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A pyrene base luminophore was designed and synthesised under ambient conditions using [4+2] annulation. The synthesised probe PYINDP exhibits good optical properties and emits greenish blue, with high colour purity in solid, solution, and thin film phases. In solution, the CIE coordinates were found to be (0.20, 0.48), and for an aggregated state emitting deep green colour, the CIE values are (0.27, 0.65). Room temperature phosphorescence (RTP) is generated by the luminophore PYINDP, owing to the ISC process. Moreover, the emitter demonstrated an excellent limit of detection values in detecting nitroaromatics (NACs). Bio‐imaging studies on HEK, A549 cell lines were successfully carried out to verify the staining capability of PYINDP in biological systems. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) though primarily affects the lungs it may also affect the other parts of the body and referred as extra pulmonary (EPTB). This study is focused on understanding the genetic diversity and molecular epidemiology of Mycobacterium tuberculosis (M.tb) among tuberculous lymphadenitis (TBL), a form of EPTB patients identified in Chennai, Tamil Nadu.Methods: The genetic diversity was identified by performing spoligotyping on the M.tb clinical isolates that were recovered from lymph node samples. A total of 71 M.tb isolates were recovered from extra pulmonary lymph node samples and subjected to Drug susceptibility testing and spoligotyping was carried out. In addition, immunological characterization from blood of same individuals from whom M.tb was isolated was carried out between the two major lineages groups East African Indian 3 (EAI3) and non-EAI3 strains by ELISA. The results of spoligotyping patterns were compared with the world Spoligotyping Database of Institute Pasteur de Guadeloupe (SpolDB4).Results: We found 41 spoligotype patterns and their associated lineages. Out of 41 spoligotype pattern, only 22 patterns are available in the spoldB4 database with Spoligotype international Type (SIT) number and remaining patterns were orphan strains without SIT number. The most predominant spoligotype lineage that was found in lymph node sample in this region of India was EAI (36), followed by central Asian strain (CAS) (6), T1 (5), Beijing (3), Latin American & Mediterranean (LAM) (2), U (1), X2 (1) and orphan (22). In addition to EAI, CAS and Beijing, our study identified the presence of orphan and unique spoligotyping patterns in Chennai region. We observed six drug resistant isolates. Out of six drug resistant isolates, four were resistant to isoniazid drug and associated with EAI family. Moreover, we observed increased levels of type 2 and type 17 cytokine profiles between EAI3 and non-EAI family, infected individuals.Conclusions: The study confirms that EAI lineage to be the most predominant lineages in EPTB patients with lymphadenitis and were found to have increased type 1 and type 17 proinflammatory cytokine profiles. [ABSTRACT FROM AUTHOR]

Biologically‐active near‐ultraviolet emitting spirooxindole‐pyrrolidine/pyrrolothiazole‐β‐ketothiolester have been synthesised via Chemo‐/regio‐/stereoselective manner. Excited‐state intramolecular proton transfer (ESIPT) of β‐ketothiolester exhibits excitation‐dependent emission with intermolecular hydrogen bonding ability with solvents. The emission could be tunable between 330 nm to 460 nm. Selected fluorescent compounds 4{4,2,1}, 4{12,2,2}, 5{4,2,1} and 5{12,2,2} shows cytotoxicity effect on PC3 cells, where the highest IC50 value (6 μM) was found for the probe 5{12,2,2}. The fluorescent behavior of 5{4,2,1} and 5{12,2,2} acted as an imaging molecule against cancer cells. [ABSTRACT FROM AUTHOR]

A nitrogen-boron based Lewis adduct was synthesized from indenophenanthridine derivatives, exhibiting a greatly extended emission wavelength (100 nm) and a Stokes shift up to 270 nm. The photophysical properties were evaluated in the solid and solution state and under low-temperature conditions. The synthesized boronated adduct 2a was found to exhibit radiometric fluorescence variations toward volatile aliphatic amines with real sample applications. [ABSTRACT FROM AUTHOR]

An efficient protocol has been developed for the synthesis of a novel fluorescent probe, 1,2-disubstituted-indeno[1,2,3-gh]phenanthridine, derived from a series of a-oxo-ketene dithioacetals (OKDTAs) and indenoquinoline under essential conditions via a [4+2] annulation in excellent yield. All the synthesized indenophenathridine derivatives were well characterized by NMR and mass spectrometry. One of the synthesized indenophenanthridine derivatives, 4b, has been involved in acidochromism studies, selectively sensing Fe3+ ions in non-aqueous solution with a low detection limit (7.5 - 10-7 M) applied in live-cell bio-imaging. [ABSTRACT FROM AUTHOR]

Background Plasma chemokines are biomarkers of greater disease severity, higher bacterial burden, and delayed sputum culture conversion in pulmonary tuberculosis (PTB). Whether plasma chemokines could also serve as biomarkers of unfavorable treatment outcomes in PTB is not known. Methods A cohort of newly diagnosed, sputum smear- and culture-positive adults with drug-sensitive PTB were recruited under the Effect of Diabetes on Tuberculosis Severity study in Chennai, India. Plasma chemokine levels measured before treatment initiation were compared between 68 cases with unfavorable outcomes (treatment failure, death, or recurrence) and 136 control individuals who had recurrence-free cure. A second validation cohort comprising newly diagnosed, culture-positive adults with drug-sensitive TB was used to measure plasma chemokine levels in 20 cases and 40 controls. Results Six chemokines (CCL2, CCL3, CCL4, CXCL8, CXCL10, and CX3CL1) were associated with increased risk, while CXCL1 was associated with decreased risk of unfavorable outcomes in unadjusted and adjusted analyses in the test cohort. Similarly, CCL3, CXCL8, and CXCL10 were associated with increased risk of unfavorable treatment outcomes in the validation cohort. Receiver operating characteristic analysis revealed that combinations of CCL3, CXCL8, and CXCL10 exhibited very high sensitivity and specificity in differentiating cases vs controls. Conclusions Our study reveals a plasma chemokine signature that can be used as a novel biomarker for predicting adverse treatment outcomes in PTB. [ABSTRACT FROM AUTHOR]

Summary: Alteration in the frequency of monocyte subsets is a hallmark of tuberculosis–diabetes co‐morbidity (TB‐DM). To study this association, we examined the plasma levels of sCD14, sCD163, C‐reactive protein (CRP) and soluble tissue factor (sTF) in individuals with TB‐DM, TB or diabetes mellitus (DM), and in healthy controls (HC). Circulating levels of sCD14, sCD163 and sTF were significantly increased in TB‐DM and DM compared with TB and HC; however, CRP was significantly increased in TB‐DM and TB compared with DM and HC. During longitudinal follow up, sCD14, CRP and sTF levels remained significantly increased in TB‐DM compared with TB from baseline (pre‐treatment), during treatment (2nd month) and at the completion (6th month) of anti‐TB treatment (ATT), whereas sCD163 was significantly higher in TB‐DM compared with TB only at baseline. Moreover, the levels of sCD14 and sCD163 were significantly higher in TB‐DM individuals with bilateral and cavitary disease and exhibited a significant positive relationship with bacterial burden. Levels of sCD14, sCD163 and CRP exhibited a positive relationship with HbA1c levels. Within the TB‐DM group, those with known diabetes before incident TB (KDM) exhibited significantly higher levels of sCD14 and sCD163 compared with individuals with newly diagnosed DM with TB (NDM). Finally, KDM individuals on metformin treatment exhibited significantly lower levels of sCD14, sCD163 and CRP compared with those on non‐metformin‐containing regimens. Our data demonstrate that systemic monocyte activation marker levels reflect baseline disease severity and extent in TB‐DM, differentiate KDM from NDM and are modulated by ATT and metformin therapy. Our data demonstrate that systemic monocyte activation marker levels reflect baseline disease severity and extent in TB with diabetes, differentiate known DM from new DM and are modulated by anti‐TB treatment and metformin therapy. [ABSTRACT FROM AUTHOR]

Background: The association of antimicrobial peptides (AMPs) with tuberculosis—diabetes comorbidity (PTB-DM) is not well understood. Methods: To study the association of AMPs with PTB-DM, we examined the systemic levels of cathelicidin (LL37), human beta defensin– 2 (HBD2), human neutrophil peptides 1–3, (HNP1-3) and granulysin in individuals with either PTB-DM, PTB, latent TB (LTB) or no TB infection (NTB). Results: Circulating levels of cathelicidin and HBD2 were significantly higher and granulysin levels were significantly lower in PTB-DM compared to PTB, LTB or NTB, while the levels of HNP1-3 were significantly higher in PTB-DM compared to LTB or NTB individuals. Moreover, the levels of cathelicidin and/or HBD2 were significantly higher in PTB-DM or PTB individuals with bilateral and cavitary disease and also exhibited a significant positive relationship with bacterial burden. Cathelidin, HBD2 and HNP1-3 levels exhibited a positive relationship with HbA1c and/or fasting blood glucose levels. Finally, anti-tuberculosis therapy resulted in significantly diminished levels of cathelicidin, HBD2, granulysin and significantly enhanced levels of HNP1-3 and granulysin in PTB-DM and/or PTB individuals. Conclusion: Therefore, our data demonstrate that PTB-DM is associated with markedly enhanced levels of AMPs and diminished levels of granulysin. [ABSTRACT FROM AUTHOR]

• Tuberculosis – diabetes co-morbidity is characterized by heterogeneity in both biochemical and immunological responses with newly diagnosed diabetic individuals with TB (TB-NDM) exhibiting significant differences from known diabetic individuals at incident TB (TB-KDM). • TB-NDM individuals have significantly lower levels of blood glucose and HbA1c in comparison to TB-KDM individuals. • TB-NDM individuals have significantly lower levels of unstimulated and TB-antigen stimulated pro-inflammatory cytokines in comparison to TB-KDM individuals. • This biochemical and cytokine pattern persists even after anti-tuberculosis treatment and consequent cure. Tuberculosis – diabetes (TB-DM) co-morbidity is characterized by heterogeneity in clinical and biochemical parameters between newly diagnosed diabetic individuals with TB (TB-NDM) and known diabetic individuals at incident TB (TB-KDM). However, the immunological profile underlying this heterogeneity is not explored. To identify the cytokine profiles in TB-NDM and TB-KDM individuals, we examined the plasma cytokine levels as well as TB-antigen stimulated levels of pro-inflammatory cytokines. TB-KDM individuals exhibit significantly higher levels of IFNγ, IL-2, TNFα, IL-17A, IL-1α, IL-1β and IL-6 in comparison to TB-NDM, TB alone and DM alone individuals. TB-NDM individuals are characterized by significantly lower levels of blood glucose and glycated hemoglobin in comparison to TB-KDM with both groups exhibiting a significant lowering of glycated hemoglobin levels at 6 months of anti-tuberculosis therapy (ATT). TB-NDM individuals are characterized by significantly diminished – unstimulated levels of IFNγ, IL-2, TNFα, IL-17A, IL-1α, IL-1β and IL-12 at pre-treatment, of IFNγ, IL-2 and IL-1α at 2 months of ATT and IL-2 at post-treatment in comparison to TB-KDM. TB-NDM individuals are also characterized by significantly diminished TB-antigen stimulated levels of IFNγ, IL-2, TNFα, IL-17A, IL-17F, IL-1α, IL-1β and/or IL-6 at pre-treatment and at 2 months of ATT and IFNγ, IL-2, IL-1α and IL-1β at post-treatment. In addition, TB-NDM individuals are characterized by significantly diminished mitogen – stimulated levels of IL-17F and IL-6 at pre-treatment and IL-6 alone at 6 months of ATT. Therefore, our data reveal considerable heterogeneity in the immunological underpinnings of TB-DM co-morbidity. Our data also suggest that TB-NDM exhibits a characteristic profile, which is both biochemically and immunologically distinct from TB-KDM. [ABSTRACT FROM AUTHOR]

Background: Ligands of the receptor for advanced glycation end products (RAGE) are key signalling molecules in the innate immune system but their role in tuberculosis-diabetes comorbidity (TB-DM) has not been investigated.Methods: We examined the systemic levels of soluble RAGE (sRAGE), advanced glycation end products (AGE), S100A12 and high mobility group box 1 (HMGB1) in participants with either TB-DM, TB, DM or healthy controls (HC).Results: Systemic levels of AGE, sRAGE and S100A12 were significantly elevated in TB-DM and DM in comparison to TB and HC. During follow up, AGE, sRAGE and S100A12 remained significantly elevated in TB-DM compared to TB at 2nd month and 6th month of anti-TB treatment (ATT). RAGE ligands were increased in TB-DM individuals with bilateral and cavitary disease. sRAGE and S100A12 correlated with glycated hemoglobin levels. Within the TB-DM group, those with known diabetes (KDM) revealed significantly increased levels of AGE and sRAGE compared to newly diagnosed DM (NDM). KDM participants on metformin treatment exhibited significantly diminished levels of AGE and sRAGE in comparison to those on non-metformin regimens.Conclusions: Our data demonstrate that RAGE ligand levels reflect disease severity and extent in TB-DM, distinguish KDM from NDM and are modulated by metformin therapy. [ABSTRACT FROM AUTHOR]

Plasma cytokines are biomarkers of disease extent and mycobacterial burden in pulmonary tuberculosis (PTB). Whether chemokines can perform the same role in PTB is not known. We examined the plasma levels of chemokines in individuals with PTB, latent TB (LTB) or healthy controls (HC) and their association with disease severity and mycobacterial burdens in PTB. We also examined the chemokines in PTB individuals at the end of anti-tuberculous chemotherapy (ATT). PTB individuals exhibited significantly higher levels of CCL1, CCL3, CXCL1, CXCL2, CXCL9 and CXCL10 in comparison to LTB and/or HC individuals. PTB individuals with bilateral or cavitary disease displayed significantly elevated levels of CCL1, CCL3, CXCL1, CXCL10 and CXCL11 compared to those with unilateral or non-cavitary disease and also exhibited a significant positive relationship with bacterial burdens. In addition, PTB individuals with slower culture conversion displayed significantly elevated levels of CCL1, CCL3, CXCL1 and CXCL9 at the time of PTB diagnosis and prior to ATT. Finally, the chemokines were significantly reduced following successful ATT. Our data demonstrate that PTB is associated with elevated levels of chemokines, which are partially reversed followed chemotherapy. Our data demonstrate that chemokines are markers of disease severity, predicting increased bacterial burden and delayed culture conversion in PTB. [ABSTRACT FROM AUTHOR]

Background: Matrix metalloproteinases (MMPs) are considered to be key mediators of tuberculosis (TB) pathology but their role in tuberculosis - diabetes comorbidity (TB-DM) is not well understood.Methods: To study the association of MMP levels with severity and extent of disease as well as bacterial burden in TB-DM, we examined the systemic levels of MMP-1, - 2, - 3, - 7, - 8, - 9, - 10, - 12 and - 13 in individuals with TB-DM and compared them to those with TB alone (TB) or healthy controls (HC).Results: Circulating levels of MMP-1, - 2, - 3, - 7, - 10 and - 12 were significantly higher in TB-DM compared to both TB and HC and MMP -13 levels were higher in comparison to HC alone. To understand the effect of standard anti-tuberculosis therapy (ATT) on these MMP levels in TB-DM, we measured the levels of MMPs at the end of treatment (post-treatment). Our findings indicate that ATT is associated with a significant reduction in the levels of MMP-1, - 2, - 3, - 8 and - 13 post-treatment. Moreover, the levels of MMP-1, - 2, - 3, - 9 and - 12 were significantly higher in TB-DM individuals with cavitary disease and/or bilateral disease at baseline but not post-treatment. Similarly, the levels of MMP -1, - 2, - 3 and - 8 exhibited a significant positive relationship with bacterial burden and HbA1c levels at baseline but not post-treatment. Within the TB-DM group, those known to be diabetic before incident TB (KDM) exhibited significantly higher levels of MMP-1, - 2, - 10 and - 12 at baseline and of MMP-1 and -3 post-treatment compared to those newly diagnosed with DM (NDM). Finally, KDM individuals on metformin treatment exhibited significantly lower levels of MMP-1, - 2, - 3, - 7, - 9 and - 12 at baseline and of MMP-7 post-treatment.Conclusions: Our data demonstrate that systemic MMP levels reflect baseline disease severity and extent in TB-DM, differentiate KDM from NDM and are modulated by ATT and metformin therapy. [ABSTRACT FROM AUTHOR]