William R. Bishai’s research while affiliated with Johns Hopkins Medicine and other places

... To improve the BCG-mediated trained immunity levels, a recombinant BCG was constructed to release high levels of c-di-AMP, an agonist recognized by stimulator of interferon genes (STING). Compared to wild type BCG, the BCG-STING demonstrates higher trained immune responses, including eliciting IFNb release in macrophages, inducing epigenetic activation marks in proinflammatory cytokine promoters, shifting monocyte metabolomic profiles toward glycolysis, and reprograming myeloid cells toward M1-like (43,44). Importantly, improved antitumor efficacy can be achieved by the BCG-STING in preclinical bladder cancer model, suggesting that the enhanced trained immunity contributes to the better inhibition of tumor growth (43,44). ...

Reference:

Trained immunity inducers in cancer immunotherapy

... The present review identified almost no trials investigating ENPP1-related tumor therapeutic drugs, and there are no examples of using ENPP1 features to diagnose or treat cancer, to the best of our knowledge. However, the present review found that between 2019 and 2024, several novel inhibitors of ENPP1 have been in development for cancer immunotherapy, such as 3,4-dihydropyrimido [4,5-d]pyrimidin-2(1H)-one, 3,4-dihydropyrido[2,3-d]pyrimidin-2(1H)-one, pyrrolopyrimidine and pyrrolopyridine derivatives and phthalazinone analogues (23,24,(105)(106)(107)(108)(109). However, these inhibitors are currently only being tested in preclinical models and are rarely, if ever, actually used in clinical trials (106,107,110). ...

Reference:

Role of ENPP1 in cancer pathogenesis: Mechanisms and clinical implications (Review)

... However, it has been observed to penetrate Mycobacterium tuberculosis and to produce its effect by being converted to its active form, pyrazinoic acid, by pyrazinamidase [3]. Pyrazinamide is an anti-inflammatory drug that explicitly reduces inflammatory cytokine signaling and lesion activity in tuberculosis patients [4]. Although pyrazinamide was initially reported to be safe, recent studies have shown that it is more hepatotoxic than isoniazid and rifampin and even causes liver failure [1]. ...

Reference:

Effects of adenosine triphosphate, thiamine pyrophosphate, melatonin, and liv-52 on subacute pyrazinamide proliferation hepatotoxicity in rats

... Preclinical studies in M.tb-infected mice have shown that rapamycin reduced pulmonary inflammation and caseating granulomas [65]. However, its application in clinical settings is restricted by high variability in absorption and Macrocyclic lactone Everolimus Inhibiting the mTOR pathway; Autophagy [9] Tyrosine kinase inhibitor Gefitinib Tyrosine-kinase inhibitors (TKI); Autophagy [10,11] Synthetic opioids Loperamide Autophagy; LL37 expression [12,13] Janus kinase (JAK) blocker Tofacitinib JAK blocker [14] Central nervous system (CNS) drugs Fluoxetine Selective serotonin reuptake inhibitor (SSRI) [15] Vitamin Vitamin D LL37 expression; Autophagy; Macrophage polarization [16][17][18] Antiparasitic drug Nitazoxanide (NTZ) Autophagy [19][20][21] Efflux pump inhibitors (EPIs) Verapamil EPI [22] Glycolysis inhibitors 2-deoxyglucose (2-DG) Glucose uptake inhibitor [23] Transglutaminase 2 (TG2) inhibitors Cystamine and cysteamine Reducing agents [24] Miscellaneous drugs Auranofin Thioredoxin reductase (TrxR) inhibition [25] Glutathione (GSH) Th1 response regulation [26] Mucolytic drug Ambroxol Autophagy [27] Therapeutic target Nuclear receptor corepressor 1 (NCOR1) Autophagy [28] Host transcriptional repressor protein zinc finger and BTB domain 25(ZBTB25) Autophagy [29] Isocitrate lyase (ICL) inhibitors Itaconate ICL inhibitor [30][31][32] Phosphodiesterase inhibitors (PDE-Is) Sildenafil PDE-I [33,34] CC-11050 PDE-I [35] Glutamine metabolism antagonist JHU083 Glutamine metabolism antagonist [36] Anticancer drugs Bevacizumab (Avastin) Anti-vascular endothelial growth factor (VEGF) antibody [37] Hypoglycemic Metformin Adenosine monophosphate-activated protein kinase (AMPK) activation; Autophagy [38][39][40] Nonsteroidal anti-inflammatory drug (NSAID) ...

Reference:

Host-directed therapy for tuberculosis

... Over the past two decades, numerous genomes ranging from kilobase-sized viruses to megabase-sized bacteria and yeast chromosomes have been artificially synthesized [1]. Notably, the Synthetic Yeast Genome Project (Sc2.0) has successfully constructed all the chromosomes of Saccharomyces cerevisiae, with a strain containing 7.5 synthetic chromosomes also being generated [2][3][4][5][6][7][8][9][10][11]. It is anticipated that collaborative efforts among scientists worldwide will soon lead to the creation of the first eukaryotic cell harboring a fully synthesized genome. ...

Reference:

Recent technology advancements in large‐scale DNA assembly

... The MTB mutation against the most potent primary drugs like R & H had further worsened the situation. The genome sequence/ genetic coding of MTB was first time achieved in 1998 by Cole et al, had open a way to discover and identify the gene responsible for mutation against drugs and resistance pattern on the basis of polymerase chain reaction (3,4) .The Whole genome sequencing (WGS) has further distinguished genetic diversity and transmission dynamics of Mycobacterium tuberculosis complex (5) . The cartridge based nucleic acid amplification test (CBNAAT) was then developed by Foundation for Innovative New Diagnostics (FIND) and was launched by Cepheid in 2004. ...

Reference:

A STUDY OF IMPACT OF CBNAAT IN THE DIAGNOSIS OF TUBERCULOSIS AT A RURAL BASED TERTIARY CARE TEACHING CENTRE IN INDIA

... Our cluster analysis of cytokine profiles revealed significantly elevated levels of IFN-related cytokines (IFN-g, IFN-a) in both serum and bronchoalveolar lavage fluid (BALF) samples from MDA5+ DM patients with RP-ILD. The MDA5 pattern recognition receptor triggers an abnormal overproduction of IFNs, which subsequently initiates a cascade of inflammatory responses and tissue damage (17). This exaggerated IFN response, mirrored in both blood and lung lavage fluids, resembles a surge of circulating cytokines, chemokines, and activated macrophage-related proteins, contributing to the release of proinflammatory factors and thereby accelerating disease progression (18). ...

Reference:

Case report: Exploring efficacy of tofacitinib in modulating interferon response in five case of anti-MDA5+ dermatomyositis with interstitial lung disease

... Combining LC3B (+) percentage of blood M1/2a monocyte, DNA methylation levels of the LC3B gene promoter and clinical factors (male, BMI), the Prediction Score 1 and 2 discriminated active TB patients from LTBI and NIHS, respectively, with good performance. In line with our findings, low BMI has been shown to be a significant risk factor for active TB disease, while data from epidemiology, humans, and animals suggest that males are more susceptible to active TB disease and associated with poorer outcomes than females [31][32][33]. Further largescale studies are required to validate these findings. ...

Reference:

Increased autophagy activity regulated by LC3B gene promoter DNA methylation is associated with progression to active pulmonary tuberculosis disease

... BCG, i.v. administration provided high levels of protection against early viral replication and subsequent disease (Hilligan et al., 2022(Hilligan et al., , 2023Zhang et al., 2022;Lee et al., 2024;Singh et al., 2023). Similar protection was observed after influenza challenge, consistent with the involvement of an innate nonspecific effector mechanism (Lee et al., 2024;Kaufmann et al., 2022;Tran et al., 2024). ...

Reference:

Deconvoluting the interplay of innate and adaptive immunity in BCG-induced nonspecific and TB-specific host resistance

... Still, epidemiological reports regarding sexbased differences in extraPTB are inconclusive. A large study in Mali, which included 1012 subjects with confirmed extraPTB, reported a male-to-female ratio of 1.59:1 [51]. This study also found differences regarding the affected organ: males are more likely to present pleural TB (OR = 1.51), and women are more likely to present lymph node (OR = 0.57) and abdominal TB (OR = 0.59) [51]. ...

Reference:

2. Colliding Challenges: An Analysis of SARS-CoV-2 Infection in Patients with Pulmonary Tuberculosis versus SARS-CoV-2 Infection Alone