Adsorption characteristics of nickel (II) from aqueous solutions by Zeolite Scony Mobile-5 (ZSM-5) incorporated in sodium alginate beads.

Nickel, a prevalent metal in the ecosystem, is released into the environment through various anthropogenic activities, leading to adverse effects. This research explored utilizing zeolite scony mobile-5 (ZSM-5) nanoparticles encapsulated in sodium alginate (SA) for nickel (II) removal from aqueous solutions. The adsorption characteristics of SA/ZSM-5 were examined concerning contact duration, initial metal ion concentration, pH level, temperature, and sorbent dosage. The findings revealed that a rising pH reduced Ni (II) uptake by the sorbent while increasing the Ni (II) concentration from 25 to 100 mg L-1 led to a decrease in removal percentage from 91 to 80% under optimal conditions. Furthermore, as sorbent dosage increased from 4 to 16 g L-1, uptake capacity declined from 9.972 to 1.55 mg g-1. Concurrently, SA/ZSM-5 beads' Ni (II) sorption capacity decreased from 96.12 to 59.14% with a temperature increase ranging from 25 to 55 °C. The Ni (II) sorption data on SA/ZSM-5 beads are aptly represented by Langmuir and Freundlich equilibrium isotherm models. Moreover, a second-order kinetic model characterizes the adsorption kinetics of Ni (II) on the SA/ZSM-5 beads. A negative free energy change (ΔG°) demonstrates that the process is both viable and spontaneous. The negative enthalpy values indicate an exothermic nature at the solid-liquid interface while negative entropy values suggest a decrease in randomness. In conclusion, this novel adsorbent exhibits promise for removing nickel from aqueous solutions and could potentially be employed in small-scale industries under similar conditions.

Muscle Transcriptome Sequencing Revealed Thermal Stress-Responsive Regulatory Genes in Farmed Rohu, Labeo rohita (Hamilton, 1822).

Rohu, Labeo rohita, is one of the most important aquaculture species in the Indian subcontinent. Understanding the molecular-level physiological responses to thermal stress or climate change is essential. In the present work, transcriptome sequencing was carried out in the muscle tissue of the rohu in response to heat stress (35 °C) in comparison with the control (28 °C). A total of 125 Gb of sequence data was generated, and the raw-reads were filtered and trimmed, which resulted in 484 million quality reads. Reference-based assembly of reads was performed using L. rohita genome, and a total of 90.17% of reads were successfully mapped. A total of 37,462 contigs were assembled with an N50 value of 1854. The differential expression analysis revealed a total of 107 differentially expressed genes (DEGs) (15 up-, 37 down-, and 55 neutrally regulated) as compared to the control group (Log2FC > 2, P < 0.05). Gene enrichment analysis of DEGs indicates that transcripts were associated with molecular, biological, and cellular activities. The randomly selected differentially expressed transcripts were validated by RT-qPCR and found consistent expression patterns in line with the RNA-seq data. Several transcripts such as SERPINE1(HSP47), HSP70, HSP90alpha, Rano class II histocompatibility A beta, PGC-1 and ERR-induced regulator, proto-oncogene c-Fos, myozenin2, alpha-crystallin B chain-like protein, angiopoietin-like protein 8, and acetyl-CoA carboxylases have been identified in muscle tissue of rohu that are associated with stress/immunity. This study identified the key biomarker SERPINE1 (HSP47), which showed significant upregulation (~ 2- to threefold) in muscle tissue of rohu exposed to high temperature. This study can pave a path for the identification of stress-responsive biomarkers linked with thermal adaptations in the farmed carps.

Recent Progress in Development and Application of DNA, Protein, Peptide, Glycan, Antibody, and Aptamer Microarrays.

Microarrays are one of the trailblazing technologies of the last two decades and have displayed their importance in all the associated fields of biology. They are widely explored to screen, identify, and gain insights on the characteristics traits of biomolecules (individually or in complex solutions). A wide variety of biomolecule-based microarrays (DNA microarrays, protein microarrays, glycan microarrays, antibody microarrays, peptide microarrays, and aptamer microarrays) are either commercially available or fabricated in-house by researchers to explore diverse substrates, surface coating, immobilization techniques, and detection strategies. The aim of this review is to explore the development of biomolecule-based microarray applications since 2018 onwards. Here, we have covered a different array of printing strategies, substrate surface modification, biomolecule immobilization strategies, detection techniques, and biomolecule-based microarray applications. The period of 2018-2022 focused on using biomolecule-based microarrays for the identification of biomarkers, detection of viruses, differentiation of multiple pathogens, etc. A few potential future applications of microarrays could be for personalized medicine, vaccine candidate screening, toxin screening, pathogen identification, and posttranslational modifications.

Fabrication of a bi-metallic metal organic framework nanocomposite for selective and sensitive detection of triclosan.

Transition metal-ion based nanocomposites are widely used owing to their ease of synthesis and cost-effectiveness in the sensor development. In this study, we have synthesized bi-metallic (iron and zinc) metal organic framework (MOF) nanorods-nanoparticles (denoted as Fe2Zn-MIL-88B) with a well-defined structure and characterized them. The bimetallic material nanocomposite (Fe2Zn-MIL-88B, nafion (Nf), and multiwalled carbon nanotube (MWCNT)) was fabricated on the electrode (glassy carbon electrode (GCE) or screen printed carbon electrode (SPCE)) surface within 10 min at room temperature. The Fe2Zn-MIL-88B/Nf/MWCNT@GCE showed an excellent electron transfer mechanism compared to a bare GCE and bare SPCE. The Fe2Zn-MIL-88B based nanocomposite electrode triggers the oxidation of the environmental carcinogenic molecule triclosan (TCS). Under optimized conditions, the sensor has a limit of detection of 0.31 nM and high selectivity to TCS in the presence of other interfering agents. The sensor has a good day-to-day TCS detection reproducibility. Fe2Zn-MIL-88B was stable even after 11 months of synthesis and detected TCS with similar sensitivity. The fabrication of the Fe2Zn-MIL-88B/Nf/MWCNT nanocomposite was successfully translated from the GCE to SPCE. TCS was detected in human plasma and commercial products such as soaps, skin care products, shampoos, and tooth pastes.

A requirement for Krüppel Like Factor-4 in the maintenance of endothelial cell quiescence.

Rationale and Goal: Endothelial cells (ECs) are quiescent and critical for maintaining homeostatic functions of the mature vascular system, while disruption of quiescence is at the heart of endothelial to mesenchymal transition (EndMT) and tumor angiogenesis. Here, we addressed the hypothesis that KLF4 maintains the EC quiescence. Methods and Results: In ECs, KLF4 bound to KLF2, and the KLF4-transctivation domain (TAD) interacted directly with KLF2. KLF4-depletion increased KLF2 expression, accompanied by phosphorylation of SMAD3, increased expression of alpha-smooth muscle actin (αSMA), VCAM-1, TGF-ß1, and ACE2, but decreased VE-cadherin expression. In the absence of Klf4, Klf2 bound to the Klf2-promoter/enhancer region and autoregulated its own expression. Loss of EC-Klf4 in Rosa mT/mG ::Klf4 fl/fl ::Cdh5 CreERT2 engineered mice, increased Klf2 levels and these cells underwent EndMT. Importantly, these mice harboring EndMT was also accompanied by lung inflammation, disruption of lung alveolar architecture, and pulmonary fibrosis. Conclusion: In quiescent ECs, KLF2 and KLF4 partnered to regulate a combinatorial mechanism. The loss of KLF4 disrupted this combinatorial mechanism, thereby upregulating KLF2 as an adaptive response. However, increased KLF2 expression overdrives for the loss of KLF4, giving rise to an EndMT phenotype.

Expression of IL-6, TNF-α, and hs-CRP in the serum of patients undergoing single-sitting and multiple-sitting root canal treatment: A comparative study.

Background: In recent times, single-sitting root canal therapy has gained momentum over multiple-sitting root canal therapy due to its superior clinical outcome and less time required for treating the patient. Aim: Thus, the aim of current study was to compare the expression of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) in the serum of patients undergoing single-sitting and multiple-sitting root canal treatment. Materials and Methods: This cross-sectional experimental study was conducted on 300 subjects who were indicated for root canal treatment. Subjects were categorized into Group I (single visit) and Group II (multiple visits).Clinical data was obtained and serum samples were collected both before and after 1 week of treatment completion. Inclusion criteria were those patients (a) over 18 years of age, (b) without any disease of inflammatory etiology, and (c) who had not previously received endodontic treatment or any related therapeutic treatment. Exclusion criteria were those (a) without a complete clinical history, (b) with greater than one indicated tooth, (c) who did not complete their treatment, and (d) with any periodontal disease. Chi-square and Student's t-test were applied. Results: It was found that in single-sitting root canal treatment, there was a statistically significant reduction in these inflammatory biomarkers, although no difference in clinical efficacy was observed. Conclusion: Single-visit root canal treatment is a better option for treatment of pulpitis compared to multiple-sitting treatment.

Automated knee cartilage segmentation for heterogeneous clinical MRI using generative adversarial networks with transfer learning.

Background: This study aimed to build a deep learning model to automatically segment heterogeneous clinical MRI scans by optimizing a pre-trained model built from a homogeneous research dataset with transfer learning. Methods: Conditional generative adversarial networks pretrained on the Osteoarthritis Initiative MR images was transferred to 30 sets of heterogenous MR images collected from clinical routines. Two trained radiologists manually segmented the 30 sets of clinical MR images for model training, validation and test. The model performance was compared to models trained from scratch with different datasets, as well as two radiologists. A 5-fold cross validation was performed. Results: The transfer learning model obtained an overall averaged Dice coefficient of 0.819, an averaged 95 percentile Hausdorff distance of 1.463 mm, and an averaged average symmetric surface distance of 0.350 mm on the 5 random holdout test sets. A 5-fold cross validation had a mean Dice coefficient of 0.801, mean 95 percentile Hausdorff distance of 1.746 mm, and mean average symmetric surface distance of 0.364 mm. It outperformed other models and performed similarly as the radiologists. Conclusions: A transfer learning model was able to automatically segment knee cartilage, with performance comparable to human, using heterogeneous clinical MR images with a small training data size. In addition, the model proved robust when tested through cross validation and on images from a different vendor. We found it feasible to perform fully automated cartilage segmentation of clinical knee MR images, which would facilitate the clinical application of quantitative MRI techniques and other prediction models for improved patient treatment planning.

ER proteins decipher the tubulin code to regulate organelle distribution.

Organelles move along differentially modified microtubules to establish and maintain their proper distributions and functions1,2. However, how cells interpret these post-translational microtubule modification codes to selectively regulate organelle positioning remains largely unknown. The endoplasmic reticulum (ER) is an interconnected network of diverse morphologies that extends promiscuously throughout the cytoplasm3, forming abundant contacts with other organelles4. Dysregulation of endoplasmic reticulum morphology is tightly linked to neurologic disorders and cancer5,6. Here we demonstrate that three membrane-bound endoplasmic reticulum proteins preferentially interact with different microtubule populations, with CLIMP63 binding centrosome microtubules, kinectin (KTN1) binding perinuclear polyglutamylated microtubules, and p180 binding glutamylated microtubules. Knockout of these proteins or manipulation of microtubule populations and glutamylation status results in marked changes in endoplasmic reticulum positioning, leading to similar redistributions of other organelles. During nutrient starvation, cells modulate CLIMP63 protein levels and p180-microtubule binding to bidirectionally move endoplasmic reticulum and lysosomes for proper autophagic responses.

A review on recent advances in the enrichment of glycopeptides and glycoproteins by liquid chromatographic methods: 2016-Present.

Among various protein post-translational modifications (PTMs), glycosylation has received special attention due to its immense role in molecular interactions, cellular signal transduction, immune response, etc. Aberration in glycan moieties of a glycoprotein is associated with cancer, diabetes, and bacterial and viral infections. In biofluids (plasma, saliva, urine, milk, etc.), glycoproteins are low in abundance and are masked by the presence of high abundant proteins. Hence, prior to their identification using mass spectrometry methods, liquid chromatography (LC)-based approaches were widely used. A general enrichment strategy involves a protein digestion step, followed by LC-based enrichment and desorption of glycopeptides, and enzymatic excision of the glycans. The focus of this review article is to highlight the articles published since 2016 that dealt with different LC-based approaches for glycopeptide and glycoprotein enrichment. The preparation of stationary phases, their surface activation, and ligand immobilization strategies have been discussed in detail. Finally, the major developments and future trends in the field have been summarized.

TIRAP in the Mechanism of Inflammation.

The Toll-interleukin-1 Receptor (TIR) domain-containing adaptor protein (TIRAP) represents a key intracellular signalling molecule regulating diverse immune responses. Its capacity to function as an adaptor molecule has been widely investigated in relation to Toll-like Receptor (TLR)-mediated innate immune signalling. Since the discovery of TIRAP in 2001, initial studies were mainly focused on its role as an adaptor protein that couples Myeloid differentiation factor 88 (MyD88) with TLRs, to activate MyD88-dependent TLRs signalling. Subsequent studies delineated TIRAP's role as a transducer of signalling events through its interaction with non-TLR signalling mediators. Indeed, the ability of TIRAP to interact with an array of intracellular signalling mediators suggests its central role in various immune responses. Therefore, continued studies that elucidate the molecular basis of various TIRAP-protein interactions and how they affect the signalling magnitude, should provide key information on the inflammatory disease mechanisms. This review summarizes the TIRAP recruitment to activated receptors and discusses the mechanism of interactions in relation to the signalling that precede acute and chronic inflammatory diseases. Furthermore, we highlighted the significance of TIRAP-TIR domain containing binding sites for several intracellular inflammatory signalling molecules. Collectively, we discuss the importance of the TIR domain in TIRAP as a key interface involved in protein interactions which could hence serve as a therapeutic target to dampen the extent of acute and chronic inflammatory conditions.

The Impact of COVID-19 on Cancer Care in the Post Pandemic World: Five Major Lessons Learnt from Challenges and Countermeasures of Major Asian Cancer Centres.

OBJECTIVE: The COVID-19 pandemic has dramatically affected healthcare services around Asia. The Asian National Cancer Centres Alliance and the Asia-Pacific Organisation for Cancer Prevention collaborated to assess the mid- and long- term impact of COVID-19 to cancer care in Asia. METHODS: The two entities organised a combined symposium and post-meeting interactions among representatives of major cancer centres from seventeen Asian countries to outlining major challenges and countermeasures. RESULTS: Participating stakeholders distilled five big questions. 1) "Will there be an explosion of late-stage cancers after the pandemic?" To address and recover from perceived delayed prevention, screening, treatment and care challenges, collaboration of key stakeholders in the region and alignment in cancer care management, policy intervention and cancer registry initiatives would be of essential value. 2) "Operations and Finance" The pandemic has resulted in significant material and financial casualties. Flagged acute challenges (shortages of supplies, imposition of lockdown) as well as longer-standing reduction of financial revenue, manpower, international collaboration, and training should also be addressed. 3) "Will telemedicine and technological innovations revolutionize cancer care?" Deploying and implementing telemedicine such as teleconsultation and virtual tumour boards were considered invaluable. These innovations could become a new regular practice, leading to expansion of tele-collaboration through collaboration of institutions in the region. 4) "Will virtual conferences continue after the pandemic?" Virtual conferences during the pandemic have opened new doors for knowledge sharing, especially for representatives of low- and middle-income countries in the region, while saving time and costs of travel. 5) "How do we prepare for the next pandemic or international emergency?" Roadmaps for action to improve access to appropriate patient care and research were identified and scrutinised. CONCLUSION: Through addressing these five big questions, focused collaboration among members and with international organisations such as City Cancer Challenge will allow enhanced preparedness for future international emergencies.
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Tetra-arylborate lipophilic anions as targeting groups.

Tetraphenylborate (TPB) anions traverse membranes but are excluded from mitochondria by the membrane potential (Δψ). TPB-conjugates also distributed across membranes in response to Δψ, but surprisingly, they rapidly entered cells. They accumulated within lysosomes following endocystosis. This pH-independent targeting of lysosomes makes possible new classes of probe and bioactive molecules.

Characterization of exosome release and extracellular vesicle-associated miRNAs for human bronchial epithelial cells irradiated with high charge and energy ions.

Exosomes are extracellular vesicles that mediate transport of nucleic acids, proteins, and other molecules. Prior work has implicated exosomes in the transmission of radiation nontargeted effects. Here we investigate the ability of energetic heavy ions, representative of species found in galactic cosmic rays, to stimulate exosome release from human bronchial epithelial cells in vitro. Immortalized human bronchial epithelial cells (HBEC3-KT F25F) were irradiated with 1.0 Gy of high linear energy transfer (LET) 48Ti, 28Si, or 16O ions, or with 10 Gy of low-LET reference γ-rays, and extracellular vesicles were collected from conditioned media. Preparations were characterized by single particle tracking analysis, transmission electron microscopy, and immunoblotting for the exosomal marker, TSG101. Based on TSG101 levels, irradiation with high-LET ions, but not γ-rays, stimulated exosome release by about 4-fold, relative to mock-irradiated controls. The exosome-enriched vesicle preparations contained pro-inflammatory damage-associated molecular patterns, including HSP70 and calreticulin. Additionally, miRNA profiling was performed for vesicular RNAs using NanoString technology. The miRNA profile was skewed toward a small number of species that have previously been shown to be involved in cancer initiation and progression, including miR-1246, miR-1290, miR-23a, and miR-205. Additionally, a set of 24 miRNAs was defined as modestly over-represented in preparations from HZE ion-irradiated versus other cells. Gene set enrichment analysis based on the over-represented miRNAs showed highly significant association with nonsmall cell lung and other cancers.

Effect of structured training in improving the ergonomic stress in laparoscopic surgery among general surgery residents.

BACKGROUND: Minimal access surgery has fast become the standard of care for many operative procedures, but is associated with lot of ergonomic stress to the surgeons performing these procedures, which may result in reduction in surgeon's performance and work capacity. In this study, we evaluated the impact of structured training program in improving the ergonomic stress in trainee laparoscopic surgeons. METHODS: Laparoscopic surgeons were divided in 2 groups: trainee surgeons (ten) and expert surgeons (three). Baseline surface electromyography (sEMG) data were collected from bilateral deltoid, biceps brachii, forearm extensors, and pronator teres during a predefined suturing task on Tuebingen trainer with integrated porcine organs in both the groups. Trainee surgeons underwent 20 h of laparoscopic intra-corporeal suturing training and surface electromyography data were recorded at the end of training again and compared with baseline. RESULTS: Experts were found to have lower muscle activation (p < 0.05) and muscle work (p < 0.05) and better bimanual dexterity than the trainee surgeons at baseline. After training, the trainee surgeons showed significant improvement (p = 0.01), but still did not reach the values of the expert surgeons (p = 0.01). Right deltoid and pronator teres muscles were found to have maximal activity while performing intra-corporeal suturing. CONCLUSION: Structured and focused training outside operation theater can significantly reduce unnecessary muscle activation of trainee laparoscopic surgeons and better dexterity leading on to lesser ergonomic stress and thus possibly may reduce the risk of development of future musculo-skeletal disorders.

Mycobacterial origin protein Rv0674 localizes into mitochondria, interacts with D-loop and regulates OXPHOS for intracellular persistence of Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb) employs diverse strategies to survive inside the host macrophages. In this study, we have identified a conserved hypothetical protein of Mtb; Rv0674, which is present in the mitochondria of the host cell. The genetic knock-out of rv0674 (Mtb-KO) showed increased growth of Mtb. The intracellular infection with recombinant Mycobacterium smegmatis (MSMEG) expressing Rv0674 (MS_Rv0674), established that the protein is involved in promoting the apoptotic cell death of the macrophage. To investigate the mechanism incurred in mitochondria, we observed that the protein physically interacts with the control region (D-loop) of the mitochondrial DNA (LSP and HSP promoters of the loop) of the macrophages and facilitates the increased expression of mRNA in all the complexes of mitochondrial encoded OXPHOS subunits. The changes in OXPHOS levels corroborated with the ATP synthesis, mitochondrial membrane potential and superoxide production. The infection with MS_Rv0674 confirmed the role of this protein in effecting the intracellular infection. The fluorescent and confocal microscopy confirmed that the protein is localized in the mitochondria of infected macrophages and in the cells of BAL of TB patients. Together these findings indicate towards the novel function of the protein which is unlike to the earlier established mechanisms of mycobacterial physiology.

Oil-Tolerant Nonionic Worm-like Micellar Solution.

The goal of this work is to study the effect of crude oil on worm-like micelles and identify any oil-tolerant systems. A new class of nonionic surfactants was synthesized that forms viscous worm-like micelles under a wide range of temperature and salinity conditions. Aqueous stability, rheology, cryogenic transmission electron microscopy imaging, and dynamic-light-scattering measurements were performed to understand properties, shape, and size of the micelles formed using these surfactants under different temperatures and salinity conditions and in the presence of hydrocarbons. These micellar solutions maintained high viscosity in the presence of small amounts (up to 8 vol %) of crude oils and pure hydrocarbons. Similar experiments were performed with conventional surfactant systems that were known to form worm-like micelles; they did not show oil tolerance. Larger alkanes and viscous crude oils affect the viscosity and transformation of cylindrical micelles less. These new surfactants are useful for oil and gas operations such as hydraulic fracturing, conformance control, and mobility control as they form viscous worm-like micelles in the presence of small amounts of crude oils.

Low-Level Nanog Expression in the Regulation of Quiescent Endothelium.

OBJECTIVE: Nanog is expressed in adult endothelial cells (ECs) at a low-level, however, its functional significance is not known. The goal of our study was to elucidate the role of Nanog in adult ECs using a genetically engineered mouse model system. Approach and Results: Biochemical analyses showed that Nanog is expressed in both adult human and mouse tissues. Primary ECs isolated from adult mice showed detectable levels of Nanog, Tert (telomerase reverse transcriptase), and eNos (endothelial nitric oxide synthase). Wnt3a (Wnt family member 3A) increased the expression of Nanog and hTERT (human telomerase reverse transcriptase) in ECs and increased telomerase activity in these cells. In a chromatin immunoprecipitation experiment, Nanog directly bound to the hTERT and eNOS promoter/enhancer DNA elements, thereby regulating their transcription. Administration of low-dose tamoxifen to ROSAmT/mG::Nanogfl/+::Cdh5CreERT2 mice induced deletion of a single Nanog allele, simultaneously labeling ECs with green fluorescent protein and resulting in decreased Tert and eNos levels. Histological and morphometric analyses of heart tissue sections prepared from these mice revealed cell death, microvascular rarefaction, and increased fibrosis in cardiac vessels. Accordingly, EC-specific Nanog-haploinsufficiency resulted in impaired EC homeostasis and angiogenesis. Conversely, re-expression of cDNA encoding the hTERT in Nanog-depleted ECs, in part, restored the effect of loss of Nanog. CONCLUSIONS: We showed that low-level Nanog expression is required for normal EC homeostasis and angiogenesis in adulthood.

Enhanced Mechanical Toughness of Isotactic Polypropylene Using Bulk Molybdenum Disulfide.

Herein, we report the use of bulk molybdenum disulfide (MoS2) as the reinforcing agent to enhance the toughness of isotactic polypropylene (iPP). The iPP-MoS2 nanocomposites with varying amounts of MoS2 (0.1 to 5 wt %) were prepared by a one-step melt extrusion method, and the effects of MoS2 on the morphology, thermal, and mechanical properties were evaluated by different instrumental techniques such as Raman, ATR-FTIR, UTM, TEM, TGA, and DSC. TEM images showed the uniform dispersion of multilayer MoS2 in the polymer matrix, and XRD results suggested the formation of the ß phase when a low amount of MoS2 is loaded in the composites. Mechanical tests revealed a significant increase in the toughness and elongation at break (300-400%) in the composites containing low amounts of MoS2 (0.25 to 0.5 wt %). Enhanced toughness and elongation in iPP could be related to the combined effect of the ß phase and the exfoliation of bulk MoS2 under applied stress. The thermal stability of the composites was also improved with the increase in MoS2 loading. Direct utilization of bulk MoS2 and one-step melt extrusion process could be a cost-effective method to induce high elasticity and toughness in iPP.

ESAT-6 regulates autophagous response through SOD-2 and as a result induces intracellular survival of Mycobacterium bovis BCG.

Mycobacterium is known for subverting the host defense machinery, and one such mechanism is the inhibition of autophagy. Here, we have demonstrated that Mycobacterium tuberculosis (MTB) secretes a virulence factor; an early secretory antigenic target protein (ESAT-6) into the phagosome, which induces the expression and activity of mitochondrial superoxide dismutase (SOD-2) of macrophages. Using a series of experiments, and Mycobacterium bovis BCG as a model strain (where ESAT-6 protein is not expressed), we have delineated that the protein regulates SOD-2 of macrophages. The expression and augmentation of SOD-2 activity were confirmed by either incubating the macrophages with ESAT-6 protein, transfection of macrophage by esat6 gene using a eukaryotic promoter vector, or by infection with different mycobacterial strains. The induction of acidification of phagosomal compartment containing bacteria was observed in cells that express low levels of SOD-2. This was further confirmed by observing a significant decrease in the M. bovis BCG intracellular load in the sod-2 knocked-down macrophages.

Tumor-derived exosomes in the regulation of macrophage polarization.

BACKGROUND: This review focuses on exosomes derived from various cancer cells. The review discusses the possibility of differentiating macrophages in alternatively activated anti-inflammatory pro-tumorigenic M2 macrophage phenotypes and classically activated pro-inflammatory, anti-tumorigenic M1 macrophage phenotypes in the tumor microenvironment (TME). The review is divided into two main parts, as follows: (1) role of exosomes in alternatively activating M2-like macrophages-breast cancer-derived exosomes, hepatocellular carcinoma (HCC) cell-derived exosomes, lung cancer-derived exosomes, prostate cancer-derived exosomes, Oral squamous cell carcinoma (OSCC)-derived exosomes, epithelial ovarian cancer (EOC)-derived exosomes, Glioblastoma (GBM) cell-derived exosomes, and colorectal cancer-derived exosomes, (2) role of exosomes in classically activating M1-like macrophages, oral squamous cell carcinoma-derived exosomes, breast cancer-derived exosomes, Pancreatic-cancer derived modified exosomes, and colorectal cancer-derived exosomes, and (3) exosomes and antibody-dependent cellular cytotoxicity (ADCC). This review addresses the following subjects: (1) crosstalk between cancer-derived exosomes and recipient macrophages, (2) the role of cancer-derived exosome payload(s) in modulating macrophage fate of differentiation, and (3) intracellular signaling mechanisms in macrophages regarding the exosome's payload(s) upon its uptake and regulation of the TME. EVIDENCE: Under the electron microscope, nanoscale exosomes appear as specialized membranous vesicles that emerge from the endocytic cellular compartments. Exosomes harbor proteins, growth factors, cytokines, lipids, miRNA, mRNA, and DNAs. Exosomes are released by many cell types, including reticulocytes, dendritic cells, B-lymphocytes, platelets, mast cells, and tumor cells. It is becoming clear that exosomes can impinge upon signal transduction pathways, serve as a mediator of signaling crosstalk, thereby regulating cell-to-cell wireless communications. CONCLUSION: Based on the vesicular cargo, the molecular constituents, the exosomes have the potential to change the fate of macrophage phenotypes, either M1, classically activated macrophages, or M2, alternatively activated macrophages. In this review, we discuss and describe the ability of tumor-derived exosomes in the mechanism of macrophage activation and polarization.