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The association of airborne particulate matter exposure with the deteriorating function of the cardiovascular system is fundamentally driven by the impairment of mitochondrial-nuclear crosstalk orchestrated by aberrant redox signaling. The loss of delicate balance in retrograde communication from mitochondria to the nucleus often culminates in the methylation of the newly synthesized strand of mitochondrial DNA (mtDNA) through DNA methyl transferases. In highly metabolic active tissues such as the heart, mtDNA's methylation state alteration impacts mitochondrial bioenergetics. It affects transcriptional regulatory processes involved in biogenesis, fission, and fusion, often accompanied by the integrated stress response. Previous studies have demonstrated a paradoxical role of mtDNA methylation in cardiovascular pathologies linked to air pollution. A pronounced alteration in mtDNA methylation contributes to systemic inflammation, an etiological determinant for several co-morbidities, including vascular endothelial dysfunction and myocardial injury. In the current article, we evaluate the state of evidence and examine the considerable promise of using cell-free circulating methylated mtDNA as a predictive biomarker to reduce the more significant burden of ambient air pollution on cardiovascular diseases.

Recent progress in the field of nanophotonics has opened up novel avenues for developing nanomaterial-based biosensing systems, which can detect various disease-specific biomarkers, including long noncoding RNAs (lncRNAs) known to circulate in biological fluids. Herein, we designed and developed a nanophotonic approach for rapid and specific capture of lncRNAs using oligonucleotide-conjugated graphene quantum-dot-nanoconjugates. The method offers accurate identification of the target lncRNAs with high selectivity, despite the presence of other molecules in the given sample. The observations also pointed toward the high feasibility and simplicity of the method in the selective determination of lncRNAs. Overall, the approach has the potential of assessing lncRNA expression as a function of disease initiation and progression.

Coumarin is a bicyclic oxygen bearing heterocyclic scaffold formed by fusion of benzene with the pyrone ring. Because of its unique physicochemical characteristics and the ease with which it may be transformed into a wide range of functionalized coumarins during synthesis, coumarin provides a privileged scaffold for medicinal chemists. As a result, many coumarin derivatives have been developed, synthesized, and evaluated to target a variety of therapeutic domains, thereby making it an attractive template for designing novel anti-breast cancer compounds. The main culprit in estrogen overproduction in the estrogen-dependent breast cancer (EDBC), is the enzyme aromatase (AR), and it is thought to be a significant target for the effective treatment of EDBC. Considering coumarins versatility, this review presents a detailed overview of diverse study of aromatase as a target for coumarins. An overview of structure-activity relationship analysis of coumarin core is also included so as to summarize the desired pharmacophoric features essential for design and development of aromatase inhibitors (AIs) using coumarin core. Identification of key synthesis techniques that could aid researchers in designing and developing novel analogues with significant anti-breast cancer properties along with their mechanism of action have also been covered in the current review.

Air pollution is a serious threat to our health and has become one of the major causes of many diseases including cardiovascular disease, respiratory disease, and cancer. The association between air pollution and various diseases has long been a topic of research interest. However, it remains unclear how air pollution actually impacts health by modulating several important cellular functions. Recently, some evidence has emerged about air pollution-induced epigenetic changes, which are linked with the etiology of various human diseases. Among several epigenetic modifications, DNA methylation represents the most prominent epigenetic alteration underlying the air pollution-induced pathogenic mechanism. Several other types of epigenetic changes, such as histone modifications, miRNA, and non-coding RNA expression, have also been found to have been linked with air pollution. Hypersensitivity pneumonitis (HP), one of the most prevalent forms of interstitial lung diseases (ILDs), is triggered by the inhalation of certain organic and inorganic substances. HP is characterized by inflammation in the tissues around the lungs’ airways and may lead to irreversible lung scarring over time. This review, in addition to other diseases, attempts to understand whether certain pollutants influence HP development through such epigenetic modifications.

For the management of Cercospora leaf spot of urdbean, seven new fungicides were tested for two year during 2018 and 2019. Of all the chemical tested, foliar spray with Azoxystrobin 8.3% + Mancozeb 66.7% WG and foliar spray with Carbendazim 12% + Mancozeb 63% WP were highly effective and provided less disease severity and high yield of urdbean crop.

Circulating cell-free miRNAs (ccf-miRs) have gained significant interest as biomarkers for lung cancer (LC) diagnosis. However, the clinical application of ccf-miRs is mainly limited by time, cost, and expertise-related problems of existing detection strategies. Recently, the development of different point-of-care (POC) approaches offers useful on-site platforms, because these technologies have important features such as portability, rapid turnaround time, minimal sample requirement, and cost-effectiveness. In this review, we discuss different POC approaches for detecting ccf-miRs and highlight the utility of incorporating nanomaterials for enhanced biorecognition and signal transduction, further improving their diagnostic applicability in LC settings.

Graphene quantum dots (GQDs) are carbonaceous nanodots that are natural crystalline semiconductors and range from 1 to 20 nm. The broad range of applications for GQDs is based on their unique physical and chemical properties. Compared to inorganic quantum dots, GQDs possess numerous advantages, including formidable biocompatibility, low intrinsic toxicity, excellent dispensability, hydrophilicity, and surface grating, thus making them promising materials for nanophotonic applications. Owing to their unique photonic compliant properties, such as superb solubility, robust chemical inertness, large specific surface area, superabundant surface conjugation sites, superior photostability, resistance to photobleaching, and nonblinking, GQDs have emerged as a novel class of probes for the detection of biomolecules and study of their molecular interactions. Here, we present a brief overview of GQDs, their advantages over quantum dots (QDs), various synthesis procedures, and different surface conjugation chemistries for detecting cell-free circulating nucleic acids (CNAs). With the prominent rise of liquid biopsy-based approaches for real-time detection of CNAs, GQDs-based strategies might be a step toward early diagnosis, prognosis, treatment monitoring, and outcome prediction of various non-communicable diseases, including cancers.

The Coronavirus Disease-2019 (COVID-19) imposed public health emergency and affected millions of people around the globe. As of January 2021, 100 million confirmed cases of COVID-19 along with more than 2 million deaths were reported worldwide. SARS-CoV-2 infection causes excessive production of pro-inflammatory cytokines thereby leading to the development of “Cytokine Storm Syndrome.” This condition results in uncontrollable inflammation that further imposes multiple-organ-failure eventually leading to death. SARS-CoV-2 induces unrestrained innate immune response and impairs adaptive immune responses thereby causing tissue damage. Thus, understanding the foremost features and evolution of innate and adaptive immunity to SARS-CoV-2 is crucial in anticipating COVID-19 outcomes and in developing effective strategies to control the viral spread. In the present review, we exhaustively discuss the sequential key immunological events that occur during SARS-CoV-2 infection and are involved in the immunopathogenesis of COVID-19. In addition to this, we also highlight various therapeutic options already in use such as immunosuppressive drugs, plasma therapy and intravenous immunoglobulins along with various novel potent therapeutic options that should be considered in managing COVID-19 infection such as traditional medicines and probiotics.

Mitochondria are maternally inherited semi-autonomous organelles that play a central role in redox balance, energy metabolism, control of integrated stress responses, and cellular homeostasis. The molecular communication between mitochondria and the nucleus is intricate and bidirectional in nature. Though mitochondrial genome encodes for several key proteins involved in oxidative phosphorylation, several regulatory factors encoded by nuclear DNA are prominent contributors to mitochondrial biogenesis and function. The loss of synergy between this reciprocal control of anterograde (nuclear to mitochondrial) and retrograde (mitochondrial to nuclear) signaling, triggers epigenomic imbalance and affects mitochondrial function and global gene expressions. Recent expansions of our knowledge on mitochondrial epigenomics have offered novel perspectives for the study of several non-communicable diseases including cancer. As mitochondria are considered beacons for pharmacological interventions, new frontiers in targeted delivery approaches could provide opportunities for effective disease management and cure through reversible epigenetic reprogramming. This review focuses on recent progress in the area of mitochondrial-nuclear cross-talk and epigenetic regulation of mitochondrial DNA methylation, mitochondrial micro RNAs, and post-translational modification of mitochondrial nucleoid-associated proteins that hold major opportunities for targeted drug delivery and clinical translation.

Background The increasing trend of Chronic Obstructive Pulmonary Disease (COPD) in becoming the third leading cause of deaths by 2020 is of great concern, globally as well as in India. Dysregulation of protease/anti-protease balance in COPD has been reported to cause tissue destruction, inflammation and airway remodelling; which are peculiar characteristics of COPD. Therefore, it is imperative to explore various serum proteases involved in COPD pathogenesis, as candidate biomarkers. COPD and Asthma often have overlapping symptoms and therefore involvement of certain proteases in their pathogenesis would render accurate diagnosis of COPD to be difficult. Methods Serum samples from controls, COPD and Asthma patients were collected after requisite institutional ethics committee approvals. The preliminary analysis qualitatively and quantitatively analyzed various serum proteases by ELISA and mass spectrometry techniques. In order to identify a distinct biomarker of COPD, serum neutrophil elastase (NE) and matrix metalloprotease-2 (MMP-2) from COPD and Asthma patients were compared; as these proteases tend to have overlapping activities in both the diseases. A quantitative analysis of the reactive oxygen species (ROS) in the serum of controls and COPD patients was also performed. Statistical analysis for estimation of p-values was performed using unpaired t-test with 95% confidence interval. Results Amongst the significantly elevated proteases in COPD patients vs the controls- neutrophil elastase (NE) [P ], caspase-7 [P ] and matrix metalloprotease-2 (MMP-2) [P ] were observed, along with increased levels of reactive oxygen species (ROS) [P ]. The serum dipeptidyl peptidase-IV (DPP-IV) [P ) concentration was found to be decreased in COPD patients as compared to controls. Interestingly, a distinct elevation of MMP-2 was observed only in COPD patients, but not in Asthma, as compared to controls. Mass spectrometry analysis further identified significant alterations (fold-change) in various proteases (carboxy peptidase, MMP-2 and human leukocyte elastase), anti-proteases (Preg. zone protein, α-2 macroglobulin, peptidase inhibitor) and signalling mediators (cytokine suppressor- SOCS-3). Conclusion The preliminary study of various serum proteases in stable COPD patients distinctly identified elevated MMP-2 as a candidate biomarker for COPD, subject to its validation in large cohort studies.

In recent years, nanotechnology has revolutionized global healthcare and has been predicted to exert a remarkable effect on clinical medicine. In this context, the clinical use of nanomaterials for cancer diagnosis, fertility preservation, and the management of infertility and other pathologies linked to pubertal development, menopause, sexually transmitted infections, and HIV (human immunodeficiency virus) has substantial promise to fill the existing lacunae in reproductive healthcare. Of late, a number of clinical trials involving the use of nanoparticles for the early detection of reproductive tract infections and cancers, targeted drug delivery, and cellular therapeutics have been conducted. However, most of these trials of nanoengineering are still at a nascent stage, and better synergy between pharmaceutics, chemistry, and cutting-edge molecular sciences is needed for effective translation of these interventions from bench to bedside. To bridge the gap between translational outcome and product development, strategic partnerships with the insight and ability to anticipate challenges, as well as an in-depth understanding of the molecular pathways involved, are highly essential. Such amalgamations would overcome the regulatory gauntlet and technical hurdles, thereby facilitating the effective clinical translation of these nano-based tools and technologies. The present review comprehensively focuses on emerging applications of nanotechnology, which holds enormous promise for improved therapeutics and early diagnosis of various human reproductive tract diseases and conditions.

Polycyclic aromatic hydrocarbons (PAHs) refer to a ubiquitous group of anthropogenic air pollutants that are generated through incomplete carbon combustion. Although the immunotoxic nature of PAHs has been previously reported, the underlying molecular mechanisms of this effect are not fully understood. In the present study, we investigated the mitochondrial-mediated epigenetic regulation of 2 PAHs, carcinogenic (benzo[a]pyrene; BaP) and noncarcinogenic (anthracene [ANT]), in peripheral lymphocytes. While ANT exposure triggered mitochondrial oxidative damage, no appreciable epigenetic modifications were observed. On the other hand, exposure to BaP perturbed the mitochondrial redox machinery and initiated cascade of epigenetic modifications. Cells exposed to BaP showed prominent changes in the expression of mitochondrial microRNAs (miR-24, miR-34a, miR-150, and miR-155) and their respective gene targets (NF-κβ, MYC, and p53). The exposure of BaP also caused significant alterations in the expression of epigenetic modifiers (DNMT1, HDAC1, HDAC7, KDM3a, EZH2, and P300) and hypomethylation within nuclear and mitochondrial DNA. This further induced methylation of histone tails, which play a crucial role in the regulation of chromatin structure. Overall, our study provides novel mechanistic insights into the mitochondrial regulation of epigenetic modifications in association with PAH-induced immunotoxicity.

Mitochondria play a central role in maintaining cellular and metabolic homeostasis during vital development cycles of foetal growth. Optimal mitochondrial functions are important not only to sustain adequate energy production but also for regulated epigenetic programming. However, these organelles are subtle targets of environmental exposures, and any perturbance in the defined mitochondrial machinery during the developmental stage can lead to the re-programming of the foetal epigenetic landscape. As these modifications can be transferred to subsequent generations, we herein performed a cross-sectional study to have an in-depth understanding of this intricate phenomenon. The study was conducted with two arms: whereas the first group consisted of in utero pro-oxidant exposed individuals and the second group included controls. Our results showed higher levels of oxidative mtDNA damage and associated integrated stress response among the exposed individuals. These disturbances were found to be closely related to the observed discrepancies in mitochondrial biogenesis. The exposed group showed mtDNA hypermethylation and changes in allied mitochondrial functioning. Altered expression of mitomiRs and their respective target genes in the exposed group indicated the possibilities of a disturbed mitochondrial-nuclear cross talk. This was further confirmed by the modified activity of the mitochondrial stress regulators and pro-inflammatory mediators among the exposed group. Importantly, the disturbed DNMT functioning, hypermethylation of nuclear DNA, and higher degree of post-translational histone modifications established the existence of aberrant epigenetic modifications in the exposed individuals. Overall, our results demonstrate the first molecular insights of in utero pro-oxidant exposure associated changes in the mitochondrial-epigenetic axis. Although, our study might not cement an exposure-response relationship for any particular environmental pro-oxidant, but suffice to establish a dogma of mito-epigenetic reprogramming at intrauterine milieu with chronic illness, a hitherto unreported interaction.

Air pollution has emerged as a serious threat to human health due to close association with spectrum of chronic ailments including cardiovascular disorders, respiratory diseases, nervous system dysfunctions, diabetes and cancer. Exposure to air-borne pollutants along with poor eating behaviours and inferior dietary quality irreversibly impacts epigenomic landscape, leading to aberrant transcriptional control of gene expression which is central to patho-physiology of non-communicable diseases. It is assumed that nutriepigenomic interventions such as vitamins can control such adverse effects through their immediate action on mitochondrial epigenomic-axis. Importantly, the exhaustive clinical utility of vitamins-interceded epigenetic synchronization is not well characterized. Therefore, improving the current limitations linked to stability and bioavailability issues in vitamin formulations is highly warranted. The present review not only sums up the available data on the role of vitamins as potential epigenetic modifiers but also discusses the importance of nano-engineered vitamins as potential epidrugs for dietary and pharmacological intervention to mitigate the long-term effects of air pollution toxicity.

Surface-enhanced Raman scattering (SERS) has emerged as one of the most promising platforms for various biosensing applications. These sensing systems encompass the advantages of specificity, ultra-high sensitivity, stability, low cost, repeatability, and easy-to-use methods. Moreover, their ability to offer a molecular fingerprint and identify the target analyte at low levels make SERS a promising technique for detecting circulating cancer biomarkers with greater sensitivity and reliability. Among the various circulating biomolecules, oncomiRs are emerging as prominent biomarkers for the early screening of breast cancers (BCs). In this review, we provide a comprehensive understanding of different SERS-based biosensors and their application to identify BC-specific oncomiRs. We also discuss different SERS-based sensing strategies, nano-analytical frameworks, and challenges to be addressed for effective clinical translation.

Engineered immune cells offer a prime therapeutic alternate for some aggressive and frequently occurring malignancies like lung cancer. These therapies were reported to result in tumor regression and overall improvement in patient survival. However, studies also suggest that the presence of cancer cell-induced immune-suppressive microenvironment, off-target toxicity, and difficulty in concurrent imaging are some prime impendent in the success of these approaches. The present article reviews the need and significance of the currently available immune cell-based strategies for lung cancer therapeutics. It also showcases the utility of incorporating nanoengineered strategies and details the available formulations of nanocarriers. In last, it briefly discussed the existing methods for nanoparticle fuctionalization and challenges in translating basic research to the clinics. Graphical Abstract.

In our quest to recognize the role of extrinsic and intrinsic environmental factors that can profoundly affect human health, the exposome paradigm proffers an exciting avenue of research. Continuous human biomonitoring would be unfeasible because the exposome is longitudinal and dynamic. Therefore, the reproductive life course of exposome should be put together from cross-sectional snapshots at critical periods such as in utero, early childhood, adolescence, and adulthood. Of course, over the following decades, the exposome paradigm will continue to evolve in terms of its conceptual and methodologic framework. Still, our overarching goal should be to delineate underlying molecular mechanisms that promote health while preventing disease at the population level.

Traffic-related air pollution exposure (TRAP) is a major public health problem. The effects of TRAP exposure on the oxidative biomarkers of exhaled breath condensate (EBC) of adults are seldom studied. We compared the oxidative EBC biomarkers in a group of individuals exposed to TRAP with those of individuals unexposed to TRAP. We conducted a case-control study in Bhopal City (Madhya Pradesh, India). Adults with a history of exposure to TRAP were enrolled as cases and adults with less exposure to TRAP were used as a control. Based on respiratory symptoms and smoking habits, study subjects were stratified into six subgroups. EBC was collected by TURBO14 (Medivac SRL, Italy) at -5 °C. The EBC pH was measured after gas standardization with argon. EBC hydrogen peroxide (H2O2), cystenine leukotrienes (Cys-LTs), 8-isoprostane were measured by commercial ELISA kit. A total of 250 consecutive adult (male: 194) subjects were recruited. Among them, 133 were TRAP-exposed (male: 128) and 117 were non-TRAP-exposed (male: 66). The respiratory symptoms between TRAP-exposed and non-TRAP-exposed subjects were not different. The post-gas standardized EBC pH (median: 7.72; interquartile range (IQR): 7.15-7.94 vs. median: 7.60, IQR: 6.72-7.87;p= 0.09) and EBC H2O2(median: 2.20µmol l-1; IQR: 1.46-3.51 vs. median: 1.99, IQR: 1.41-3.10;p= 0.29) in TRAP-exposed subjects were statistically not different from the non-TRAP-exposed subjects. The EBC Cys-LTs (median: 69.81; IQR: 57.0-83.38 vs. median: 47.21 pg ml-1; IQR: 39.90-54.87,p< 0.001) and EBC 8-isoprostane (median: 12.55 pg ml-1; IQR: 5.51-18.09 vs. median: 7.12; IQR: 4.60-16.04,p= 0.026) in TRAP-exposed subjects were higher compared to those in non-TRAP-exposed subjects. The subgroup analysis showed that TRAP-exposed subjects, irrespective of their smoking habits and respiratory symptoms, had higher EBC Cys-LTs compared to the non-TRAP-exposed subjects. TRAP exposure increases oxidative biomarkers of the EBC in adults.

Increasing evidence in recent years has suggested that regulatory B cells (Bregs) are one of the crucial modulators in various inflammatory disease conditions. However, no study to date has investigated the significance of Bregs in modulating osteoclastogenesis. To the best of our knowledge, in the present study, we for the first time examined the anti-osteoclastogenic potential of Bregs under in vitro conditions and observed that Bregs suppress RANKL-induced osteoclastogenesis in a dose-dependent manner. We further elucidated the mechanism behind the observed suppression of osteoclasts differentiation via Bregs. Our results clearly suggested that the observed anti-osteoclastogenic property of Bregs is mediated via the production of IL-10 cytokine. Next, we explored whether Bregs have any role in mediating inflammatory bone loss under post-menopausal osteoporotic conditions in ovx mice. Remarkably, our in vivo data clearly suggest that the frequencies of both CD19+IL-10+ Bregs and CD19+CD1dhiCD5+IL-10+ “B10” Bregs were significantly reduced in case of osteoporotic mice model. Moreover, we also found a significant reduction in serum IL-10 cytokine levels in osteoporotic mice, thereby further supporting our observations. Taken together, the present study for the first time establishes the direct role of regulatory B cells in modulating osteoclastogenesis in vitro. Further, our in vivo data suggest that modulations in the percentage of Bregs population along with its reduced potential to produce IL-10 might further exacerbate the observed bone loss in ovx mice.

Lateral flow assay (LFA) is a flexible, simple, low-costpoint-of-care platform for rapid detection of disease-specific biomarkers. Importantly, the ability of the assay to capture the circulating bio-molecules has gained significant attention, as it offers a potential minimal invasive system for early disease diagnosis and prognosis. In the present article, we review an innovative concept of LFA-based detection of circulating long non-coding RNAs (lncRNAs), one of the key regulators of fundamental biological processes. In addition, their disease-specific expression pattern and presence in biological fluids at differential levels make them excellent biomarker candidates for cancer detection. Our article also provides an update on the requirements for developing and improving such systems and discusses the key aspects of material selection, operational concepts, principles and conceptual design. We assume that the reviewed points will be helpful to improve the diagnostic applicability of LFA based lncRNA detection in cancer diagnosis.

Increasing evidences in recent years have suggested that regulatory B cells (Bregs) are crucial modulator in various inflammatory disease conditions. However, the role of Bregs in case of postmenopausal osteoporosis remains unknown. Also, no study till date have ever investigated the significance of Bregs in modulating osteoclastogenesis. In the present study, we for the first time examined the anti-osteoclastogenic potential of Bregs under in vitro conditions and we observed that Bregs suppressed RANKL mediated osteoclastogenesis in bone marrow cells in a dose dependent manner. We further elucidated the mechanism behind the suppression of osteoclasts differentiation by Bregs and found that Bregs inhibit osteoclastogenesis via IL-10 production. To further confirm the bone health modulating potential of Bregs we employed post-menopausal osteoporotic mice model. Remarkably, our in vivo data clearly suggest a significant reduction (p < 0.01) in both CD19+IL-10+ and CD19+CD1dhiCD5+IL-10+ B10 Bregs in case of osteoporotic mice model. Moreover, our serum cytokine data further confirms the significant reduction of IL-10 levels in osteoporotic mice. Taken together, the present study for the first time unravels and establish the unexplored role of regulatory B cells in case of osteoporosis and provide new insight into Bregs biology in the context of post-menopausal osteoporosis.

Osteoporosis is a systemic-skeletal disorder characterized by enhanced fragility of bones leading to increased rates of fractures and morbidity in large number of populations. Probiotics are known to be involved in management of various-inflammatory diseases including osteoporosis. But no study till date had delineated the immunomodulatory potential of Lactobacillus rhamnosus (LR) in bone-health. In the present study, we examined the effect of probiotic-LR on bone-health in ovariectomy (Ovx) induced postmenopausal mice model. In the present study, we for the first time report that LR inhibits osteoclastogenesis and modulates differentiation of Treg-Th17 cells under in vitro conditions. We further observed that LR attenuates bone loss under in vivo conditions in Ovx mice. Both the cortical and trabecular bone-content of Ovx+LR treated group was significantly higher than Ovx-group. Remarkably, the percentage of osteoclastogenic CD4+Rorγt+Th17 cells at distinct immunological sites such as BM, spleen, LN and PP were significantly reduced, whereas the percentage of anti-osteoclastogenic CD4+Foxp3+Tregs and CD8+Foxp3+Tregs were significantly enhanced in LR-treated group thereby resulting in inhibition of bone loss. The osteoprotective role of LR was further supported by serum cytokine data with a significant reduction in osteoclastogenic cytokines (IL-6, IL-17 and TNF-α) along with enhancement in anti-osteoclastogenic cytokines (IL-4, IL-10, IFN-γ) in LR treated-group. Altogether, the present study for the first time establishes the osteoprotective role of LR on bone health, thus highlighting the immunomodulatory potential of LR in the treatment and management of various bone related diseases including osteoporosis.

The immune system is one of the primary targets of airborne particulate matter. Recent evidence suggests that mitochondria lie at the center of particulate matter-induced immunotoxicity. Particulate matter can directly interact with mitochondrial components (proteins, lipids, and nucleic acids) and impairs the vital mitochondrial processes including redox mechanisms, fusion-fission, autophagy, and metabolic pathways. These disturbances impede different mitochondrial functions including ATP production, which acts as an important platform to regulate immunity and inflammatory responses. Moreover, the mitochondrial DNA released into the cytosol or in the extracellular milieu acts as a danger-associated molecular pattern and triggers the signaling pathways, involving cGAS-STING, TLR9, and NLRP3. In the present review, we discuss the emerging role of mitochondria in airborne particulate matter-induced immunotoxicity and its myriad biological consequences in health and disease.

Background: Novel bioactive plant secondary metabolites, including flavonoids, offer a spectrum of chemo-protective responses against a range of human tumor models. However, the clinical translation of these promising anti-cancer agents has been hindered largely by their poor solubility, rapid metabolism, or a combination of both, ultimately resulting in poor bioavailability upon oral administration. Objective: To circumvent the challenges associated with herbal drug development and for effective integration into clinical setting, nano-engineering is one of the emerging pragmatic strategies which has promise to deliver therapeutic concentrations of bio-actives upon oral administration. Method: We assessed the nano-encapsulated flavonoid-rich fraction isolated from a traditional Indian herb Selaginella bryopteris (Sanjeevani) (NP.SB). Both in vitro and in vivo studies were performed to evidence the epigenetic protection mechanisms of NP.SB through a mitochondrial-targeted pre-clinical validation strategy. Results: The mito-protective activity of NP.SB revealed a dose-dependent effect when tested in GC-1 spg (mouse spermatogonial epithelial) and B/CMBA.Ov (mouse ovarian epithelial) following exposure to Nsuccinimidyl N-methylcarbamate, a potential human carcinogen. Smaller size, rapid internalization, faster mobility and site specific delivery conferred significant cancer protection in cultured cells. Notably, this encapsulated flavonoid supplementation; prevented emergence of neoplastic daughter clones from senescent mother phenotypes in pro-oxidant treated GC-1 spg and B/CMBA.Ov cells by selective abrogation of mitochondrial oxidative stress-induced aberrant epigenetic modifications. In vivo studies using a diethylnitrosamine and 2- acetylaminofluorene mouse model demonstrated that NP.SB has a significant inhibitory effect on tumor growth which clearly substantiated our in vitro findings. Conclusion: Anti-carcinogenic property in conjunction with low toxicity of NP.SB, underscores the translational significance of dietary flavonoids as cancer-protective agents for preferential application in clinical settings.

This review targets valuable insight into the application of water dispersed luminescent quantum dots (QDs) for detection of microRNA (miRNA). Recently, considerable efforts have been devoted to obtain QDs for biosensing and bioimaging. Quantum dots with bright stable photoluminescence, synthesized directly in the water phase, offered an unparalleled advantage for the assay development involving small size, high colloidal stability, and presence of groups for bioconjugation. In this review we have delineated the fundamental principles guiding the rational design, synthesis, and application of photoluminescent water-dispersed QDs. Diverse analysis methods for miRNA detection based on the photoluminescence, electrochemiluminescence, Forster resonance energy transfer and electrochemiluminescence energy transfer with different enhancement strategies are discussed.

Background Particulate matter directly emitted into the air by sources such as combustion processes and windblown dust, or formed in the atmosphere by transformation of emitted gases are the major contributors to air pollution that triggers a diverse array of human pathologies including lung cancer. The mortality in lung cancer is usually high as the disease is not symptomatic at its early treatable stage. Moreover, available methods for screening are costly and mainly rely on imaging techniques which lack sufficient sensitivity and specificity. Despite progress in the identification of biomarkers, gene mutation based approaches still face formidable challenges as the disease evolves from a complex interplay between environment and host. Therefore, identification of an epigenomic signature might be useful for early diagnosis with the potential to reduce the environmental-associated disease burden. Objective The review discusses the utility of epigenomic signature in identification and management of the environmental-associated lung cancers. Conclusion Non-invasive 'liquid biopsy' based epigenomic screening has recently emerged as a methodology which has potential to characterize tumor heterogeneity at initial stages. Epigenetic signatures (methylated DNA, miRNA, and post transcriptionally modified histones) known to reflect the vital cellular changes, circulate at higher levels in the individuals with lung cancer. These circulating biological entities are reported to be closely associated with the clinical outcome of lung cancer patients and thus strongly stand as the probable candidate to identify disease at an early stage and monitor treatment response, thereby, benefiting patients and improving their lives. However, for effective implementation of the strategy as "point-of-care" test for screening population-at-risk will require exhaustive clinical validation.

Osteoporosis or enhanced bone loss is one of the most commonly occurring bone conditions in the world, responsible for higher incidence of fractures leading to increased morbidity and mortality in adults. Bone loss is affected by various environmental factors including diet, age, drugs, toxins etc. Microcystins are toxins produced by cyanobacteria with microcystin-LR being the most abundantly found around the world effecting both human and animal health. The present study demonstrates that MC-LR treatment induces bone loss and impairs both trabecular and cortical bone microarchitecture along with decreasing the mineral density and heterogeneity of bones in mice. This effect of MC-LR was found due to its immunomodulatory effects on the host immune system, wherein MC-LR skews both T cell (CD4+ and CD8+ T cells) and B cell populations in various lymphoid tissues. MC-LR further was found to significantly enhance the levels of osteoclastogenic cytokines (IL-6, IL-17 and TNF-α) along with simultaneously decreasing the levels of anti-osteoclastogenic cytokines (IL-10 and IFN-γ). Taken together, our study for the first time establishes a direct link between MC-LR intake and enhanced bone loss thereby giving a strong impetus to the naive field of "osteo-toxicology", to delineate the effects of various toxins (including cyanotoxins) on bone health.

In the context of the high risk of heart failure (HF), rapid assessment of biomarker levels in patients appears to be a quick and accurate approach to diagnosis and timely treatment. Brain natriuretic peptide (BNP) and N-terminal fragment of the prohormone BNP (NT-proBNP) are widely used as biomarkers of HF, primarily ventricular dysfunction, for diagnosis, treatment and risk assessment. A major strength of BNP and NT-proBNP is their high negative predictive value: they are useful in exclusion of HF as a cause of non-specific symptoms. In this review we consider the features of the presence of BNP and NT-proBNP in a cocktail of natriuretic peptides in the bloodstream, as well as challenges, skeleton concepts and characteristic methods for BNP and NT-proBNP detection using optical labels. We consider the most important points for analysis and diagnostics, approaches for improving diagnostic value, as well as sensitivity and reproducibility.

Circulating cell free mitochondrial DNA (ccf-mtDNA) has emerged as a potential marker for diagnosis and prognosis of different chronic and age associated non-communicable diseases. Therefore, owing to its biomarker potential, we herein assessed a novel nano-photonic dual hybrid assay system for rapid and specific detection of ccf-mtDNA. The assay comprised of two systems, i.e. a capture and screen facet containing aminopyrene tethered carbon quantum dots for effective screening of circulating cell free nucleic acids (ccf-NAs) and a quantum dot conjugated probe for precise detection of ccf-mtDNA in the screened ccf-NAs. Our observations suggested that the developed dual-assay system possesses high feasibility and selectivity in screening of ccf-NAs and estimation of ccfmtDNA in a given sample. It also offers high versatility of measurement in different analytical platforms, indicating the translational potential of the method for possible disease risk assessment in control and field settings.

Particulate matter (PM), broadly defined as coarse (2.5–10 μm), fine (0.1–2.5 μm) and ultrafine particles (≤0.1 μm), is a major constituent of ambient air pollution. Recent studies have linked PM exposure (coarse and fine particles) with several human diseases including cancer. However, the molecular mechanisms underlying ultrafine PM exposure induced cellular and sub-cellular repercussions are ill-defined. Since mitochondria are one of the major targets of different environmental pollutants, we herein aimed to understand the molecular repercussion of ultrafine PM exposure on mitochondrial machinery in peripheral blood lymphocytes. Upon comparative analysis, a significantly higher DCF fluorescence was observed in ultrafine PM exposed cells that confirmed the strong pro-oxidant nature of these particles. In addition, the depleted activity of antioxidant enzymes, glutathione reductase and superoxide dismutase suggested the strong association of ultrafine PM with oxidative stress. These results further coincided with mitochondrial membrane depolarization, altered mitochondrial respiratory chain enzyme activity and decline in mtDNA copy number. Moreover, the higher accumulation of DNA damage response proteins (γH2AX, pATM, p-p53), suggested that exposure to ultrafine PM induces DNA damage and triggers phosphatidylinositol 3 kinase mediated response pathway. Further, the alterations in mitochondrial machinery and redox balance among ultrafine PM exposed cells were accompanied by a considerably elevated pro-inflammatory cytokine response. Interestingly, the lower apoptosis levels observed in ultrafine particle treated cells suggest the possibility that the marked alterations may lead to the impairment of mitochondrial-nuclear cross talk. Together, our results showed that ultrafine PM, because of their smaller size possesses significant ability to disturb mitochondrial redox homeostasis and activates phosphatidylinositol 3 kinase mediated DNA damage response pathway, an unknown molecular paradigm of ultrafine PM exposure. Our findings also indicate that maneuvering through the mitochondrial function might be a viable, indirect method to modulate lymphocyte homeostasis in air pollution associated immune disorders.

Osteoporosis is one of the most important but often neglected bone disease associated with aging and postmenopausal condition leading to bone loss and fragility. Probiotics have been associated with various immunomodulatory properties and have the potential to ameliorate several inflammatory conditions including osteoporosis. Lactobacillus acidophilus (LA) was selected as probiotic of choice in our present study due its common availability and established immunomodulatory properties. In the present study, we report for the first time that administration of LA in ovariectomized (ovx) mice enhances both trabecular and cortical bone microarchitecture along with increasing the mineral density and heterogeneity of bones. This effect of LA administration is due to its immunomodulatory effect on host immune system. LA thus skews the Treg-Th17 cell balance by inhibiting osteoclastogenic Th17 cells and promoting anti-osteoclastogenic Treg cells in ovx mice. LA administration also suppressed expression of osteoclastogenic factors (IL-6, IL-17, TNF-α and RANKL) and increased expression of anti-osteoclastogenic factors (IL-10, IFN-γ). Taken together the present study for the first time clearly demonstrates the therapeutic potential of LA as an osteo-protective agent in enhancing bone health (via tweaking Treg-Th17 cell balance) in postmenopausal osteoporosis., Graphical abstract Lactobacillus acidophilus administration bone mass in post-menopausal osteoporotic mice by skewing Treg-Th17 balance.Unlabelled Image, Highlights • Post-menopausal osteoporosis is one of most commonly occurring skeletal diseases leading to bone loss and fragility. • Probiotics possess various immunomodulatory properties and have the potential to ameliorate several inflammatory conditions including post-menopausal osteoporosis. • We report for the first time that administration of a common probiotic Lactobacillus acidophilus (LA) in ovx mice skews Treg-Th17 cell balance in vivo by inhibiting osteoclastogenic Th17 cells and promoting anti-osteoclastogenic Treg cells. • Also, LA administration suppresses expression of osteoclastogenic (IL-6, IL-17, TNF-α and RANKL) and enhances expression of anti-osteoclastogenic (IL-10, IFN-γ) factors in ovx mice. • The present study for the first time clearly demonstrates the therapeutic potential of LA as a potent osteo-protective agent in enhancing bone health in post-menopausal osteoporosis.

Food items that are unprocessed and do not contain preservatives, artifi cial colours, chemicals, fi llers, artifi cial fl avours etc are called as Natural foods.

The burden of cardio-vascular and other age-related non-communicable diseases are rapidly increasing worldwide. Majority of these chronic ailments are curable, if diagnosed at early stages. Candidate biomarkers of early detection are therefore essential for identification of high-risk individuals, prompt and accurate disease diagnosis, and to monitor therapeutic response. The functional significance of circulating nucleic acids that recapitulate specific disease profiles is now well established. But subtle changes in DNA sequence may not solely reflect the differentiation of gene expression patterns observed in diverse set of diseases as epigenetic phenomena play a larger role in aetiology and patho-physiology. Unlike genetic markers, knowledge about the diagnostic utility of circulating epigenetic signatures: methylated DNA; micro RNA and modified histones are deficient. Characterization of these novel entities through omics-based molecular technologies might prompt development of a range of laboratory-based strategies, thereby accelerating their broader translational purpose for early disease diagnosis, monitoring therapeutic response and drug resistance. However, largest opportunity for innovation lies in developing point-of-care tests with accurate diagnostic and higher prognostic score that is applicable for screening of high-risk populations.

Supplemental_Material for Mapping the Mitochondrial Regulation of Epigenetic Modifications in Association With Carcinogenic and Noncarcinogenic Polycyclic Aromatic Hydrocarbon Exposure by Arpit Bhargava, Roshani Kumari, Surbhi Khare, Ruchita Shandilya, Pushpendra Kumar Gupta, Rajnarayan Tiwari, Akhlaqur Rahman, Koel Chaudhury, Irina Yu Goryacheva and Pradyumna Kumar Mishra in International Journal of Toxicology