Multifunctional role of nanoparticles for the diagnosis and therapeutics of cardiovascular diseases.

The increasing burden of cardiovascular disease (CVD) remains responsible for morbidity and mortality worldwide; their effective diagnostic or treatment methods are of great interest to researchers. The use of NPs and nanocarriers in cardiology has drawn much interest. The present comprehensive review provides deep insights into the use of current and innovative approaches in CVD diagnostics to offer practical ways to utilize nanotechnological interventions and the critical elements in the CVD diagnosis, associated risk factors, and management strategies of patients with chronic CVDs. We proposed a decision tree-based solution by discussing the emerging applications of NPs for the higher number of rules to increase efficiency in treating CVDs. This review-based study explores the screening methods, tests, and toxicity to provide a unique way of creating a multi-parametric feature that includes cutting-edge techniques for identifying cardiovascular problems and their treatments. We discussed the benefits and drawbacks of various NPs in the context of cost, space, time and complexity that have been previously suggested in the literature for the diagnosis of CVDs risk factors. Also, we highlighted the advances in using NPs for targeted and improved drug delivery and discussed the evolution toward the nano-cardiovascular potential for medical science. Finally, we also examined the mixed-based diagnostic approaches crucial for treating cardiovascular disorders, broad applications and the potential future applications of nanotechnology in medical sciences.

The antibacterial efficiency of Chitosan photodynamically activated Phycocyanin, and Morinda Oleifera against S.mutans and the bonding strength between composite resin and caries-affected dentin.

Objective: Evaluation of contemporary disinfection techniques, Moringa Oleifera (M.Oleifera), Phycocyanin activated by photodynamic therapy (PDT), and Chitosan, on S.mutans survival rate and bond integrity of composite to carious-affected dentin (CAD). Methods: The in vitro study was conducted at King Saud University and concluded within three months. Sixty mandibular teeth with cavities extending to the middle third of the dentin were sterilized. S.mutans was inoculated onto the CAD surface of twenty samples. The samples were randomly divided into four groups (n: 15) based on various disinfection regimes. Group-1 received 2% CHX, Group-2 Phycocyanin activated by photodynamic therapy (PDT), Group-3 Chitosan, and Group-4 M.oleifera. S.mutans survival rate was calculated. Ten CAD samples from each group were restored using composite. The bond integrity of samples was assessed using a Universal testing machine (UTM) and failure mode using a stereomicroscope. Analysis of variance (ANOVA) and Tukey's Post Hoc test were used to calculate statistical significance (p=0.05). Results: Group-2 samples subjected to Phycocyanin activated using PDT, displayed minimal survival rate (0.24 ± 0.05 CFU/ml) of S.mutans.Group-1 samples treated with CHX exhibited the highest count of S.mutans (0.69 ± 0.12 CFU/ml). The most robust bond was observed in Group-3 (Chitosan) samples (19.33 ± 0.47 MPa). In contrast, SBS values were lowest in Group-1 (CHX) treated study samples (13.17 ± 1.88 MPa). Conclusion: Chitosan, Phycocyanin activated by PDT, and Moringa Oleifera extract exhibit potential as viable substitutes for chlorhexidine (CHX) in clinical settings, presenting the possibility of better eradication of S.mutans and greater adhesive strength to CAD.

Treatments against Polymorphosal discrepancies in Glioblastoma Multiforme.

Glioblastoma (GB) are aggressive tumors that obstruct normal brain function. While the skull cannot expand in response to cancer growth, the growing pressure in the brain is generally the first sign. It can produce more frequent headaches, unexplained nausea or vomiting, blurred peripheral vision, double vision, a loss of feeling or movement in an arm or leg, and difficulty speaking and concentrating; all depend on the tumor's location. GB can also cause vascular thrombi, damaging endothelial cells and leading to red blood cell leakage. Latest studies have revealed the role of single nucleotide polymorphisms (SNPs) in developing and spreading cancers such as GB and breast cancer. Many discovered SNPs are associated with GB, particularly in great abundance in the promoter region, creating polygenetic vulnerability to glioma. This study aims to compile a list of some of the most frequent and significant SNPs implicated with GB formation and proliferation.

Chronic Inflammation's Transformation to Cancer: A Nanotherapeutic Paradigm.

The body's normal immune response against any invading pathogen that causes infection in the body results in inflammation. The sudden transformation in inflammation leads to the rise of inflammatory diseases such as chronic inflammatory bowel disease, autoimmune disorders, and colorectal cancer (different types of cancer develop at the site of chronic infection and inflammation). Inflammation results in two ways: short-term inflammation i.e., non-specific, involves the action of various immune cells; the other results in long-term reactions lasting for months or years. It is specific and causes angiogenesis, fibrosis, tissue destruction, and cancer progression at the site of inflammation. Cancer progression relies on the interaction between the host microenvironment and tumor cells along with the inflammatory responses, fibroblast, and vascular cells. The two pathways that have been identified connecting inflammation and cancer are the extrinsic and intrinsic pathways. Both have their own specific role in linking inflammation to cancer, involving various transcription factors such as Nuclear factor kappa B, Activator of transcription, Single transducer, and Hypoxia-inducible factor, which in turn regulates the inflammatory responses via Soluble mediators cytokines (such as Interleukin-6, Hematopoietin-1/Erythropoietin, and tumor necrosis factor), chemokines (such as Cyclooxygenase-2, C-X-C Motif chemokines ligand-8, and IL-8), inflammatory cells, cellular components (such as suppressor cells derived from myeloid, tumor-associated macrophage, and acidophils), and promotes tumorigenesis. The treatment of these chronic inflammatory diseases is challenging and needs early detection and diagnosis. Nanotechnology is a booming field nowadays for its rapid action and easy penetration inside the infected destined cells. Nanoparticles are widely classified into different categories based on their different factors and properties such as size, shape, cytotoxicity, and others. Nanoparticles emerged as excellent with highly progressive medical inventions to cure diseases such as cancer, inflammatory diseases, and others. Nanoparticles have shown higher binding capacity with the biomolecules in inflammation reduction and lowers the oxidative stress inside tissue/cells. In this review, we have overall discussed inflammatory pathways that link inflammation to cancer, major inflammatory diseases, and the potent action of nanoparticles in chronic inflammation-related diseases.

Nanoparticles guided drug delivery and imaging in gastric cancer.

Gastric cancer represents a deadly malignancy worldwide, yet current therapeutic regimens remain ineffective. Nanoparticle (NP) -based solutions could allow the design of novel therapeutic methods to eliminate this fatal disease. NPs typically carry out a significant role in multifunctional, multimodal imaging, and drug delivery carriers. In the recent decade, they have emerged as candidate approaches for the design of novel treatment strategies. Tumor nanotherapeutics characteristically possess various distinct advantages compared to conventional anti-cancer medications, which suffer from nonspecific bio-distribution, low solubility, and poor bioavailability. In this review, we will discuss the application of NPs in diagnosis and controlled drug delivery in gastric cancer (GC). We will focus on various NPs-based strategies employed against GC.

Specific targeting cancer cells with nanoparticles and drug delivery in cancer therapy.

Nanotechnology has been the latest approach for diagnosis and treatment for cancer, which opens up a new alternative therapeutic drug delivery option to treat disease. Nanoparticles (NPs) display a broad role in cancer diagnosis and has various advantages over the other conventional chemotherapeutic drug delivery. NPs possess more specific and efficient drug delivery to the targeted tissue, cell, or organs and minimize the risk of side effects. NPs undergo passive and active mode of drug targets to tumor area with less elimination of the drug from the system. Size and surface characteristics of nanoparticles play a crucial role in modulating nanocarrier efficiency and the biodistribution of chemo drugs in the body. Several types of nanocarriers, such as polymers, dendrimers, liposome-based, and carbon-based, are studied widely in cancer therapy. Although FDA approved very few nanotechnology drugs for cancer therapy, a large number of studies are undergoing for the development of novel nanocarriers for potent cancer therapy. In this review, we discuss the details of the nano-based therapeutics and diagnostics strategies, and the potential use of nanomedicines in cancer therapy and cancer drug delivery.

Nanotechnological based miRNA intervention in the therapeutic management of neuroblastoma.

Neuroblastoma (NB) is a widely diagnosed cancer in children, characterized by amplification of the gene encoding the MYCN transcription factor, which is highly predictive of poor clinical outcome and metastatic disease. microRNAs (a class of small non-coding RNAs) are regulated by MYCN transcription factor in neuroblastoma cells. The current research is focussed on identifying differential role of miRNAs and their interactions with signalling proteins, which are intricately linked with cellular processes like apoptosis, proliferation or metastasis. However, the therapeutic success of miRNAs is limited by pharmaco-technical issues which are well counteracted by nanotechnological advancements. The nanoformulated miRNAs unload anti-cancer drugs in a controlled and prespecified manner at target sites, to influence the activity of target protein in amelioration of NB. Recent advances and developments in the field of miRNAs-based systems for clinical management of NBs and the role of nanotechnology to overcome challenges with drug delivery of miRNAs have been reviewed in this paper.

Flavonoids nanoparticles in cancer: Treatment, prevention and clinical prospects.

The conventional therapies for cancer have a major concern of poor accessibility to tumor tissues. Furthermore, the requirement of higher doses and non-selective nature of therapeutic are associated with a range of adverse drug reactions (ADRs). However, flavonoids are documented to be effective against various types of cancer, but they are not evaluated for their safety profile and tumor site-specific action. Low solubility, rapid metabolism and poor absorption of dietary flavonoids in gastrointestinal tract hinder their pharmacological potential. Some studies have also suggested that flavonoids may act as pro-oxidant in some cases and may interact with other therapeutic agents, especially through biotransformation. Nanocarriers can alter pharmacokinetics and pharmacodynamic profile of incorporating drug. Moreover, nanocarriers are designed for targeted drug delivery, improving the bioavailability of poorly water-soluble drugs, delivery of macromolecules to site of action within the cell, combining therapeutic agents with imaging techniques which may visualize the site of drug delivery and co-delivery of two or more drugs. Combining two or more anti-cancer agents can reduce ADRs and nanotechnology played a pivotal role in this regard. In vitro and in vivo studies have shown the potential of flavonoids nano-formulations, especially quercetin, naringenin, apigenin, catechins and fisetin in the prevention and treatment of several types of cancer. Similarly, clinical trials have been conducted using flavonoids alone or in combination, however, the nano-formulations effect still needs to be elucidated. This review focuses on the impact of flavonoids nano-formulations on the improvement of their bioavailability, therapeutic and safety profile and will open new insights in the field of drug discovery for cancer therapeutics.

Horizons of nanotechnology applications in female specific cancers.

Female-specific cancers are the most common cancers in women worldwide. Early detection methods remain unavailable for most of these cancers, signifying that most of them are diagnosed at later stages. Furthermore, current treatment options for most female-specific cancers are surgery, radiation and chemotherapy. Although important milestones in molecularly targeted approaches have been achieved lately, current therapeutic strategies for female-specific cancers remain limited, ineffective and plagued by the emergence of chemoresistance, which aggravates prognosis. Recently, the application of nanotechnology to the medical field has allowed the development of novel nano-based approaches for the management and treatment of cancers, including female-specific cancers. These approaches promise to improve patient survival rates by reducing side effects, enabling selective delivery of drugs to tumor tissues and enhancing the uptake of therapeutic compounds, thus increasing anti-tumor activity. In this review, we focus on the application of nano-based technologies to the design of novel and innovative diagnostic and therapeutic strategies in the context of female-specific cancers, highlighting their potential uses and limitations.

Nanomedicine in treatment of breast cancer - A challenge to conventional therapy.

Amongst the various types of cancer, breast cancer is a highly heterogeneous disease and known as the leading cause of death among women globally. The extensive interdisciplinary investigation in nanotechnology and cancer biomedical research has been evolved over the years for its effective treatment. However, the advent of chemotherapeutic resistance in breast cancer is one of the major confront researchers are facing in achieving successful chemotherapy. Research in the area of cancer nanotechnology over the years have now been revolutionized through the development of smart polymers, lipids, inorganic materials and eventually their surface-engineering with targeting ligands. Moreover, nanotechnology further extended and brings in the notice the new theranostic approach which combining the therapy and imaging simultaneously. Currently, research is being envisaged in the area of novel nano-pharmaceutical design viz. liposome, nanotubes, polymer lipid hybrid system, which focuses to make the chemotherapy curative and long-lasting. In this review, we aimed to discuss the recent advancement of different surface-engineered/targeted nanomedicines that improved the drug efficacy in breast cancer.

Engineered nanoparticles for imaging and drug delivery in colorectal cancer.

Colorectal cancer (CRC) is one of the deadliest diseases worldwide due to a lack of early detection methods and appropriate drug delivery strategies. Conventional imaging techniques cannot accurately distinguish benign from malignant tissue, leading to frequent misdiagnosis or diagnosis at late stages of the disease. Novel screening tools with improved accuracy and diagnostic precision are thus required to reduce the mortality burden of this malignancy. Additionally, current therapeutic strategies, including radio- and chemotherapies carry adverse side effects and are limited by the development of drug resistance. Recent advances in nanotechnology have rendered it an attractive approach for designing novel clinical solutions for CRC. Nanoparticle-based formulations could assist early tumor detection and help to overcome the limitations of conventional therapies including poor aqueous solubility, nonspecific biodistribution and limited bioavailability. In this review, we shed light on various types of nanoparticles used for diagnosis and drug delivery in CRC. In addition, we will explore how these nanoparticles can improve diagnostic accuracy and promote selective drug targeting to tumor sites with increased efficiency and reduced cytotoxicity against healthy colon tissue.

Emergence of SARS-CoV-2 Omicron (B.1.1.529) variant, salient features, high global health concerns and strategies to counter it amid ongoing COVID-19 pandemic.

Since the appearance in the late of December 2019, SARS-CoV-2 is rapidly evolving and mutating continuously, giving rise to various variants with variable degrees of infectivity and lethality. The virus that initially appeared in China later mutated several times, wreaking havoc and claiming many lives worldwide amid the ongoing COVID-19 pandemic. After Alpha, Beta, Gamma, and Delta variants, the most recently emerged variant of concern (VOC) is the Omicron (B.1.1.529) that has evolved due to the accumulation of high numbers of mutations especially in the spike protein, raising concerns for its ability to evade from pre-existing immunity acquired through vaccination or natural infection as well as overpowering antibodies-based therapies. Several theories are on the surface to explain how the Omicron has gathered such a high number of mutations within less time. Few of them are higher mutation rates within a subgroup of population and then its introduction to a larger population, long term persistence and evolution of the virus in immune-compromised patients, and epizootic infection in animals from humans, where under different immune pressures the virus mutated and then got reintroduced to humans. Multifaceted approach including rapid diagnosis, genome analysis of emerging variants, ramping up of vaccination drives and receiving booster doses, efficacy testing of vaccines and immunotherapies against newly emerged variants, updating the available vaccines, designing of multivalent vaccines able to generate hybrid immunity, up-gradation of medical facilities and strict implementation of adequate prevention and control measures need to be given high priority to handle the on-going SARS-CoV-2 pandemic successfully.

Risk of colorectal cancer in inflammatory bowel diseases.

Inflammatory bowel diseases (IBDs) are chronic problems of gastrointestinal tract (GIT) with poorly understood aetiology. Patients with any of the two common entities, Crohn's disease (CD) or ulcerative colitis (UD) have significant increased risk of gastrointestinal and extra-intestinal malignancies. Particularly, the colorectal cancer (CRC) and lymphomas are the most frequently associated cancers with IBD. Although the incidence of CRC has declined in the European countries during last 30 years yet the risk among IBD patients remains higher than the healthy people. In the present study, we have described many common factors influencing the onset and advancement of IBD and CRC including the alterations in gut microbiota, changes in the interleukin pathways and tumour necrosis factor. The other common factors are patient age, race, genetics, family history, diet composition, obesity and level of vitamins and minerals in the body. These multiple factors contribute to the higher incidence of CRC among IBD patients.

Association of autoimmunity and cancer: An emphasis on proteolytic enzymes.

Cancer and autoimmune diseases are the two devastating conditions that together constitute a leading health problem worldwide. The rising burden of these disorders in the developing world demands a multifaceted approach to address the challenges it poses. Understanding the root causes and specific molecular mechanisms by which the progression of the diseases takes place is need of the hour. A strong inflammatory background and common developmental pathways, such as activation of immune cells, proliferation, increased cell survival and migration which are controlled by growth factors and inflammatory cytokines have been considered as the critical culprits in the progression and complications of these disorders. Enzymes are the potential immune modulators which regulate various inflammatory events and can break the circulating immune complexes via macrophages production. In the current manuscript, we have uncovered the possible role of proteolytic enzymes in the pathogenesis and progression of cancer and autoimmune diseases. In the light of the available scientific literature, we advocate in-depth comprehensive studies which will shed light towards the role of proteolytic enzymes in the modulation of inflammatory responses in cancer and autoimmune diseases together.

Inflammation and Alzheimer's Disease: Mechanisms and Therapeutic Implications by Natural Products.

Alzheimer's disease (AD) is a neurodegenerative disorder with no clear causative event making the disease difficult to diagnose and treat. The pathological hallmarks of AD include amyloid plaques, neurofibrillary tangles, and widespread neuronal loss. Amyloid-beta has been extensively studied and targeted to develop an effective disease-modifying therapy, but the success rate in clinical practice is minimal. Recently, neuroinflammation has been focused on as the event in AD progression to be targeted for therapies. Various mechanistic pathways including cytokines and chemokines, complement system, oxidative stress, and cyclooxygenase pathways are linked to neuroinflammation in the AD brain. Many cells including microglia, astrocytes, and oligodendrocytes work together to protect the brain from injury. This review is focused to better understand the AD inflammatory and immunoregulatory processes to develop novel anti-inflammatory drugs to slow down the progression of AD.

Neural Stem Cell-Based Therapies and Glioblastoma Management: Current Evidence and Clinical Challenges.

Gliomas, which account for nearly a quarter of all primary CNS tumors, present significant contemporary therapeutic challenges, particularly the highest-grade variant (glioblastoma multiforme), which has an especially poor prognosis. These difficulties are due to the tumor's aggressiveness and the adverse effects of radio/chemotherapy on the brain. Stem cell therapy is an exciting area of research being explored for several medical issues. Neural stem cells, normally present in the subventricular zone and the hippocampus, preferentially migrate to tumor masses. Thus, they have two main advantages: They can minimize the side effects associated with systemic radio/chemotherapy while simultaneously maximizing drug delivery to the tumor site. Another feature of stem cell therapy is the variety of treatment approaches it allows. Stem cells can be genetically engineered into expressing a wide variety of immunomodulatory substances that can inhibit tumor growth. They can also be used as delivery vehicles for oncolytic viral vectors, which can then be used to combat the tumorous mass. An alternative approach would be to combine stem cells with prodrugs, which can subsequently convert them into the active form upon migration to the tumor mass. As with any therapeutic modality still in its infancy, much of the research regarding their use is primarily based upon knowledge gained from animal studies, and a number of ongoing clinical trials are currently investigating their effectiveness in humans. The aim of this review is to highlight the current state of stem cell therapy in the treatment of gliomas, exploring the different mechanistic approaches, clinical applicability, and the existing limitations.

Enzyme targeting strategies for prevention and treatment of cancer: Implications for cancer therapy.

Extensive growth of cancer in humans is a major cause of death. Numerous studies are being conducted to improve the early diagnosis, prevention, and treatment of cancer. Recent technological advancements in medical science and research indicate molecular target therapy holds much promise in cancer treatment. In the past, therapeutic and diagnostic targeting of non-glycolytic and glycolytic enzymes in cancer have been successful, and discoveries of biomarker enzymes in cancer hold promise for therapeutic treatments. In this review, we discuss the roles of several cancer-associated enzymes that could potentially act as therapeutic targets, and place special focus on non-glycolytic and glycolytic enzymes. This review indicates that the targeting of metabolic signaling offers a promising means of developing novel anti-cancer therapies.

Small molecule tyrosine kinase inhibitors and pancreatic cancer-Trials and troubles.

Pancreatic cancer (PC) is an aggressive carcinoma and the fourth cause of cancer deaths in Western countries. Although surgery is the most effective therapeutic option for PC, the management of unresectable, locally advanced disease is highly challenging. Our improved understanding of pancreatic tumor biology and associated pathways has led to the development of various treatment modalities that can control the metastatic spread of PC. This review intends to present trials of small molecule tyrosine kinase inhibitors (TKIs) in PC management and the troubles encountered due to inevitable acquired resistance to TKIs.

Lactoperoxidase immobilization on silver nanoparticles enhances its antimicrobial activity.

Lactoperoxidase (LPO) is an antimicrobial protein present in milk that plays an important role in natural defence mechanisms during neonatal and adult life. The antimicrobial activity of LPO has been commercially adapted for increasing the shelf life of dairy products. Immobilization of LPO on silver nanoparticles (AgNPs) is a promising way to enhance the antimicrobial activity of LPO. In the current study, LPO was immobilized on AgNPs to form LPO/AgNP conjugate. The immobilized LPO/AgNP conjugate was characterized by various biophysical techniques. The enhanced antibacterial activity of the conjugate was tested against E. coli in culture at 2 h intervals for 10 h. The results showed successful synthesis of spherical AgNPs. LPO was immobilized on AgNPs with agglomerate sizes averaging approximately 50 nm. The immobilized conjugate exhibited stronger antibacterial activity against E. coli in comparison to free LPO. This study may help in increasing the efficiency of lactoperoxidase system and will assist in identifying novel avenues to enhance the stability and antimicrobial function of LPO system in dairy and other industries.

Optimization of antibacterial activity of ethanolic extracts of Eucalyptus tereticornis and Nigella sativa: Response surface Methodology.

The screening of plants for medicinal purposes represents an effort to discover newer, safer, and possibly more effective drugs. Design of the present study was made aiming to the optimization of the antibacterial activity of ethanolic extracts of Eucalyptus tereticornis (leaves) and Nigella sativa (seeds) against bacteria belongings to both Gram-positive (Bacillus subtilis and Staphylococcus aureus) and Gram-negative (Escherichia coli) spectrum by using response surface methodology. 20 g powder of each E. tereticornis (leaf) and N. sativa (seeds) were mixed with 200ml of ethanol at room temperature, and then it was centrifuged at 4000 rpm for 10 min to separate the supernatants, and allowed to dry in order to obtain ethanol free extracts. A fresh bacterial culture of 100µl of test microorganism was inoculated onto media and spread homogeneously. The antimicrobial activity of ethanolic extracts showed that all the concentrations tested were effective against the test microorganisms. The diameters of zones of inhibition exhibited by S. aureus PCSIR-83 were in the range of 0-28mm, E. coli PCSIR-102 (0-28mm) and B. subtilis PCSIR-05 (15-26mm). The combination of N. sativa (15mg/µl) and E. tereticornis (20mg/µl) were found most effective at pH 9.0 and temperature 35°C. Our results clearly indicate that Gram positive bacteria showed more sensitivity than Gram-negative bacteria.