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International Journal of Molecular... Aug 2023Urothelial carcinoma (UC), the sixth most common cancer in Western countries, includes upper tract urothelial carcinoma (UTUC) and bladder carcinoma (BC) as the most... (Review)
Review
Urothelial carcinoma (UC), the sixth most common cancer in Western countries, includes upper tract urothelial carcinoma (UTUC) and bladder carcinoma (BC) as the most common cancers among UCs (90-95%). BC is the most common cancer and can be a highly heterogeneous disease, including both non-muscle-invasive (NMIBC) and muscle-invasive (MIBC) forms with different oncologic outcomes. Approximately 80% of new BC diagnoses are classified as NMIBC after the initial transurethral resection of the bladder tumor (TURBt). In this setting, intravesical instillation of Bacillus Calmette-Guerin (BCG) is the current standard treatment for intermediate- and high-risk patients. Unfortunately, recurrence occurs in 30% to 40% of patients despite adequate BCG treatment. Radical cystectomy (RC) is currently considered the standard treatment for NMIBC that does not respond to BCG. However, RC is a complex surgical procedure with a recognized high perioperative morbidity that is dependent on the patient, disease behaviors, and surgical factors and is associated with a significant impact on quality of life. Therefore, there is an unmet clinical need for alternative bladder-preserving treatments for patients who desire a bladder-sparing approach or are too frail for major surgery. In this review, we aim to present the strategies in BCG-unresponsive NMIBC, focusing on novel molecular therapeutic targets.
Topics: Humans; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; BCG Vaccine; Non-Muscle Invasive Bladder Neoplasms; Quality of Life; Mycobacterium bovis
PubMed: 37628785
DOI: 10.3390/ijms241612596 -
Ugeskrift For Laeger Sep 2023Intravesical instillation of bacillus Calmette-Guérin (BCG) is used for the maintenance treatment of some types of bladder cancer. Although rare, ocular complications...
Intravesical instillation of bacillus Calmette-Guérin (BCG) is used for the maintenance treatment of some types of bladder cancer. Although rare, ocular complications can develop following intravesical BCG treatment. This is a case report of culture-positive Mycobacterium bovis BCG endophthalmitis following intravesical BCG installation. The case highlights a rare complication of BCG installation and the need for an eye examination when patients after BCG installation develop eye symptoms.
Topics: Humans; Mycobacterium bovis; BCG Vaccine; Urinary Bladder Neoplasms; Endophthalmitis; Administration, Intravesical
PubMed: 37772652
DOI: No ID Found -
Pathogens (Basel, Switzerland) Jul 2023Tuberculosis is an ancient disease that humanity struggled with for centuries and continues to struggle with. The bacteria often infects the lungs through respiratory... (Review)
Review
Tuberculosis is an ancient disease that humanity struggled with for centuries and continues to struggle with. The bacteria often infects the lungs through respiratory transmission and manifests itself through various symptoms, including cutaneous infections. Cutaneous tuberculosis (CTB) comprises about 1% to 1.5% of all extrapulmonary manifestations and is often accompanied by polymorphous lesions, including papules, nodules, plaques, ulcers, gummas, and verrucous lesions. CTB is most commonly observed in low-income, HIV, and immunosuppressed populations, similar to intrapulmonary manifestations. The main pathogen for CTB is but less commonly with and BCG vaccine, and the modes of transmission are largely classified into exogenous and endogenous CTB. Current treatment options for CTB include oral therapy of antibiotic medications such as rifampicin, streptomycin, ethambutol, isoniazid, and pyrazinamide, which is occasionally combined with surgical intervention.
PubMed: 37513768
DOI: 10.3390/pathogens12070920 -
Cells Aug 2023is a facultative intracellular bacterium that produces cellular necrosis in granulomatous lesions in bovines. Although -induced inflammation actively participates in...
is a facultative intracellular bacterium that produces cellular necrosis in granulomatous lesions in bovines. Although -induced inflammation actively participates in granuloma development, its role in necrotic cell death and in bovine macrophages has not been fully explored. In this study, we evaluate the effect of AN5 and its culture filtrate protein extract (CFPE) on inflammasome activation in bovine macrophages and its consequences on cell death. Our results show that both stimuli induce necrotic cell death starting 4 h after incubation. CFPE treatment and infection also induce the maturation of IL-1β (>3000 pg/mL), oligomerization of ASC (apoptosis-associated speck-like protein containing CARD), and activation of caspase-1, following the canonical activation pathway of the NLRP3 inflammasome. Inhibiting the oligomerization of NLRP3 and caspase-1 decreases necrosis among the infected or CFPE-stimulated macrophages. Furthermore, histological lymph node sections of bovines naturally infected with contained cleaved gasdermin D, mainly in macrophages and giant cells within the granulomas. Finally, the induction of cell death (apoptosis and pyroptosis) decreased the intracellular bacteria count in the infected bovine macrophages, suggesting that cell death helps to control the intracellular growth of the mycobacteria. Our results indicate that induces pyroptosis-like cell death that is partially related to the NLRP3 inflammasome activation and that the cell death process could control bacterial growth.
Topics: Cattle; Animals; Mycobacterium bovis; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Necrosis; Cell Death; Caspase 1; Macrophages
PubMed: 37626889
DOI: 10.3390/cells12162079 -
CMAJ : Canadian Medical Association... Oct 2023
Topics: Female; Humans; Adolescent; Mycobacterium bovis; Mycobacterium Infections, Nontuberculous; Lymphadenitis
PubMed: 37903520
DOI: 10.1503/cmaj.230700-f -
Irish Veterinary Journal Sep 2023Two characteristics of the Mycobacterium tuberculosis complex (MTC) are particularly relevant for tuberculosis (TB) epidemiology and control, namely the ability of this...
Two characteristics of the Mycobacterium tuberculosis complex (MTC) are particularly relevant for tuberculosis (TB) epidemiology and control, namely the ability of this group of pathogens to survive in the environment and thereby facilitate indirect transmission via water or feed, and the capacity to infect multiple host species including human beings, cattle, wildlife, and domestic animals other than cattle. As a consequence, rather than keeping the focus on certain animal species regarded as maintenance hosts, we postulate that it is time to think of complex and dynamic multi-host MTC maintenance communities where several wild and domestic species and the environment contribute to pathogen maintenance. Regarding the global situation of animal TB, many industrialized countries have reached the Officially Tuberculosis Free status. However, infection of cattle with M. bovis still occurs in most countries around the world. In low- and middle-income countries, human and animal TB infection is endemic and bovine TB control programs are often not implemented because standard TB control through testing and culling, movement control and slaughterhouse inspection is too expensive or ethically unacceptable. In facing increasingly complex epidemiological scenarios, modern integrated disease control should rely on three main pillars: (1) a close involvement of farmers including collaborative decision making, (2) expanding the surveillance and control targets to all three host categories, the environment, and their interactions, and (3) setting up new control schemes or upgrading established ones switching from single tool test and cull approaches to integrated ones including farm biosafety and vaccination.
PubMed: 37737206
DOI: 10.1186/s13620-023-00254-9 -
Gut Pathogens Oct 2023Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of paratuberculosis, a chronic gastrointestinal disease affecting ruminants. This disease...
Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of paratuberculosis, a chronic gastrointestinal disease affecting ruminants. This disease remains widespread in part due to the limitations of available diagnostics and vaccines. A representative small animal model of disease could act as a valuable tool for studying its pathogenesis and to develop new methods for paratuberculosis control, but current models are lacking. Streptomycin pre-treatment can reduce colonization resistance and has previously been shown to improve enteric infection in a Salmonella model. Here, we investigated whether streptomycin pre-treatment of mice followed by MAP gavage could act as a model of paratuberculosis which mimics the natural route of infection and disease development in ruminants. The infection outcomes of MAP were compared to M. avium subsp. hominissuis (MAH), an environmental mycobacterium, and M. bovis and M. orygis, two tuberculous mycobacteria. Streptomycin pre-treatment was shown to consistently improve bacterial infection post-oral inoculation. This model led to chronic MAP infection of the intestines and mesenteric lymph nodes (MLNs) up to 24-weeks post-gavage, however there was no evidence of inflammation or disease. These infection outcomes were found to be specific to MAP. When the model was applied to a bacterium of lesser virulence MAH, the infection was comparatively transient. Mice infected with bacteria of greater virulence, M. bovis or M. orygis, developed chronic intestinal and MLN infection with pulmonary disease similar to zoonotic TB. Our findings suggest that a streptomycin pre-treatment mouse model could be applied to future studies to improve enteric infection with MAP and to investigate other modifications underlying MAP enteritis.
PubMed: 37789445
DOI: 10.1186/s13099-023-00573-w -
Irish Veterinary Journal Sep 2023Here we provide a summary of a plenary lecture delivered on Mycobacterium bovis, the bovine TB bacillus, at the M. bovis 2022 meeting held in Galway, Ireland, in June... (Review)
Review
Here we provide a summary of a plenary lecture delivered on Mycobacterium bovis, the bovine TB bacillus, at the M. bovis 2022 meeting held in Galway, Ireland, in June 2022. We focus on the analysis of genetic differences between M. bovis and the human pathogen Mycobacterium tuberculosis as a route to gain knowledge on what makes M. bovis function as an animal pathogen. We provide a brief historical background around M. bovis and comparative virulence experiments with M. tuberculosis, before moving to what we have learned from the studies of the M. bovis genome sequence. We discuss the need to translate knowledge on the molecular basis of virulence in M. bovis into improved control of bovine tuberculosis.
PubMed: 37770951
DOI: 10.1186/s13620-023-00257-6 -
Science Advances Sep 2023Trained immunity is a long-term memory of innate immune cells, generating an improved response upon reinfection. is an important human pathogen and inflammatory...
Trained immunity is a long-term memory of innate immune cells, generating an improved response upon reinfection. is an important human pathogen and inflammatory paradigm for which there is no effective vaccine. Using zebrafish larvae, we demonstrate that after training, neutrophils are more efficient at bacterial clearance. We observe that -induced protection is nonspecific and has differences with training by BCG and β-glucan. Analysis of histone ChIP-seq on trained neutrophils revealed that training deposits the active H3K4me3 mark on promoter regions of 1612 genes, dramatically changing the epigenetic landscape of neutrophils toward enhanced microbial recognition and mitochondrial ROS production. Last, we demonstrate that mitochondrial ROS plays a key role in enhanced antimicrobial activity of trained neutrophils. It is envisioned that signals and mechanisms we discover here can be used in other vertebrates, including humans, to suggest new therapeutic strategies involving neutrophils to control bacterial infection.
Topics: Enterobacteriaceae Infections; Animals; Zebrafish; Larva; Neutrophils; Trained Immunity; Shigella flexneri; Mycobacterium bovis; beta-Glucans; Epigenesis, Genetic; Mitochondria; Reactive Oxygen Species
PubMed: 37672585
DOI: 10.1126/sciadv.adf9706