Polymer nanotherapeutics: A promising approach toward microglial inhibition in neurodegenerative diseases.

Nanoparticles (NPs) that target multiple transport mechanisms facilitate targeted delivery of active therapeutic agents to the central nervous system (CNS) and improve therapeutic transport and efficacy across the blood-brain barrier (BBB). CNS nanotherapeutics mostly target neurons and endothelial cells, however, microglial immune cells are the first line of defense against neuronal damage and brain infections. Through triggering release of inflammatory cytokines, chemokines and proteases, microglia can however precipitate neurological damage-a significant factor in neurodegenerative diseases. Thus, microglial inhibitory agents are attracting much attention among those researching and developing novel treatments for neurodegenerative disorders. The most established inhibitors of microglia investigated to date are resveratrol, curcumin, quercetin, and minocycline. Thus, there is great interest in developing novel agents that can bypass or easily cross the BBB. One such approach is the use of modified-nanocarriers as, or for, delivery of, therapeutic agents to the brain and wider CNS. For microglial inhibition, polymeric NPs are the preferred vehicles for choice. Here, we summarize the immunologic and neuroinflammatory role of microglia, established microglia inhibitor agents, challenges of CNS drug delivery, and the nanotherapeutics explored for microglia inhibition to date. We also discuss applications of the currently considered "most useful" polymeric NPs for microglial-inhibitor drug delivery in CNS-related diseases.

Folate-engineered chitosan nanoparticles: next-generation anticancer nanocarriers.

Chitosan nanoparticles (NPs) are well-recognized as promising vehicles for delivering anticancer drugs due to their distinctive characteristics. They have the potential to enclose hydrophobic anticancer molecules, thereby enhancing their solubilities, permeabilities, and bioavailabilities; without the use of surfactant, i.e., through surfactant-free solubilization. This allows for higher drug concentrations at the tumor sites, prevents excessive toxicity imparted by surfactants, and could circumvent drug resistance. Moreover, biomedical engineers and formulation scientists can also fabricate chitosan NPs to slowly release anticancer agents. This keeps the drugs at the tumor site longer, makes therapy more effective, and lowers the frequency of dosing. Notably, some types of cancer cells (fallopian tube, epithelial tumors of the ovary, and primary peritoneum; lung, kidney, ependymal brain, uterus, breast, colon, and malignant pleural mesothelioma) have overexpression of folate receptors (FRs) on their outer surface, which lets folate-drug conjugate-incorporated NPs to target and kill them more effectively. Strikingly, there is evidence suggesting that the excessively produced FR&αgr (isoforms of the FR) stays consistent throughout treatment in ovarian and endometrial cancer, indicating resistance to conventional treatment; and in this regard, folate-anchored chitosan NPs can overcome it and improve the therapeutic outcomes. Interestingly, overly expressed FRs are present only in certain tumor types, which makes them a promising biomarker for predicting the effectiveness of FR-targeted therapy. On the other hand, the folate-modified chitosan NPs can also enhance the oral absorption of medicines, especially anticancer drugs, and pave the way for effective and long-term low-dose oral metronomic scheduling of poorly soluble and permeable drugs. In this review, we talked briefly about the techniques used to create, characterize, and tailor chitosan-based NPs; and delved deeper into the potential applications of folate-engineered chitosan NPs in treating various cancer types.

Dexamethasone in COVID-19 treatment: Analyzing monotherapy and combination therapy approaches.

The COVID-19 pandemic has prompted the exploration of effective treatment options, with dexamethasone emerging as a key corticosteroid for severe cases. This review evaluates the efficacy and safety of dexamethasone, highlighting its ability to reduce mortality rates, alleviate acute respiratory distress syndrome (ARDS), and mitigate hyperinflammation. While dexamethasone shows therapeutic promise, potential adverse effects-including cardiovascular issues, neuropsychiatric complications, lung infections, and liver damage-necessitate careful monitoring and individualized treatment strategies. The review also addresses the debate over using dexamethasone alone versus in combination with other therapies targeting SARS-CoV-2, examining potential synergistic effects and drug resistance. In summary, dexamethasone is a valuable treatment option for COVID-19 but its risks highlight the need for tailored surveillance approaches. Further research is essential to establish clear guidelines for optimizing treatment and improving patient outcomes.

Superoxide dismutase: a key target for the neuroprotective effects of curcumin.

Over the past few years, the prevalence of neurodegenerative diseases (NDD) has increased dramatically. The community health system is burdened by the high healthcare costs associated with NDD. Superoxide dismutase (SOD) is a type of metalloenzyme that possesses a distinct characteristic of protecting the body from oxidative stress through antioxidants. In this way, SOD supplementation may activate the endogenous antioxidant mechanism in various pathological conditions and could be used to neutralize free radical excess. Several factors are responsible for damaging DNA and RNA in the body, including the overproduction of reactive species, particularly reactive oxygen species (ROS) and reactive nitrogen species (RNS). Excessive ROS/RNS have deleterious effects on mitochondria and their metabolic processes, mainly through increased mitochondrial proteins, lipids and DNA oxidation. Studies have shown that oxidative stress is implicated in the etiology of many diseases, including NDD. It is thought that anti-inflammatory compounds, particularly phytochemicals, can interfere with these pathways and regulate inflammation. Extensive experimental and clinical research has proven that curcumin (Cur) has anti-inflammatory and anti-neurologic properties. In this review, we have compiled the available data on Cur's anti-inflammatory properties, paying special attention to its therapeutic impact on NDD through SOD.

The association between oxidized low-density lipoprotein and cancer: An emerging targeted therapeutic approach?

Lipids play an important role in varying vital cellular processes including cell growth and division. Elevated levels of low-density lipoprotein (LDL) and oxidized-LDL (ox-LDL), and overexpression of the corresponding receptors including LDL receptor (LDLR), lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), and cluster of differentiation 36 (CD36), have shown strong correlations with different facets of carcinogenesis including proliferation, invasion, and angiogenesis. Furthermore, a high serum level of LOX-1 is considered as a poor prognostic factor in many types of cancer including colorectal cancer. Ox-LDL could contribute to cancer progression and metastasis through endothelial-to-mesenchymal transition (EMT) and autophagy. Thus, many studies have shed light on the significant role of ox-LDL as a potential therapeutic target for cancer therapy. In various repurposing approaches, anti-dyslipidemia agents, phytochemicals, autophagy modulators as well as recently developed ldl-like nanoparticles have been investigated as potential tumor therapeutic agents by targeting oxidized-LDL/LOX-1 pathways. Herein, we reviewed the role of oxidized-LDL and LOX-1 in cancer progression, invasion, metastasis, and also cancer-associated angiogenesis. Moreover, we addressed therapeutic utility of several compounds that proved to be capable of targeting the metabolic moieties in cancer. This review provides insights on the potential impact of targeting LDL and ox-LDL in cancer therapy and their future biomedical implementations.

Ferroptosis and its modulators: A raising target for cancer and Alzheimer's disease.

The process of ferroptosis, a recently identified form of regulated cell death (RCD) is associated with the overloading of iron species and lipid-derived ROS accumulation. Ferroptosis is induced by various mechanisms such as inhibiting system Xc, glutathione depletion, targeting excess iron, and directly inhibiting GPX4 enzyme. Also, ferroptosis inhibition is achieved by blocking excessive lipid peroxidation by targeting different pathways. These mechanisms are often related to the pathophysiology and pathogenesis of diseases like cancer and Alzheimer's. Fundamentally distinct from other forms of cell death, such as necrosis and apoptosis, ferroptosis differs in terms of biochemistry, functions, and morphology. The mechanism by which ferroptosis acts as a regulatory factor in many diseases remains elusive. Studying the activation and inhibition of ferroptosis as a means to mitigate the progression of various diseases is a highly intriguing and actively researched topic. It has emerged as a focal point in etiological research and treatment strategies. This review systematically summarizes the different mechanisms involved in the inhibition and induction of ferroptosis. We have extensively explored different agents that can induce or inhibit ferroptosis. This review offers current perspectives on recent developments in ferroptosis research, highlighting the disease's etiology and presenting references to enhance its understanding. It also explores new targets for the treatment of cancer and Alzheimer's disease.

Engineering carbon-based nanomaterials for the delivery of platinum compounds: An innovative cancer disarming frontier.

Carbon-based nanomaterials have been frequently used as one of the most advanced and fascinating nanocarriers for drug delivery applications due to their unique physicochemical properties. Varying types of carbon nanomaterials (CNMs) including carbon nanotubes, graphene, graphene oxides, carbon nanohorns, fullerenes, carbon nanodots, and carbon nanodiamonds are promising candidates for designing novel systems to deliver platinum compounds. CNMs modification with various moieties renders vast bio-applications in the area of targeted and organelle-specific cancer therapy. This review featured an updated and concise summarizations of various types of CNMs, their synthesis, advantages and disadvantages including potential bio-toxicity for biomedical applications. The therapeutic utility of CNMs and their efficacy have been noticed and for the first time, this review addressed CNMs-focused applications on the delivery of platinum-derivatives to the cancer site. Collectively, the contents of this review will assist researchers to focus on the possible fabrication, bio-functionalization and designing methods of CNMs to the further development of their future biomedical implementations.

CRISPR-Cas system as a promising player against bacterial infection and antibiotic resistance.

The phenomenon of antibiotic resistance (AR) and its increasing global trends and destructive waves concerns patients and the healthcare system. In order to combat AR, it is necessary to explore new strategies when the current antibiotics fail to be effective. Thus, knowing the resistance mechanisms and appropriate diagnosis of bacterial infections may help enhance the sensitivity and specificity of novel strategies. On the other hand, resistance to antimicrobial compounds can spread from resistant populations to susceptible ones. Antimicrobial resistance genes (ARGs) significantly disseminate AR via horizontal and vertical gene transfer. The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system is a member of the bacterial immune system with the ability to remove the ARGs; therefore, it can be introduced as an effective and innovative strategy in the battle against AR. Here, we reviewed CRISPR-based bacterial diagnosis technologies. Moreover, the strategies to battle AR based on targeting bacterial chromosomes and resistance plasmids using the CRISPR-Cas system have been explained. Besides, we have presented the limitations of CRISPR delivery and potential solutions to help improve the future development of CRISPR-based platforms.

Silver-dendrimer nanocomposite as emerging therapeutics in anti-bacteria and beyond.

To develop next-generation nanomedicine, theranostic nanotherapeutic strategies are increasingly being emphasized. In recent years, it is observed that the effective lifetime of anti-bacterial and anti-cancer agent is diminishing, which undermines the economic incentives necessary for clinical development and therapeutic applications. Thus, novel formulations ought to not only kill drug resistant strains and cancerous cells but also inhibit their formation. Recently, metallic nanoparticles [for example- silver (Ag) nanoparticles] have been widely investigated for their biomedical applications. The so-called applications necessitate the inclusion of these nanoparticles inside polymeric matrices (for example- dendrimer) leading to chemical functionalization of the metallic nanoparticles. Silver and silver nanoparticles' antibacterial activity has already been well established over years. Dendrimers due to their homogeneous highly branched structure and uniform composition are perfectly suitable for the inclusion of silver nanoparticles [Ag NPs]. Recently, the increasing trend in the development of Ag-dendrimer nanocomposites is attributed to the excellent antibacterial activity of Ag as well as dendrimer's unique properties like variable functional terminal ends and potential antibacterial effect necessarily. This review provides an informative overview regarding the numerous aspects of bactericidal and other biomedical applications of Ag-dendrimer nanocomposites, particularly emphasizing analysis of existing research and prospective worth to the pharmaceutical sector in future.

Revisiting the significance of nano-vitamin D for food fortification and therapeutic application.

OBJECTIVE: Vitamin D (a prohormone) is an important micronutrient required by the body for skeletal homeostasis and a range of non-skeletal actions. Calcitriol, the active form of vitamin D, regulates a variety of cellular and metabolic processes through both genomic and nongenomic pathways. Often prescribed for treating rickets and osteoporosis, vitamin D deficiency can exacerbate various other medical conditions. SIGNIFICANCE, METHODS, AND RESULTS: Despite its multifunctional uses, the sensitivity of vitamin D makes formulating an efficient drug delivery system a challenging task, which is further complicated by its poor aqueous solubility. Enhancing the oral absorption of vitamin D is vital in utilizing its full efficacy. Recent developments in encapsulation and nanotechnology have shown promising results in overcoming these constraints. CONCLUSION: This review thus offers an insight to adequately comprehend the mechanistic pharmacology of vitamin D, its pathophysiological role, and justification of its medical indications, along with the benefits of utilizing nanotechnology for vitamin D delivery.

Nanoparticle-based drug delivery systems in cancer: A focus on inflammatory pathways.

It has become necessary to accept the clinical reality of therapeutic agents targeting the cancer-associated immune system. In recent decades, several investigations have highlighted the role of inflammation in cancer development. It has now been recognized that inflammatory cells secrete mediators, including enzymes, chemokines, and cytokines. These secreted substances produce an inflammatory microenvironment that is critically involved in cancer growth. Inflammation may enhance genomic instability leading to DNA damage, activation of oncogenes, or compromised tumor suppressor activity, all of which may promote various phases of carcinogenesis. Conventional cancer treatment includes surgery, radiation, and chemotherapy. However, treatment failure occurs because current strategies are unable to achieve complete local control due to metastasis. Nanoparticles (NPs) are a broad spectrum of drug carriers typically below the size of 100 nm, targeting tumor sites while reducing off-target consequences. More importantly, NPs can stimulate innate and adaptive immune systems in the tumor microenvironment (TME); hence, they induce a cancer-fighting immune response. Strikingly, targeting cancer cells with NPs helps eliminate drug resistance and tumor recurrence, as well as prevents inflammation. Throughout this review, we provide recent data on the role of inflammation in cancer and explore nano-therapeutic initiatives to target significant mediators, for example, nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and interleukins (ILs) associated with cancer-related inflammation, to escort the immunomodulators to cancer cells and associated systemic compartments. We also highlight the necessity of better identifying inflammatory pathways in cancer pathophysiology to develop effective treatment plans.

Lipid polymer hybrid nanoparticles: a custom-tailored next-generation approach for cancer therapeutics.

Lipid-based polymeric nanoparticles are the highly popular carrier systems for cancer drug therapy. But presently, detailed investigations have revealed their flaws as drug delivery carriers. Lipid polymer hybrid nanoparticles (LPHNPs) are advanced core-shell nanoconstructs with a polymeric core region enclosed by a lipidic layer, presumed to be derived from both liposomes and polymeric nanounits. This unique concept is of utmost importance as a combinable drug delivery platform in oncology due to its dual structured character. To add advantage and restrict one's limitation by other, LPHNPs have been designed so to gain number of advantages such as stability, high loading of cargo, increased biocompatibility, rate-limiting controlled release, and elevated drug half-lives as well as therapeutic effectiveness while minimizing their drawbacks. The outer shell, in particular, can be functionalized in a variety of ways with stimuli-responsive moieties and ligands to provide intelligent holding and for active targeting of antineoplastic medicines, transport of genes, and theragnostic. This review comprehensively provides insight into recent substantial advancements in developing strategies for treating various cancer using LPHNPs. The bioactivity assessment factors have also been highlighted with a discussion of LPHNPs future clinical prospects.

New opportunities for RGD-engineered metal nanoparticles in cancer.

The advent of nanotechnology has opened new possibilities for bioimaging. Metal nanoparticles (such as gold, silver, iron, copper, etc.) hold tremendous potential and offer enormous opportunities for imaging and diagnostics due to their broad optical characteristics, ease of manufacturing technique, and simple surface modification. The arginine-glycine-aspartate (RGD) peptide is a three-amino acid sequence that seems to have a considerably greater ability to adhere to integrin adhesion molecules that exclusively express on tumour cells. RGD peptides act as the efficient tailoring ligand with a variety of benefits including non-toxicity, greater precision, rapid clearance, etc. This review focuses on the possibility of non-invasive cancer imaging using metal nanoparticles with RGD assistance.

Skin cancer: understanding the journey of transformation from conventional to advanced treatment approaches.

Skin cancer is a global threat to the healthcare system and is estimated to incline tremendously in the next 20 years, if not diagnosed at an early stage. Even though it is curable at an early stage, novel drug identification, clinical success, and drug resistance is another major challenge. To bridge the gap and bring effective treatment, it is important to understand the etiology of skin carcinoma, the mechanism of cell proliferation, factors affecting cell growth, and the mechanism of drug resistance. The current article focusses on understanding the structural diversity of skin cancers, treatments available till date including phytocompounds, chemotherapy, radiotherapy, photothermal therapy, surgery, combination therapy, molecular targets associated with cancer growth and metastasis, and special emphasis on nanotechnology-based approaches for downregulating the deleterious disease. A detailed analysis with respect to types of nanoparticles and their scope in overcoming multidrug resistance as well as associated clinical trials has been discussed.

Unravelling the enigma of siRNA and aptamer mediated therapies against pancreatic cancer.

Pancreatic cancer (PC) is a fatal disease that has a poor 5-year survival rate. The poor prognosis can be attributed to both troublesome detections at the initial stage, which makes the majority of the treatment options largely unsuccessful and leads to extensive metastasis, as well as to its distinct pathophysiological characteristics, such as rich desmoplastic tumours bounded by dysplastic and hypo perfused vessels restricting the mobility of therapeutic agents. Continued attempts have been made to utilise innovative measures for battling PC to increase the therapeutic effectiveness of therapies and overcome their cytotoxicity. Combined cancer targeting and gene silencing approach has shown improved outcomes in patients' survival rates and quality of life, offering a potential solution to therapeutic complications. It particularly targets various barriers to alleviate delivery problems and diminish tumour recurrence and metastasis. While aptamers, a type of single-stranded nucleic acids with strong binding affinity and specificity to target molecules, have recently surfaced as a viable PC strategy, siRNA can interfere with the expression of certain genes. By concurrently suppressing genes and boosting targeted approach, the cocktail of siRNA/Aptamer and other therapeutic drugs can circumvent the multi-drug resistance phenomena. Additionally, combination therapy with additive or synergistic effects can considerably increase the therapeutic efficacy of anti-cancer medications. This study outlines the primary difficulties in treating PC, along with recent developments in siRNA/Aptamer mediated drug delivery to solve the major hiccup of oncology field.

Advancements in nanoparticle-based treatment approaches for skin cancer therapy.

Skin cancer has emerged as the fifth most commonly reported cancer in the world, causing a burden on global health and the economy. The enormously rising environmental changes, industrialization, and genetic modification have further exacerbated skin cancer statistics. Current treatment modalities such as surgery, radiotherapy, conventional chemotherapy, targeted therapy, and immunotherapy are facing several issues related to cost, toxicity, and bioavailability thereby leading to declined anti-skin cancer therapeutic efficacy and poor patient compliance. In the context of overcoming this limitation, several nanotechnological advancements have been witnessed so far. Among various nanomaterials, nanoparticles have endowed exorbitant advantages by acting as both therapeutic agents and drug carriers for the remarkable treatment of skin cancer. The small size and large surface area to volume ratio of nanoparticles escalate the skin tumor uptake through their leaky vasculature resulting in enhanced therapeutic efficacy. In this context, the present review provides up to date information about different types and pathology of skin cancer, followed by their current treatment modalities and associated drawbacks. Furthermore, it meticulously discusses the role of numerous inorganic, polymer, and lipid-based nanoparticles in skin cancer therapy with subsequent descriptions of their patents and clinical trials.

Gold nanoparticles and gold nanorods in the landscape of cancer therapy.

Cancer is a grievous disease whose treatment requires a more efficient, non-invasive therapy, associated with minimal side effects. Gold nanoparticles possessing greatly impressive optical properties have been a forerunner in bioengineered cancer therapy. This theranostic system has gained immense popularity and finds its application in the field of molecular detection, biological imaging, cancer cell targeting, etc. The photothermal property of nanoparticles, especially of gold nanorods, causes absorption of the light incident by the light source, and transforms it into heat, resulting in tumor cell destruction. This review describes the different optical features of gold nanoparticles and summarizes the advance research done for the application of gold nanoparticles and precisely gold nanorods for combating various cancers including breast, lung, colon, oral, prostate, and pancreatic cancer.

Anti-inflammatory effects of sodium-glucose cotransporter-2 inhibitors in COVID-19.

The ongoing pandemic of COVID-19 is intrinsically a systemic inflammatory disorder; hence, those patients suffering an underlying chronic inflammatory disease such as diabetes mellitus are at high risk of severe complications. Preventing or suppressing the inflammatory responses are of importance in diabetic patients. Sodium-glucose cotransporters-2 inhibitors (SGLT2i) are a newly introduced anti-diabetic drugs that have hypoglycemic effects through the urinary excretion of glucose. They also have an anti-inflammatory potential in diabetes patients, in addition to improving glycemic control, and while there is no direct data available in diabetic patients with COVID-19 disease, there is evidence that suggests that SGLT2i can reduce systemic inflammation and diminish the cytokine storm effect via several cellular mechanisms. In the current review, our aim was to classify and describe the molecular and cellular pathways by which SGLT2i have anti-inflammatory effects in diabetic patients with COVID-19 disease.

Surface plasmon resonance-based oligonucleotide biosensor for Salmonella Typhi detection.

Due to high mortality rates, typhoid fever still is one of the major health problems in the world, particularly in developing countries. The lack of highly specific and sensitive diagnostic tests and the great resemblance of typhoid fever symptoms to other diseases made the false-negative diagnosis a major challenge in typhoid fever management. Hence, we decided to design a Surface Plasmon Resonance (SPR) based biosensor for specific detection of Salmonella typhi through DNA hybridization. The results showed that the 10 nM of the synthetic target sequence, as well as 1 nM of PCR product, were the lowest feasible detected concentrations by the designed biosensor. This genosensor was also found to significantly distinguish the complementary sequence with the accuracy of one base mismatch sequence. The surface of the chip can be regenerated with NaOH solution and used for consecutive diagnosis. Therefore, the function of the designed biosensor indicates its high potential for Salmonella typhi detection practice.

Nanomedicine innovations in spinal cord injury management: Bridging the gap.

Spinal cord injury (SCI) has devastating effects on a person's physical, social, and professional well-being. It is a life-altering neurological condition that significantly impacts individuals and their caregivers on a socioeconomic level. Recent advancements in medical therapy have greatly improved the diagnosis, stability, survival rates, and overall well-being of SCI patients. However, there are still limited options available for enhancing neurological outcomes in these patients. The complex pathophysiology of SCI, along with the numerous biochemical and physiological changes that occur in the damaged spinal cord, contribute to this gradual improvement. Currently, there are no therapies that offer the possibility of recovery for SCI, although several therapeutic approaches are being developed. However, these therapies are still in the early stages and have not yet demonstrated effectiveness in repairing the damaged fibers, which hinders cellular regeneration and the full restoration of motor and sensory functions. Considering the importance of nanotechnology and tissue engineering in treating neural tissue injuries, this review focuses on the latest advancements in nanotechnology for SCI therapy and tissue healing. It examines research articles from the PubMed database that specifically address SCI in the field of tissue engineering, with an emphasis on nanotechnology as a therapeutic approach. The review evaluates the biomaterials used for treating this condition and the techniques employed to create nanostructured biomaterials.