luciferase reporter assay, endothelial tube formation assay, protein labeling and detection, transfection of siRNAs and the miRNA mimic and inhibitor, chemotaxis assay, immunohistochemical staining, flow cytometry, Real-time PCR, and ELISA experiments were performed. Results: We show that CD93 of pMCs reduced lung tumor migration of dendritic cells by preventing pMCs from secreting CCL21, thereby suppressing systemic anti-lung tumor T-cell responses. TEV-derived miR-5110 promotes CCL21 secretion by downregulating pMC CD93, whereas C1q, increasing in tumor individuals, suppresses CD93-mediated CCL21 secretion. CD93-blocking antibodies (anti-CD93) inhibit lung tumor growth better than VEGF receptor-blocking antibodies because anti-CD93 inhibit tumor angiogenesis and promote CCL21 secretion from pMCs. Anti-CD93 also overcome lung tumor resistance to anti-PD-1 therapy. Furthermore, lung cancer patients with higher serum EV-derived miR-5193 (human miR-5110 homolog) are more sensitive to anti-PD-1 therapy, while patients with higher serum C1q are less sensitive, consistent with their regulatory functions on CD93. Conclusions: Our study identifies a crucial role of CD93 in controlling anti-lung tumor immunity and suggests a promising approach for lung tumor therapy.


Subject(s)
Lung Neoplasms , MicroRNAs , Receptors, Complement , Animals , Humans , Mice , Antibodies , Antibodies, Blocking , Complement C1q , Immunity , Lung Neoplasms/drug therapy , Lung Neoplasms/immunology , Receptors, Complement/genetics
11.
ACS Nano ; 18(40): 27597-27616, 2024 Oct 08.
Article in English | MEDLINE | ID: mdl-39342637

ABSTRACT

Unfavorable phenotypes characterized by low immunogenicity and acidity within the tumor microenvironment (TME) contribute to immunosuppression and therapeutic resistance. Herein, we rationally synthesized a multifunctional nanoregulator by encapsulating DOX and erianin into calcium carbonate (CaCO3)-based nanoparticles using a modified double emulsion method. The DOX and erianin-loaded CaCO3-based nanoparticles, termed DECaNPs, could effectively induce the calcium overload by triggering calcium influx and absorbing CaCO3 nanoparticles. Additionally, DECaNPs also neutralize the acidic TME by interacting with extracellular protons and limiting lactic acid production, a result of metabolic remodeling in cancer cells. As a result, DECaNPs elicit cellular oxidative stress damage, which mediates the activation of ferroptosis/apoptosis hybrid pathways, and profound immunogenic cell death. Treatment with DECaNPs could inhibit the growth of tumors by promoting oxidative stress, acid neutralization, metabolic remodeling, and protective antitumor immunity in vivo. In addition, DECaNPs could synergistically amplify the antitumor effects of αPD-L1 in a bilateral tumor model by eliciting systemic immune responses. In all, our work presents the preparation of CaCO3-based nanoregulators designed to reverse the unfavorable TME and enhance αPD-L1 immunotherapy through multiple mechanisms.


Subject(s)
Calcium Carbonate , Calcium , Doxorubicin , Immunotherapy , Calcium Carbonate/chemistry , Calcium Carbonate/pharmacology , Animals , Humans , Mice , Calcium/metabolism , Calcium/chemistry , Doxorubicin/pharmacology , Doxorubicin/chemistry , Liver Neoplasms/drug therapy , Liver Neoplasms/immunology , Liver Neoplasms/pathology , Liver Neoplasms/therapy , Nanoparticles/chemistry , Tumor Microenvironment/drug effects , Tumor Microenvironment/immunology , Cell Proliferation/drug effects , Oxidative Stress/drug effects , Drug Screening Assays, Antitumor , Mice, Inbred BALB C , Female , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry
12.
Article in English | MEDLINE | ID: mdl-38032026

ABSTRACT

Surface engineering is an effective strategy to improve the photoelectrochemical (PEC) catalytic activity of hematite, and the defect states with abundant coordinative unsaturation atoms can serve as anchoring sites for constructing intimate connections between semiconductors. On this basis, we anchored an ultrathin FeSe2 layer on Nb5+-doped Fe2O3 (FeSe2/Nb:Fe2O3) via interfacial Se-O chemical bonds to tune the surface potential. Density functional theory (DFT) calculations indicate that amorphous FeSe2 decoration could generate electron delocalization over the composite photoanodes so that the electron mobility was improved to a large extent. Furthermore, electrons could be transferred via the newly formed Se-O bonds at the interface and holes were collected at the surface of electrode for PEC water oxidation. The desired charge redistribution is in favor of suppressing charge recombination and extracting effective holes. Later, work function calculations and Mott-Schottky (M-S) plots demonstrate that a type-II heterojunction was formed in FeSe2/Nb:Fe2O3, which further expedited carrier separation. Except for spatial carrier modulation, the amorphous FeSe2 layer also provided abundant active sites for intermediates adsorption according to the d band center results. In consequence, the target photoanodes attained an improved photocurrent density of 2.42 mA cm-2 at 1.23 V versus the reversible hydrogen electrode (RHE), 2.5 times as that of the bare Fe2O3. This study proposed a defect-anchoring method to grow a close-connected layer via interfacial chemical bonds and revealed the spatial charge distribution effects of FeSe2 on Nb:Fe2O3, giving insights into rational designation in composite photoanodes.

13.
Respirol Case Rep ; 10(10): e01032, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36090019

ABSTRACT

Interstitial lung diseases (ILDs) are common respiratory diseases with limited treatment options and poor prognoses. Early and accurate diagnosis of ILD is challenging and requires a multidisciplinary discussion. We report a 32-year-old patient admitted to our hospital with cough and increasing dyspnea on exertion. Computerized tomography scan of his chest demonstrated diffuse interstitial abnormalities, emphysematous changes, and a pneumothorax. Whole-exome sequencing (WES) and Sanger sequencing indicated a compound mutation of heterozygosity in RTEL1 gene c.2992C > T(p.Arg998*) and c.482T > C(p.Val161Ala). In-silicon analysis revealed the pathogenic nonsense mutation c.2992C > T, which introduced a premature stop codon in exon 30 of RTEL1. The patient is still alive with progressive dyspnea to now. We reviewed the pathophysiology of ILD patients carrying RTEL1 mutations and the roles of RTEL1 mutation in guiding treatment and prognostication in ILD.

14.
Front Oncol ; 12: 1036543, 2022.
Article in English | MEDLINE | ID: mdl-36531060

ABSTRACT

Lactate and tumor cell-derived extracellular vesicles (TEVs) both contribute to tumor progression. However, it is still unclear whether lactate can accelerate tumor development by directly promoting TEV production. Here, we show that lactate decreases intracellular cAMP levels and subsequent PKA activation via GPR81, which inhibits the PKA-induced ubiquitination of HIF-1α that causes degradation. Then, the HIF-1α-mediated transcription of Rab27a is enhanced, leading to increased TEV release. In this way, lactate promotes lung metastasis by murine melanoma. In addition, we show that serum lactate levels are positively correlated with serum EV levels and Rab27a and HIF-1α protein levels in the tumor tissues of lung cancer patients. Thus, our results reveal a novel mechanism underlying lactate-mediated tumor progression induced by TEVs and provide new strategies for tumor therapy.

15.
Respirol Case Rep ; 10(11): e01054, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36258694

ABSTRACT

Acquired resistance to osimertinib is inevitable and heterogeneous despite its documented efficacy against EGFR-mutated non-small cell lung cancer (NSCLC). Subsequent therapeutic options assume the dominant form of the resistance mechanism; however, the more rare oncogenic driver, NTRK1 fusion, has also reportedly conferred osimertinib resistance. Nevertheless, clear-cut options when NSCLCs are driven by EGFR mutation and the subsequent NTRK fusion are lacking. This is a case of NSCLC wherein exon 19 deletion in EGFR (19del) and acquired LMNA-NTRK1 fusion were accompanied by the persistence of EGFR T790M. The patient underwent peritoneal metastasis after multiple targeted therapies: gefitinib, osimertinib, chemotherapy, and anlotinib plus docetaxel (in clinical trials). Osimertinib was subsequently re-administered with the NTRK fusion inhibitor entrectinib, resulting in remission of peritoneal metastases even after slow progression of pancreatic metastasis over the following 5 months. An extensive literature review to identify the efficacies of therapies for NTRK fusion as the means to acquired resistance to EGFR TKIs revealed that blocking both the EGFR mutation and the subsequent NTRK fusion can provide clinical benefits following EGFR TKIs resistance; however, the efficacy and safety of combination therapies must be further investigated. To precisely manage EGFR-mutated NSCLCs, it is also essential to identify the resistance mechanisms by repeating biopsies.

16.
Chem Commun (Camb) ; 58(40): 6020-6023, 2022 May 17.
Article in English | MEDLINE | ID: mdl-35502694

ABSTRACT

The current polymerase-based nucleic acid amplification techniques cannot maintain continuous polymerization reactions unless by changing the temperature or adding additional reagents (e.g. the second enzyme or betaine), which undoubtedly increases the cost and operation steps. Herein, a new isothermal nucleic acid amplification technique, termed auto-cycling primer extension (APE), is presented. It repeatedly extends short DNA primers to longer DNA hairpins, by combining a DNA-based copy-and-release hairpin (CRH) and palindromic sequence design. The experimental results showed that we could realize the amplification detection of miRNA by a reasonable probe design.


Subject(s)
MicroRNAs , DNA/genetics , DNA Primers , MicroRNAs/genetics , Nucleic Acid Amplification Techniques/methods , Temperature
17.
Org Lett ; 24(43): 7918-7923, 2022 11 04.
Article in English | MEDLINE | ID: mdl-36278884

ABSTRACT

An efficient difunctionalization at C5/C8 of imidazo[1,2-a]pyrazines has been developed using disulfides and Grignard reagents under cheap cobalt catalysis. This one-pot, two-step, three-component transformation is performed under mild conditions; various Grignard reagents (aryl and alkyl) and disulfides are tolerated. Mechanistic studies and control experiments demonstrate this reaction proceeded via an anionic intermediate.


Subject(s)
Disulfides , Pyrazines , Indicators and Reagents , Pyrazines/chemistry , Molecular Structure , Catalysis
18.
Chem Commun (Camb) ; 58(9): 1414-1417, 2022 Jan 27.
Article in English | MEDLINE | ID: mdl-34994763

ABSTRACT

A novel FRET-based dendritic hybridization chain reaction (D-HCR) for TK1 mRNA imaging in living cells was developed. Compared with traditional complex D-HCR methods, it includes the advantages of having a simple design, an accurate signal and is suitable for use with living cells.


Subject(s)
Fluorescent Dyes/chemistry , Nanostructures/chemistry , RNA, Messenger/chemistry , Fluorescence Resonance Energy Transfer , Hep G2 Cells , Humans , Limit of Detection , MCF-7 Cells , Nucleic Acid Hybridization , Optical Imaging
20.
Front Pharmacol ; 13: 852604, 2022.
Article in English | MEDLINE | ID: mdl-35847015

ABSTRACT

Background: Community-acquired bacterial pneumonia (CABP) is an important health care concern in the worldwide, and is associated with significant morbidity, mortality, and health care expenditure. Streptococcus pneumoniae is the most frequent causative pathogen of CABP. Common treatment for hospitalized patients with CABP is empiric antibiotic therapy using ß-lactams in combination with macrolides, respiratory fluoroquinolones, or tetracyclines. However, overuse of antibiotics has led to an increased incidence of drug-resistant S. pneumoniae, exacerbating the development of community-acquired drug-resistant bacterial pneumonia (CDBP) and providing a challenge for physicians to choose empirical antimicrobial therapy. Methods: Traditional Chinese medicine (TCM) is widely used as a complementary treatment for CDBP. Yinhuapinggan granules (YHPG) is widely used in the adjuvant treatment of CDBP. Experimental studies and small sample clinical trials have shown that YHPG can effectively reduce the symptoms of CDBP. However, there is a lack of high-quality clinical evidence for the role of YHPG as a complementary drug in the treatment of CDBP. Here, we designed a randomized, double-blind, placebo-controlled clinical trial to explore the efficacy and safety of YHPG. A total of 240 participants will be randomly assigned to the YHPG or placebo group in a 1:1 ratio. YHPG and placebo will be added to standard treatment for 10 days, followed by 56 days of follow-up. The primary outcome is the cure rate of pneumonia, and the secondary outcomes includes conversion rate of severe pneumonia, lower respiratory tract bacterial clearance, lactic acid (LC) clearance rate, temperature, C-reactive protein (CRP), criticality score (SMART-COP score), acute physiological and chronic health assessment system (APACHEII score) and clinical endpoint events. Adverse events will be monitored throughout the trial. Data will be analyzed according to a pre-defined statistical analysis plan. This research will disclose the efficacy of YHPG in acquired drug-resistant pneumonia. Clinical Trial Registration: https://clinicaltrials.gov, identifier ChiCTR2100047501.

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