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1.
Biol Pharm Bull ; 45(3): 260-267, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35034930

RESUMO

Non-alcoholic fatty liver disease (NAFLD) has become prevalent worldwide, but sufficient pharmaceutical treatments for this condition are lacking. Previous literature suggests that vitexin offers beneficial effects in the treatment of NAFLD, but the underlying mechanisms are not well understood. In this study, the in vivo effects of vitexin were investigated in high-fat-diet (HFD)-induced NAFLD mice. Liver pathology, biochemical parameters, lipid levels, hepatocyte ultrastructure, and related regulatory proteins were measured at the end of treatment. Treatment consisted of four weeks of daily administration of vitexin at a dose of 6 mg/kg of body weight. This treatment markedly improved hepatic architecture, attenuated lipid accumulation, and regulated lipid abnormalities. In addition, the treatment reduced endoplasmic reticulum (ER) stress, restored mitochondrial biological proteins, and increased autophagy. Furthermore, the treatment increased peroxisome proliferator-activated receptor-γ (PPAR-γ) protein, which was inhibited by HFD. Thus, it was speculated that vitexin degraded lipids in HFD-induced NAFLD mice liver by inducing autophagy and restoring both ER and mitochondrial biological proteins.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Apigenina , Autofagia , Dieta Hiperlipídica/efeitos adversos , Estresse do Retículo Endoplasmático , Metabolismo dos Lipídeos , Lipídeos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/patologia
2.
Anal Chem ; 93(6): 3280-3286, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33528247

RESUMO

By mimicking nature, various artificial nanofluidic platforms have been widely applied in a range of scientific fields. However, their low performance in terms of gating efficiency (<25) still hinders their practical applications. Herein, we present a highly efficient ionic gating nanosensor by fusing the merits of host-guest chemistry and Au nanoparticles (AuNPs). Based on this strategy, the pillar[6]arene (WP6)-functionalized AuNPs facilely regulated an azobenzene (AZO)-modified nanosensor with an excellent ion rectification ratio (∼22.2) and gating efficiency (∼89.5). More importantly, this gating nanosensor system also demonstrated promising stability and recyclability under conditions of alternative irradiation of visible and ultraviolet light. These excellent results would significantly help in expanding the utilization of artificial nanosensors for controllable drug delivery and biosensors.

3.
Biochem Biophys Res Commun ; 549: 1-7, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33647537

RESUMO

PURPOSE: Ixazomib is a selective, effective, and reversible inhibitor of 20S proteasome and is approved for the treatment of multiple myeloma. Ubiquitin-conjugating enzyme E2 (UBE2K) is involved in the synthesis of K48-linked ubiquitin chains and is the target of certain drugs used for the treatment of tumors. The purpose of this study was to investigate the relationship between ixazomib and UBE2K in myeloma cells. METHODS: We used CCK-8 and Annexin V-FITC/propidium iodide kit to detect the effects of ixazomib on survival and apoptosis of RPMI-8226 and U-266 myeloma cell lines. Quantitative polymerase chain reaction and western blot were used to detect the change in gene and protein expression levels of myeloma cells treated with ixazomib. Furthermore, the regulatory effects of ixazomib on UBE2K and its downstream targets were investigated following the overexpression of UBE2K. RESULTS: In myeloma cells, ixazomib decreased cell survival and increased apoptosis in a dose-dependent manner. Ixazomib significantly increased the expression of HIST1H2BD, MNAT1, NEK3, and TARS2, while decreasing the expression of HSPA1B and UBE2K. In addition, ixazomib inhibited the proliferation of myeloma cells, blocked cell cycle, induced cell apoptosis, and increased the production of reactive oxygen species by inhibiting UBE2K expression. Lastly, ixazomib regulates mitosis- and apoptosis-related genes by lowering UBE2K expression. CONCLUSION: In summary, ixazomib leads to impaired proliferation of myeloma cells by targeting UBE2K.


Assuntos
Compostos de Boro/uso terapêutico , Glicina/análogos & derivados , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Enzimas de Conjugação de Ubiquitina/metabolismo , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/metabolismo , Compostos de Boro/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glicina/farmacologia , Glicina/uso terapêutico , Humanos , Mitose/efeitos dos fármacos , Mieloma Múltiplo/genética
4.
Sex Transm Dis ; 48(8): 523-528, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-33346591

RESUMO

BACKGROUND: Chlamydia trachomatis detection plays a crucial role in early diagnosis and treatment of C. trachomatis infection. In the current study, the capability of sexually transmitted disease (STD) laboratories to detect C. trachomatis was investigated in Guangdong, China. METHODS: An external quality assessment panel, including 5 positive samples with different C. trachomatis loads and 2 negative samples was distributed to 654 participating laboratories in October 2019, and the test results were analyzed by Guangdong Central STD Laboratory. The use of various C. trachomatis detection methods in Guangdong from 2015 to 2019 was also retrospectively investigated. RESULTS: Of the 654 participating STD laboratories, 559 (85.47%) used immune chromatographic-rapid diagnostic tests (IC-RDTs) to detect C. trachomatis in 2019, and 95 (14.53%) used nucleic acid amplification tests (NAATs). The rate of NAATs use increased approximately 4-fold from 2015 to 2019. The sensitivity of IC-RDTs decreased markedly from 97.32% to 30.89% with decreasing C. trachomatis load, whereas that of NAATs was 97.62% to 100% in all positive samples. With respect to negative samples the specificity of IC-RDTs was 97.13% to 97.30% and that of NAATs was 98.95% to 100%. Laboratories using IC-RDTs were less likely to detect C. trachomatis than those using NAATs in samples with C. trachomatis loads of 20000 copies/mL or less (P < 0.0001). Further analysis indicated no significant difference (P > 0.05) in detection rate among the 4 IC-RDT assays commonly used by the participating laboratories. CONCLUSIONS: Immune chromatographic-rapid diagnostic tests are commonly used for C. trachomatis detection by many laboratories in Guangdong, but their low sensitivity may lead to missed diagnoses. Nucleic acid amplification tests exhibit high sensitivity and specificity and should be recommended for C. trachomatis detection in STD laboratories.


Assuntos
Infecções por Chlamydia , Infecções Sexualmente Transmissíveis , China/epidemiologia , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/epidemiologia , Chlamydia trachomatis/genética , Humanos , Laboratórios , Técnicas de Amplificação de Ácido Nucleico , Estudos Retrospectivos , Sensibilidade e Especificidade , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/epidemiologia
5.
BMC Infect Dis ; 21(1): 649, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34225661

RESUMO

BACKGROUND: Mycoplasma genitalium (MG) causes urogenital tract infections and is associated with reproductive morbidity. Although MG has been reported across many regions and population groups, it is not yet routinely tested for in China. Our study contributes to current research by reporting the prevalence and correlates of MG infection in patients attending a sexually transmitted infection (STI) clinic in Guangdong from Jan 2017-May 2018. METHODS: Urethral (from 489 men) and endo-cervical (from 189 women) samples, blood samples, and patient histories (via questionnaires) were collected. Doctors clinically diagnosed anogenital warts (GW) during the examination (n = 678). The presence of MG was evaluated using an in-house via polymerase chain reaction protocol. We also tested all participants for herpes simplex virus-2 (HSV-2), Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), syphilis and HIV. Univariate and multivariate logistic regression were used to evaluate factors associated with MG. RESULTS: MG was detected in 7.2% (49/678) of the patients (men, 7.4%; women, 6.9%). The MG positivity rate was 14.2% among symptomatic patients, and 5.6% for asymptomatic patients, respectively. Only 36.7% (18/49) Mg positive patients were symptomatic. Among the MG-infected patients, 10.2% were co-infected with CT, 6.1% with NG, 8.2% with HSV-2, 4.1% with syphilis and 22.4% with GW. Presentation with clinical symptoms was significantly associated with MG infection [OR = 2.52 (2.03-3.13)]. In our analysis, MG was not associated with other STIs. CONCLUSIONS: MG is a relatively common infection among individuals attending an STI clinic in Guangdong Province. Routine testing of symptomatic patients may be necessary, and more epidemiological studies are needed to provide evidence for future testing guidelines.


Assuntos
Coinfecção/epidemiologia , Infecções por Mycoplasma/epidemiologia , Mycoplasma genitalium , Infecções Sexualmente Transmissíveis/epidemiologia , Adolescente , Adulto , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência
6.
Anal Chem ; 92(5): 4131-4136, 2020 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-31990530

RESUMO

Bioinspired nanochannel based biosensors have been widely applied for sensing ions, small molecules, and biomolecules. However, the low selectivity and difficulty in recycle sensing still heavily hamper their widespread applications. Herein, we designed and fabricated a nanochannel based biosensor for high-efficiency bisulfite (HSO3-) sensing and removal through forming a reversible covalent bond between HSO3- and 4-aminophenyl-phenyl-methanone (APPM). This nanofluidic biosensor displays a promising HSO3- selectivity with high ion rectification/gating ratio (47 and 5) and excellent reversibility and stability. Of note, the L02 cell line containing excess HSO3- could still maintain high vitality in the presence of such an APPM-functionalized biosensor based membrane. These results will not only help to better understand the biological function of HSO3- in living organisms but also inspire us to develop smart artificial nanochannel based biosensors for biological applications.


Assuntos
Técnicas Biossensoriais/métodos , Sulfitos/análise , Linhagem Celular , Sobrevivência Celular , Corantes Fluorescentes/química , Humanos , Microfluídica , Microscopia de Fluorescência , Nanotecnologia , Sulfitos/isolamento & purificação
7.
BMC Infect Dis ; 15: 412, 2015 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-26453557

RESUMO

BACKGROUND: Gonococcal antimicrobial resistance is a global problem. Different resistance plasmids have emerged and spread among the isolates of Neisseria gonorrhoeae worldwide and in China. We conducted this study to monitor the plasmid-mediated penicillin and tetracycline resistance among N. gonorrhoeae isolates in Guangzhou from 2002 to 2012. METHODS: Consecutive isolates of N. gonorrhoeae were collected from outpatients with gonorrhea attending the STD clinic in Guangdong Provincial Centre for Skin Diseases and STIs Control and Prevention. Penicillinase-producing N. gonorrhoeae (PPNG) isolates were analyzed by the paper acidometric method. Plasmid-mediated resistance to tetracycline in N. gonorrhoeae (TRNG) isolates was screened by the agar plate dilution method. Plasmid types were determined for TRNG and PPNG isolates using polymerase chain reaction (PCR). Minimum inhibitory concentrations (MICs) to penicillin and tetracycline were detected by the agar plate dilution. RESULTS: Of 1378 consecutive N. gonorrhoeae isolates, 429 PPNG and 639 TRNG isolates were identified. The prevalence of PPNG, TRNG, and PPNG/TRNG increased from 18.3 to 47.1 % (χ (2) = 31.57, p < 0.001), from 29.4 to 52.1 % (χ (2) = 16.28, p < 0.001) and from 10.0 to 26.2 % (χ (2) = 10.46, p < 0.001) between 2002 and 2012, respectively. Genotyping of plasmids among PPNGs showed that the majority (93.7 %) of the isolates were the Asian type plasmids, while the African type plasmid emerged in 2008 and rapidly increased to 14.0 % in 2012 (χ (2) = 25.03, p < 0.001). For TRNGs, all 639 isolates carried the Dutch type plasmid. MICs of penicillin G and tetracycline persisted at high levels and the MIC90s were 32-fold higher than the resistant cutoff point over 11 years. The prevalence rates of penicillin- and tetracycline-resistant N. gonorrhoeae varied from 90.9 to 91.1 % and from 88.3 to 89.3 % during 2002 to 2012, respectively. CONCLUSIONS: Resistance to penicillin and tetracycline among N. gonorrhoeae isolates remained at high levels in Guangzhou. The Asian type PPNG continued to spread and Dutch type TRNG was still the dominant strain. The African type PPNG has emerged and is spreading rapidly.


Assuntos
Farmacorresistência Bacteriana/genética , Gonorreia/epidemiologia , Gonorreia/microbiologia , Neisseria gonorrhoeae/efeitos dos fármacos , Neisseria gonorrhoeae/genética , Penicilinas/farmacologia , Antibacterianos/farmacologia , China/epidemiologia , Gonorreia/tratamento farmacológico , Humanos , Testes de Sensibilidade Microbiana , Neisseria gonorrhoeae/isolamento & purificação , Penicilina G , Penicilinase/genética , Penicilinase/metabolismo , Plasmídeos , Reação em Cadeia da Polimerase , Resistência a Tetraciclina/genética , beta-Lactamases/genética
8.
Arthritis Res Ther ; 26(1): 31, 2024 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-38243295

RESUMO

OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by abnormal activation of the type I interferon (IFN) pathway, which results in tissue inflammation and organ damage. We explored the role of the RhoA GTPase in the type I IFN activation pathway to provide a potential basis for targeting GTPase signaling for the treatment of SLE. METHODS: Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) of SLE patients and healthy controls, and the mRNA expression levels of RhoA and IFN-stimulated genes were measured by SYBR Green quantitative reverse transcriptase-polymerase chain reaction. IFN-a-stimulated response element (ISRE)-luciferase reporter gene assays and Western blotting were conducted to assess the biologic function of RhoA. An enzyme-linked immunoassay (ELISA) measured C-X-C motif chemokine ligand 10 (CXCL10) protein expression. RESULTS: Our studies demonstrate that the expression of RhoA in the PBMCs of SLE subjects was significantly higher than in healthy controls and positively correlated with type I IFN scores and type I IFN-stimulated gene (ISGs) expression levels. SiRNA-mediated knockdown of RhoA and the RhoA/ROCK inhibitor Y27632 reduced the activity of the type I IFN-induced ISRE, the signal transducer and activator of transcription 1 (STAT-1) phosphorylation, and the expression of CXCL10 and 2'-5'-oligoadenylate synthetase 1 (OAS1). Finally, we verified that Y27632 could significantly down-regulate the OAS1 and CXCL10 expression levels in the PBMCs of SLE patients. CONCLUSION: Our study shows that RhoA positively regulates the activation of the type I IFN response pathway. Reducing the expression level of RhoA inhibits the abnormal activation of the type I IFN system, and the RhoA/ROCK inhibitor Y27632 decreases aberrant type I IFN signaling in SLE PBMCs, suggesting the possibility of targeting the RhoA GTPase for the treatment of SLE.


Assuntos
Amidas , Interferon Tipo I , Lúpus Eritematoso Sistêmico , Piridinas , Humanos , Leucócitos Mononucleares/metabolismo , GTP Fosfo-Hidrolases/metabolismo , Quinases Associadas a rho/metabolismo
9.
Dalton Trans ; 52(11): 3458-3471, 2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36826454

RESUMO

Mn4+-activated phosphors have shown wide prospective applications in phosphor-converted white light-emitting diodes (pc-WLEDs) and pc-LEDs used in illumination and indoor plant cultivation, respectively. Recently, double perovskites A2B'B''O6 with a tunable crystal structure and versatile octahedral sites have been extensively studied as good host matrixes for Mn4+-emitters to realize tunable far-red emissions. Herein, a series of double-double perovskite-type ALaLiTeO6:Mn4+ (A = Ba, Ba0.5Sr0.5, Sr, Sr0.5Ca0.5, Ca) phosphors were synthesized and structurally characterized, and the correlations between their structure and luminescence were also studied systematically. With a decrease of the A-cation size, an increased distortion in the average structure and a structure symmetry lowering (I2/m → P21/n) were observed for ALaLiTeO6:Mn4+. In contrast, on the local scale, the degree of (Li/Te)O6-octahedral distortion is positively correlated with the ΔIR value, which is the ionic radius difference between A2+ and La3+. The local structural changes were found to be irrelevant to the significant improvements in photoluminescence properties. In combination with careful spectroscopic analysis, we deciphered that a decreased A-cation is in fact helpful for the enhancements in crystal field strength (Dq/B = 2.12-2.82) and Mn-O covalent bonding, thereby resulting in an improved quantum efficiency, a suppressed nonradiative transition, and a redshift in photoluminescence spectra. Amongst the ALaLiTeO6:Mn4+ phosphor series, CaLaLiTeO6:Mn4+ exhibits the highest external quantum efficiency of 70.1% and internal quantum efficiency of 96.4% and superior thermal stability (93.3%@423 K), making CaLaLiTeO6:Mn4+ very promising as far-red phosphors for pc-LEDs. The findings of this work will serve as a new guide for rational design of high-performance Mn4+-activated double-double perovskite-type far-red phosphors.

10.
Open Life Sci ; 18(1): 20220744, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37744454

RESUMO

In the human immunodeficiency virus (HIV)-infected population, especially HIV with concomitant tuberculosis (TB) or Hodgkin's lymphoma (HL), numerous risk factors have been reported in recent years. Among them, the decreased CD4+ T cell count was recognized as the common risk factor. We report a case of a patient with HIV and TB and HL co-occurrence, in which patient's CD4+ T cell count was inconsistent with disease. A 58-year-old male presented with fever and shortness of breath that persisted for 2 months. The patient had a 4-year history of HIV infection and underwent antiretroviral therapy (ART) effectively. After blood test, computed tomography, bone biopsy, and lymphoma biopsy, the patient was diagnosed with skeletal TB and HL, underwent TB treatment and received ART, and underwent four cycles of chemotherapy. CD4+ T cell count was not decreased before diagnosed with TB/HL and increased in this case after the fourth cycle of chemotherapy. We collected and analyzed CD4+ T cell counts in our case and reviewed relevant literature. It is suggested that CD4+ T cell count may be insufficient to predict the risk of HIV-related disease, especially lymphoproliferative disorders.

11.
Res Sq ; 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37790522

RESUMO

Objective: Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by abnormal activation of the type I interferon (IFN) pathway, which results in tissue inflammation and organ damage. We explored the role of the RhoA GTPase in the type I IFN activation pathway to provide a potential basis for targeting GTPase signaling for the treatment of SLE. Methods: Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) of SLE patients and healthy controls, and the mRNA expression levels of RhoA and IFN-stimulated genes were measured by SYBR Green quantitative reverse transcriptase-polymerase chain reaction. IFN-stimulated response element (ISRE)-luciferase reporter gene assays and Western blotting were conducted to asssess the biologic function of RhoA. An Enzyme-Linked Immunoassay (ELISA) measured C-X-C motif chemokine ligand 10(CXCL10)protein expression. Results: Our studies demonstrated that the expression of RhoA in the PBMCs of SLE subjects was significantly higher than healthy controls and positively correlated with type I IFN scores and type I IFN-stimulated gene (ISGs) expression levels. SiRNA-mediated knockdown of RhoA and the RhoA/ROCK inhibitor Y27632 reduced the activity of the type I IFN-induced ISRE, the signal transducer and activator of transcription 1 (STAT-1) phosphorylation, and the expression of CXCL10 and 2'-5'-oligoadenylate synthetase 1(OAS1). Finally,we verified that Y27632 could significantly down-regulate the OAS1 and CXCL10 expression levels in PBMCs of SLE patients. Conclusion: Our study shows that RhoA positively regulates the activation of the type I IFN response pathway. Reducing the expression level of RhoA inhibits the abnormal activation of the type I IFN system, and the RhoA/ROCK inhibitor Y27632 decreases aberrant type I IFN signaling in SLE PBMCs, suggesting the possibility of targeting the RhoA GTPase for the treatment of SLE.

12.
Heliyon ; 9(10): e20806, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37916085

RESUMO

Background: Systemic Lupus Erythematosus (SLE) is a prototypic autoimmune disease, which is accompanied by liver damage. However, it remains unknown whether liver damage is associated with SLE progression. Method: ology: HepG2 and L-02 cells were stimulated with cytokines, and FGL1 mRNA and protein expression levels were determined using Real-time PCR and ELISA, respectively. Regulatory T cells (Treg) isolated from healthy individuals as well as patients with SLE and SLE and liver damage (SLE-LD) were cultured with autologous effector CD4+T cells in the presence of a functional antibody or isotype control. The expression levels of LAG3, CD25, PD-1, CXCR5, ICOS and OX40 were evaluated by flow cytometry. FGL1, IL-10, IL-17a and IL-21 levels in serum or culture supernatants were quantified by ELISA. Results: Patients with SLE-LD exhibits higher disease activity indices and anti-dsDNA antibody levels. Importantly, fibrinogen-like protein 1 (FGL1), a key factor released from the injured liver, is up-regulated in patients with SLE-LD and is associated with disease activity. FGL1 expression is induced by the inflammatory cytokine IL-6 signaling in hepatocytes. Higher expression of the FGL1 receptor lymphocyte activation gene 3 (LAG3) is detected in Treg cells from patients with SLE-LD. The FGL1-LAG3 signaling axis inhibits Treg cell proliferation and impairs the suppressive activity of Treg cells by limiting IL-10 secretion. Furthermore, FGL1-LAG3 signaling promotes the production of pathogenic IL-17a and IL-21 by CD4+T cells by reducing IL-10 level produced by Treg in patients with SLE. Conclusions: The FGL1-LAG3 signal axis is a key mechanism that subverts the suppressive function of Treg cells. This may provide a new therapeutic target for SLE and SLE-induced liver damage.

13.
Front Med (Lausanne) ; 9: 1042015, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36703885

RESUMO

Background: The incidence of diabetes-related wounds is widespread, and the treatment is challenging. We found that Moist Exposed Burn Ointment (MEBO) promotes the healing of diabetes-related wounds, but the mechanism is not clear. Methods: This study aimed to explore the mechanism of MEBO on diabetic wound healing, which may be related to the promotion of re-epithelialization. A full-thickness skin resection model was established in streptozotocin (STZ)-induced diabetic mice. MEBO and Kangfuxin (KFX) were applied to the wound area, and the wound healing rate was analyzed by photographing. The granulation tissue and epidermal thickness, the collagen remodeling rate, and the expression of cytokeratin 10 (CK10), cytokeratin 14 (CK14), Ki67, Collagen I, and Collagen III in the regenerated skin were detected by H&E staining, Masson staining, and immunofluorescence staining, respectively. MEBO and KFX were applied to human immortalized keratinocytes (HaCaT), mouse dermal fibrolasts (MDF) cells, and cell viability, cell migration, and differentiation were determined by CCK-8, scratching assay, RT-qPCR, and Western blot (WB), respectively. Results: We found that MEBO significantly promoted the formation of wound granulation tissue and collagen remodeling in diabetic mice. The application of MEBO to diabetic wounds not only promoted the formation of hair follicles and sebaceous glands but also promoted the expression of Ki67, CK10, and CK14 in epidermal cells. MEBO had no significant effect on the differentiation process of keratinocytes. Conclusion: Our study further proved that MEBO plays a positive role in diabetic wound healing, and its excellent ability to promote re-epithelialization may be an important reason for promoting wound healing.

14.
Transl Oncol ; 24: 101488, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35872478

RESUMO

Scutellaria baicalensis (SB) has been shown to improve the therapeutic effects of colorectal cancer (CRC) and perform well for reversing radio-resistance in different cancers. However, its potential function and mechanism related to radio-resistance in CRC has not been explored. A radio-resistant human CRC cell line (HCT116R) was applied. A network pharmacological analysis was performed to reveal the potential mechanism of SB for reversing radio-resistance in CRC, and computational pathological analysis was applied to indicate the clinicopathological significance of the key targets. Then, our hypothesis was further verified by molecular docking. The network pharmacology analysis showed that wogonin is the key compound of SB for reversing the radio-resistance of CRC. A Kyoto Encyclopedia of Genes and Genomes analysis showed that the genes for SB that reverse radio-resistance in CRC are mainly involved in steroid hormone biosynthesis. An enrichment analysis pointed out that Sulfotransferase family 2B member 1 (SULT2B1) is a potentially vital gene. SULT2B1 was demonstrated as being highly expressed in CRC and upregulated in radio-resistant rectal tissues or cell lines. A CCK-8 and clone formation test showed that the viability and clone formation ability of HCT116R were significantly decreased by wogonin combined with radiotherapy, compared to radiotherapy alone. By contrast, flow cytometry revealed that the apoptosis of HCT116R was significantly increased when wogonin treatment combined with radiotherapy, compared with radiotherapy alone. Molecular docking verification indicated that SULT2B1 and wogonin have a good binding ability. Taken together, SULT2B1 may be the potential drug target in treating radio-resistant CRC. Wogonin may be the core compound of SB for reversing radio-resistance in CRC by targeting SULT2B1.

15.
RSC Adv ; 12(46): 30174-30180, 2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36329935

RESUMO

Foodborne or water-borne pathogens pose great threats to human beings and animals. There is an urgent need to detect pathogens with cheap, rapid and sensitive point-of-care diagnostic assays. Herein, we report the electrochemiluminescent (ECL) behaviors of NaBiF4 : Yb3+/Er3+ upconversion nanoparticles (UCNPs) which were synthesized via a fast and environment-friendly method at room temperature for the first time. The UCNPs together with K2S2O8 exhibit high ECL intensity and stable cathodic signals. Further, the Au nanoparticles (Au NPs) and Anti-E. coli O157 : H7 antibody were assembled on the surface of UCNPs successively to construct a novel ECL immunosensor for the detection of deadly E. coli O157 : H7. The as-prepared ECL immunosensor reveals high sensitivity to E. coli O157 : H7 in a linear range of 200-100 000 CFU mL-1, and the minimum detection limit could reach up to 138 CFU mL-1. The designed UCNP-based biosensor demonstrates high specificity, good stability and remarkable repeatability, and the strategy will provide a sensitive and selective method for rapid detection of E. coli O157 : H7 in food safety and preclinical diagnosis.

16.
Front Microbiol ; 13: 947640, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35910610

RESUMO

Phages show promise in replacing antibiotics to treat or prevent bacterial diseases in the chicken breeding industry. Chicks are easily affected by their environment during early growth. Thus, this study investigated whether oral phages could affect the intestinal barrier function of chicks with a focus on the cecal microbiome. In a two-week trial, forty one-day-old hens were randomly divided into four groups: (1) NC, negative control; (2) Phage 1, 109 PFU phage/day (days 3-5); (3) Phage 2, 109 PFU phage/day (days 8-10); and (4) AMX, 1 mg/mL amoxicillin/day (days 8-10). High-throughput sequencing results of cecal contents showed that oral administration of phages significantly affected microbial community structure and community composition, and increased the relative abundance of Enterococcus. The number of different species in the Phage 1 group was much higher than that in the Phage 2 group, and differences in alpha and beta diversity also indicated that the magnitude of changes in the composition of the cecal microbiota correlated with the time of phage use. Particularly in the first stage of cecal microbiota development, oral administration of bacteriophages targeting Salmonella may cause substantial changes in chicks, as evidenced by the results of the PICRUSt2 software function prediction, reminding us to be cautious about the time of phage use in chicks and to avoid high oral doses of phages during the first stage. Additionally, the Phage 2 samples not only showed a significant increase in the relative abundance of Bifidobacterium and Subdoligranulum, but also improved the intestinal morphology (jejunum) and increased the mRNA expression level of occludin and ZO-1. We concluded that phages do not directly interact with eukaryotic cells. The enhancement of intestinal barrier function by phages in chicks may be related to changes in the intestinal flora induced by phages. This implies that phages may affect intestinal health by regulating the intestinal flora. This study provides new ideas for phage prevention of intestinal bacterial infections and promotes large-scale application of phages in the poultry industry.

17.
Tissue Eng Regen Med ; 19(4): 823-837, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35467329

RESUMO

BACKGROUND: Although newly formed constructs of feasible pressure-preadjusted bone marrow mesenchymal stem cells (BMSCs) and platelet-rich fibrin (PRF) showed biomechanical flexibility and superior capacity for cartilage regeneration, it is still not very clear how BMSCs and seed cells feel mechanical stimuli and convert them into biological signals, and the difference in signal transduction underlying mechanical and chemical cues is also unclear. METHODS: To determine whether mechanical stimulation (hydrostatic pressure) and chemical cues (platelet-rich fibrin, PRF) activate canonical or noncanonical Wnt signaling in BMSCs, BMSCs cocultured with PRF were subjected to hydrostatic pressure loading, and the activation of the Wnt signaling molecules and expression of cartilage-associated proteins and genes were determined by western blotting and polymerase chain reaction (PCR). Inhibitors of canonical or noncanonical Wnt signaling, XVX-939 or L690,330, were adopted to investigate the role of Wnt signaling molecules in mechanically promoted chondrogenic differentiation of BMSCs. RESULTS: Hydrostatic pressure of 120 kPa activated both Wnt/ß-catenin signaling and Wnt/Ca2+ signaling, with the the maximum promotion effect at 60 min. PRF exerted no synergistic effect on Wnt/ß-catenin signaling activation. However, the growth factors released by PRF might reverse the promotion effects of pressure on Wnt/Ca2+ signaling. Real-time PCR and Western blotting results showed that pressure could activate the expression of Col-II, Sox9, and aggrecan in BMSCs cocultured with PRF. Blocking experiment found a positive role of Wnt/ß-catenin signaling, and a negative role of Wnt/Ca2+ signaling in chondrogenic differentiation of the BMSCs. Mutual inhibition exists between canonical and noncanonical Wnt signaling in BMSCs under pressure. CONCLUSION: Wnt signaling participates in the pressure-promoted chondrogenesis of the BMSCs co-cultured with PRF, with canonical and noncanonical pathways playing distinct roles during the process.


Assuntos
Células-Tronco Mesenquimais , Fibrina Rica em Plaquetas , Células Cultivadas , Condrogênese , Células-Tronco Mesenquimais/metabolismo , Fibrina Rica em Plaquetas/metabolismo , Via de Sinalização Wnt , beta Catenina/metabolismo
18.
Front Oncol ; 12: 859735, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35769716

RESUMO

Patients diagnosed with more than one cancer generally develop the individual tumors sequentially. There are a few cases of co-occurring multiple myeloma and lung cancer reported in the literature. Here, we report two cases of co-occurring multiple myeloma and lung cancer in patients who presented with the chief complaint of pain. The diagnoses of multiple myeloma and lung cancer were supported by hematologic and biochemical investigations, as well as bone marrow and lung histopathologic examination. We provided suitable interventions for both two patients. The patients are still currently undergoing treatment and followed up closely. We first performed a bioinformatic analysis to determine commonly shared genes and pathways in the two types of cancer types. Fortunately, we identified the hub gene mitochondrial trans-2-enoyl-CoA reductase (MECR), which was overexpressed in both tumors. Survival analysis correlated higher MECR expression with poorer overall survival. Signaling pathway analysis suggested possible transduction pathways implicated in the co-occurrence of both tumors. The clinical cases combined with bioinformatic analysis may provide insight for the pathogenesis of synchronous tumors.

19.
Chem Commun (Camb) ; 58(66): 9278-9281, 2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-35904069

RESUMO

The rapid extraction of high-purity nucleic acids from complex biological samples using conventional methods is complicated. Therefore, in this study, glycine-pillar[6]arene (Gly-P6)-functionalized tapered nanochannels were constructed using 32-mer single-stranded E. coli DNA (ssDNA) as a model sequence, which can selectively transport ssDNA by multiple noncovalent forces (transport flux of 2.65 nM cm-2 h-1) under the interference of amino acids and other substances. In view of these prospective results, the selective transport of nucleic acids with nanochannels could be applied in the design of nucleic acid enrichment and separation systems in the future.


Assuntos
Ácidos Nucleicos , DNA de Cadeia Simples , Escherichia coli , Estudos Prospectivos , Compostos de Amônio Quaternário
20.
J Immunol Res ; 2022: 3012218, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36157882

RESUMO

A disintegrin and metalloprotease 10 (ADAM-10), a member of the ADAM protease family, has biological activities related to TNF-α activation, cell adhesion, and migration, among other functions. Macrophages are important immune cells that are involved in the inflammatory response of the body. ADAM-10 is involved in inflammatory responses, but the specific regulatory mechanisms are not fully understood. In this study, we investigated the regulatory mechanism of ADAM-10 in the lipopolysaccharide-promoted proliferation (LPS) of the macrophage inflammatory response. Differentially expressed or regulated proteins were identified in interfered ADAM-10 (sh ADAM-10) macrophages using tandem mass tag (TMT) proteomics. The changes and regulatory role of ADAM-10 during LPS-induced inflammatory response in normal, interfering, and overexpressing ADAM-10 (EX ADAM-10) cells were determined. Results indicated that ADAM-10 interference affected inflammation-related pathways and reduced matrix metalloproteinase 12 (MMP-12) protein levels, as identified by TMT proteomics. In normal cells, LPS decreased ADAM-10 gene expression, but promoted ADAM-10 secretion, MMP-12 and TNF-α gene expression, and MMP-12, iNOS, IL-10, and cyclinD1 protein expression. Additionally, ADAM-10 knockdown decreased macrophage viability in sh-ADAM-10 cells. Moreover, an MMP-12 inhibitor had no impact on the viability effect of LPS on cells or the expression of ADAM-10. iNOS expression decreased, whereas IL-10 expression increased after ADAM-10 depletion. ADAM-10 knockdown decreased MMP-12, iNOS, TNF-α, IL-1ß, and FKN, while overexpression had an opposite effect. ADAM-10 overexpression further increased MMP-12, iNOS, and TNF-α gene expression in response to LPS. Cell viability was increased in EX ADAM-10 cells, and ADAM-10 secretion was further increased in the EX and LPS groups. Flow cytometry and immunofluorescence staining revealed that EX-ADAM 10 cells had increased iNOS expression, which acted as an IL-6 expression driver. In summary, we found that ADAM-10 is activated by LPS and positively participates in LPS-stimulated macrophage inflammatory responses by positively regulating MMP-12 during the inflammatory process.


Assuntos
Lipopolissacarídeos , Metaloproteinase 12 da Matriz , Desintegrinas/metabolismo , Desintegrinas/farmacologia , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos , Metaloproteinase 12 da Matriz/genética , Metaloproteinase 12 da Matriz/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
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