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1.
J Med Life ; 16(7): 1098-1104, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37900068

RESUMEN

This study aimed to investigate the effectiveness of combined negative pressure wound therapy (NPWT) and human amniotic membrane in patients with chronic wounds associated with diabetes. A total of five patients with type 2 diabetes, including ischemic and mixed forms of diabetic foot syndrome, presenting with ischemic wounds of the lower extremities were included in this study. Patients with uncorrected limb ischemia were excluded. The treatment protocol included diabetes compensation (treatment with fractional insulin therapy), anticoagulant, metabolic therapy and angiotropic therapy, physical treatment methods, osteoporosis therapy with calcium preparations, and wound-specific interventions. The primary treatment approach involved the application of a vacuum bandage to the transplanted human amniotic membrane, which improved the adaptation of the flap to the wound surface, allowed the removal of excess wound exudate, and stimulated angiogenesis and reparative properties. The combined approach of NPWT and biotherapy was a safe and effective cure for diabetic wounds, promoting faster wound healing, reducing the need for autodermoplasty, and possibly reducing the necessity for high-level amputations.


Asunto(s)
Diabetes Mellitus Tipo 2 , Pie Diabético , Terapia de Presión Negativa para Heridas , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Pie Diabético/cirugía , Cicatrización de Heridas , Amputación Quirúrgica , Tratamiento Basado en Trasplante de Células y Tejidos , Terapia de Presión Negativa para Heridas/métodos
2.
Heliyon ; 9(3): e14202, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36938403

RESUMEN

Milk is a complete and highly nutritious source of food for human beings. However, in many developing countries, including Ethiopia, the quality of milk products has become a major health concern for consumers, particularly for infants and children. Therefore, the aim of the present study was to assess the quality of raw and pasteurized milk marketed in Gondar city, Northwest Ethiopia. A laboratory-based cross-sectional study was conducted on 90 milk samples. The samples were chosen using a simple random sampling technique. For statistical analysis, ANOVA and the Pearson correlation coefficient were used. The specific gravity of pasteurized milk, farm milk, and milk vendors were found to be 1.021, 1.027, and 1.026, respectively. Farm milk, milk vendors, and pasteurized milk had fat contents of 3.38%, 3.22%, and 3.09%, respectively. The total bacterial count in pasteurized milk, farm milk, and milk vendors was found to be 7.08, 6.73, and 6.94 log10 CFU/mL, respectively. In raw milk, hydrogen peroxide (7.7%), formalin (7.7%), and water (3.8%) were found, whereas in pasteurized milk, hydrogen peroxide (50%), formalin (50%), and water (19.8%) were found. Based on the findings of this study, the quality of both raw and pasteurized milk was found to be poor as per the milk quality standards. This may cause significant public health-related problems. Therefore, an appropriate intervention should be conducted to improve the quality of milk.

3.
Heliyon ; 9(2): e12645, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36793964

RESUMEN

Extremozymes are innovative and robust biocatalysts produced by various microorganisms from harsh environments. As thermophilic organisms can only develop in a few places, studying them in geothermal environments has provided new insights into the origins and evolution of early life and access to significant bio-resources with potential biotechnology applications. The work aimed to isolate and identify likely multiple extracellular enzyme-producing thermophilic bacteria from an Addis Ababa landfill (Qoshe). The streaking approach was used to purify 102 isolates acquired by serial dilution and spread plate method. The isolates were morphologically and biochemically characterized. Thirty-five cellulases, 22 amylase, 17 protease, and nine lipase-producing bacteria were identified using primary screening methods. Further secondary screening using Strain safety evaluation; two bacterial strains (TQ11 and TQ46) were identified. Based on morphological and biochemical tests, they were found to be gram-positive and rod-shaped. Furthermore, molecular identification and phylogenic analysis of selected promising isolates confirmed the identity of the isolates, Paenibacillus dendritiformis (TQ11) and Anoxybacillus flavithermus (TQ46). The results indicated that, multiple extracellular enzyme-producing thermophilic bacteria isolated from a waste dumping area in Addis Ababa offer useful features for environmental sustainability in a wide range of industrial applications due to their biodegradability and specialized stability under extreme conditions, increased raw material utilization, and decreased waste.

4.
Saudi J Biol Sci ; 30(3): 103582, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36852413

RESUMEN

Antimicrobial susceptibility testing is an essential task for selecting appropriate antimicrobial agents to treat infectious diseases. Constant evolution has been observed in methods used in the diagnostic microbiology laboratories. Disc diffusion or broth microdilution are classical and conventional phenotypic methods with long turnaround time and labour-intensive but still widely practiced as gold-standard. Scientists are striving to develop innovative, novel and faster methods of antimicrobial susceptibility testing to be applicable for routine microbiological laboratory practice and research. To meet the requirements, there is an increasing trend towards automation, genotypic and micro/nano technology-based innovations. Automation in detection systems and integration of computers for online data analysis and data sharing are giant leaps towards versatile nature of automated methods currently in use. Genotypic methods detect a specific genetic marker associated with resistant phenotypes using molecular amplification techniques and genome sequencing. Microfluidics and microdroplets are recent addition in the continuous advancement of methods that show great promises with regards to safety and speed and have the prospect to identify and monitor resistance mechanisms. Although genotypic and microfluidics methods have many exciting features, however, their applications into routine clinical laboratory practice warrant extensive validation. The main impetus behind the evolution of methods in antimicrobial susceptibility testing is to shorten the overall turnaround time in obtaining the results and to enhance the ease of sample processing. This comprehensive narrative review summarises major conventional phenotypic methods and automated systems currently in use, and highlights principles of some of the emerging genotypic and micro/nanotechnology-based methods in antimicrobial susceptibility testing.

5.
J Mass Spectrom Adv Clin Lab ; 26: 36-46, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36388058

RESUMEN

Introduction: Although Staphylococcus aureus is the leading cause of biofilm-related infections, the lipidomic distributions within these biofilms is poorly understood. Here, lipidomic mapping of S. aureus biofilm cross-sections was performed to investigate heterogeneity between horizontal biofilm layers. Methods: S. aureus biofilms were grown statically, embedded in a mixture of carboxymethylcellulose/gelatin, and prepared for downstream matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS). Trapped ion mobility spectrometry (TIMS) was also applied prior to mass analysis. Results: Implementation of TIMS led to a âˆ¼ threefold increase in the number of lipid species detected. Washing biofilm samples with ammonium formate (150 mM) increased signal intensity for some bacterial lipids by as much as tenfold, with minimal disruption of the biofilm structure. MALDI TIMS IMS revealed that most lipids localize primarily to a single biofilm layer, and species from the same lipid class such as cardiolipins CL(57:0) - CL(66:0) display starkly different localizations, exhibiting between 1.5 and 6.3-fold intensity differences between layers (n = 3, p < 0.03). No horizontal layers were observed within biofilms grown anaerobically, and lipids were distributed homogenously. Conclusions: High spatial resolution analysis of S. aureus biofilm cross-sections by MALDI TIMS IMS revealed stark lipidomic heterogeneity between horizontal S. aureus biofilm layers demonstrating that each layer was molecularly distinct. Finally, this workflow uncovered an absence of layers in biofilms grown under anaerobic conditions, possibly indicating that oxygen contributes to the observed heterogeneity under aerobic conditions. Future applications of this workflow to study spatially localized molecular responses to antimicrobials could provide new therapeutic strategies.

6.
Build Environ ; 219: 109176, 2022 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-35599669

RESUMEN

The pandemic of COVID-19 currently shadows the world; the whole earth has been on an unprecedented lockdown. Social distancing among people interrupted domestic and international air traffic, suspended industrial productions and economic activities, and had various far-reaching and undetermined implications on air quality. Improvement in air quality has been reported in many cities during the lockdown. On March 22, 2020, the Turkish government enforced strict lockdown measures to reduce coronavirus disease transmission. This lockdown had a significant impact on the movement of people within the country, which resulted in a major drop in worldwide commercial activities. During this period, university campuses were emptied due to the transition to distance education. In this study, various air pollutants sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3), fine particulate matter (PM2.5), total bacteria, and total fungi were measured in different indoor environments at Eskisehir Technical University Campus in Eskisehir, Turkey during COVID-19 lock down period. Also, to calculate the indoor and outdoor ratios (I/O) of the pollutants, simultaneous outdoor measurements were also carried out. The average indoor SO2, NO2, O3, and PM2.5 concentrations in different indoor environments ranged between 2.10 and 54.58, 1.36-30.89, 12.01-39.05, and 21-94 µg/m3, respectively. The total number of bacteria and fungi ranged between 21.83-514.15 and 13.10-83.36 CFU/m3, respectively. Our study intends to give a glimpse to quantify the impact of a pandemic on air quality in different indoor environments in a university campus in Eskisehir, Turkey and calls for follow-up studies. Indoor concentrations were evaluated together with outdoor concentrations. In general, it can be said that the calculated I/O ratios for SO2, NO2, O3, bacteria, and fungi were less than 1 in most indoor environments.

7.
Food Chem X ; 13: 100225, 2022 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-35498980

RESUMEN

In the present study, E. coli was taken as a model bacterium, anti-E. coli functionalized magnetic beads were constructed and used to capture E. coli from aqueous extracts of fish sarcoplasmic protein (FSP) and fish muscle protein of sablefish. The excellency of the reproducibility of the present protocol was demonstrated by capturing E. coli from sablefish FSP extracts. The presence of 10 CFU/mL E. coli is still detectable. A microbial safety test on the surface of fish muscle was successfully performed. The bacterial identification accuracy from samples with different matrices was found to be excellent with RSD = 3%. High specific detection of target bacteria in complex biological samples was testified by spiking Staphylococcus aureus and Klebsiella pneumoniae in samples as interference. Ten biomarker ions were discovered for E. coli's recognition. It is promising to apply the present protocol in bacterial analysis in muscle food samples to ensure their safety.

8.
Food Chem X ; 14: 100306, 2022 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-35492253

RESUMEN

The study evaluated prebiotic potential and the enzyme inhibition of extracts and isolated compounds of Rumex vesicarius (ruby dock), family Polygonaceae. Eight known compounds were identified in the roots of R. vesicarius. Extracts and compounds (1-8) increased the growth rate of Escherichia coli Nissle 1917 differentially compared to controls. The highest prebiotic index (PI) and activity score was recorded for EcN in the presence of compound 4, followed by, in descending order, petroleum ether, ethyl acetate, and total methanol extracts. The compounds and extracts reduced protease, α-amylase, and angiotensin-converting enzyme activities. This inhibitory activity was positively correlated with PI, Pscore, µu, and Ymax. These findings suggest that R. vesicarius is a good source of potential prebiotic and can boost beneficial bacteria. It may also be considered promising for treatment of diabetes mellitus, controlling weight, and regulating blood pressure.

9.
Saudi J Biol Sci ; 29(2): 1191-1196, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35197786

RESUMEN

Xanthones C-glycosides are plants secondary metabolites with diverse biological activities. Among the C-glycoside xanthones, the mangiferin (MF) is of widespread occurrence in plants while isomangiferin (IsoMF) is not very common. For the present study mangiferin (MF) and isomangiferin (IsoMF) were isolated from Dryopteris ramosa. The antibacterial potential of MF and IsoMF was evaluated by using agar well diffusion method while cytotoxic properties of MF and IsoMF were assessed by brine shrimp lethality test (BSLT). The antibacterial potential of MF and IsoMF increases in dose dependent manner. The minimum inhibitory concentration (MIC) indicated strong antibacterial potential of MF against Salmonella setubal (125 µg/mL) and Bacillus subtilis (125 µg/mL) while MF showed weak antibacterial potential against Escherichia coli (500 µg/mL). On the other hand the IsoMF showed better antibacterial potential against all the tested strain including Escherichia coli (MIC = 250 µg/mL). The MF and IsoMF showed poor cytotoxicity towards Brine shrimp nauplii as indicated by their LD50 (969.77 ± 0.67 and 768.92 ± 0.81 µg/mL respectively). The present study has highlighted the antibacterial potential of MF and IsoMF. Further evaluation of these two isomeric compounds may prove to be the future remedies for various bacterial infections and other human ailments.

10.
Artículo en Inglés | MEDLINE | ID: mdl-34769642

RESUMEN

(1) Background: Numerous educational interventions have been conducted to improve hand hygiene (HH) compliance and effectiveness among nursing students, with mixed results. The aim is to evaluate the effectiveness of posters as a teaching tool and factors associated with HH quality. (2) Methods: A pre-post experimental intervention study was conducted with a total of 293 nursing students randomly assigned to two groups (experimental and control) who, before and after HH, took cell culture samples from their non-dominant hands. Only the experimental group was exposed to the poster. (3) Results: In the experimental group, significant differences were observed among students older than 22 years (p = 0.017; V = 0.188), with a higher percentage of failures (15.7% vs. 3.6%). Poster displaying was associated with passing, other variables being equal, although without statistical significance (ORa = 2.07; 95% CI = 0.81-5.26). Pre-practice hand contamination was weakly associated with lower HH quality (ORa = 0.99, 95% CI = 0.99-0.99). (4) Conclusions: The use of posters as a teaching method shows indications of efficacy. Prior hand contamination slightly affects the quality of HH. Further evaluation of teaching methods is needed to ensure good technical performance of HH to prevent the spread of infectious diseases during the COVID-19 pandemic.


Asunto(s)
COVID-19 , Infección Hospitalaria , Higiene de las Manos , Estudios de Casos y Controles , Adhesión a Directriz , Desinfección de las Manos , Humanos , Pandemias , SARS-CoV-2 , Estudiantes
11.
Acta Pharm Sin B ; 11(10): 3165-3177, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34729307

RESUMEN

mediated cancer therapy has achieved remarkable anti-tumor effects in experimental animal models, but the detailed mechanism remains unsolved. In this report, the active involvement of the host immune response in this process was confirmed by comparing the tumor-suppressive effects of Salmonella in immunocompetent and immunodeficient mice bearing melanoma allografts. Since flagella are key inducers of the host immune response during bacterial infection, flagella were genetically disrupted to analyse their involvement in Salmonella-mediated cancer therapy. The results showed that flagellum-deficient strains failed to induce significant anti-tumor effects, even when more bacteria were administered to offset the difference in invasion efficiency. Flagella mainly activate immune cells via Flagellin/Toll-like receptor 5 (TLR5) signalling pathway. Indeed, we showed that exogenous activation of TLR5 signalling by recombinant Flagellin and exogenous expression of TLR5 both enhanced the therapeutic efficacy of flagellum-deficient Salmonella against melanoma. Our study highlighted the therapeutic value of the interaction between Salmonella and the host immune response through Flagellin/TLR5 signalling pathway during Salmonella-mediated cancer therapy, thereby suggesting the potential application of TLR5 agonists in the cancer immune therapy.

12.
Mol Genet Metab Rep ; 29: 100813, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34712576

RESUMEN

Glycogen Storage Disease type 1b (GSDIb) is a genetic disorder with long term severe complications. Accumulation of the glucose analog 1,5-anhydroglucitol-6-phosphate (1,5AG6P) in neutrophils inhibits the phosphorylation of glucose in these cells, causing neutropenia and neutrophil dysfunctions. This condition leads to serious infections and inflammatory bowel disease (IBD) in GSDIb patients. We show here that dapagliflozin, an inhibitor of the renal sodium-glucose co-transporter-2 (SGLT2), improves neutrophil function in an inducible mouse model of GSDIb by reducing 1,5AG6P accumulation in myeloid cells.

13.
Acta Pharm Sin B ; 11(9): 2859-2879, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34589401

RESUMEN

Parkinson's disease (PD) is the second most common neurodegenerative disease, but none of the current treatments for PD can halt the progress of the disease due to the limited understanding of the pathogenesis. In PD development, the communication between the brain and the gastrointestinal system influenced by gut microbiota is known as microbiota-gut-brain axis. However, the explicit mechanisms of microbiota dysbiosis in PD development have not been well elucidated yet. FLZ, a novel squamosamide derivative, has been proved to be effective in many PD models and is undergoing the phase I clinical trial to treat PD in China. Moreover, our previous pharmacokinetic study revealed that gut microbiota could regulate the absorption of FLZ in vivo. The aims of our study were to assess the protective effects of FLZ treatment on PD and to further explore the underlying microbiota-related mechanisms of PD by using FLZ as a tool. In the current study, chronic oral administration of rotenone was utilized to induce a mouse model to mimic the pathological process of PD. Here we revealed that FLZ treatment alleviated gastrointestinal dysfunctions, motor symptoms, and dopaminergic neuron death in rotenone-challenged mice. 16S rRNA sequencing found that PD-related microbiota alterations induced by rotenone were reversed by FLZ treatment. Remarkably, FLZ administration attenuated intestinal inflammation and gut barrier destruction, which subsequently inhibited systemic inflammation. Eventually, FLZ treatment restored blood-brain barrier structure and suppressed neuroinflammation by inhibiting the activation of astrocytes and microglia in the substantia nigra (SN). Further mechanistic research demonstrated that FLZ treatment suppressed the TLR4/MyD88/NF-κB pathway both in the SN and colon. Collectively, FLZ treatment ameliorates microbiota dysbiosis to protect the PD model via inhibiting TLR4 pathway, which contributes to one of the underlying mechanisms beneath its neuroprotective effects. Our research also supports the importance of microbiota-gut-brain axis in PD pathogenesis, suggesting its potential role as a novel therapeutic target for PD treatment.

14.
Infect Prev Pract ; 3(4): 100180, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34988422

RESUMEN

Infection prevention and control team members (IPCTM) are often intimidated by aspects of ventilation as they relate to healthcare, because they consider them technical and outside their area of comfort and expertise. However, engineers, estates departments and planners need IPCTM input to ensure appropriate design and use. The main areas of importance centre on the operating theatre, the provision of air-controlled ventilated isolation rooms, and how to respond to major outbreaks/pandemics. Concentrating on basic principles of infection prevention and control, developing relationships with key departments and individuals, and applying best practice to these and other areas as they arise, are of great value. Some background, information and suggestions are provided for IPCTM with a view to providing simple practical advice in these areas.

15.
EClinicalMedicine ; 25: 100451, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32954234

RESUMEN

BACKGROUND: Multiple infection outbreaks have been linked to contaminated duodenoscopes worldwide. However, the contamination rate of patient-ready duodenoscopes varies highly amongst published studies testing this subject. We aimed to estimate the contamination rate of reprocessed patient-ready duodenoscopes for endoscopic retrograde cholangio-pancreatography (ERCP) based on currently available data. METHODS: We searched the PubMed and Embase databases from January 1, 2010 until March 10, 2020, for citations investigating contamination rates of reprocessed patient-ready duodenoscopes. Studies not assessing other types of endoscopes than duodenoscopes were excluded from the analysis. Study eligibility and data extraction was evaluated by three reviewers independently. A random-effects model (REM) based on the proportion distribution was used to calculate the pooled total contamination rate of reprocessed patient-ready duodenoscopes. Subgroup analyses were carried out to assess contamination rates when using different reprocessing methods by comparing single high-level disinfection (HLD) with double HLD and ethylene oxide (EtO) gas sterilization. Additionally, we investigated the contamination rate between studies conducted following an outbreak compared to non-outbreak-initiated studies. FINDINGS: We identified 15 studies that fulfilled the inclusion, which included 925 contaminated duodenoscopes from 13,112 samples. The calculated total weighted contamination rate was 15.25% ± 0.018 (95% confidence interval [Cl]: 11.74% - 18.75%). The contamination rate after only using HLD was 16.14% ± 0.019 (95% Cl: 12.43% - 19.85%) and after using either dHLD or EtO the contamination rate decreased to 9.20% ± 0.025 (95% Cl: 4.30% - 14.10%). Studies conducted following an outbreak (n=4) showed a 5.72% ± 0.034 (95% Cl: 0.00% - 12.43%) contamination rate, and non-outbreak-initiated studies (n=11) revealed a contamination rate of 21.50% ± 0.031 (95% Cl: 15.35% - 27.64%). INTERPRETATION: This is the first meta-analysis to estimate the contamination rate of patient-ready duodenoscopes used for ERCP. Based on the available literature, our analysis demonstrates that there is a 15.25% contamination rate of reprocessed patient-ready duodenoscopes. Additionally, the analysis indicates that dHLD and EtO reprocessing methods are superior to single HLD but still not efficient in regards to cleaning the duodenoscopes properly. Furthermore, studies conducted following an outbreak did not entail a higher contamination rate compared to non-outbreak-initiated studies. FUNDING: The authors received no financial support for the research, authorship, and/or publication of this article.

16.
Biotechnol Rep (Amst) ; 26: e00461, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32420051

RESUMEN

Coinoculation of plants with mixtures of beneficial microbes sometimes produces synergistic effects. In this study, the effect of soybean coinoculation with the N2-fixing Bradyrhizobium japonicum E109 and the biocontrol fungus Trichoderma harzianum Th5cc was analyzed. Nodulation by E109 was not hampered by Th5cc, which antagonized five out of seven soybean pathogens tested. Furthermore, Th5cc relieved nitrate-inhibition of nodulation, enabling the formation of nodules containing infected cells with bacteroids in the presence of the otherwise inhibitory 10 mM KNO3. Th5cc released micromolar amounts of auxin, and addition of 11 µM indoleacetic acid to soybean plants inoculated with E109 in the absence of Th5cc also induced nodulation in the presence of 10 mM KNO3. Thus, Th5cc may release auxins into the soybean rhizosphere, which hormones might participate in overcoming the nitrate-inhibition of nodulation. Our results suggest that soybean plants coinoculated with these microorganisms might benefit from biocontrol while contributing to soil-nitrogen preservation.

17.
Acta Pharm Sin B ; 10(3): 475-487, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32140393

RESUMEN

ProBiotic-4 is a probiotic preparation composed of Bifidobacterium lactis, Lactobacillus casei, Bifidobacterium bifidum, and Lactobacillus acidophilus. This study aims to investigate the effects of ProBiotic-4 on the microbiota-gut-brain axis and cognitive deficits, and to explore the underlying molecular mechanism using senescence-accelerated mouse prone 8 (SAMP8) mice. ProBiotic-4 was orally administered to 9-month-old SAMP8 mice for 12 weeks. We observed that ProBiotic-4 significantly improved the memory deficits, cerebral neuronal and synaptic injuries, glial activation, and microbiota composition in the feces and brains of aged SAMP8 mice. ProBiotic-4 substantially attenuated aging-related disruption of the intestinal barrier and blood-brain barrier, decreased interleukin-6 and tumor necrosis factor-α at both mRNA and protein levels, reduced plasma and cerebral lipopolysaccharide (LPS) concentration, toll-like receptor 4 (TLR4) expression, and nuclear factor-κB (NF-κB) nuclear translocation in the brain. In addition, not only did ProBiotic-4 significantly decreased the levels of γ-H2AX, 8-hydroxydesoxyguanosine, and retinoic-acid-inducible gene-I (RIG-I), it also abrogated RIG-I multimerization in the brain. These findings suggest that targeting gut microbiota with probiotics may have a therapeutic potential for the deficits of the microbiota-gut-brain axis and cognitive function in aging, and that its mechanism is associated with inhibition of both TLR4-and RIG-I-mediated NF-κB signaling pathway and inflammatory responses.

18.
Bioorg Med Chem ; 28(1): 115213, 2020 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-31810890

RESUMEN

Analogues of the anti-tuberculosis drug bedaquiline, bearing a 3,5-dimethoxy-4-pyridyl C-unit, retain high anti-bacterial potency yet exert less inhibition of the hERG potassium channel, in vitro, than the parent compound. Two of these analogues (TBAJ-587 and TBAJ-876) are now in preclinical development. The present study further explores structure-activity relationships across a range of related 3,5-disubstituted-4-pyridyl C-unit bedaquiline analogues of greatly varying lipophilicity (clogP from 8.16 to 1.89). This broader class shows similar properties to the 3,5-dimethoxy-4-pyridyl series, being substantially more potent in vitro and equally active in an in vivo (mouse) model than bedaquiline, while retaining a lower cardiovascular risk profile through greatly attenuated hERG inhibition.


Asunto(s)
Antituberculosos/farmacología , Diarilquinolinas/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Animales , Antituberculosos/síntesis química , Antituberculosos/química , Diarilquinolinas/síntesis química , Diarilquinolinas/química , Relación Dosis-Respuesta a Droga , Humanos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Mycobacterium tuberculosis/crecimiento & desarrollo , Relación Estructura-Actividad
19.
Anim Feed Sci Technol ; 253: 125-134, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31293291

RESUMEN

Selenium (Se) is a non-metallic trace element essential for normal cellular function, which has been linked with reduced risk of cancer, cardiovascular disease, cognitive decline and thyroid disease in humans. Se deficiency in livestock is associated with white muscle disease, retained placenta, ill-thrift and mastitis. Where Se status or bioavailability from the soil for plants is poor, livestock rely on supplemental Se in their diets predominantly as either sodium selenite (inorganic form) or selenised-yeast (organic form). As lactic acid bacteria (LAB) have been shown to incorporate Se as either organic or elemental (Nano-Se) there may be potential to use silage inoculant bacteria to improve the Se status of feed to provide the Se requirements of livestock. We screened twenty-seven LAB in MRS broth in the presence of sodium selenite for growth and uptake of Se as organic (selenocysteine and selenomethionine), inorganic (selenite and selenate) or/and Nano-Se, with the aim to identify potential candidates for a mini-silo study. Sodium selenite addition into the growth medium of LAB reduced growth rates but also resulted in the conversion of the inorganic sodium selenite into predominately Nano-Se and small quantities of organic-Se. Based on a rank analysis of growth and ability to take up (total Se content) and convert inorganic Se (Nano and organic Se content), three LAB were selected for further investigation as silage inoculants: L. brevis DSMZ (A), L. plantarum LF1 (B), and L. plantarum SSL MC15 (C). Each LAB was used as an inoculant within a grass mini-silo trial, either cultured in the presence of sodium selenite before inoculation or sodium selenite added to the inoculum at inoculation versus controls with no Se. The addition of sodium selenite either into the growth media of LAB or applied at inoculation of grass silage did not interfere with the ability of the LAB to act as a silage inoculant with no difference in silage fermentation characteristic between LAB with no Se added. The addition of sodium selenite either to the LAB growth medium or at inoculation resulted in the conversion of sodium selenite into Nano-Se and organic-Se (Nano-Se, ca. 103 higher than organic), as previously shown in the screening trial. There was no difference between the three LAB for incorporation of Se or in silage quality, indicating the potential to develop silage inoculants to increase the bioavailable form of Se (elemental and organic) to livestock through conversion of inorganic forms during ensiling.

20.
Phytomedicine ; 63: 152968, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31280140

RESUMEN

BACKGROUND: Gastric cancer has a high morbidity and is a leading cause of cancer-related mortality worldwide. Helicobacter pylori (H. pylori) infection is commonly found in the early stage of gastric cancer pathogenesis, which induces chronic gastritis. Artemisinin (ART) and its derivatives (ARTS, artesunate and DHA, dihydroartemisinin), a new class of potent antimalarials, have been reported to exert both preventive and anti-gastric cancer effects. However, the underlying mechanisms of the chemopreventive effects of ART and its derivatives in H. pylori infection induced-gastric cancer are not fully elucidated. PURPOSE: We investigated the effects of H. pylori infection in gastric cancer; and the preventive mechanisms of ART, ARTS and DHA. METHODS: The H. pylori growth was determined by the broth macro-dilution method, and its adhesion to gastric cancer cells was evaluated by using the urease assay. The protein and mRNA levels, reactive oxygen species (ROS) production, as well as the production of inflammatory cytokines were evaluated by Western blot, real-time PCR, flow cytometry and ELISA, respectively. Moreover, an in vivo MNU (N-methyl-N-nitroso-urea) and H. pylori-induced gastric adenocarcinoma mouse model was established for the investigation of the cancer preventive effects of ART and its derivaties, and the underlying mechanisms of action. RESULTS: ART, DHA and ARTS inhibited the growth of H. pylori and gastric cancer cells,suppressed H. pylori adhesion to the gastric cancer cells, and reduced the H. pylori-enhanced ROS production. Moreover, ART, DHA and ARTS significantly reduced tumor incidence, number of tumor nodules and tumor size in the mouse model. Among these three compounds, DHA exerted the most potent chemopreventive effect. Mechanistic studies showed that ART and its derivatives potently inhibited the NF-κB activation. CONCLUSION: ART, DHA and ARTS have potent preventive effects in H. pylori-induced gastric carcinogenesis. These effects are, at least in part, attributed to the inhibition of NF-κB signaling pathway. Our findings provide a molecular justification of using ART and its derivatives for the prevention and treatment of gastric cancer.


Asunto(s)
Anticarcinógenos/farmacología , Artemisininas/farmacología , Infecciones por Helicobacter/complicaciones , Helicobacter pylori/efectos de los fármacos , Neoplasias Gástricas/prevención & control , Animales , Artesunato/farmacología , Adhesión Bacteriana/efectos de los fármacos , Línea Celular Tumoral , Citocinas/metabolismo , Helicobacter pylori/patogenicidad , Humanos , Ratones Endogámicos C57BL , Pruebas de Sensibilidad Microbiana , FN-kappa B/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patología
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