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Aims: The medical management of multidrug-resistant tuberculosis (MDR-TB) has become a major public health issue. Apolipoproteins play a key role in lipoprotein metabolism such as the recognition of receptors involved in lipoprotein metabolism. Thus, the study of the inter- relationships between apolipoproteins (A1 and B) and MDR-TB could represent an important approach to the biological management of MDR-TB patients.Methodology: This is an experimental study carried out on eighty-two (82) patients including thirty-eight (38) MDR-TB patients which age ranged from 18 to 60 years old recruited from three tuberculosis centers (CAT) in the city of Abidjan and forty-four (44) non-tuberculosis patients used as control aged 18 to 60 years old recruited at the National Blood Transfusion Center (CNTS) in Treichville (Abidjan, C魌e d扞voire). Total cholesterol, HDL-cholesterol and triglycerides were measured by the colorimetric-enzymatic method. Apolipoproteins A1 and B were measured using the immunoturbidimetric method.Results and Conclusion: Showed a dyslipidemia concerning cholesterol and its HDL fraction, triglycerides and apolipoproteins A1 and B suggest an atherogenic profile in multidrug-resistant TB patients.
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Aims@#The increasing incidence of Klebsiella pneumoniae infections in the community and hospitals is a considerable health problem. This is due to the rising resistance of the bacteria to antibiotics, biofilm formation and the presence of a capsule. The aim of this study was to survey the most common capsular types in local isolates for the first time in Iraq on a molecular level. @*Methodology and results@#Seventy isolates were screened for multidrug resistance (MDR) using a standard test. Genomic DNA was extracted from all isolates and PCR was performed using a multiplex PCR assay to detect the capsular type genes for K1, K2, K5, K20, K54 and K57. Forty-eight (68.5%) isolates demonstrated resistance to at least one agent of three or more antimicrobial categories and were therefore considered as MDR isolates. Multiplex PCR showed that 16/48 (33.3%) of MDR isolates belonged to the K2 capsular type and two isolates belonged to the K57 capsular type. The other four capsular types were not detected.@*Conclusion, significance and impact of study@#The K2 capsular type was the most common capsular type among MDR K. pneumoniae isolates from urinary tract infections (UTI) in Ramadi, Iraq. Monitoring capsular type is essential in addition to monitoring antibiotic resistance, as highly resistant strains with hypervirulent types can be particularly dangerous.
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The ATP-binding cassette (ABC) transporter superfamily comprises membrane proteins that efflux various substrates across extra- and intracellular membranes. Among them, ABCB1, ABCG2, and ABCC1 are directly linked to tumor multidrug resistance (MDR). This review provides an overview of the current understanding on the novel mechanisms and functions of ABCB1, ABCG2, and ABCC1 transporters in tumor MDR, discusses the latest strategies to target these transporters, and explores further opportunities to overcome MDR.
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RESUMEN La tuberculosis multirresistente surge de cepas de Mycobacterium tuberculosis con resistencia in vitro al menos a isoniacida y rifampicina, dos drogas de primera línea claves para el tratamiento. Anualmente, alrededor de treinta mil niños en el mundo contraen esta forma de tuberculosis, y menos del 5 % recibe tratamiento adecuado. El enfoque para estos casos debe seguir el perfil de sensibilidad del germen y tratar de lograr la curación del paciente con el menor número de complicaciones y secuelas po sibles, y prevenir la transmisión comunitaria de la enfermedad. En 2022 la Organización Mundial de la Salud recomendó la bedaquilina para el tratamiento de la tuberculosis multirresistente en adultos y niños de todas las edades. Nuestro objetivo es comunicar nuestra experiencia sobre la administración de bedaquilina en niños y adolescentes en el contexto del tratamiento de la tuberculosis multirresistente de acuerdo con las últimas recomendaciones.
ABSTRACT Multidrug-resistant tuberculosis arises from strains of Mycobacterium tuberculosis with in vitro resistance to at least isoniazid and rifampicin, two key first-line drugs for treatment. Annually, around 30 000 children worldwide contract this form of tuberculosis, and less than 5 % receive adequate treatment. The approach for these cases should follow the sensitivity profile of the germ, trying to achieve the patient's cure with the fewest pos sible complications and sequelae, and prevent community transmission of the disease. In 2022, the World Health Organization recommended bedaquiline for the treatment of multidrug-resistant tuberculosis in adults and children of all ages. Our objective is to communicate our experience on the administration of bedaquiline in children and adolescents in the context of multidrug-resistant tuberculosis treatment in accordance with the latest recommendations.
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The emergence of antimicrobial resistance (AMR) among different species of microbes, or infectious agents, has become a major public health concern worldwide. This alarming trend is due to the rapid development of new resistance mechanisms and the decreasing effectiveness of treating common infectious diseases. As a result, standard treatments often fail to elicit a proper microbial response, leading to prolonged illness, increased healthcare costs, and a higher risk of mortality. Many infectious agents, including bacteria, fungi, viruses, and parasites, have developed high levels of multidrug resistance, resulting in increased morbidity and mortality rates, and being called as "superbugs." While the development of MDR is a natural process, it is exacerbated by the inappropriate use of antimicrobial drugs, inadequate sanitary conditions, improper food handling, and subpar infection prevention and control practices. Given the importance of AMR, this paper enlists the AMR issue along with its significance, mechanism and its possible impact in the future. The creation of innovative treatments to fight these persistent infections should be made easier by a better strategy of educating the population about the drivers of AMR.
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ABSTRACT Bacterial keratitis caused by multidrug-resistant strains of Pseudomonas aeruginosa is a therapeutic challenge due to a limited number of active antimicrobials and rapid progression to corneal necrosis and perforation. To report the use of topical colistin and surgical tarsorrhaphy in a case of keratitis caused by extensively drug-resistant Pseudomonas aeruginosa in a patient with severe coronavirus disease-2019 (COVID-19) pneumonia. A 56-year-old male was admitted to the intensive care unit with clinical symptoms of severe COVID-19 pneumonia. During his stay in the unit, he developed rapidly progressive keratitis with Pseudomonas aeruginosa resistant to all drugs except for colistin on culture. Due to incomplete lid closure, a temporary tarsorrhaphy was performed, and a regimen of descending-dose topical colistin was initiated. After five weeks, keratitis resolved completely. Extensively drug-resistant Pseudomonas aeruginosa is an unusual cause of bacterial keratitis. We describe the safe and effective use of topical colistin in a case with severe corneal involvement.
RESUMO A ceratite bacteriana causada por cepas multirresistentes de Pseudomonas aeruginosa é um desafio terapêutico, devido à disponibilidade limitada de antimicrobianos e à rápida progressão para necrose e perfuração da córnea. O objetivo deste artigo é relatar o uso de colistina tópica e tarsorrafia cirúrgica em um caso de ceratite por Pseudomonas aeruginosa amplamente resistente a medicamentos em um paciente com pneumonia grave por COVID19. Um homem de 56 anos foi internado em uma unidade de terapia intensiva com sintomas clínicos de pneumonia grave por COVID19. Durante sua permanência na unidade de terapia intensiva, o paciente desenvolveu uma ceratite rapidamente progressiva, cuja cultura foi positiva para Pseudomonas aeruginosa resistente a todos os antimicrobianos, exceto colistina. Devido ao fechamento incompleto da pálpebra, foi realizada uma tarsorrafia temporária e foi instituído um esquema de colistina tópica em doses decrescentes. Após cinco semanas, a resolução completa da ceratite foi alcançada. Pseudomonas aeruginosa amplamente resistente a medicamentos é uma causa incomum de ceratite bacteriana. Este relato descreve o uso seguro e eficaz da colistina tópica em um caso com comprometimento corneano grave.
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Background: Diagnosis of EPTB is often delayed due to its paucibacillary nature. Diagnostic modalities like conventional methods and molecular methods like GeneXpert are employed for Mycobacteria detection and their results are compared. Line Probe Assay is used for determination of resistance in first line and in second line anti-tubercular drugs. Methods: In this study 302 extrapulmonary samples from suspected cases of all age groups were included. Samples were first homogenised and decontaminated and then subjected to various diagnostic modalities like microscopy, culture and GeneXpert for Mycobacteria detection. Culture and smear positive isolates were subjected to LPA for determination of drug resistance in first and second-line anti-tubercular drugs. Results: Out of the 302 extrapulmonary samples, maximum samples were of lymph nodes (19.86%) followed by pus (17.88%). Male to female ratio was 1:3. GeneXpert detected 45.04% positive cases and 5.96% were rifampicin resistant. Positive samples detected by microscopy and culture were 21.19% and 24.17% respectively. When compared to culture, microscopy showed a sensitivity of 86.30% and specificity of 99.56%. GeneXpert reported 100% sensitivity and 72.48% specificity. LPA reported 9.45% isoniazid resistant cases, 4.05% rifampicin resistant cases and 5.40% both isoniazid and rifampicin resistant cases (MDR-TB). Out of the MDR-TB cases, 25% cases were resistant to fluoroquinolones indicating pre-XDR TB. Conclusions: For Mycobacterium tuberculosis detection in extrapulmonary samples, multiple modalities should be employed so that the bacilli in these samples is not missed and the turn-around time is lowered which is a key to TB control strategy.
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Background: Diagnosis of EPTB is often delayed due to its paucibacillary nature. Diagnostic modalities like conventional methods and molecular methods like GeneXpert are employed for Mycobacteria detection and their results are compared. Line Probe Assay is used for determination of resistance in first line and in second line anti-tubercular drugs. Methods: In this study 302 extrapulmonary samples from suspected cases of all age groups were included. Samples were first homogenised and decontaminated and then subjected to various diagnostic modalities like microscopy, culture and GeneXpert for Mycobacteria detection. Culture and smear positive isolates were subjected to LPA for determination of drug resistance in first and second-line anti-tubercular drugs. Results: Out of the 302 extrapulmonary samples, maximum samples were of lymph nodes (19.86%) followed by pus (17.88%). Male to female ratio was 1:3. GeneXpert detected 45.04% positive cases and 5.96% were rifampicin resistant. Positive samples detected by microscopy and culture were 21.19% and 24.17% respectively. When compared to culture, microscopy showed a sensitivity of 86.30% and specificity of 99.56%. GeneXpert reported 100% sensitivity and 72.48% specificity. LPA reported 9.45% isoniazid resistant cases, 4.05% rifampicin resistant cases and 5.40% both isoniazid and rifampicin resistant cases (MDR-TB). Out of the MDR-TB cases, 25% cases were resistant to fluoroquinolones indicating pre-XDR TB. Conclusions: For Mycobacterium tuberculosis detection in extrapulmonary samples, multiple modalities should be employed so that the bacilli in these samples is not missed and the turn-around time is lowered which is a key to TB control strategy.
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Chemotherapy is one of the important methods to treat cancer, and the emergence of multidrug resistance (MDR) is one major cause for the failure of cancer chemotherapy. Almost all anti-tumor drugs develop drug resistance over a period of time of application in cancer patients, reducing their effects on killing cancer cells. Chemoresistance can lead to a rapid recurrence of cancers and ultimately patient death. MDR may be induced by multiple mechanisms, which are associated with a complex process of multiple genes, factors, pathways, and multiple steps, and today the MDR-associated mechanisms are largely unknown. In this paper, from the aspects of protein-protein interactions, alternative splicing (AS) in pre-mRNA, non-coding RNA (ncRNA) mediation, genome mutations, variance in cell functions, and influence from the tumor microenvironment, we summarize the molecular mechanisms associated with MDR in cancers. In the end, prospects for the exploration of antitumor drugs that can reverse MDR are briefly discussed from the angle of drug systems with improved targeting properties, biocompatibility, availability, and other advantages.
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Objective To analyze the disease burden of multidrug-resistant tuberculosis (MDR-TB) in China and regions with different income levels in the world from 1990 to 2019. Methods Using the Global Burden of Disease Study 2019 (GBD2019) results, the changes of the disease burden of MDR-TB in China and regions with different income levels in the world were described and analyzed using the Joinpoint Regression Program 4.8.0.1 software. Results From 1990 to 2019, the age standardized incidence, mortality and DALY rates in China and other areas with different income levels in the world basically showed a trend of first rising and then decreasing at the turning point of the late 20th century and early 21st century, except for low-income areas where the age standardized incidence rate showed an overall upward trend. In 2019, the incidence rate, mortality and DALY rate of MDR-TB in China were 9 times, 6.67 times and 6.89 times higher than those in high-income areas, respectively. The incidence rate in China was 6 times lower than that in low and middle-income areas, while the mortality and DALY rate in China were 26 times and 32.53 times lower than those in low-income areas, respectively. The age standardized incidence, mortality rate and DALY rate of MDR-TB in men were higher than those in women. Risk factors for the burden of MDR-TB disease included alcohol consumption, smoking, and high fasting blood glucose. Conclusion From 1990 to 2019, there are significant regional and gender differences in the disease burden of multidrug-resistant tuberculosis in China and regions with different income levels in the world. Multidrug-resistant tuberculosis is still a major challenge for tuberculosis control in the world. It is necessary to develop more effective control strategies and health care systems to deal with multidrug-resistant tuberculosis.
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Aims@#This study was aimed at evaluating the phytochemical components and antibacterial activity of crude extracts of Allium sativum and Gongronema latifolium on multidrug-resistant isolates from clinical samples.@*Methodology and results@#Collection of clinical samples [wounds (43) and throat (17)] and plant leaves, preparation of extracts, gas chromatography-mass spectrophotometer (GC-MS), isolation and characterization of bacterial isolates were all carried out using standard microbiological techniques. Antibiotic resistance studies were conducted using the Kirby-Bauer disc diffusion method. Antibacterial assay of plant extracts was evaluated using the agar well diffusion method. From the results obtained, Gram-negative bacteria isolated were found to be 73.7% while Gram-positive were 26.3%. The result also showed that Staphylococcus aureus had the highest occurrence rate of 12(21.1%), while Citrobacter sp. 2(3.5%) was the least occurring bacteria organism isolated from the clinical samples. The antibiotic susceptibility pattern evaluated showed at least one resistance in all the clinical bacterial isolates. The results showed that all the isolates were resistant to imipenem with the exception of Citrobacter sp. The results of GC-MS analysis of plant extracts identified fourteen and twelve bioactive compounds in the leaf extracts of G. latifolium and A. sativum, respectively. All extracts showed antibacterial activity with zones of inhibition ranging from 04 to 28 mm against the different resistant bacteria used. Ethanol extracts showed higher antibacterial activity as compared to aqueous extracts. @*Conclusion, significance and impact of study@#The overall results of the present work provide baseline information for the possible use of these plants in treating bacterial infections involving MDR phenotypes. Thus, this study could serve as a foundation for exploring the potential of bioactive compounds of G. latifolium and A. sativum for the discovery of new antimicrobial drugs.
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Aims@#The aim of this study was to evaluate the antibacterial activity of bacteria associated with sea sponge Amphimedon sp. against multi-drug resistant (MDR) bacteria that cause wound infections.@*Methodology and results @#The antibacterial activity was evaluated by the overlay method. Identification of active bacterial symbionts was carried out using the 16S rRNA gene sequence-based method of bacterial identification. The results suggest that one of nine isolates had antibacterial activity against MDR bacteria. Isolate Z9VIII was identified as Bacillus subtilis and demonstrated robust antibacterial activity against bacteria: MRSA (11 mm), MDR-AB (17 mm) and CRPA (12 mm). @*Conclusion, significance and impact of study@#This study concludes that the one of the bacterial species associated with the sea sponge of Amphimedon sp. was B. subtilis, which has the potential as antibacterial agent against MDR bacteria.
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Objective:To explore the relationship and underlying mechanism between exosomes derived from doxorubicin-resistant osteosarcoma cells and MDR1 and miRNAs. Methods:MG63 and U2OS cell lines were selected to construct doxorubicin-resistant strains, and the 50% inhibitory concentration (half maximal inhibitory concentration, IC 50) of drug-resistant and sensitive strains was detected by MTT, and fluorescence staining was performed at intervals of 15 min between 15 and 120 min to detect the change of fluorescence intensity. RT-PCR and Western Blot were used to detect the expression levels of MDR1 P-gp to verify the drug resistance of osteosarcoma cells. Exosomes were identified by particle size analysis and Western Bolt detection. The endocytosis of PKH26-labeled exosomes from doxorubicin-resistant cells was observed, and the proliferation level and migration of exosomes from doxorubicin-resistant cells co-cultured with osteosarcoma cells were detected by MTT assay and cell scratch assay. The differential expression levels of miRNAs in osteosarcoma-sensitive and drug-resistant cells were verified by sequencing and bioinformatics analysis and RT-PCR assay. Tumor growth, serum exosome identification and mRNA expression level of miR-21-5p in tumor-bearing nude mice between normal osteosarcoma cell group and drug-resistant group, drug-resistant+normal exosome group, drug-resistant+drug-resistant+drug-resistant exosome group were observed. MDR1 expression level in tumor tissue was detected by RT-PCR, Western Blot and immunohistochemistry. Results:The IC 50 of two adriamycin resistant strains were 2.21 vs. 11.81 μg/ml and 0.93 vs. 11.81 μg/ml, respectively, and the fluorescence intensity decreased faster than that of normal strains. The relative mRNA expression levels of MDR1 in two cell lines were normal 1.12±0.16, 1.02±0.11 and drug-resistant 2.15±0.10, 2.127±0.12, respectively. The relative protein expression of P-gp was normal 0.92±0.11, 0.73±0.10 and drug-resistant 0.46±0.03, 0.30±0.04, the differences were statistically significant ( P<0.05). Drug-resistant exosomes can enter osteosarcoma cells through endocytosis and concentrate in the cytoplasm when co-cultured with normal strains. Osteosarcoma cells were co-cultured with drug-resistant exosomes at 2, 4, 6, and 8 μg/ml adriamycin, respectively. Compared with normal group, the proliferation level in drug-resistant group was significantly increased. Compared with the normal cell group 35.95±3.92, 6.72±3.55 and the normal exosome group 51.22±5.55, 19.31±1.93, the drug-resistant cell group 54.20±9.32, 19.24±2.88 and drug-resistant exosome group 76.40±5.41, 30.26±4.87, all had significantly higher cell mobility, the difference was statistically significant ( P<0.05). Exosome sequencing and biogenic analysis of 10 highly upregated miRNAs to validate mRNA expression differences between normal and drug-resistant strains by RT-PCR, showing a significant increase in miR-21-5p expression level of drug-resistant strains (5.89±0.26 vs. 0.99±0.06; 1.05±0.07 vs. 8.80±0.93, P<0.05), the difference was statistically significant ( P<0.05). In MG63 and U2OS, the normal cell group and drug-resistant cell group, and the normal exosome group and drug-resistant exosome group were compared, the tumor volume and the terminal tumor weight of nude mice were increased to varying degrees. MRNA relative expression levels of miR-21-5p in serum exosomes of nude mice after drug intervention were 0.86±0.07 and 0.86±0.05 in normal cell group, respectively. The values were 1.13±0.12, 1.14±0.12 in drug-resistant cell group, 0.71±0.05, 0.75±0.03 in normal exosome group, and 0.90±0.07, 0.93±0.04 in drug-resistant exosome group. Compared with normal and drug-resistant strains, the expression levels of normal and drug-resistant exosome groups were increased, with statistical significance ( P<0.05). Conclusion:The exosomes of drug-resistant cells in osteosarcoma could enhance the proliferation level and migration ability of cells through intercellular transfer of MDR1 and miRNAs. The expression of MDR1 and miR-21-5p in drug-resistant cells and tumor-forming nude mouse serum and tumor tissues were up-regulated which suggested that it might be involved in regulating the drug resistance process of osteosarcoma.
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Objective:To analyze the antimicrobial resistance and genomic characteristics of Salmonella enterica serovar Derby strains isolated from human and food sources in Hangzhou. Methods:A total of 60 Salmonella enterica serovar Derby strains isolated in Hangzhou during the period from 2015 to 2020 were subjected to antimicrobial susceptibility testing, pulsed field gel electrophoresis (PFGE) typing and whole-genome sequencing. Multilocus sequence typing (MLST), core genome multilocus sequence typing (cgMLST) and the identification of antimicrobial resistance genes were performed using the sequencing data. Phylogenetic tree based on the single nucleotide polymorphism (SNP) sites in the 60 genomes from Hangzhou and 379 genomes from public databases was constructed. Results:No significant difference was observed in the drug resistance rates between the clinical strains and food strains in Hangzhou. The multidrug resistance (MDR) rate was 76.7% (46/60). All of the 60 Salmonella Derby strains were positive for the antimicrobial resistance genes aac(6′)- Iaa and fosA7. The 60 strains were subtyped into 46 molecular types by PFGE and 53 molecular types by cgMLST(HC2). Except for one strain belonging to ST3220, the other Salmonella Derby strains were ST40. The phylogenetic analysis showed that some strains isolated in Hangzhou were close to the strains in Southeast Asia, suggesting the possibility of cross-border transmission of ST40 strains, with the main food sources being pork and fish; other strains were close to those circulating in Beijing, Guangzhou, Hubei, Chongqing and other provinces, suggesting the possibility of cross-province transmission of the strains, with the main food sources being pork, beef and chicken. Conclusions:The epidemic of Salmonella Derby in Hangzhou was mainly caused by the spread of ST40 strains and MDR was common. Clinical infections might be closely related to the consumption of pork, beef, chicken and fish. There was the possibility of cross-border transmission of Salmonella Derby between Hangzhou and Southeast Asia and cross-province transmission in China.
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Aim To study the synergistic effect of withaferin A (WA) combined with cisplatin (DDP) on cervical cancer and its mechanism. Methods MTT assay was employed to detect the synergistic effect of WA on DDP in cervical cancer cell lines. Annexin V-FITC/PI staining, TUNEL assay and immunoblotting were used to investigate the effect of WA combined with DDP on apoptosis of cervical cancer cells. Immunofluorescence and immunoblotting were used to detect NF-kB/MDR1 pathway related proteins. DCFH-DA and MitoSOX were applied to determine the intracellular reactive oxygen species (ROS) levels. A xenograft model was also used to evaluate the synergistic effect of WA on DDP. Results The combination of WA and DDP could inhibit the survival of cervical cancer cells, promote apoptosis, and inhibit the growth of tumor in mice. WA could inhibit DDP-induced NF-kB/MDR1 signaling pathway and promote ROS production. Conclusions WA plays a synergistic role in anti-cervical cancer by inhibiting DDP-induced NF-kB/MDR1 pathway activation and enhancing DDP induced ROS production.
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@#The present study was conducted to investigate the antimicrobial potential of essential oils of Curcuma longa and Syzygium aromaticum against multidrug-resistant pathogenic bacteria. Four identified bacterial isolates including Methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii were selected and their antibiotic sensitivity was checked by disc diffusion assay. C. longa and S. aromaticum were subjected to steam distillation to obtain their essential oils. The crude essential oils were fractioned by employing column chromatography. Crude essential oils and their fractions were evaluated for their antibacterial activity by agar well diffusion assay and minimum inhibitory concentrations were calculated. All the selected bacterial isolates showed resistance to three or more than three antibiotic groups and were declared as multidrugresistant (MDRs). Crude essential oils of C. longa and S. aromaticum exhibited antimicrobial activity against all selected isolates but S. aromaticum activity was better than the C. longa with a maximum 19.3±1.50 mm zone of inhibition against A. baumannii at 1.04 µL/mL MIC. GC/MS analysis revealed the abundance of components including eugenol, eugenyl acetate, b- caryophyllene, and a- Humulene in both crude oil and fractions of S. aromaticum. While the main components of C. longa essential oil were Ar-tumerone, a–tumerone, b- Tumerone, I-Phellandrene, a-zingibirene, b- sesquiphellandrene, and p- Cymene. This study highlights that plant-based essential oils could be a promising alternative to antibiotics for which pathogens have developed resistance. C. longa and S. aromaticum carry compounds that have antimicrobial potential against multiple drug-resistant bacteria including MRSA. E. coli, K. pneumoniae and A. baumannii.
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ABSTRACT Objective. Colistin is an antibiotic of last resort for treating serious Gram-negative bacterial infections. However, the misuse of colistin, especially as an animal growth promoter, has contributed to increasing antimicrobial resistance, mediated mainly through plasmid transfer of the mcr-1 gene. This study assessed the prevalence of phenotypic and molecular colistin resistance in Escherichia coli and Klebsiella pneumoniae in Ecuador in healthy humans and their chickens and pigs. Methods. Fecal samples were collected from humans and their chickens and pigs in two rural coastal and Amazon regions between April and August 2020. Gram-negative bacteria were isolated and identified using conventional techniques. Phenotypic resistance was determined using the broth microdilution technique, and the mcr-1 gene was detected using conventional polymerase chain reaction. Results. A total of 438 fecal samples were obtained from 137 humans, 147 pigs and 154 chickens. The prevalence of E. coli isolates was 86.3% (378/438) and K. pneumoniae, 37.4% (164/438). Overall, the mcr-1 gene was found in 90% (340/378) of E. coli isolates, with higher prevalences found in isolates from coastal regions (96.5%, 191/198), humans (95.6%, 111/116) and chickens (91.8%, 123/134); for K. pneumoniae, the gene was found in 19.5% (32/164) of isolates, with equal distribution between regions and hosts. Only four isolates, two E. coli and two K. pneumoniae, showed phenotypic resistance: mcr-1 was present in both E. coli strains but absent in the K. pneumoniae strains. Conclusions. Despite a low prevalence of phenotypic resistance to colistin, the high prevalence of the mcr-1 gene in E. coli is of concern. Ecuador's ban on using colistin in animal husbandry must be enforced, and continual monitoring of the situation should be implemented.
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RESUMO Objetivo. A colistina é um antibiótico de último recurso para o tratamento de infecções graves por bactérias Gram-negativas. Entretanto, o uso indevido da colistina, principalmente como promotor de crescimento animal, tem contribuído para o aumento da resistência a antimicrobianos, principalmente por transferência horizontal do gene mcr-1 mediada por plasmídeos. Este estudo avaliou a prevalência de resistência fenotípica e molecular à colistina em Escherichia coli e Klebsiella pneumoniae no Equador em humanos hígidos e em galinhas e porcos por eles criados. Métodos. Entre abril e agosto de 2020, foram coletadas amostras de fezes de habitantes de duas regiões litorâneas e amazônicas do Equador e de galinhas e porcos por eles criados. Bactérias Gram-negativas foram isoladas e identificadas por meio de técnicas convencionais. A resistência fenotípica foi determinada pela técnica de microdiluição em caldo, e o gene mcr-1 foi detectado por reação em cadeia da polimerase convencional. Resultados. Foram obtidas 438 amostras fecais de 137 humanos, 147 suínos e 154 galinhas. A prevalência de isolados de E. coli foi de 86,3% (378/438), e de K. pneumoniae, 37,4% (164/438). Em geral, o gene mcr-1 foi encontrado em 90% (340/378) dos isolados de E. coli, com maiores prevalências encontradas em isolados de regiões litorâneas (96,5%, 191/198), humanos (95,6%, 111/116) e galinhas (91,8%, 123/134); para K. pneumoniae, o gene foi encontrado em 19,5% (32/164) dos isolados, com igual distribuição entre regiões e hospedeiros. Somente quatro isolados, dois de E. coli e dois de K. pneumoniae, demonstraram resistência fenotípica: o gene mcr-1 estava presente em ambas as cepas de E. coli, mas ausente nas de K. pneumoniae. Conclusões. Apesar da baixa prevalência de resistência fenotípica à colistina, a alta prevalência do gene mcr-1 em E. coli é preocupante. É preciso fiscalizar a proibição ao uso agropecuário de colistina no Equador e implementar o monitoramento contínuo da situação.
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Abstract Paclitaxel (PTX) is one of the most effective drugs used in the treatment of breast cancer. Nonetheless, the appearance of MDR1 (multidrug resistance 1) in tumor cells has become a significant hindrance for efficacious chemotherapy. In this study, we show that the expression level of Egr-1 (early growth response gene-1) in cancer tissues (from paclitaxel chemotherapy failure patients) and MCF-7/PTX cells (the breast cancer cell line that was resistant to paclitaxel) was increased. Cell proliferation assay and apoptosis assay revealed that Egr-1 could promote cell growth and inhibit apoptosis in MCF-7/PTX. Mechanistic studies indicated that Egr-1 could bind to the proximal MDR1 promoter and enhance MDR1 transcription. These findings indicate that paclitaxel induced Egr-1 accumulation and upregulated the expression of MDR1, thereby inducing the drug resistance in MCF-7/PTX. Our results suggest a novel pathway by which paclitaxel induces MDR1 expression, possibly illuminating a potential target pathway for the prevention of MDR1-mediated drug resistance.
Subject(s)
Breast Neoplasms/pathology , Drug Resistance , ATP Binding Cassette Transporter, Subfamily B, Member 1/analysis , Pharmaceutical Preparations/analysisABSTRACT
La nueva norma técnica para el control y la eliminación de la tuberculosis es un gran avance para el diagnóstico de este microorganismo en Chile. Actualmente la principal técnica microbiológica para el diagnóstico de laboratorio es la biología molecular, que reduce el tiempo del resultado a tan solo un par de horas. La normativa actual indica que en el paciente caso presuntivo de tuberculosis (CPT) la técnica exclusiva a realizar es Biología molecular. La literatura indica que la detección a través de amplificación de material genético de la micobacteria tiene un límite de detección de 15,6 UFC/ ml, por tanto, todas las muestras bajo ese límite umbral potencialmente podrían no ser diagnosticadas bajo esta estructura emanada por el ministerio de Salud en Chile. Nuestra recomendación es continuar con el estudio de cultivo en medios líquidos o sólidos para todas las muestras hasta obtener literatura que avale lo contrario
The new technical standard for the control and elimination of tuberculosis in Chile is a great advance for the diagnosis of this microorganism. Currently the main microbiological technique for laboratory diagnosis is PCR, which reduces the time to result to just a couple of hours. The current regulations indicate that in the patient with a presumptive case of tuberculosis (CPT) t he exclusive technique to be performed is PCR. The literature indicates that the detection through amplification of genetic material of the mycobacterium has a detection limit of 15.6 CFU/ml, therefore, all samples under this threshold limit could potentially not be diagnosed under this structure emanated by the Ministry of Health in Chile. Our recommendation is to continue with the study of culture in liquid or solid media for all samples until literature confirms otherwise
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Tuberculosis/diagnosis , COVID-19 Nucleic Acid Testing , Mycobacterium tuberculosis/isolation & purification , Tuberculosis/microbiologyABSTRACT
Due to emerging drug resistance in pathogenic organisms, most of the second generation antibiotics are not effective in controlling the disease. As a consequence, the dosage and duration of drug intake has increased leading to drug induced toxicity and various side effects. A large number of natural products are being reported to ameliorate the toxicity and oxidative stress caused by antibiotics. Here, we explored the antioxidative potential of honey bee product propolis alone as well as in combination with antibiotics in Staphylococcus aureus infected BALB/c mice. For experimental design, mice were divided in to seven groups and decapitated after experimental period. Kidney was excised, homogenized and then used for different biochemical and histopathological estimations. Results observed after treatment with propolis and antibiotics were compared with those of S. aureus infected group. Results showed increase in lipid peroxidation, decrease in reduced glutathione levels and antioxidant enzymes such as; catalase, superoxide dismutase, glutathione-S-transferase, glutathione peroxidase and glutathione reductase. On the contrary, treatment with propolis, led to reduction in levels of LPO and increase in activities of antioxidant enzymes. Also, histopathology of kidney and all kidney function enzymes were restored to near normal.