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Nanomaterial-based tissue engineering strategies are precisely designed and tweaked to contest specific patient needs and their end applications. Though theragnostic is a radical term very eminent in cancer prognosis, of late, theragnostic approaches have been explored in the fields of tissue remodulation and reparation. The engineering of theragnostic nanomaterials has opened up avenues for disease diagnosis, imaging, and therapeutic treatments. The instantaneous monitoring of therapeutic strategy is expected to co-deliver imaging and pharmaceutical agents at the same time, and nanoscale carrier moieties are convenient and efficient platforms in theragnostic applications, especially in soft and hard tissue regeneration. Furthermore, imaging modalities have extensively contributed to the signal-to-noise ratio. Simultaneously, there is an accumulation of high concentrations of therapeutic mediators at the defect site. Given the confines of contemporary bone diagnostic systems, the clinical rationale demands nano/biomaterials that can localize to bone-diseased sites to enhance the precision and prognostic value for osteoporosis, non-healing fractures, and/or infections, etc. Furthermore, bone theragnostics may have an even greater clinical impact and multimodal imaging procedures can overcome the restrictions of individual modalities. The present review introduces representative theragnostic polymeric nanomaterials and their advantages and disadvantages in practical use as well as their unique properties.

Numerous environmental contaminants significantly contribute to human disease, affecting climate change and public and individual health, resulting in increased mortality and morbidity. Because of the scarcity of information regarding pollution exposure from less developed nations with inadequate waste management, higher levels of poverty, and limited adoption of new technology, the relationship between pollutants and health effects needs to be investigated more. A similar situation is present in many developed countries, where solutions are only discovered after the harm has already been done and the necessity for safeguards has subsided. The connection between environmental toxins and health needs to be better understood due to difficulties in quantifying exposure levels and a lack of systematic monitoring. Different pollutants are to blame for both chronic and acute disorders.Additionally, research becomes challenging when disease problems are seen after prolonged exposure. This review aims to discuss the present understanding of the association between environmental toxins and human health in bridging this knowledge gap. The genesis of cancer and the impact of various environmental pollutants on the human body's cardiovascular, respiratory, reproductive, prenatal, and neural health are discussed in this overview.

Osteoarthritis (OA) is a degenerative disorder involving the joint, including cartilage and synovial fluids. Recent studies have sought to find curative therapeutics to decrease the adverse effects of OA and relieve associated pain. Globally, knee osteoarthritis (KOA) is the most common type of arthritis. The present study aimed to evaluate the anti-inflammatory effect copper albumen complex (cu-albumin complex) for the treatment of mono-iodoacetate (MIA)- induced KOA in Albino rats. A total of 50 adult male albino rats were involved and divided as follows; 10 rats were kept normal as negative control; 20 arthritic rats were kept untreated (positive control), and 20 arthritic rats were treated with cu-albumin complex orally for a month. Treated and untreated arthritic rats were divided equally (10 rats each) into mild and severe groups according to the severity of signs. The intra-articular injection of MIA in the right knee joint was used for induction of osteoarthritis. Using Mankin grading score, the results demonstrated that the treated groups had a better histological appearance than the control positive group. Additionally, except for a few shrunken chondrocytes, the mildly treated group showed less degenerative alterations and appeared virtually normal. While the severe treated group showed increased cellularity with decreased degenerated chondrocytes. It concluded that balanced copper consumption has a positive impact on the prevention and treatment of KOA

Nitrosodiethylamine (NDEA) is a potent oxidant induces neurodegeneration via (reactive oxygen species) ROS. Copper is an important metal essential for scavenging free radicals, development of central nervous system (CNS) and redox angiogenesis signaling. Vascular endothelial growth factor (VEGF) is well known as efficacious and long-term signal that stimulates angiogenesis, where its expression is copper dependent. We examined the copper protective effect against brain vascular damage initiated by NDEA. NDEA induces brain vascular wall damage, necrosis with interstitial hemorrhage and diminishes VEGF expression. Histopathological examination showing a great improvement of brain tissue in copper treated mice with significant increase in VEGF expression. Higher levels of intracellular copper can stimulate angiogenesis and exhibited a significant protection against NDEA induced brain vascular damage, confirming its ability to enhance antioxidant activity and angiogenesis initiation. Our report presents first evidence that inducible VEGF expression in brain is sensitive to copper; moreover, copper-based therapeutics represents a novel approach to reduce brain vascular damage induced by NDEA generated ROS

Exosomes, which are nano-sized transport bio-vehicles, play a pivotal role in maintaining homeostasis by exchanging genetic or metabolic information between different cells. Exosomes can also play a vital role in transferring virulent factors between the host and parasite, thereby regulating host gene expression and the immune interphase. The association of inflammation with disease development and the potential of exosomes to enhance or mitigate inflammatory pathways support the notion that exosomes have the potential to alter the course of a disease. Clinical trials exploring the role of exosomes in cancer, osteoporosis, and renal, neurological, and pulmonary disorders are currently underway. Notably, the information available on the signatory efficacy of exosomes in immune-related disorders remains elusive and sporadic. In this review, we discuss immune cell-derived exosomes and their application in immunotherapy, including those against autoimmune connective tissue diseases. Further, we have elucidated our views on the major issues in immune-related pathophysiological processes. Therefore, the information presented in this review highlights the role of exosomes as promising strategies and clinical tools for immune regulation.

Infection with viruses, bacteria, and parasites are thought to be the underlying cause of about 8–17% of the world’s cancer burden, i.e., approximately one in every five malignancies globally is caused by an infectious pathogen. Oncogenesis is thought to be aided by eleven major pathogens. It is crucial to identify microorganisms that potentially act as human carcinogens and to understand how exposure to such pathogens occur as well as the following carcinogenic pathways they induce. Gaining knowledge in this field will give important suggestions for effective pathogen-driven cancer care, control, and, ultimately, prevention. This review will mainly focus on the major onco-pathogens and the types of cancer caused by them. It will also discuss the major pathways which, when altered, lead to the progression of these cancers.

Toxic heavy metals (THMs) are non-essential hazardous environmental pollutants with intractable health challenges in humans and animals. Exposure to lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As), nickel (Ni), and chromium (Cr) are ubiquitous and unavoidable due to food contamination, mining, and industrial mobilization. They are triggers of tissue impairment and aberrant signaling pathways that cascade into several toxicities and pathologies. Each of Pb, Cd, Hg, As, Ni, and Cr aggravate oxidative inflammation, protein dysregulation, apoptotic induction, DNA damage, endocrine deficits, and mitochondrial dysfunction contributing to the pathophysiology of diseases. Hesperidin (HSD) and hesperetin (HST) are flavonoids from citrus fruits, and systematic investigations suggest their potential to combat the molecular alterations and toxicities induced by THMs. They mitigate heavy metal toxicity via antioxidant, anti-inflammatory, and anti-apoptotic effects via scavenging free radicals and modulation of ATPases, cell cycle proteins, and various cellular signaling pathways, including Nrf2/HO-1/ARE, PI3K/mTOR/Akt, MAPK/caspase-3/Bax/Bcl-2, iNOS/NF-κB/TNF-α/COX-2. This review summarized the mechanistic effects of heavy metal toxicity and the insights on molecular mechanisms underlying mitigation of heavy metal toxicity by HSD and HST. Hesperidin and hesperetin are potential flavonoids for the modulation of pathological signaling networks associated with THMs. Therefore, HSD and HST can be suggested as natural dietary agents and blockers of harmful effects of THMs.

Abstract Extraction of biosurfactants from plants is advantageous than from microbes. The properties and robustness of biosurfactant derived from the mesocarp of Balanites aegyptiaca have been reported. However, the dark brown property of biosurfactant and lack of knowledge of its biocompatibility limits its scope. In the present work, the decolorization protocol for this biosurfactant was optimized using hydrogen peroxide. The hemolytic potential and biocompatibility based on cell toxicity and proliferation were also investigated. This study is the first report on the decolorization and toxicity assay of this biosurfactant. For decolorization of biosurfactant, 34 full factorial design was used, and the data were subjected to ANOVA. Results indicate that 1.5% of hydrogen peroxide can decolorize the biosurfactant most efficiently at 40 °C in 70 min at pH 7. Mitochondrial reductase (MTT) and reactive oxygen species (ROS) assays on M5S mouse skin fibroblast cells revealed that decolorized biosurfactant up to 50 µg/mL for 6 h had no significant toxic effect. Hemolysis assay showed ~ 2.5% hemolysis of human RBCs, indicating the nontoxic effect of this biosurfactant. The present work established a decolorization protocol making the biosurfactant chromatically acceptable. Biocompatibility assays confirm its safer use as observed by experiments on M5S skin fibroblast cells under in vitro conditions.

Currently, there is a great demand for the development of nanomedicine aided wound tissue regeneration via silver doped nanoceuticals. Unfortunately, very little research is being carried out on antioxidants-doped silver nanometals and their interaction on the signaling axis during the bio-interface mechanism. In this study, c-phycocyanin primed silver nano hybrids (AgcPCNP) were prepared and analyzed for properties such as cytotoxicity, metal decay, nanoconjugate stability, size expansion, and antioxidant features. Fluctuations in the expression of marker genes during cell migration phenomena in in vitro wound healing scenarios were also validated. Studies revealed that physiologically relevant ionic solutions did not exhibit any adverse effects on the nanoconjugate stability. However, acidic, alkali, and ethanol solutions completely denatured the AgcPCNP conjugates. Signal transduction RT2PCR array demonstrated that genes associated with NFĸB- and PI3K-pathways were significantly (p < 0.5%) altered between AgcPCNP and AgNP groups. Specific inhibitors of NFĸB (Nfi) and PI3K (LY294002) pathways confirmed the involvement of NFĸB signaling axes. In vitro wound healing assay demonstrated that NFĸB pathway plays a prime role in the fibroblast cell migration. In conclusion, the present investigation revealed that surface functionalized AgcPCNP accelerated the fibroblast cell migration and can be further explored for wound healing biomedical applications.

Lung cancer (LC) is considered as one of the leading causes of cancer-associated mortalities. Cancer cells’ reprogrammed metabolism results in changes in metabolite concentrations, which can be utilized to identify a distinct metabolic pattern or fingerprint for cancer detection or diagnosis. By detecting different metabolic variations in the expression levels of LC patients, this will help and enhance early diagnosis methods as well as new treatment strategies. The majority of patients are identified at advanced stages after undergoing a number of surgical procedures or diagnostic testing, including the invasive procedures. This could be overcome by understanding the mechanism and function of differently regulated metabolites. Significant variations in the metabolites present in the different samples can be analyzed and used as early biomarkers. They could also be used to analyze the specific progression and type as well as stages of cancer type making it easier for the treatment process. The main aim of this review article is to focus on rewired metabolic pathways and the associated metabolite alterations that can be used as diagnostic and therapeutic targets in lung cancer diagnosis as well as treatment strategies.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a respiratory disorder. Various organ injuries have been reported in response to this virus, including kidney injury and, in particular, kidney tubular injury. It has been discovered that infection with the virus does not only cause new kidney disease but also increases treatment difficulty and mortality rates in people with kidney diseases. In individuals hospitalized with COVID-19, urinary metabolites from several metabolic pathways are used to distinguish between patients with acute kidney injury (AKI) and those without. This review summarizes the pathogenesis, pathophysiology, treatment strategies, and role of metabolomics in relation to AKI in COVID-19 patients. Metabolomics is likely to play a greater role in predicting outcomes for patients with kidney disease and COVID-19 with varying levels of severity in the near future as data on metabolic profiles expand rapidly. Here, we also discuss the correlation between COVID-19 and kidney diseases and the available metabolomics approaches.

Infection, trauma, and autoimmunity trigger tissue inflammation, often leading to pain and loss of function. Therefore, approaches to control inflammation based on nanotechnology principles are being developed in addition to available methods. The metal-based nanoparticles are particularly attractive due to the ease of synthesis, control over physicochemical properties, and facile surface modification with different types of molecules. Here, we report curcumin conjugated silver (Cur-Ag) nanoparticles synthesis, followed by their surface functionalization with isoniazid, tyrosine, and quercetin, leading to Cur-AgINH, Cur-AgTyr, and Cur-AgQrc nanoparticles, respectively. These nanoparticles possess radical scavenging capacity, haemocompatibility, and minimal cytotoxicity to macrophages. Furthermore, the nanoparticles inhibited the secretion of pro-inflammatory cytokines such as interleukin-6, tumor necrosis factor-α, and interleukin-1β from macrophages stimulated by lipopolysaccharide (LPS). The findings reveal that the careful design of surface corona of nanoparticles could be critical to increasing their efficacy in biomedical applications.

Despite the progress in the comprehension of LC progression, risk, immunologic control, and treatment choices, it is still the primary cause of cancer-related death. LC cells possess a very low and heterogeneous antigenicity, which allows them to passively evade the anticancer defense of the immune system by educating cytotoxic lymphocytes (CTLs), tumor-infiltrating lymphocytes (TILs), regulatory T cells (Treg), immune checkpoint inhibitors (ICIs), and myeloid-derived suppressor cells (MDSCs). Though ICIs are an important candidate in first-line therapy, consolidation therapy, adjuvant therapy, and other combination therapies involving traditional therapies, the need for new predictive immunotherapy biomarkers remains. Furthermore, ICI-induced resistance after an initial response makes it vital to seek and exploit new targets to benefit greatly from immunotherapy. As ICIs, tumor mutation burden (TMB), and microsatellite instability (MSI) are not ideal LC predictive markers, a multi-parameter analysis of the immune system considering tumor, stroma, and beyond can be the future-oriented predictive marker. The optimal patient selection with a proper adjuvant agent in immunotherapy approaches needs to be still revised. Here, we summarize advances in LC immunotherapy approaches with their clinical and preclinical trials considering cancer models and vaccines and the potential of employing immunology to predict immunotherapy effectiveness in cancer patients and address the viewpoints on future directions. We conclude that the field of lung cancer therapeutics can benefit from the use of combination strategies but with comprehension of their limitations and improvements.

Ellagitannins (esters composed of glucose and ellagic acid) are hydrolyzed to generate ellagic acid in gut followed by conversion of ellagic acid to urolithins such as urolithin A by intestinal bacteria. Since urolithins are absorbed by gut easier than ellagitannins and ellagic acid, and show various physiological activities (e.g. anti-cancer, anti-cardiovascular disease, anti-diabetes mellitus, anti-obesity and anti-Alzheimer disease activities), they are expected as excellent health-promoting phytochemicals. Here, using human monoblast U937 cells, we investigated the effect of ellagic acid and urolithin A on the superoxide anion (O2−)-generating system of phagocytes, which is consisted of five specific protein factors (membrane proteins: p22-phox and gp91-phox, cytosolic proteins: p40-phox, p47-phox and p67-phox). Twenty micromolar of urolithin A enhanced the all-trans retinoic acid (ATRA)-induced O2−-generating activity (to ~175%) while 20 μM ellagic acid inhibited the ATRA-induced O2−-generating activity (to ~70%). Semiquantitative RT-PCR showed that transcription level of gp91-phox was certainly decreased (to ~70%) in ATRA plus ellagic acid-treated cells, while that of gp91-phox was significantly increased (to ~160%) in ATRA plus urolithin A-treated cells. Chromatin immunoprecipitation assay suggested that urolithin A enhanced acetylations of Lys-9 residues of histone H3 within chromatin surrounding the promoter region of gp91-phox gene, but ellagic acid suppressed the acetylations. Immunoblotting also revealed that ATRA plus urolithin A-treatment up-regulated protein levels of p22-phox (to ~160%) and gp91-phox (to ~170%) although ATRA plus ellagic acid-treatment down-regulated protein levels of p22-phox (to ~70%) and gp91-phox (to ~60%). These results suggested that conversion of ellagic acid to urolithin A in gut may bring about reverse effects on the gp91-phox gene expression, resulting in opposite alterations in O2−-generating activity of intestinal macrophages.

Dermal wound healing describes the progressive repair and recalcitrant mechanism of 12 damaged skin, and eventually, reformatting and reshaping the skin. Many probiotics, nutritional supplements, metal nanoparticles, composites, skin constructs, polymers, and so forth have been associated with the improved healing process of wounds. The exact mechanism of material-cellular interaction is a point of immense importance, particularly in pathological conditions such as diabetes. Bioengineered alternative agents will likely continue to dominate the outpatient and perioperative management of chronic, recalcitrant wounds as new products continue to cut costs and improve the wound healing process. This review article provides an update on the various remedies with confirmed wound healing activities of metal-based nanoceutical adjuvanted agents and also other nano-based counterparts from previous experiments conducted by various researchers.

Oroxylum indicum , of the Bignoniaceae family, has various ethnomedical uses such as an astringent, anti-inflammatory, anti-bronchitis, anti-helminthic and anti-microbial, including anticancer properties. The druggability of OI stem bark extract was determined by its molecular docking interactions with PARP and Caspase-3, two proteins involved in cell survival and death. Note that 50 µg/mL of Oroxylum indicum extract (OIE) showed a significant ( p < 0.05%) toxicity to HSC-3 cells. MTT aided cell viability and proliferation assay demonstrated that 50 µg/mL of OIE displayed significant ( p < 0.5%) reduction in cell number at 4 h of incubation time. Cell elongation and spindle formation was noticed when HSC-3 cells were treated with 50 µg/mL of OIE. OIE initiated DNA breakage and apoptosis in HSC-3 cells, as evident from DNA ladder assay and calcein/EB staining. Apoptosis potential of OIE is confirmed by flow cytometer and triple-staining (live cell/apoptosis/necrosis) assay. Caspase-3/7 fluorescence quenching (LANCE) assay demonstrated that 50 µg/mL of OIE significantly enhanced the RFU of caspases-3/7, indicating that the apoptosis potential of OIE is probably through the activation of caspases. Immuno-cytochemistry of HSC-3 cells treated with 50 µg/mL of OIE showed a significant reduction in mitochondrial bodies as well as a reduction in RFU in 60 min of incubation time. Immunoblotting studies clearly showed that treatment of HSC-3 cells with OI extract caused caspase-3 activation and PARP deactivation, resulting in apoptotic cell death. Overall, our data indicate that OIE is an effective apoptotic agent for human squamous carcinoma cells and it could be a future cancer chemotherapeutic target.

Exosomes are the master transporters of genes, RNAs, microRNAs, proteins, and lipids. They have applications in major diseases, including cancer, cardiovascular diseases, neurological disorders, and diabetes mellitus. Delivery of the exosomes to recipient cells is governed by the functional heterogenicity of the tissues. Engineered exosomes are promising tools in tissue regeneration. In addition to their role as intracellular communication cargos, exosomes are increasingly primed as standard biomarkers in the progression of diseases, thereby solving the diagnostic dilemma. Futuristic empowerment of exosomes with OMICS strategy can undoubtedly be a bio-tool in translational medicine. This review discusses the advent transformation of exosomes in regenerative medicine and limitations that are caveats to broader applications in clinical use.

Objective: We examined regional specificity of microglial activation in the developing rat brain for 72 hours after hypoxia-ischemia (HI) and the effect of acetylcholine receptor (AChR) agonist on microglial activation., Study Design: Seven-day-old Wistar rats were divided into two groups: one receiving a single dose of AChR agonist just before hypoxia (carbachol; 0.1mg/kg) to investigate the reducing effect on brain damage with decreasing activation of microglia and the other group receiving saline as a control. Rats were subjected to left carotid artery ligation followed by 8% hypoxia. Brains were analyzed immunohistochemically at 24, 48, and 72 hours after HI. TNFα production was measured at respective times after HI., Results: Activation of microglia on the hippocampus of the control group was strong for the first 48 hours and then weakened. In contrast, activation of microglia on white matter and the cortex was weak at 24 hours and then became stronger. A single dose of carbachol significantly reduced brain damage with a marked reduction of microglial activation on the hippocampus, whereas it was less effective regarding microglial activation on white matter and the cortex. TNFα production was low in both groups., Conclusion: Regional specificity was observed for both microglial activation and susceptibility to carbachol for the first 72 hours after HI. Our data suggested that timely intervention along with region-specific microglial activation, apart from TNFα production, may be critical for the prevention of further brain damage after HI in the newborn., (Copyright © 2014 Elsevier B.V. All rights reserved.)

In the present investigation, we examined the effect of Hyuganatsu (Citrus tamurana) extract (HE) on skin fibroblast (TIG-119) proliferation and migration during in vitro wound healing. HE selectively inhibited proliferation of TIG-119 cells at higher concentration (>1.0 mg/mL); at lower concentrations (0.1, 0.25, 0.5, and 0.75 mg/mL), it exhibited linear and time-dependent cell proliferation. In vitro scratch wound healing studies showed that the HE also accelerated the migration of cells towards the wounded region. Cytometric analysis demonstrated that HE extract did not alter G1/0 and S phases of cell cycle in any concentration studied; however, G2/M phases of cell cycle were significantly (P < 0.05) accelerated at 0.75 mg/mL dose. RT-PCR and Western blotting analysis indicated that HE markedly overexpressed levels of Rac-1, Rho-A, and Cdc-42 mRNA and the respective proteins. Cyclin-dependent kinases (Cdk-1 and -2) gene expression activity was significantly (P < 0.05) increased, but protein content decreased during treatment with HE. The induction of Cdk-1 and -2 by HE was abolished by inhibitors, transcription (DRB), and translation (CHX), implying transcriptional regulation that required de novo protein synthesis.

Urokinase plasminogen activator (uPA) system, comprising of uPA, its receptor uPAR and inhibitor, type 1 plasminogen activator inhibitor (PAI-1), plays a vital role in various biological processes involving extracellular proteolysis, fibrinolysis, cell migration and proliferation. The timely occurence of these processes are essential for normal wound healing. This study examines the regulation of uPA and PAI-1 by a natural polyphenol-rich compound, grape seed extract (GSE). GSE is reported to have beneficial effects in promoting wound healing. Fibroblast cells exposed to different doses of GSE for 18hours were processed for further studies such as ELISA, RT-PCR, western blotting, fibrinolytic assay, cell surface plasmin activity assay and in vitro wound healing assay. GSE treatment caused a significant downregulation of uPA and PAI-1 expression, both at the RNA and protein levels. ELISA also revealed a dose-dependent decrease in uPA and PAI-1 activities. Functional significance of the downregulation was evident in decreased fibrinolytic activity, concomittant with decreased cell-surface plasmin activity. In vitro wound healing studies showed that GSE also retarded the migration of cells towards the wounded region.