Antagonists of CD39 and CD73 potentiate doxycycline repositioning to induce a potent antitumor immune response.

Studies have reported that cellular metabolism at the tumor-immune microenvironment (TiME) serves as a critical checkpoint and perturbs/supports anti-cancer immunity. Extra cellular ATP (eATP) may mediate anti-cancer immune response; however, its catabolism by ectonucleotidase generates immunosuppressive adenosine. In the presented work, we have tried to repurpose doxycycline with or without an antagonist of ectonucleotidase for mitigating ATP metabolism and immunosuppression.

CSF-1R blockade to alleviate azithromycin mediated immunosuppression in a mouse model of intracellular infection.

Colony Stimulating Factor-1 Receptor (CSF-1R) signalling plays an important role in maturation, differentiation and activation of macrophages. Apposite generation and activation of macrophage phenotypes and subsequent adaptive immune response against any infection is decisive for a positive disease outcome. Antibiotic therapy is imperative for treating bacterial infections however antibiotics have off-target effects on host immune-cells.

Metabolic crosstalk: Extracellular ATP and the tumor microenvironment in cancer progression and therapy.

Adenosine 5'-triphosphate (ATP) is a vital element in energy information. It plays a critical role in transmitting signals inside the body, which is necessary for controlling the life activities of all cells, including tumor cells [1]. Its significance extends from intracellular signaling pathways to tumor regression.

IFNγ insufficiency during mouse intra-vaginal Chlamydia trachomatis infection exacerbates alternative activation in macrophages with compromised CD40 functions.

Chlamydia trachomatis (C.tr), an obligate intracellular pathogen, causes asymptomatic genital infections in women and is a leading cause of preventable blindness. We have developed in vivo mouse models of acute and chronic C.

Azithromycin alters Colony Stimulating Factor-1R (CSF-1R) expression and functional output of murine bone marrow-derived macrophages: A novel report.

Antibiotic treatment may lead to side effects that require mechanistic explanation. We investigated the effect of azithromycin (AZM) treatment on bone marrow-derived macrophage (Mφ) generation, their functional output, and the subsequent effect on bacterial clearance in a mouse model of S. flexneri infection.

The tale of antibiotics beyond antimicrobials: Expanding horizons.

Antibiotics had proved to be a godsend for mankind since their discovery. They were once the magical solution to the vexing problem of infection-related deaths. German scientist Paul Ehrlich had termed salvarsan as the silver bullet to treatsyphilis.

Chlamydia trachomatis infection co-operatively enhances HPV E6-E7 oncogenes mediated tumorigenesis and immunosuppression.

Chlamydia trachomatis and human papilloma virus (HPV) are the two most common sexually transmitted infections among women. HPV infection can increase the risk of cervical cancer and infertility while C. trachomatis induces pelvic inflammatory disease.

Macrophage subsets and their role: co-relation with colony-stimulating factor-1 receptor and clinical relevance.

Macrophages are one of the first innate immune cells to reach the site of infection or injury. Diverse functions from the uptake of pathogen or antigen, its killing, and presentation, the release of pro- or anti-inflammatory cytokines, activation of adaptive immune cells, clearing off tissue debris, tissue repair, and maintenance of tissue homeostasis have been attributed to macrophages. Besides tissue-resident macrophages, the circulating macrophages are recruited to different tissues to get activated.

Design, synthesis, characterization and anticancer activity evaluation of deoxycholic acid-chalcone conjugates.

A series of deoxycholic acid-chalcone amides were synthesised and tested against the human lung cancer cell line, A549 and the cervical cancer cell line, SiHa. Among the synthesised deoxycholic acid-chalcone conjugates, some conjugates showed encouraging results as anticancer agents with good in vitro activity. More precisely, deoxycholic acid-chalcone conjugates 4b (IC50: 0.

Saga of monokines in shaping tumour-immune microenvironment: Origin to execution.

Cellular communication mediated by cytokines is an important mechanism dictating immune responses, their cross talk and final immune output. Cytokines play a major role in dictating the immune outcome to cancer by regulating the events of development, differentiation and activation of innate immune cells. Cytokines are pleiotropic in nature, hence understanding their role individually or as member of network cytokines is critical to delineate their role in tumour immunity.

Insights into inflammasome regulation: cellular, molecular, and pathogenic control of inflammasome activation.

Maintenance of immune homeostasis is an intricate process wherein inflammasomes play a pivotal role by contributing to innate and adaptive immune responses. Inflammasomes are ensembles of adaptor proteins that can trigger a signal following innate sensing of pathogens or non-pathogens eventuating in the inductions of IL-1β and IL-18. These inflammatory cytokines substantially influence the antigen-presenting cell's costimulatory functions and T helper cell differentiation, contributing to adaptive immunity.

Berberine mediates tumor cell death by skewing tumor-associated immunosuppressive macrophages to inflammatory macrophages.

Background: Berberine is a plant-derived alkaloid with potent anti-cancer activities. Berberine may redirect the tumor-promoting immunosuppressive M2 macrophages, to tumoricidal activated M1 macrophages. But such an anti-tumor function remains to be demonstrated.

Caspase-1 inhibition by YVAD generates tregs pivoting IL-17 to IL-22 response in β-glucan induced airway inflammation.

Background: During mediated lung inflammation, NLRP3 inflammasome is rapidly activated that aggravates IL-1β production contributing to lung inflammation. Previously, we have shown the protective role of SYK-1 inhibition in inhibiting inflammasome activation during lung inflammation. In the current manuscript, we explored the protective role of direct caspase-1 inhibition during β-glucan-induced lung inflammation.

microRNAs (miR 9, 124, 155 and 224) transdifferentiate mouse macrophages to neurons.

Development is an irreversible process of differentiating the undifferentiated cells to functional cells. Brain development involves generation of cells with varied phenotype and functions, which is limited during adulthood, stress, damage/degeneration. Cellular reprogramming makes differentiation reversible process with reprogramming somatic/stem cells to alternative fate with/without stem cells.

Amyloid-like Structures Formed by Single Amino Acid Self-Assemblies of Cysteine and Methionine.

We report for the very first time the discovery of amyloid-like self-assemblies formed by the nonaromatic single amino acids cysteine (Cys) and methionine (Met) under neutral aqueous conditions. The structure formation was assessed and characterized by various microscopic and spectroscopic techniques such as optical microscopy, phase contrast microscopy, scanning electron microscopy, and transmission electron microscopy. The mechanism of self-assembly and the role of hydrogen bonding and thiol interactions of Cys and Met were assessed by Fourier transform infrared spectroscopy, thermogravimetric analysis, X-ray diffraction, and solid state NMR along with various control experiments.

Spleen tyrosine kinase inhibition ameliorates airway inflammation through modulation of NLRP3 inflammosome and Th17/Treg axis.

Repeated exposure to the fungal pathogen Aspergillus fumigates triggers spleen tyrosine kinase (SYK) signalling through dectin-1 activation, which is associated with deleterious airway inflammation. β-Glucan-induced dectin-1 signalling activates the NLRP3 inflammasome, which in turn rapidly produces IL-1β, a master regulator of inflammation. IL-1β expression results in Th17/Treg imbalance, pulmonary inflammation, and bystander tissue injury.

Berberine induces neuronal differentiation through inhibition of cancer stemness and epithelial-mesenchymal transition in neuroblastoma cells.

Background: Berberine, a plant alkaloid, has been used since many years for treatment of gastrointestinal disorders. It also shows promising medicinal use against metabolic disorders, neurodegenerative disorders and cancer; however its efficacy in neuroblastoma (NB) is poorly explored.

Hypothesis: EMT is important in cancer stemness and metastasis resulting in failure to differentiate; thus targeting EMT and related pathways can have clinical benefits.

CD40 Negatively Regulates ATP-TLR4-Activated Inflammasome in Microglia.

During acute brain injury and/or sterile inflammation, release of danger-associated molecular patterns (DAMPs) activates pattern recognition receptors (PRRs). Microglial toll-like receptor (TLR)-4 activated by DAMPs potentiates neuroinflammation through inflammasome-induced IL-1β and pathogenic Th17 polarization which critically influences brain injury. TLR4 activation accompanies increased CD40, a cognate costimulatory molecule, involved in microglia-mediated immune responses in the brain.

Lipopolysaccharide from Rhodobacter sphaeroides Attenuates Microglia-Mediated Inflammation and Phagocytosis and Directs Regulatory T Cell Response.

Microglia activation and neuroinflammation are key events during the progression of neurodegenerative disorders. Microglia exhibits toll-like receptors (TLRs), with predominant expression of TLR4, inducing aberrant neuroinflammation and exacerbated neurotoxicity. Studies suggest that microglia initiate infiltration of T cells into the brain that critically influence disease conditions.