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Antioxidants (Basel, Switzerland) Jun 2024Melanin, the pigment responsible for human skin color, increases susceptibility to UV radiation, leading to excessive melanin production and hyperpigmentation disorders....
Melanin, the pigment responsible for human skin color, increases susceptibility to UV radiation, leading to excessive melanin production and hyperpigmentation disorders. This study investigated the ethanolic extract of fruits for its phenolic and flavonoid contents, antioxidant activity, and impact on melanogenesis pathways using qRT-PCR and Western blot analysis. Utilizing network pharmacology, molecular docking, and dynamics simulations, researchers explored fruit extract's active compounds, targets, and pharmacological effects on hyperpigmentation. fruit extract exhibited antioxidant properties, scavenging DPPH and ABTS radicals radicals and chelating copper. It inhibited cellular tyrosinase activity and melanin content in stimulated B16F10 cells, downregulating TYR, TRP-1, phosphorylated CREB, CREB, and MITF proteins along with transcription levels of MITF, TYR, and TRP-2. LC-MS analysis identified thirty-three metabolites, with seventeen compounds selected for further investigation. Network pharmacology revealed 41 hyperpigmentation-associated genes and identified significant GO terms and KEGG pathways, including cancer-related pathways. Kaempferol-3-O-α-L-rhamnoside exhibited high binding affinity against MAPK3/ERK1, potentially regulating melanogenesis by inhibiting tyrosinase activity. Stable ligand-protein interactions in molecular dynamics simulations supported these findings. Overall, this study suggests that the ethanolic extract of fruits possesses significant antioxidant, tyrosinase inhibitory, and anti-melanogenic properties mediated through key molecular targets and pathways.
PubMed: 38929152
DOI: 10.3390/antiox13060713 -
Microbiology Spectrum Jun 2024() is a Gram-negative intracellular pathogen that causes melioidosis in humans, a neglected, underreported, and lethal disease that can reach a fatal outcome in over...
UNLABELLED
() is a Gram-negative intracellular pathogen that causes melioidosis in humans, a neglected, underreported, and lethal disease that can reach a fatal outcome in over 50% of the cases. It can produce both acute and chronic infections, the latter being particularly challenging to eliminate because of the intracellular life cycle of the bacteria and its ability to generate a "persister" dormant state. The molecular mechanism that allows the switch between growing and persister phenotypes is not well understood but it is hypothesized to be due at least in part to the participation of toxin-antitoxin (TA) systems. We have previously studied the link between one of those systems (defined as HigBA) with specific expression patterns associated with levofloxacin antibiotic exposure. Through methods, we predicted the presence of another three pairs of genes encoding for additional putative HigBA systems. Therefore, our main goal was to establish which mechanisms are conserved as well as which pathways are specific among different TA systems from the same family. We hypothesize that the high prevalence, and sometimes even redundancy of these systems in the chromosomes indicates that they can interact with each other and not function as only individual systems, as it was traditionally thought, and might be playing an undefined role in lifecycle. Here, we show that both the toxin and the antitoxin of the different systems contribute to bacterial survival and that toxins from the same family can have a cumulative effect under environmental stressful conditions.
IMPORTANCE
Toxin-antitoxin (TA) systems play a significant role in bacterial persistence, a phenomenon where bacterial cells enter a dormant or slow-growing state to survive adverse conditions such as nutrient deprivation, antibiotic exposure, or host immune responses. By studying TA systems in , we can gain insights into how this pathogen survives and persists in the host environment, contributing to its virulence and ability to cause melioidosis chronic infections.
PubMed: 38916327
DOI: 10.1128/spectrum.00748-24 -
IJID Regions Jun 2024Melioidosis, an emerging infectious disease caused by the Gram-negative bacillus , is massively underdiagnosed in many low- and middle-income countries. The disease is... (Review)
Review
Melioidosis, an emerging infectious disease caused by the Gram-negative bacillus , is massively underdiagnosed in many low- and middle-income countries. The disease is clinically extremely variable, has a high case fatality rate, and is assumed to be highly endemic in South Asian countries, including Nepal. The reasons for underdiagnosis include the lack of awareness among clinicians and laboratory staff and limited microbiological capacities. Because costly laboratory equipment and consumables are likely to remain a significant challenge in many melioidosis-endemic countries in the near future, it will be necessary to make optimum use of available tools and promote their stringent implementation. Therefore, we suggest that health facilities in resource-poor countries, such as Nepal, introduce a simple and low-cost diagnostic laboratory algorithm for the identification of cultures. This screening algorithm should be applied specifically to samples from patients with fever of unknown origin and risk factors for melioidosis, such as diabetes. In addition, there could also be a role of low-cost, novel, promising serological point-of-care tests, which are currently under research and development.
PubMed: 38872919
DOI: 10.1016/j.ijregi.2024.100377 -
Respiratory Medicine Case Reports 2024Melioidosis is a tropical infectious disease that ranks as northeastern Thailand's third most common infectious cause of death. The manifestations of melioidosis vary...
Melioidosis is a tropical infectious disease that ranks as northeastern Thailand's third most common infectious cause of death. The manifestations of melioidosis vary depending on the organs involved and often resemble malignancy and tuberculosis. We present a case of an atypical melioidosis presentation in a patient with low-grade fever and facial swelling without any risk factors. Chest CT revealed a 3.3-cm heterogeneous enhancing right lower paratracheal lymph nodes with thrombosis of the superior vena cava and azygos vein. Endobronchial ultrasound-guided transbronchial needle aspiration of lymph node was performed, and was identified through lymph node culture. The patient underwent a three-week intravenous course of ceftazidime and a 12-week oral course of trimethoprim-sulfamethoxazole. Oral anticoagulation was also administered. Follow-up computed tomography of the thorax after completion of treatment revealed no residual lymphadenopathy and thrombosis.
PubMed: 38868163
DOI: 10.1016/j.rmcr.2024.102048 -
Quantitative Imaging in Medicine and... Jun 2024Melioidosis pneumonia, caused by the bacterium , is a serious infectious disease prevalent in tropical regions. Chest computed tomography (CT) has emerged as a valuable...
BACKGROUND
Melioidosis pneumonia, caused by the bacterium , is a serious infectious disease prevalent in tropical regions. Chest computed tomography (CT) has emerged as a valuable tool for assessing the severity and progression of lung involvement in melioidosis pneumonia. However, there persists a need for the quantitative assessment of CT characteristics and staging methodologies to precisely anticipate disease progression. This study aimed to quantitatively extract CT features and evaluate a CT score-based staging system in predicting the progression of melioidosis pneumonia.
METHODS
This study included 97 patients with culture-confirmed melioidosis pneumonia who presented between January 2002 and December 2021. Lung segmentation and annotation of lesions (consolidation, nodules, and cavity) were used for feature extraction. The features, including the involved area, amount, and intensity, were extracted. The CT scores of the lesion features were defined by the feature importance weight and qualitative stage of melioidosis pneumonia. Gaussian process regression (GPR) was used to predict patients with severe or critical melioidosis pneumonia according to CT scores.
RESULTS
The melioidosis pneumonia stages included acute stage (0-7 days), subacute stage (8-28 days), and chronic stage (>28 days). In the acute stage, the CT scores of all patients ranged from 2.5 to 6.5. In the subacute stage, the CT scores for the severe and mild patients were 3.0-7.0 and 2.0-5.0, respectively. In the chronic stage, the CT score of the mild patients fluctuated approximately between 2.5 and 3.5 in a linear distribution. Consolidation was the most common type of lung lesion in those with melioidosis pneumonia. Between stages I and II, the percentage of severe scans with nodules dropped from 72.22% to 47.62% (P<0.05), and the percentage of severe scans with cavities significantly increased from 16.67% to 57.14% (P<0.05). The GPR optimization function yielded area under the receiver operating characteristic curves of 0.71 for stage I, 0.92 for stage II, and 0.87 for all stages.
CONCLUSIONS
In patients with melioidosis pneumonia, it is reasonable to divide the period (the whole progression of melioidosis pneumonia) into three stages to determine the prognosis.
PubMed: 38846316
DOI: 10.21037/qims-23-1476 -
Nature Communications Jun 2024Mitophagy is critical for mitochondrial quality control and function to clear damaged mitochondria. Here, we found that Burkholderia pseudomallei maneuvered host...
Mitophagy is critical for mitochondrial quality control and function to clear damaged mitochondria. Here, we found that Burkholderia pseudomallei maneuvered host mitophagy for its intracellular survival through the type III secretion system needle tip protein BipD. We identified BipD, interacting with BTB-containing proteins KLHL9 and KLHL13 by binding to the Back and Kelch domains, recruited NEDD8 family RING E3 ligase CUL3 in response to B. pseudomallei infection. Although evidently not involved in regulation of infectious diseases, KLHL9/KLHL13/CUL3 E3 ligase complex was essential for BipD-dependent ubiquitination of mitochondria in mouse macrophages. Mechanistically, we discovered the inner mitochondrial membrane IMMT via host ubiquitome profiling as a substrate of KLHL9/KLHL13/CUL3 complex. Notably, K63-linked ubiquitination of IMMT K211 was required for initiating host mitophagy, thereby reducing mitochondrial ROS production. Here, we show a unique mechanism used by bacterial pathogens that hijacks host mitophagy for their survival.
Topics: Burkholderia pseudomallei; Mitophagy; Animals; Mice; Mitochondria; Bacterial Proteins; Humans; Macrophages; Ubiquitination; Melioidosis; Host-Pathogen Interactions; Reactive Oxygen Species; Type III Secretion Systems; Mice, Inbred C57BL; Mitochondrial Membranes; HEK293 Cells; RAW 264.7 Cells
PubMed: 38834545
DOI: 10.1038/s41467-024-48824-x -
Journal of Infection and Public Health Jul 2024Burkholderia pseudomallei, a Gram-negative pathogen, causes melioidosis. Although various clinical laboratory identification methods exist, culture-based techniques lack... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Burkholderia pseudomallei, a Gram-negative pathogen, causes melioidosis. Although various clinical laboratory identification methods exist, culture-based techniques lack comprehensive evaluation. Thus, this systematic review and meta-analysis aimed to assess the diagnostic accuracy of culture-based automation and non-automation methods.
METHODS
Data were collected via PubMed/MEDLINE, EMBASE, and Scopus using specific search strategies. Selected studies underwent bias assessment using QUADAS-2. Sensitivity and specificity were computed, generating pooled estimates. Heterogeneity was assessed using I statistics.
RESULTS
The review encompassed 20 studies with 2988 B. pseudomallei samples and 753 non-B. pseudomallei samples. Automation-based methods, particularly with updating databases, exhibited high pooled sensitivity (82.79%; 95% CI 64.44-95.85%) and specificity (99.94%; 95% CI 98.93-100.00%). Subgroup analysis highlighted superior sensitivity for updating-database automation (96.42%, 95% CI 90.01-99.87%) compared to non-updating (3.31%, 95% CI 0.00-10.28%), while specificity remained high at 99.94% (95% CI 98.93-100%). Non-automation methods displayed varying sensitivity and specificity. In-house latex agglutination demonstrated the highest sensitivity (100%; 95% CI 98.49-100%), followed by commercial latex agglutination (99.24%; 95% CI 96.64-100%). However, API 20E had the lowest sensitivity (19.42%; 95% CI 12.94-28.10%). Overall, non-automation tools showed sensitivity of 88.34% (95% CI 77.30-96.25%) and specificity of 90.76% (95% CI 78.45-98.57%).
CONCLUSION
The study underscores automation's crucial role in accurately identifying B. pseudomallei, supporting evidence-based melioidosis management decisions. Automation technologies, especially those with updating databases, provide reliable and efficient identification.
Topics: Burkholderia pseudomallei; Melioidosis; Humans; Sensitivity and Specificity; Automation, Laboratory; Bacteriological Techniques; Automation
PubMed: 38820898
DOI: 10.1016/j.jiph.2024.04.022 -
PLoS Neglected Tropical Diseases May 2024Melioidosis is a bacterial infection caused by Burkholderia pseudomallei, that is common in tropical and subtropical countries including Southeast Asia and Northern...
Melioidosis is a bacterial infection caused by Burkholderia pseudomallei, that is common in tropical and subtropical countries including Southeast Asia and Northern Australia. The magnitude of undiagnosed and untreated melioidosis across the country remains unclear. Given its proximity to regions with high infection rates, Riau Province on Sumatera Island is anticipated to have endemic melioidosis. This study reports retrospectively collected data on 68 culture-confirmed melioidosis cases from two hospitals in Riau Province between January 1, 2009, and December 31, 2021, with full clinical data available on 41 cases. We also describe whole genome sequencing and genotypic analysis of six isolates of B. pseudomallei. The mean age of the melioidosis patients was 49.1 (SD 11.5) years, 85% were male and the most common risk factor was diabetes mellitus (78%). Pulmonary infection was the most common presentation (39%), and overall mortality was 41%. Lung as a focal infection (aOR: 6.43; 95% CI: 1.13-36.59, p = 0.036) and bacteremia (aOR: 15.21; 95% CI: 2.59-89.31, p = 0.003) were significantly associated with death. Multilocus sequence typing analysis conducted on six B.pseudomallei genomes identified three sequence types (STs), namely novel ST1794 (n = 3), ST46 (n = 2), and ST289 (n = 1). A phylogenetic tree of Riau B. pseudomallei whole genome sequences with a global dataset of genomes clearly distinguished the genomes of B. pseudomallei in Indonesia from the ancestral Australian clade and classified them within the Asian clade. This study expands the known presence of B. pseudomallei within Indonesia and confirms that Indonesian B. pseudomallei are genetically linked to those in the rest of Southeast Asia. It is anticipated that melioidosis will be found in other locations across Indonesia as laboratory capacities improve and standardized protocols for detecting and confirming suspected cases of melioidosis are more widely implemented.
Topics: Humans; Burkholderia pseudomallei; Melioidosis; Male; Middle Aged; Female; Indonesia; Genetic Variation; Adult; Retrospective Studies; Whole Genome Sequencing; Phylogeny; Genotype; Aged; Risk Factors
PubMed: 38805481
DOI: 10.1371/journal.pntd.0012195 -
International Journal of Environmental... May 2024Melioidosis is an endemic infectious disease caused by bacteria, which contaminates soil and water. To better understand the environmental changes that have contributed...
Melioidosis is an endemic infectious disease caused by bacteria, which contaminates soil and water. To better understand the environmental changes that have contributed to melioidosis outbreaks, this study used spatiotemporal analyses to clarify the distribution pattern of melioidosis and the relationship between melioidosis morbidity rate and local environmental indicators (land surface temperature, normalised difference vegetation index, normalised difference water index) and rainfall. A retrospective study was conducted from January 2013 to December 2022, covering data from 219 sub-districts in Northeast Thailand, with each exhibiting a varying morbidity rate of melioidosis on a monthly basis. Spatial autocorrelation was determined using local Moran's , and the relationship between the melioidosis morbidity rate and the environmental indicators was evaluated using a geographically weighted Poisson regression. The results revealed clustered spatiotemporal patterns of melioidosis morbidity rate across sub-districts, with hotspots predominantly observed in the northern region. Furthermore, we observed a range of coefficients for the environmental indicators, varying from negative to positive, which provided insights into their relative contributions to melioidosis in each local area and month. These findings highlight the presence of spatial heterogeneity driven by environmental indicators and underscore the importance of public health offices implementing targeted monitoring and surveillance strategies for melioidosis in different locations.
Topics: Melioidosis; Thailand; Humans; Retrospective Studies; Burkholderia pseudomallei; Remote Sensing Technology; Morbidity; Spatio-Temporal Analysis; Rain
PubMed: 38791828
DOI: 10.3390/ijerph21050614 -
Diagnostics (Basel, Switzerland) May 2024Early diagnosis is essential for the successful management of infection, but it cannot be achieved by the current gold standard culture technique. Therefore, this study...
Early diagnosis is essential for the successful management of infection, but it cannot be achieved by the current gold standard culture technique. Therefore, this study aimed to develop a lateral flow immunoassay (LFIA) targeting capsular polysaccharide. The development was performed by varying nitrocellulose membrane reaction pads and chase buffers. The prototype LFIA is composed of Unisart CN95 and chase buffer containing tris-base, casein, and Surfactant 10G. The assay showed no cross-reactivity with , , and The limit of detections (LODs) of the prototype LFIA was 10 and 10 CFU/mL in hemoculture medium and artificial urine, respectively. These LODs suggest that this prototype can detect melioidosis from positive hemoculture bottles but not straight from urine. Additionally, these LODs are still inferior compared to Active Melioidosis Detect (AMD). Overall, this prototype holds the potential to be used clinically with hemoculture bottles. However, further improvements should be considered, especially for use with urine samples.
PubMed: 38786331
DOI: 10.3390/diagnostics14101033