Search Results (76)

Background: Dendritic cells (DCs) play an important role as a bridge between innate and adaptive immunity, and changes in gene expression of DCs during the immune response to Mycobacterium tuberculosis (M.tb) may affect the development of tuberculosis. Methods: Using systems biology methods, mRNA and miRNA expression profile data of DCs infected with M.tb were obtained. A total of 1398 differentially expressed mRNAs and 79 differentially expressed miRNAs were identified, and a corresponding miRNA–mRNA regulatory network was constructed using Cytoscape 3.9.1 software. The functional annotations and pathway classifications of the miRNA–mRNA network were identified using the DAVID tool. Then, the key pathway modules in the miRNA–mRNA network were screened and subjected to PPI network analysis to identify hub nodes. Subsequently the miRNA/mRNA axis was determined, validated by qRT-PCR, and evaluated through ROC curve analysis. Results: The TNF signaling pathway and the Tuberculosis pathway were key pathway modules, with miR-34a-3p/TNF and miR-190a-3p/IL1B being the greatest correlations with the two pathway modules. qRT-PCR results showed that IL1B and miR-190a-3p exhibited significant differences in both the H37Ra and BCG infection groups. The AUC of two factors (IL1B and miR-190a-3p) was 0.9561 and 0.9625, respectively, showing high sensitivity and specificity. Conclusions: Consequently, miR-190a-3p/IL1B might be a good candidate marker to characterize the immune response of DCs to M.tb and a transition signal from innate to adaptive immunity. Full article

Background: The Bacille Calmette–Guérin (BCG) vaccine is part of the Extended Programme on Immunization (EPI) and as such is generally administered at birth. The global introduction of BCG not only protected many vaccinated infants against severe complications of tuberculosis but also resulted in markedly reduced overall childhood mortality. Studies in human adults determined that BCG vaccination induces epigenetic reprogramming of innate immune cells (also known as trained immunity) and can also enhance T cell responses to both mycobacterial and non-mycobacterial antigens. Goal and Methods: The current study tested the hypothesis that BCG immunization similarly impacts the functionally distinct infant immune system. Towards this goal, we applied RNA sequencing to assess transcriptome changes in circulating CD4⁺ T cells of Malawian infants prior to and 2 to 13 weeks after BCG immunization. Results: In the first three months of life, transcriptome changes of infant CD4 T cells implied a functional shift towards T helper 1 and Th17 immunity. Vaccination with BCG resulted in additional modulation of the CD4 T cell transcriptome and differentially expressed genes could be linked to metabolomic function. Conclusions: These findings are consistent with data reported in BCG vaccinated adults and contribute to the understanding of molecular changes in infant CD4 T cells that may explain the improved capacity of the infant immune system to respond to pathogens after BCG vaccination. Full article

Mycobacterium tuberculosis (Mtb) is a major global health threat, exacerbated by the emergence of antibiotic-resistant strains. This study investigated fluoroquinolone resistance protein A (MfpA), which enhances mycobacterial survival by targeting host mitochondria and regulating apoptosis. Wild-type (WT) and knockout (KO) Mycobacterium bovis Bacillus Calmette-Guérin (BCG) strains, a common model for Mtb, were utilized to examine host cell responses. Compared to WT strains, KO strains showed reduced colony-forming units (CFUs), elevated TNF-α and IL-6 levels, and increased apoptosis. MfpA was found to localize to mitochondria, increasing ROS production and disrupting mitochondrial membrane potential. Transcriptomic analysis revealed that MfpA modulated the NF-κB signaling pathway, regulating the expression of gadd45β. These results suggest that MfpA drives both antibiotic resistance and virulence by suppressing apoptosis via the mitochondrial and NF-κB pathways, promoting mycobacterial persistence. Studies using BCG provide valuable insight into Mtb’s survival mechanisms, highlighting MfpA’s dual role in resistance and pathogenesis. Full article

Several studies showed that the incidence of Alzheimer’s disease (AD) is significantly lower in patients with non-muscle invasive bladder cancer (NMIBC) treated with intravesical bacillus Calmette–Guérin (BCG) instillations compared to treatment by alternative methods. Hypothetically, failure to clear misfolded and aggregated proteins (i.e., beta-amyloid) in AD brains and peripheral blood mononuclear cells (PBMCs) implicates BCG in upgrading the unfolded protein response (UPR). To test this hypothesis, pre- versus post-BCG PBMC proteins of the UPR pathway were compared in six NMIBC patients by capillary immunoelectrophoresis on an Abby instrument. PERK, the endoplasmic reticulum (ER) resident kinase, a stress-activated sensor, and its substrate alpha component of the eIF2 translation factor (eIF2a) complex inactivation were considered as potentially proapoptotic via a downstream proapoptotic transcription factor only if persistently high. GAPDH, a glycolytic marker of innate immunocyte training by BCG, and eight other UPR proteins were considered antiapoptotic. Summation of antiapoptotic %change scores per patient showed that the older the age, the lower the antiapoptotic %change. Higher antiapoptotic scores were observed upon a longer time from BCG treatment (with the exception of the patient in her ninth decade of life). Studies with more individuals could substantiate that BCG enhances the antiapoptotic aggregate-clearance effect of the UPR in PBMCs of NMIBC patients, which hypothetically protects brain cells against AD. Full article

This study evaluated the application of the BCG Sense1 wearable device for monitoring the heart rate (HR) and the respiratory rate (RR) in dogs, comparing its performance to the gold standard ECG under awake and anesthetized conditions. Data were collected from twelve dogs, with six awake beagles and six anesthetized client-owned dogs. Bland–Altman analysis and linear regression revealed strong correlations between BCG and ECG under both awake and anesthetized conditions (HR: r = 0.97, R² = 0.94; RR: r = 0.78, R² = 0.61, and p < 0.001). While slight irregularities were noted in respiratory rate measurements in both groups, potentially affecting the concordance between methods, BCG maintained a significant correlation with ECG under anesthesia (HR: r = 0.96, R² = 0.92; RR: r = 0.85, R² = 0.72, and p < 0.01). The wearable BCG-Sense 1 sensor enables continuous monitoring over 24 h, while ECG serves as the gold standard reference. These findings prove that BCG can be a good alternative to ECG for the monitoring of vital signs in clinical, perioperative, intraoperative, and postoperative settings. The strong correlation between the BCG and ECG signals in awake and anesthetized states highlights the prospects of BCG technology as a revolutionary method in veterinary medicine. As a non-invasive and real-time monitoring system, the BCG Sense1 device strengthens clinical diagnosis and reduces physiological variations induced by stress. Full article

Hypertension (HPT) is a chronic disease characterized by the consistent elevation of arterial blood pressure, which is considered to be a significant risk factor for conditions such as stroke, coronary artery disease, and heart failure. The detection and continuous monitoring of HPT can be a demanding process. As a non-contact measuring method, the ballistocardiography (BCG) signal characterizes the repetitive body motion resulting from the forceful ejection of blood into the major blood vessels during each heartbeat. Therefore, it can be applied for HPT detection. HPT detection with BCG signals remains a challenging task. In this study, we propose an end-to-end deep convolutional model BH-Net for HPT detection through BCG signals. We also propose a data augmentation scheme by selecting the J-peak neighborhoods from the BCG time sequences for hypertension detection. Rigorously evaluated via a public data-set, we report an average accuracy of 97.93% and an average F1-score of 97.62%, outperforming the comparative state-of-the-art methods. We also report that the performance of the traditional machine learning methods and the comparative deep learning models was improved with the proposed data augmentation scheme. Full article

Blood pressure (BP) measurement is a major physiological information for people with cardiovascular diseases, such as hypertension, heart failure, and atherosclerosis. Moreover, elders and patients with kidney disease and diabetes mellitus also are suggested to measure their BP every day. The cuffless BP measurement has been developed in the past 10 years, which is comfortable to users. Now, ballistocardiogram (BCG) and impedance plethysmogram (IPG) could be used to perform the cuffless BP measurement. Thus, the aim of this study is to realize edge computing for the BP measurement in real time, which includes measurements of BCG and IPG signals, digital signal process, feature extraction, and BP estimation by machine learning algorithm. This system measured BCG and IPG signals from a bodily weight-fat scale with the self-made circuits. The signals were filtered to reduce the noise and segmented by 2 s. Then, we proposed a flowchart to extract the parameter, pulse transit time (PTT), within each segment. The feature included two calibration-based parameters and one calibration-free parameter was used to estimate BP with XGBoost. In order to realize the system in STM32F756ZG NUCLEO development board, we limited the hyperparameters of XGBoost model, including maximum depth (max_depth) and tree number (n_estimators). Results show that the error of systolic blood pressure (SBP) and diastolic blood pressure (DBP) in server-based computing are 2.64 ± 9.71 mmHg and 1.52 ± 6.32 mmHg, and in edge computing are 2.2 ± 10.9 mmHg and 1.87 ± 6.79 mmHg. This proposed method significantly enhances the feasibility of bodily weight-fat scale in the BP measurement for effective utilization in mobile health applications. Full article

Non-muscle invasive bladder cancer (NMIBC) accounts for approximately 70–75% of all bladder cancer cases. The standard treatment for high-risk NMIBC involves transurethral tumour resection followed by intravesical Bacillus Calmette–Guerin (BCG) immunotherapy. While BCG immunotherapy is both safe and effective, it frequently leads to the development of lower urinary tract symptoms (LUTS) such as urinary urgency, frequency, dysuria, and pelvic discomfort. These symptoms can significantly diminish patients’ quality of life and may result in the discontinuation of BCG treatment, adversely affecting oncological outcomes. Despite the considerable clinical impact of BCG-induced LUTS, the underlying mechanisms remain unclear, hindering the implementation or development of effective treatments. This review provides novel insights into the potential mechanisms underlying BCG-induced LUTS, focusing on the integrated roles of afferent and efferent nerves in both normal and pathological bladder sensation and function. Specifically, this review examines how the body’s response to BCG—through the development of inflammation, increased urothelial permeability, and altered urothelial signalling—might contribute to LUTS development. Drawing from known mechanisms in other common urological disorders and data from successful clinical trials involving NMIBC patients, this review summarises evidence supporting the likely changes in both sensory nerve signalling and bladder muscle function in the development of BCG-induced LUTS. However, further research is required to understand the intricate mechanisms underlying the development of BCG-induced LUTS and identify why some patients are more likely to experience BCG intolerance. Addressing these knowledge gaps could have profound implications for patients’ quality of life, treatment adherence, and overall outcomes in NMIBC care. Full article

This comprehensive review offers a thorough examination of fetal heart rate (fHR) monitoring methods, which are an essential component of prenatal care for assessing fetal health and identifying possible problems early on. It examines the clinical uses, accuracy, and limitations of both modern and traditional monitoring techniques, such as electrocardiography (ECG), ballistocardiography (BCG), phonocardiography (PCG), and cardiotocography (CTG), in a variety of obstetric scenarios. A particular focus is on the most recent developments in textile-based wearables for fHR monitoring. These innovative devices mark a substantial advancement in the field and are noteworthy for their continuous data collection capability and ergonomic design. The review delves into the obstacles that arise when incorporating these wearables into clinical practice. These challenges include problems with signal quality, user compliance, and data interpretation. Additionally, it looks at how these technologies could improve fetal health surveillance by providing expectant mothers with more individualized and non-intrusive options, which could change the prenatal monitoring landscape. Full article

The antioxidant defense is critical for the survival of intracellular pathogens such as Mycobacterium tuberculosis complex (MTBC) species, including Mycobacterium bovis, which are often exposed to an oxidative environment caused by reactive oxygen species (ROS) in hosts. However, the signaling pathway in mycobacteria for sensing and responding to oxidative stress remains largely unclear. In this study, we characterize a TetR-type transcription regulator BCG_3893c, designated AotM, as a novel redox sensor in Mycobacterium bovis that increases mycobacterial tolerance to oxidative stress. AotM is required for the growth of M. bovis in the presence of 1 mM hydrogen peroxide. Loss of the aotM gene leads to altered transcriptional profiles with 352 genes significantly up-regulated and 25 genes significantly down-regulated. AotM recognizes a 14-bp palindrome sequence motif and negatively regulates the expression of a FAD-dependent oxidoreductase encoded by bcg_3892c. Overexpression of BCG_3892c increases intracellular ROS production and reduces the growth of M. bovis. In summary, we propose that AotM enhances the mycobacterial resistance against oxidative stress probably by inhibiting intracellular ROS production. Our findings reveal a novel underlying regulatory mechanism behind mycobacterial oxidative stress adaptation. Full article

Mycobacterium tuberculosis causes 6.4 million cases of tuberculosis and claims 1.6 million lives annually. Mycobacterial adhesion, invasion of host cells, and subsequent intracellular survival are crucial for the infection and dissemination process, yet the cellular mechanisms underlying these phenomena remain poorly understood. This study created a Bacillus Calmette–Guérin (BCG) transposon library using a MycomarT7 phage carrying a Himar1 Mariner transposon to identify genes related to mycobacteria adhesion and invasion. Using adhesion and invasion model screening, we found that the mutant strain B2909 lacked adhesion and invasion abilities because of an inactive fadD18 gene, which encodes a fatty-acyl CoA ligase, although the specific function of this gene remains unclear. To investigate the role of FadD18, we constructed a complementary strain and observed that fadD18 expression enhanced the colony size and promoted the formation of a stronger cord-like structure; FadD18 expression also inhibited BCG growth and reduced BCG intracellular survival in macrophages. Furthermore, FadD18 expression elevated levels of the proinflammatory cytokines IL-6, IL-1β, and TNF-α in infected macrophages by stimulating the NF-κB and MAPK signaling pathways. Overall, the FadD18 plays a key role in the adhesion and invasion abilities of mycobacteria while modulating the intracellular survival of BCG by influencing the production of proinflammatory cytokines. Full article

A high-quality genome sequence from an Indian isolate of Blumeria graminis f. sp. tritici Wtn1, a persistent threat in wheat farming, was obtained using a hybrid method. The assembly of over 9.24 million DNA-sequence reads resulted in 93 contigs, totaling a 140.61 Mb genome size, potentially encoding 8480 genes. Notably, more than 73.80% of the genome, spanning approximately 102.14 Mb, comprises retro-elements, LTR elements, and P elements, influencing evolution and adaptation significantly. The phylogenomic analysis placed B. graminis f. sp. tritici Wtn1 in a distinct monocot-infecting clade. A total of 583 tRNA anticodon sequences were identified from the whole genome of the native virulent strain B. graminis f. sp. tritici, which comprises distinct genome features with high counts of tRNA anticodons for leucine (70), cysteine (61), alanine (58), and arginine (45), with only two stop codons (Opal and Ochre) present and the absence of the Amber stop codon. Comparative InterProScan analysis unveiled “shared and unique” proteins in B. graminis f. sp. tritici Wtn1. Identified were 7707 protein-encoding genes, annotated to different categories such as 805 effectors, 156 CAZymes, 6102 orthologous proteins, and 3180 distinct protein families (PFAMs). Among the effectors, genes like Avra10, Avrk1, Bcg-7, BEC1005, CSEP0105, CSEP0162, BEC1016, BEC1040, and HopI1 closely linked to pathogenesis and virulence were recognized. Transcriptome analysis highlighted abundant proteins associated with RNA processing and modification, post-translational modification, protein turnover, chaperones, and signal transduction. Examining the Environmental Information Processing Pathways in B. graminis f. sp. tritici Wtn1 revealed 393 genes across 33 signal transduction pathways. The key pathways included yeast MAPK signaling (53 genes), mTOR signaling (38 genes), PI3K-Akt signaling (23 genes), and AMPK signaling (21 genes). Additionally, pathways like FoxO, Phosphatidylinositol, the two-component system, and Ras signaling showed significant gene representation, each with 15–16 genes, key SNPs, and Indels in specific chromosomes highlighting their relevance to environmental responses and pathotype evolution. The SNP and InDel analysis resulted in about 3.56 million variants, including 3.45 million SNPs, 5050 insertions, and 5651 deletions within the whole genome of B. graminis f. sp. tritici Wtn1. These comprehensive genome and transcriptome datasets serve as crucial resources for understanding the pathogenicity, virulence effectors, retro-elements, and evolutionary origins of B. graminis f. sp. tritici Wtn1, aiding in developing robust strategies for the effective management of wheat powdery mildew. Full article

This work proposes a highly sensitive sandwich heterostructure multimode optical fiber microbend sensor for heart rate (HR), respiratory rate (RR), and ballistocardiography (BCG) monitoring, which is fabricated by combining a sandwich heterostructure multimode fiber Mach–Zehnder interferometer (SHMF-MZI) with a microbend deformer. The parameters of the SHMF-MZI sensor and the microbend deformer were analyzed and optimized in detail, and then the new encapsulated method of the wearable device was put forward. The proposed wearable sensor could greatly enhance the response to the HR signal. The performances for HR, RR, and BCG monitoring were as good as those of the medically approved commercial monitors. The sensor has the advantages of high sensitivity, easy fabrication, and good stability, providing the potential for application in the field of daily supervision and health monitoring. Full article

Mycobacterium tuberculosis (Mtb) employs various strategies to manipulate the host’s cellular machinery, overriding critical molecular mechanisms such as phagosome-lysosome fusion, which are crucial for its destruction. The Protein Kinase C (PKC) signaling pathways play a key role in regulating phagocytosis. Recent research in Interferon-activated macrophages has unveiled that PKC phosphorylates Coronin-1, leading to a shift from phagocytosis to micropinocytosis, ultimately resulting in Mtb destruction. Therefore, this study aims to identify additional PKC targets that may facilitate Mycobacterium bovis (M. bovis) infection in macrophages. Protein extracts were obtained from THP-1 cells, both unstimulated and mycobacterial-stimulated, in the presence or absence of a general PKC inhibitor. We conducted an enrichment of phosphorylated peptides, followed by their identification through mass spectrometry (LC-MS/MS). Our analysis revealed 736 phosphorylated proteins, among which 153 exhibited alterations in their phosphorylation profiles in response to infection in a PKC-dependent manner. Among these 153 proteins, 55 are involved in various cellular processes, including endocytosis, vesicular traffic, autophagy, and programmed cell death. Importantly, our findings suggest that PKC may negatively regulate autophagy by phosphorylating proteins within the mTORC1 pathway (mTOR2/PKC/Raf-1/Tsc2/Raptor/Sequestosome-1) in response to M. bovis BCG infection, thereby promoting macrophage infection. Full article

Seven increasing levels of water salinity from 0.029 to 0.600 M (as NaCl) were used to investigate the dependence of pH measurement, performed using colorimetric sensor arrays (CSAs), on ionic strength. The CSAs were arrays of sensing spots prepared in the form of sol–gel-embedding Bromothymol Blue (BB) and Bromocresol Green (BCG) in a porous nitrocellulose support. The support was impregnated over the entire thickness (≈100 µm), allowing for the signal (Hue) acquisition on the opposite side to the contact with the sample solution. Three CSAs were prepared, M1, M2, and M3. M1 contained a free cationic surfactant, hexadecyltrimethylammonium p-toluenesulfonate (CTApTs), for modulating the ${pK}_a$ of the indicators. In M2, the surfactant dimethyloctadecyl[3-(trimethoxysilyl)propyl]ammonium chloride (DTSACl) was covalently bonded to the sol–gel. M3 was prepared like M2 but using a larger amount of ethanol as the solvent for the synthesis. The modulation of the CTApTs or the DTSACl concentration enabled the tuning of the ${pK}_a$. In general, the ${pK}_a$ modulation ability decreased with the increase in salinity. The presence of a surfactant covalently linked to the backbone partially reduced the competitiveness of the anionic species, improving the results. Nevertheless, the salt effect was still present, and a correction algorithm was required. Between pH 5.00 and 12.00, this correction could be made automatically by using spots taken as references to produce sensors independent of salinity. As the salt effect is virtually absent above 0.160 M, M2 and M3 can be used for future applications in seawater. Full article