RESUMO
This study developed a class of novel structural antifungal hydrazylnaphthalimidols (HNs) with multitargeting broad-spectrum potential via multicomponent hybridization to confront increasingly severe fungal invasion. Some prepared HNs exhibited considerable antifungal potency; especially nitrofuryl HN 4a (MIC = 0.001 mM) exhibited a potent antifungal activity against Candida albicans, which is 13-fold higher than that of fluconazole. Furthermore, nitrofuryl HN 4a displayed low cytotoxicity, hemolysis and resistance, as well as a rapid fungicidal efficacy. Preliminary mechanistic investigations revealed that nitrofuryl HN 4a could inhibit lactate dehydrogenase to decrease metabolic activity and promote the accumulation of reactive oxygen species, leading to oxidative stress. Moreover, nitrofuryl HN 4a did not exhibit membrane-targeting ability; it could embed into DNA to block DNA replication but could not cleave DNA. These findings implied that HNs are promising as novel structural scaffolds of potential multitargeting broad-spectrum antifungal candidates for treating fungal infection.
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Antifúngicos , Candida albicans , Testes de Sensibilidade Microbiana , Animais , Humanos , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/síntese química , Candida albicans/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade , Naftalenos/síntese química , Naftalenos/química , Naftalenos/farmacologia , Hidrazinas/síntese química , Hidrazinas/química , Hidrazinas/farmacologiaRESUMO
BACKGROUND: Accurate diagnosis of Helicobacter pylori (H. pylori) infection status is a crucial premise for eradication therapy, as well as evaluation of risk for gastric cancer. Recent progress on imaging enhancement endoscopy (IEE) made it possible to not only detect precancerous lesions and early gastrointestinal cancers but also to predict H. pylori infection in real time. As a novel IEE modality, linked color imaging (LCI) has exhibited its value on diagnosis of lesions of gastric mucosa through emphasizing minor differences of color tone. AIM: To compare the efficacy of LCI for H. pylori active infection vs conventional white light imaging (WLI). METHODS: PubMed, Embase, Embase and Cochrane Library were searched up to the end of April 11, 2022. The random-effects model was adopted to calculate the diagnostic efficacy of LCI and WLI. The calculation of sensitivity, specificity, and likelihood ratios were performed; symmetric receiver operator characteristic (SROC) curves and the areas under the SROC curves were computed. Quality of the included studies was chosen to assess using the quality assessment of diagnostic accuracy studies-2 tool. RESULTS: Seven original studies were included in this study. The pooled sensitivity, specificity, positive likelihood rate, and negative likelihood rate of LCI for the diagnosis of H. pylori infection of gastric mucosa were 0.85 [95% confidence interval (CI): 0.76-0.92], 0.82 (95%CI: 0.78-0.85), 4.71 (95%CI: 3.7-5.9), and 0.18 (95%CI: 0.10-0.31) respectively, with diagnostic odds ratio = 26 (95%CI: 13-52), SROC = 0.87 (95%CI: 0.84-0.90), which showed superiority of diagnostic efficacy compared to WLI. CONCLUSION: Our results showed LCI can improve efficacy of diagnosis on H. pylori infection, which represents a useful endoscopic evaluation modality for clinical practice.
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Constructing a new antibacterial structural framework is an effective strategy to combat drug resistance. This work discovered a class of naphthalimidopropanediols (NIOLs) as a novel structural type of potential broad-spectrum antibacterial agents. Especially, NIOLs 9u, 12i, 15 against Staphylococcus aureus and NIOLs 9l, 13a against Pseudomonas aeruginosa showed excellent inhibitory activities, and they displayed high membrane selectivity from an electrostatic distinction on the membranes between bacteria and mammalian cells. These highly active NIOLs could effectually inhibit the bacterial growths, and relieve the resistance developments. Moreover, the facts of membrane depolarization, outer/inner membrane permeabilization and leakage of intracellular materials, demonstrated that these NIOLs could target and destroy the S. aureus or P. aeruginosa membranes. In particular, they could disrupt the antioxidant defense systems of S. aureus or P. aeruginosa through up-regulation of reactive oxygen species. Simultaneously, they could render the metabolic inactivation of the tested strains, and eradicate the formed biofilms and efficiently kill the strains within the biofilms. The in vitro and in vivo cytotoxicity assay indicated that these compounds possessed low toxicity. These findings of novel NIOLs as potential broad-spectrum antibacterial members provided a bright hope for conquering drug resistance.
Assuntos
Antibacterianos , Staphylococcus aureus , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Biofilmes , Mamíferos , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosaRESUMO
A novel type of coumarin thiazoles as unique multi-targeting antimicrobial agents were developed through four steps including cyclization, nucleophilic substitution and condensation starting from commercial resorcine. Most of the prepared coumarin thiazoles displayed favorable inhibitory potency against the tested strains. Noticeably, methyl oxime V-a exerted potent inhibitory efficacy against methicillin-resistant Staphylococcus aureus (MRSA) at low concentration (1 µg/mL) and showed broad antimicrobial spectrum. Medicinal bioevaluations revealed that the active molecule V-a exhibited low toxicity toward mammalian cells, rapidly killing effect, good capability of eradicating MRSA biofilms and unobvious probability to engender drug resistance. Chemical biological methods were employed to investigate preliminary mechanism, which indicated that compound V-a was able to damage the integrity of membrane to trigger leakage of protein, insert into MRSA DNA to block its replication and induce the generation of reactive oxygen species (ROS) to inhibit bacterial growth. Computational study manifested that low HOMO-LUMO energy gap of molecule V-a was favorable to exert high antimicrobial activity.
Assuntos
Staphylococcus aureus Resistente à Meticilina , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Biofilmes , Cumarínicos/química , Cumarínicos/farmacologia , Mamíferos , Testes de Sensibilidade Microbiana , Esqueleto , Tiazóis/química , Tiazóis/farmacologiaRESUMO
OBJECTIVE: To investigate the effect of intra-articular berberine injection on the structural remodeling of subchondral bone plate and osteoprotegerin/receptor activator of nuclear factor kappa-B ligand(OPG/RANKL) system expression in rabbits with osteoarthritis(OA). METHODS: Forty 12-month-old male rabbits with an average of(2.73±0.18) kg of body weight, underwent left anterior cruciate ligament transection(ACLT), and were divided into berberine group and placebo groups after operation, 20 rabbits in each group. The berberine group received intra-articular injection of 100 µmol/L berberine 0.3 ml every week for 6 weeks. In placebo group, the same dose of 0.9% sodium chloride injection was injected into the left knee joint cavity every week for 6 weeks. Another 20 12-month-old male rabbits, weighing (2.68±0.18) kg, underwent sham operation on the left knee joint without intra-articular injection intervention (sham operation group). On the last day of the sixth week after operation, three groups of animals were sacrificed to obtain knee joint specimens. The femoral medial condyle samples were obtained for histological evaluation of cartilage and subchondral bone, Mankin scoring system was used to evaluate articular cartilage structure. Image-Pro Plus(IPP) software was used to evaluate subchondral bone plate bone volume(BV), bone volume/total volume(BV/TV), trabecular circumference(TC), mean trabecular thickness (Tb.Th). Real-time quantitative reverse transcription polymerization Enzyme chain reaction(reverse transcription-polymerase chain reaction, RT-PCR) was used to detect the mRNA expression levels of OPG and RANKL in subchondral bone tissue at 6 weeks after operation. RESULTS: The cartilage structure evaluation showed that the surface of cartilage tissue in the sham operation group was smooth and flat, and the safranin coloration was full in the full thickness of the cartilage;the cartilage tissue in the berberine group showed uneven surface layer, and the staining of safranin O was mildly decreased;the surface layer fibrosis was seen in placebo group, Safranin O faded significantly. The Mankin score in the berberine group was lower than that in placebo group(P<0.01), but higher than that in sham operation group(P<0.01). The structural evaluation of subchondral bone plate showed that the trabecular bone in sham-operated group was densely arranged;after berberine intervention, the trabeculae were closely arranged;the subchondral bone trabeculae in placebo group were relatively sparse, and the distance between trabeculae was wider. Subchondral bone plate IPP software evaluation showed that BV, BV/TV, TC, Tb.Th in berberine group were higher than those in placebo group(P<0.01), BV, BV/TV, TC, Tb.Th in berberine group were higher than those in placebo group(P<0.01), while lower than the sham operation group (P<0.01). PCR test results showed that the expression of OPG mRNA in the berberine group was significantly higher than that in placebo group(P<0.01), and OPG mRNA in the berberine group was lower than that in sham operation group (P<0.01). There was no significant difference in mRNA expression of RANKL among three groups(P>0.05);the ratio of OPG/RANKL in berberine group was higher than that in placebo group(P<0.01), but lower than that in sham operation group(P<0.01). CONCLUSION: Intra-articular injection of berberine can effectively inhibit the resorption of subchondral bone in the early stage of OA and delay the development of the disease. The specific mechanism may be that berberine maintains the balance of OPG/RANKL system by up-regulating the expression of OPG gene in subchondral bone.
Assuntos
Berberina , Conservadores da Densidade Óssea , Cartilagem Articular , Osteoartrite , Animais , Masculino , Coelhos , Berberina/metabolismo , Berberina/farmacologia , Berberina/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Placas Ósseas , Ligantes , NF-kappa B/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Osteoprotegerina/genética , Osteoprotegerina/metabolismo , RNA Mensageiro/metabolismo , RNA Mensageiro/farmacologia , RNA Mensageiro/uso terapêuticoRESUMO
The dreadful bacterial resistance to clinical drugs calls for the development of novel antibacterials. This work developed a class of unique metronidazole-derived three-component hybrids as promising antibacterial therapeutic alternatives. Bioactive assay discovered that p-chlorophenylhydrazone derivative 6b possessed excellent ability to suppress the growth of drug-resistant E. coli (MIC = 0.5 µg/mL), being 16 folds more potent than norfloxacin (MIC = 8 µg/mL). The active molecule 6b with imperceptible hemolysis could effectively retard the development of bacterial drug resistance within 30 passages. Moreover, compound 6b displayed a favorable inhibitory effect on E. coli biofilms and could act rapidly in bactericidal efficacy. Subsequent exploration of mechanism revealed that 6b could destruct the bacterial cytoplasmic membrane, leading to the leakage of intracellular protein. The inactivation of lactate dehydrogenase, metabolic stagnation and the accumulation of reactive oxygen species caused by 6b were observed. Furthermore, molecule 6b could form a supramolecular complex with DNA to obstruct DNA replication. These results demonstrated that metronidazole-derived three-component hybrids provided a large potential for deep development as prospective antibacterial agents.
Assuntos
Escherichia coli , Metronidazol , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Metronidazol/farmacologia , Testes de Sensibilidade Microbiana , Estudos ProspectivosRESUMO
Unique coumarin conjugates with thiazolidinone as novel structural antibacterial modulators were exploited to combat the lethal multidrug-resistant bacterial infections. Bioactivity evaluation identified that indole-incorporated coumarin thiazolidinone conjugate 14a with low cytotoxicity to mammalian cells showed a broad antibacterial spectrum and exerted potent inhibition efficiencies to the tested germs at low concentrations (0.25-2 µg/mL). Moreover, the favorable performance of 14a in eradicating bacterial biofilm was beneficial to avert developing drug resistance. Mechanistic explorations revealed that molecule 14a was able to destroy cell membrane, leading to the leakage of intracellular materials and metabolism inhibition. The accumulation of excess reactive oxygen species (ROS) mediated by compound 14a could impede glutathione (GSH) activity and induce lipid peroxidation to suppress bacteria growth. Furthermore, compound 14a could not only intercalate into DNA base pair but also take part in non-covalent interaction with DNA gyrase B to hinder their biological function. Quantum chemical study indicated that molecule 14a had low HOMO-LUMO energy gap, which resulted in more stabilizing interactions and was conducive to displaying better antibacterial activity. ADMET analysis manifested that 14a possessed promising pharmacokinetic properties.
Assuntos
Antibacterianos , DNA Girase , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Cumarínicos/química , Cumarínicos/farmacologia , Farmacorresistência Bacteriana Múltipla , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: Insect pests seriously decrease the yield and quality of agricultural crops. Resistance to commonly used insecticides is increasingly undermining their effectiveness, and therefore the development of agents with novel modes of action is desirable. Isoxazolines are a new class of insecticides that act on γ-aminobutyric acid (GABA) gated chloride channels. In this work, we used the highly active 4-triazolyphenyl isoxazoline DP-9 as a parent structure to design and synthesize a series of quaternary ammonium salt (QAS) derivatives, and we systematically evaluated their insecticidal and antifungal activities. RESULTS: Many of the synthesized QASs exhibit insecticidal activities equivalent to or higher than that of DP-9. In particular, compounds I-31 (93%, 0.00005 mg/L) and I-34 (80%, 0.00001 mg/L) showed insecticidal activities against diamondback moth larvae that were 2-10 times higher than those of fluralaner (70%, 0.0001 mg/L) and DP-9 (80%, 0.0001 mg/L), in addition to showing excellent activities against oriental armyworm, fall armyworm, cotton bollworm, corn borer, and mosquito larvae. Furthermore, all of the synthesized compounds also showed broad-spectrum fungicidal activities. CONCLUSION: The insecticidal activities of QAS derivatives of DP-9 were the same as or better than the activity of DP-9. Compounds I-31 and I-34 showed better insecticidal activities against diamondback moth larvae than fluralaner and DP-9, and thus are promising new candidates for insecticide research.
Assuntos
Compostos de Amônio , Inseticidas , Mariposas , Animais , Desenho de Fármacos , Inseticidas/química , Larva , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
Available therapeutic strategies are urgently needed to conquer multidrug resistance of MRSA. A visible effort was guided towards the advancement of novel antibacterial framework of naphthalimide corbelled aminothiazoximes, and desired to assert some insight on the conjunction of individual pharmacophore with distinct biological activities and unique action mechanism. Preliminary assessment displayed that dimethylenediamine derivative 13d presented a wonderful inhibition on MRSA (MIC = 0.5 µg/mL), and showed excellent membrane selectivity (HC50 > 200 µg/mL) from an electrostatic distinction of the electronegative bacterial membranes and the electroneutral mammalian membranes. Moreover, 13d could effectually relieve the development of MRSA resistance. Investigations into explaining the mechanism of anti-MRSA disclosed that 13d displayed strong lipase affinity, which facilitated its permeation into cell membrane, causing membrane depolarization, leakage of cytoplasmic contents and lactate dehydrogenase (LDH) inhibition. Meanwhile, 13d could exert interaction with DNA to hinder biological function of DNA, and disrupt the antioxidant defense system of MRSA through up-regulation of ROS subjected the strain to oxidative stress. In particular, the unanticipated mechanism for naphthalimide corbelled aminothiazoximes that 13d could suppress the expression of PBP2a by inducing allosteric modulation of PBP2a and triggering the open of the active site, was discovered for the first time. These findings of naphthalimide corbelled aminothiazoximes as a small-molecule class of anti-MRSA agents held promise in strategies for treatment of MRSA infections.
Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Desenho de Fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Naftalimidas/química , Oximas/química , Proteínas de Ligação às Penicilinas/metabolismo , Regulação Alostérica/efeitos dos fármacos , Sítio Alostérico , Antibacterianos/química , Antibacterianos/metabolismo , Proteínas de Bactérias/química , Sítios de Ligação , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Estresse Oxidativo/efeitos dos fármacos , Proteínas de Ligação às Penicilinas/química , Relação Estrutura-AtividadeRESUMO
Aim: The high incidence and prevalence of fungal infections call for new antifungal drugs. This work was to develop naphthalimide thiazoles as potential antifungal agents. Results & methodology: These compounds showed significant antifungal potency toward some tested fungi. Especially, naphthalimide thiazole 4h with excellent anti-Candida tropicalis efficacy possessed good hemolysis level, low toxicity and no obvious resistance. Deciphering the mechanism showed that 4h interacted with DNA and disrupted the antioxidant defense system of C. tropicalis. Compound 4h also triggered membrane depolarization, leakage of cytoplasmic contents and LDH inhibition. Simultaneously, 4h rendered metabolic inactivation and eradicated the formed biofilms of C. tropicalis. Conclusion: The multifaceted synergistic effect initiated by naphthalimide thiazoles is a reasonable treatment window for prospective development.
Assuntos
Antifúngicos/farmacologia , Candida tropicalis/efeitos dos fármacos , Naftalimidas/farmacologia , Tiazóis/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Naftalimidas/síntese química , Naftalimidas/química , Tiazóis/síntese química , Tiazóis/químicaRESUMO
A series of 2-aminothiazole sulfanilamide oximes were developed as new membrane active antibacterial agents to conquer the microbial infection. Benzoyl derivative 10c was preponderant for the treatment of drug-resistant A. baumannii infection in contrast to norfloxacin and exerted excellent biocompatibility against mammalian cells including erythrocyte and LO2 cell line. Meanwhile, it had ability to eradicate established biofilm to alleviate the resistance burden. Mechanism investigation elucidated that compound 10c was able to disturb the membrane effectively and inhibit lactic dehydrogenase, which led to cytoplasmic content leakage. The cellular redox homeostasis was interfered via the production of reactive oxygen and nitrogen species (RONS), which further contributed to respiratory pathway inactivation and reduction of GSH activity. This work indicated that 2-aminothiazole sulfanilamide oximes could be a promising start for the exploitation of novel antibacterial agents against pathogens.
Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Desenho de Fármacos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Oximas/química , Acinetobacter baumannii/fisiologia , Animais , Antibacterianos/química , Biofilmes/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Conformação Molecular , Estresse Oxidativo/efeitos dos fármacos , Oximas/farmacologia , Relação Estrutura-Atividade , Sulfanilamida/química , Tiazóis/químicaRESUMO
Escherichia coli (E. coli) is abundantly present in nature. It is generally harmless to humans but some strains have been deemed very dangerous. Therefore, as an indicator of hygienic testing, the detection of E. coli is essential. In this work, a fluorescent assembly was synthesized and characterized by spectroscopic methods. It was found that the amantadine (Ad) conjugated dye (BOD-Ad) intercalated into Cmyc G4 (aptamer) forming a non-emission assembly (BOD-Ad-Cmyc), which could be lighted-up by BSA due to the formation of fluorescence nanoparticle BOD-Ad-Cmyc@BSA. Further, BOD-Ad-Cmyc@BSA can selectively bind Cu2+ forming non-emission species BOD-Ad-Cmyc@BSA-Cu2+. E. coli can turn-on the emission of BOD-Ad-Cmyc@BSA-Cu2+ system due to the copper accumulation or reduction by E. coli. Therefore, a fluorescence method for the determination of E. coli was built. The detection limit of BOD-Ad-Cmyc@BSA-Cu2+ of E. coli is 6.3 CFU/mL. Thus, this BOD-Ad-Cmyc@BSA-Cu2+ fluorescent assembly can be used for the detection of live E. coli in the environment.
Assuntos
Cobre , Soroalbumina Bovina , Amantadina , Escherichia coli , Humanos , Espectrometria de Fluorescência , Análise EspectralRESUMO
Animal osteoarthritis (OA) models have been developed to understand OA progression and evaluate new OA therapies. However, individual variations in joint lesions remain a critical problem in most current OA models. We established a novel rabbit model by creating a longitudinal tear in the medial meniscus body that was reproducible and similar to posttraumatic biomechanical disturbances in human OA. New Zealand rabbits underwent surgery and were assessed for 9 weeks. The rabbits were randomized into the sham control, medial meniscal tear (MMT), and anterior cruciate ligament transection (ACLT) groups. The animals were sacrificed at 4, 6, and 9 weeks posttreatment. The knee joints were harvested for histological and gene expression assessments. Both the MMT and ACLT procedures led to time-dependent degenerative changes in the femoral condyle cartilage. At each time point, the MMT group cartilage showed more severe degenerative changes than did the ACLT group cartilage. Consistently, inflammatory cytokine and catabolic gene expression were significantly higher, and anabolic gene expression was significantly lower in the MMT group than in the ACLT group. MMT treatment caused more severe structural damage to the cartilage and higher catabolic gene expression levels than the ACLT model at each time point. The MMT model may be highly beneficial in investigating posttraumatic OA (PTOA) development, especially PTOA from a meniscal injury. The MMT model replicated key features of human PTOA, including meniscal lesions, inflammatory responses, and the progression to osteoarthritic cartilage degeneration, thereby providing an exciting new avenue for translating promising treatments to clinical practice.
Assuntos
Lesões do Ligamento Cruzado Anterior/complicações , Artrite Experimental/etiologia , Osteoartrite/etiologia , Lesões do Menisco Tibial/complicações , Animais , Lesões do Ligamento Cruzado Anterior/patologia , Cartilagem Articular/patologia , Masculino , Meniscos Tibiais/patologia , Coelhos , Distribuição Aleatória , Lesões do Menisco Tibial/patologiaRESUMO
In an effort for the development of novel antimicrobial agents, ethylenic conjugated coumarin thiazolidinediones as potential multi-targeting new antimicrobial compounds were synthesized through convenient procedures from commercially available resorcinol and were evaluated for their antimicrobial potency. Bioactive evaluation revealed that some of the prepared compounds showed strong antimicrobial activities towards the tested microorganisms including clinically drug-resistant strains. Especially, propargyl derivative 12b exhibited effective anti-MRSA potency with MIC value of 0.006⯵mol/mL, which was highly advantageous over clinical antibacterial drug norfloxacin. Compound 12b showed rapid killing effect, low toxicity against hepatocyte LO2 cell line, and no obvious drug resistance development against MRSA. Preliminary exploration of action mechanism manifested that molecule 12b acted upon MRSA through forming stable supramolecular complex with bacterial DNA which might impede DNA replication. Molecular docking showed that compound 12b could bind with DNA-gyrase through hydrogen bonds.
Assuntos
Antibacterianos/farmacologia , Cumarínicos/farmacologia , Etilenos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Tiazolidinedionas/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Cumarínicos/química , Relação Dose-Resposta a Droga , Etilenos/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Tiazolidinedionas/químicaRESUMO
Drug-resistant bacteria challenge the antimicrobial agents and antibacterial strategy. To develop environmental friendly smart technology for treating pathogens, we report a kind of photoactivated nano-BODIPY (BCNBA@ZIF). First BODIPY compound (BC) was synthesized by coupling phenethyl caffeate (CAPE) with brominated BODIPY through B-O bonds. Next, BC was encapsulated in ZIF-8 together with 2-nitrobenzaldehyde (o-NBA) to form photoactivated BCNBA@ZIF nanoparticles. TEM confirm the structural change of BCNBA@ZIF after illumination. BCNBA@ZIF is less toxic to cells without illumination. Under illumination of blue LED light, the BCNBA@ZIF worked as a photoacid generator initiating the damage of ZIF shell with the release of BC, metal ions, and the production of singlet oxygen for achieving multifunctional antibacterial uses. Therefore, BCNBA@ZIF is a kind of photodriven smart "Domino" agent for bacterial inhibition.
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OBJECTIVE: To study and compare the clinical effects of Rehmannia Decoction and alendronate sodium for the treatment of primary osteoporosis. METHODS: From January 2016 to December 2017, 72 patients with primary osteoporosis who took Dihuang Decoction(DHD) orally and alendronate regularly for more than one year were randomly divided into 2 groups:experimental group and control group. The experimental group consisted of 14 males and 22 females, with an average age of(63.97±3.70) years old. The patients in the experimental group took Chinese medicine DHD, one dose each time, one time in the morning and one time in the evening, twice a week. The control group consisted of 16 males and 20 females with an average age of(63.36±3.07) years old. Patients in the control group were given alendronate 70 mg orally once a week. The basic treatment for osteoporosis remained unchanged in both groups(600 mg of calcium carbonate D3 and 0.5 µg of calcitriol capsules were taken daily). Bone mineral density (BMD) of femoral neck and lumbar vertebrae was measured by dual energy X-ray absorptiometry before and after treatment for one year. The levels of serum collagen type I C-terminal peptide (beta-CTX) and serum osteoclast (SOST) were measured before and after treatment for two groups. RESULTS: The age, bone mineral density, SOST and beta-CTX baseline values between the two groups before and after anti-osteoporosis treatment were compared. The difference was not statistically significant(P>0.05). Compared with the two groups, the BMD of femoral neck and lumbar vertebrae were increased after 1 year of anti-osteoporosis treatment. The differences were statistically significant (P<0.001). The value of serum beta-CTX was significantly lower than before. The t values were 52.002 and 50.071 respectively. The value of serum SOST was increased than that before treatment. The t values were -29.242 and -30.807 respectively. The differences were statistically significant (P<0.001). BMD of the femoral neck and lumbar spine was compared between the two groups after treatment. The P values were 0.294 and 0.478 respectively. The difference was not statistically significant (P>0.05). The serum beta-CTX values were compared between the two groups after treatment. The P value was 0.908. The serum SOST values were compared between the two groups after treatment. The P value was 0.888. The difference was not statistically significant (P>0.05). CONCLUSIONS: In this study, traditional Chinese medicine DHD is used to treat osteoporosis. It is found that DHD and alendronate have a good effect. The DHD can be used as a choice of Chinese medicine in the treatment of primary osteoporosis.
Assuntos
Alendronato/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Osteoporose , Absorciometria de Fóton , Idoso , Densidade Óssea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/tratamento farmacológicoRESUMO
The G-quadruplex aptamer is a high-order structure formed by folding of guanine-rich DNA or RNA. The recognition and assembly of G-quadruplex and compounds are important to find biocompatible drugs. Herein, triphenylamine conjugated 4, 4-difluoro-4-bora-3a, 4a-diaza-s-indacene (BODIPY) compound (BPTPA) was synthesized, and the interaction of BPTPA with G4 DNA was studied. It is found that BPTPA selectively binds with G3T3 G4 DNA forming a water-compatible nanocomplex (BPTPA-G3T3). BPTPA-G3T3 can image mitochondria and inhibit the expression of TrxR2. Cytotoxicity results indicate BPTPA-G3T3 can decrease the membrane potential of mitochondria and inhibit the proliferation of BGC-823 cancer cells. Therefore, BPTPA-G3T3 can be the biocompatible attenuator of mitochondria for cancer image and chemotherapy.
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Quadruplex G , Mitocôndrias/metabolismo , Humanos , Estrutura MolecularRESUMO
Simultaneous anterior and posterior traumatic dislocations of both hips are very rare. Only 33 cases have been previously reported in the English language literature. Although they were all due to high-energy injuries, they were hemodynamically stable and had a stable pelvic ring. We report a unique case of asymmetrical hip dislocations with an unstable pelvic ring and hemodynamic instability. A 40-year-old man was injured in a high-energy motor vehicle accident. He was hemodynamically unstable when he presented in the emergency department. Radiolographs showed asymmetrical dislocations of both hips with an unstable pelvic ring. Under general anesthesia, he had closed reduction of the dislocations of both hips, followed by temporary stabilization with an external fixator. Transcatheter arterial embolization was performed to stop active pelvic bleeding. Delayed open reduction and internal fixation was performed 12 days later with anterior and posterior plates. The patient recovered well with an uneventful post-operative course. Asymmetrical bilateral hip dislocations with pelvic ring instability caused by trauma, as presented in this case, is very rare and potentially life threatening. Prompt treatment can give a good outcome.