The role of microbiota in nasopharyngeal cancer: Where do we stand?

Nasopharyngeal carcinoma (NPC) is a common head and neck cancer with a poor prognosis. One of the crucial challenges regarding NPC is its pathogenesis. Recent findings highlight the significance of host microbiota in the development of NPC, affected locally by nasopharyngeal microbiota or remotely by oral microbiota. The oral microbiota can migrate to the nasopharyngeal space, thereby impacting the composition of the nasopharyngeal microbiota. Specific bacterial strains have been linked to the development of nasopharyngeal cancer, including Neisseria, Staphylococcus, Leptotrichia, Staphylococcaceae, Granulicatella, Corynebacterium, Fusobacterium, and Prevotella. Several mechanisms have been proposed to elucidate how microbiota dysbiosis contributes to the development of NPC, including triggering tumor-promoting inflammation, reactivating the Epstein-Barr virus (EBV), inducing oxidative stress, weakening the immune system, and worsening tumor hypoxia. In addition, the composition of nasopharyngeal microbiota and the number of tumor-infiltrating microbiota can influence the prognosis and treatment response in patients with NPC. To the best of our knowledge, this is the first review discussing the impacts of the host microbiota on nasopharyngeal cancer pathogenesis, progression, and treatment response.

Crosstalk between ROS-inflammatory gene expression axis in the progression of lung disorders.

A significant number of deaths and disabilities worldwide are brought on by inflammatory lung diseases. Many inflammatory lung disorders, including chronic respiratory emphysema, resistant asthma, resistance to steroids, and coronavirus-infected lung infections, have severe variants for which there are no viable treatments; as a result, new treatment alternatives are needed. Here, we emphasize how oxidative imbalance contributes to the emergence of provocative lung problems that are challenging to treat. Endogenic antioxidant systems are not enough to avert free radical-mediated damage due to the induced overproduction of ROS. Pro-inflammatory mediators are then produced due to intracellular signaling events, which can harm the tissue and worsen the inflammatory response. Overproduction of ROS causes oxidative stress, which causes lung damage and various disease conditions. Invasive microorganisms or hazardous substances that are inhaled repeatedly can cause an excessive amount of ROS to be produced. By starting signal transduction pathways, increased ROS generation during inflammation may cause recurrent DNA damage and apoptosis and activate proto-oncogenes. This review provides information about new targets for conducting research in related domains or target factors to prevent, control, or treat such inflammatory oxidative stress-induced inflammatory lung disorders.

Unlocking the possibilities of therapeutic potential of silymarin and silibinin against neurodegenerative Diseases-A mechanistic overview.

Silymarin, a bioflavonoid derived from the Silybum marianum plant, was discovered in 1960. It contains C25 and has been extensively used as a therapeutic agent against liver-related diseases caused by alcohol addiction, acute viral hepatitis, and toxins-inducing liver failure. Its efficacy stems from its role as a potent anti-oxidant and scavenger of free radicals, employed through various mechanisms. Additionally, silymarin or silybin possesses immunomodulatory characteristics, impacting immune-enhancing and immune-suppressive functions. Recently, silymarin has been recognized as a potential neuroprotective therapy for various neurological conditions, including Parkinson's and Alzheimer's diseases, along with conditions related to cerebral ischemia. Its hepatoprotective qualities, primarily due to its anti-oxidant and tissue-regenerating properties, are well-established. Silymarin also enhances health by modifying processes such as inflammation, ß-amyloid accumulation, cellular estrogenic receptor mediation, and apoptotic machinery. While believed to reduce oxidative stress and support neuroprotective mechanisms, these effects represent just one aspect of the compound's multifaceted protective action. This review article further delves into the possibilities of potential therapeutic advancement of silymarin and silibinin for the management of neurodegenerative disorders via mechanics modules.

The Interplay between Mitochondrial Metabolism and Nasal Mucociliary Function as a Surrogate Method to Diagnose Thyroid Dysfunction: Insights from a Population-Based Study.

Aim and Background. This study aims to explore alternative diagnostic methods to assess thyroid function in patients unable to undergo blood tests for thyroid-stimulating hormones (TSH) and thyroxine (T4), such as individuals with trypanophobia, severe medical conditions, or coagulopathy. Considering the impact of thyroid dysfunction on mitochondrial metabolism and the essential role of proper mitochondrial function in ciliary motility, we postulate that assessing nasal ciliary function could serve as a surrogate diagnostic approach for thyroid dysfunction. Methods. This cross-sectional study was performed on individuals with no history of thyroid diseases. The primary endpoint was the diagnostic value of the nasal mucociliary (NMC) test using Iranica Picris (Asteraceae) aqueous extract in differentiating hypo- or hyperthyroidism cases from euthyroid cases. Results. 232 individuals were recruited (71% females, 86% euthyroid). Receiver operating characteristic (ROC) analysis showed a good diagnostic value for the NMC test in differentiating overt hypothyroidism (area under the ROC curve [AUROC] = 0.82, p = 0.004) and its fair value in diagnosing subclinical hyperthyroidism (AUROC = 0.78, p = 0.01) from the euthyroid condition. The NMC test had a significant positive correlation with TSH (r = 0.47, p < 0.001) and a significant negative correlation with T4 (r = -0.32, p < 0.001). The NMC rate was significantly different in distinct thyroid function groups (p < 0.001). Compared with euthyroid cases, the post-hoc analysis showed that the NMC test is significantly higher in overt hypothyroidism (15.06 vs. 21.07 min, p = 0.003) and significantly lower in subclinical hyperthyroidism (15.05 vs. 10.9 min, p = 0.02). Conclusions. The Iranica Picris-based NMC test might serve as a diagnostic method to distinguish overt hypothyroidism and subclinical hyperthyroidism.

Cutting-edge Approach of Carbon Nanostructures: Targeted Drug Delivery to Central Nervous System.

Drug delivery through the blood-brain barrier (BBB) is one of the key challenges in the modern era of medicine due to the highly semipermeable characteristics of BBB that restrict the entry of various drugs into the central nervous system (CNS) for the management of brain disorders. Drugs can be easily incorporated into carbon nanocarriers that can cross the bloodbrain barrier. Numerous nanocarriers have been developed, including polymeric nanoparticles, carbon nanoparticles, lipid-based nanoparticles, etc. Among these, carbon nanostructures could be superior due to their easier BBB penetration and strong biocompatibility. Several CDs (Carbon dots) and CD-ligand conjugates have explored effectively penetrating the BBB, which enables significant progress in using CD-based drug delivery systems (DDS) to manage CNS diseases. Despite the drug delivery applications, they might also be used as a central nervous system (CNS) drug; few of the carbon nanostructures show profound neurodegenerative activity. Further, their impact on neuronal growth and anti- amyloid action is quite interesting. The present study covers diverse carbon nanostructures for brain-targeted drug delivery, exploring a variety of CNS activities. Moreover, it emphasizes recent patents on carbon nanostructures for CNS disorders.

Gut-brain axis: A cutting-edge approach to target neurological disorders and potential synbiotic application.

The microbiota-gut-brain axis (MGBA) represents a sophisticated communication network between the brain and the gut, involving immunological, endocrinological, and neural mediators. This bidirectional interaction is facilitated through the vagus nerve, sympathetic and parasympathetic fibers, and is regulated by the hypothalamic-pituitary-adrenal (HPA) axis. Evidence shows that alterations in gut microbiota composition, or dysbiosis, significantly impact neurological disorders (NDs) like anxiety, depression, autism, Parkinson's disease (PD), and Alzheimer's disease (AD). Dysbiosis can affect the central nervous system (CNS) via neuroinflammation and microglial activation, highlighting the importance of the microbiota-gut-brain axis (MGBA) in disease pathogenesis. The microbiota influences the immune system by modulating chemokines and cytokines, impacting neuronal health. Synbiotics have shown promise in treating NDs by enhancing cognitive function and reducing inflammation. The gut microbiota's role in producing neurotransmitters and neuroactive compounds, such as short-chain fatty acids (SCFAs), is critical for CNS homeostasis. Therapeutic interventions targeting the MGBA, including dietary modulation and synbiotic supplementation, offer potential benefits for managing neurodegenerative disorders. However, more in-depth clinical studies are necessary to fully understand and harness the therapeutic potential of the MGBA in neurological health and disease.

Unveiling the role of exosomes as cellular messengers in neurodegenerative diseases and their potential therapeutic implications.

Exosomes are a subgroup of extracellular vesicles that function as transmitters, allowing cells to communicate more effectively with each other. However, exosomes may have both beneficial and harmful impacts on central nervous system disorders. Hence, the fundamental molecular mechanisms of the origin of illness and its progression are currently being investigated. The involvement of exosomes in the origin and propagation of neurodegenerative illness has been demonstrated recently. Exosomes provide a representation of the intracellular environment since they include various essential bioactive chemicals. The latest studies have demonstrated that exosomes transport several proteins. Additionally, these physiological vesicles are important in the regeneration of nervous tissue and the healing of neuronal lesions. They also offer a microenvironment to stimulate the conformational variation of concerning proteins for aggregation, resulting in neurodegenerative diseases. The biosynthesis, composition, and significance of exosomes as extracellular biomarkers in neurodegenerative disorders are discussed in this article, with a particular emphasis on their neuroprotective effects.

Therapeutic potential of Aloe vera-coated curcumin encapsulated nanoparticles in an Alzheimer-induced mice model: behavioural, biochemical and histopathological evidence.

OBJECTIVE: The main purpose of the present study was to evaluate the therapeutic efficacy of Aloe vera-coated curcumin encapsulated nanoparticles in mitigating Alzheimer's disease progression in mice, by examining behavioural changes, biochemical markers, and histopathological alterations, thus elucidating its potential as a treatment strategy. METHODS: The green synthesis method was used to synthesise this nanoformulation, which was then characterised using a variety of techniques, including percentage encapsulation efficacy, UV-visible spectroscopy, DLS, FT-IR, FESEM, and EDX. Several in-vivo assessments, including behavioural evaluations, dose optimisation studies, oxidative stress marker estimation, and histological studies, were conducted to determine the potential therapeutic impact of nanoformulation on the Alzheimer-induced mice model. RESULTS: The synthesised nanoparticles show a mean diameter of 76.12 nm ±1.23, a PDI of 0.313 ± 0.02, a zeta potential of 6.27 ± 0.65 mV, and the percentage encapsulation efficiency between 90% and 95% indicating good stability of synthesised nanoformulation. With the help of Morris water maze, Y-maze, and novel object recognition assay, the learning capacity and memory were assessed, and the results show that the synthesised nanoformulation significantly decreased the transfer latency to reach baited arm or to the hidden platform within 7 days. CONCLUSION: The formulation demonstrated significant biochemical benefits and remarkable cognitive advantages, establishing it as a prospective therapeutic intervention option that is both safe and effective.

Inorganic nanoparticle-based treatment approaches for colorectal cancer: recent advancements and challenges.

Colorectal cancer, the third most prevalent cancer globally, contributes significantly to mortality rates, with over 1.9 million reported cases and nearly 935,000 fatalities annually. Surgical resection is a primary approach for localized colorectal tumors, with adjunct therapies like chemotherapy, radiotherapy, and targeted/immunotherapy considered depending on the tumor stage. However, despite preferences for targeted and immunotherapy post-surgery, chemotherapy remains commonly chosen due to its lower cost and high cancer-killing efficiency. Yet, chemotherapy faces issues such as tumor resistance and severe side effects. Nanotechnology has emerged in cancer therapy by alleviating the drawbacks of current treatment approaches. In the past few decades, inorganic nanoparticles have shown promise in combating colorectal cancer, offering advantages over conventional chemotherapy. Compared to organic nanoparticles, inorganic nanoparticles exhibit properties like photosensitivity, conductivity, magnetic allure, and thermal proficiency, allowing them to function as both drug carriers and therapeutic agents. Derived primarily from carbon, silica, metals, and metal oxides, they offer superior drug-loading capacity, heightened quantum yield, and participation in advanced photothermal and photodynamic therapies. This review provides a brief overview of the pathophysiology of colorectal cancer and the pivotal role of inorganic nanoparticles in photothermal therapy photodynamic therapy, and drug delivery. Additionally, it discusses numerous inorganic nanoparticles in colorectal cancer therapy based on recent literature.

Unlocking the role of herbal cosmeceutical in anti-ageing and skin ageing associated diseases.

The process of skin ageing is a natural biological phenomenon characterised by the emergence of wrinkles, age spots, sagging skin, and dryness over time. The increasing significance of skin in physical attractiveness has heightened skincare concerns. Anti-ageing cosmetics play a pivotal role in nurturing the skin, enhancing its quality, and promoting overall health. Today, cosmetics have evolved beyond mere aesthetics and are now integral to individual wellness. The contemporary quest for perpetual youth has intensified, prompting a deeper exploration into the skin ageing process. This comprehensive exploration delves into various elements involved in skin ageing, encompassing cells such as stem and endothelial cells, blood vessels, soft tissues, and signalling pathways. The molecular basis of skin ageing, including biochemical factors like reactive oxygen species, damaged DNA, free radicals, ions, and proteins (mRNA), is scrutinised alongside relevant animal models. The article critically analyzes the outcomes of utilising herbal components, emphasising their advantageous anti-ageing properties. The factors contributing to skin ageing, mechanistic perspectives, management approaches involving herbal cosmeceutical, and associated complications (especially cardiovascular diseases, Parkinson's, Alzheimer's, etc.) are succinctly addressed. In addition, the manuscript further summarises the recent patented innovations and toxicity of the herbal cosmeceuticals for anti-ageing and ageing associated disorders. Despite progress, further research is imperative to unlock the full potential of herbal components as anti-ageing agents.

A Critical Review on the Role of Probiotics in Lung Cancer Biology and Prognosis.

Lung cancer remains the leading cause of cancer-related deaths worldwide. According to the American Cancer Society (ACS), it ranks as the second most prevalent type of cancer globally. Recent findings have highlighted bidirectional gut-lung interactions, known as the gut-lung axis, in the pathophysiology of lung cancer. Probiotics are live microorganisms that boost host immunity when consumed adequately. The immunoregulatory mechanisms of probiotics are thought to operate through the generation of various metabolites that impact both the gut and distant organs (e.g., the lungs) through blood. Several randomized controlled trials have highlighted the pivotal role of probiotics in gut health especially for the prevention and treatment of malignancies, with a specific emphasis on lung cancer. Current research indicates that probiotic supplementation positively affects patients, leading to a suppression in cancer symptoms and a shortened disease course. While clinical trials validate the therapeutic benefits of probiotics, their precise mechanism of action remains unclear. This narrative review aims to provide a comprehensive overview of the present landscape of probiotics in the management of lung cancer.

Novel antiviral approaches for Marburg: a promising therapeutics in the pipeline.

Marburg virus disease (MVD) presents a significant global health threat, lacking effective antivirals and with current supportive care offering limited therapeutic options. This mini review explores the emerging landscape of novel antiviral strategies against MVD, focusing on promising therapeutics currently in the development pipeline. We delve into direct-acting antiviral approaches, including small molecule inhibitors targeting viral entry, replication, and assembly, alongside nucleic acid antisense and RNA interference strategies. Host-targeting antivirals are also considered, encompassing immune modulators like interferons and cytokine/chemokine modulators, broad-spectrum antivirals, and convalescent plasma and antibody-based therapies. The paper then examines preclinical and clinical development for the novel therapeutics, highlighting in vitro and in vivo models for antiviral evaluation, safety and efficacy assessments, and the critical stages of clinical trials. Recognizing the challenges of drug resistance and viral escape, the mini review underscores the potential of combination therapy strategies and emphasizes the need for rapid diagnostic tools to optimize treatment initiation. Finally, we discuss the importance of public health preparedness and equitable access to these promising therapeutics in achieving effective MVD control and global health security. This mini review presents a comprehensive overview of the burgeoning field of MVD antivirals, highlighting the potential of these novel approaches to reshape the future of MVD treatment and prevention.

Insights into Intra Periodontal Pocket Pathogenesis, Treatment, In Vitro-In Vivo Models, Products and Patents, Challenges and Opportunity.

Periodontal disease is a multifactorial pathogenic condition involving microbial infection, inflammation, and various systemic complications. Here, a systematic and comprehensive review discussing key-points such as the pros and cons of conventional methods, new advancements, challenges, patents and products, and future prospects is presented. A systematic review process was adopted here by using the following keywords: periodontal diseases, pathogenesis, models, patents, challenges, recent developments, and 3-D printing scaffolds. Search engines used were "google scholar", "web of science", "scopus", and "pubmed", along with textbooks published over the last few decades. A thorough study of the published data rendered an accurate and deep understanding of periodontal diseases, the gap of research so far, and future opportunities. Formulation scientists and doctors need to be interconnected for a better understanding of the disease to prescribe a quality product. Moreover, prime challenges (such as a lack of a vital testing model, scarcity of clinical and preclinical data, products allowing for high drug access to deeper tissue regions for prolonged residence, lack of an international monitoring body, lack of 4D or time controlled scaffolds, and lack of successful AI based tools) exist that must be addressed for designing new quality products. Generally, several products have been commercialized to treat periodontal diseases with certain limitations. Various strategic approaches have been attempted to target certain delivery regions, maximize residence time, improve efficacy, and reduce toxicity. Conclusively, the current review summarizes valuable information for researchers and healthcare professional to treat a wide range of periodontal diseases.

Impact of NF-κB Signaling and Sirtuin-1 Protein for Targeted Inflammatory Intervention.

This detailed review disclosed the NF-κB pro-inflammatory gen's activity regulation and explored the therapeutic significance, activation, and inhibition. This study uncovers the structural intricacies of the NF-κB proteins and highlights the key role of SIRT1 in NF-kB signaling pathway regulation. Particularly the Rel Homology Domain (RHD), elucidating interactions and the regulatory mechanisms involving inhibitory proteins like IκB and p100 within the NF-κB signaling cascade. Disruption of the pathway is important in uncontrolled inflammation and immune disorders. This study extensively describes the role connections of canonical and non-canonical signaling pathways of NF-κB with inflammatory and cellular responses. SIRT1 belongs to the class III histone deacetylase, via RelA/p65 deacetylation, it regulates the activity of NF-κB, closely linked with the NAD+/NADH cellular ratio, influencing stress responses, aging processes, gene regulation, and metabolic pathways. This detailed study reveals SIRT1 as a crucial avenue for uncovering the role of imbalanced NF-κB in diabetes, obesity, and atherosclerosis. This study provides valuable knowledge about the therapeutic targets of inflammatory disorders.

Role of miRNAs in Brain Development.

Non-coding RNAs that are small in size, called microRNAs (miRNAs), exert a conse-quence in neutralizing gene activity after transcription. The nervous system is a massively ex-pressed organ, and an expanding body of research reveals the vital functions that miRNAs play in the brain's growth and neural activity. The significant benefit of miRNAs on the development of the central nervous system is currently shown through new scientific methods that concentrate on targeting and eradicating vital miRNA biogenesis pathways the elements involving Dicer and DGCR8. Modulation of miRNA has been associated with numerous essential cellular processes on neural progenitors, like differentiation, proliferation, and destiny determination. Current re-search discoveries that emphasize the significance of miRNAs in the complex process of brain development are included in this book. The miRNA pathway plays a major role in brain devel-opment, its operational dynamics, and even diseases. Recent studies on miRNA-mediated gene regulation within neural discrepancy, the circadian period and synaptic remodeling are signs of this. We also discussed how these discoveries may affect our comprehension of the fundamental processes behind brain diseases, highlighting the novel therapeutic opportunities miRNAs pro-vide for treating various human illnesses.

A Critical Review on the Long-Term COVID-19 Impacts on Patients With Diabetes.

BACKGROUND: The world is currently grappling with the potentially life-threatening coronavirus disease 2019 (COVID-19), marking it as the most severe health crisis in the modern era. COVID-19 has led to a pandemic, with the World Health Organization (WHO) predicting that individuals with diabetes are at a higher risk of contracting the virus compared to the general population. This review aims to provide a practical summary of the long-term impacts of COVID-19 on patients with diabetes. Specifically, it focuses on the effects of SARS-CoV-2 on different types of diabetic patients, the associated mortality rate, the underlying mechanisms, related complications, and the role of vitamin D and zinc in therapeutic and preventive approaches. METHODS: Relevant literature was identified through searches on PubMed, Web of Science, and Science Direct in English, up to April 2023. RESULTS: COVID-19 can lead to distressing symptoms and pose a significant challenge for individuals living with diabetes. Older individuals and those with pre-existing conditions such as diabetes, coronary illness, and asthma are more susceptible to COVID-19 infection. Managing COVID-19 in individuals with diabetes presents challenges, as it not only complicates the fight against the infection but also potentially prolongs the recovery time. Moreover, the virus may thrive in individuals with high blood glucose levels. Various therapeutic approaches, including antidiabetic drugs, are available to help prevent COVID-19 in diabetic patients. CONCLUSIONS: Diabetes increases the morbidity and mortality risk for patients with COVID-19. Efforts are globally underway to explore therapeutic interventions aimed at reducing the impact of diabetes on COVID-19.

Xylazine: An Abused Tranq Dope and its Safety Concern.

A drug called Xylazine has gained notoriety in recent times, earning the nickname "zombie drug" due to reported alarming effects on its users. Although Xylazine is primarily intended for veterinary use as a sedative and muscle relaxant for animals, there have been growing concerns about its misuse among humans, particularly in the context of illicit drug use. However, it is essential to rely on accurate and evidence-based information when discussing the health risks associated with any substance, rather than resorting to sensationalized terms like "zombie drug." The situation involving Xylazine misuse is a matter of concern, and the United States Drug Enforcement Administration has highlighted it as a significant threat to public health.

Mechanistic insights into the potential role of dietary polyphenols and their nanoformulation in the management of Alzheimer's disease.

Alzheimer's disease (AD) is a very common neurodegenerative disorder associated with memory loss and a progressive decline in cognitive activity. The two major pathophysiological factors responsible for AD are amyloid plaques (comprising amyloid-beta aggregates) and neurofibrillary tangles (consisting of hyperphosphorylated tau protein). Polyphenols, a class of naturally occurring compounds, are immensely beneficial for the treatment or management of various disorders and illnesses. Naturally occurring sources of polyphenols include plants and plant-based foods, such as fruits, herbs, tea, vegetables, coffee, red wine, and dark chocolate. Polyphenols have unique properties, such as being the major source of anti-oxidants and possessing anti-aging and anti-cancerous properties. Currently, dietary polyphenols have become a potential therapeutic approach for the management of AD, depending on various research findings. Dietary polyphenols can be an effective strategy to tackle multifactorial events that occur with AD. For instance, naturally occurring polyphenols have been reported to exhibit neuroprotection by modulating the Aß biogenesis pathway in AD. Many nanoformulations have been established to enhance the bioavailability of polyphenols, with nanonization being the most promising. This review comprehensively provides mechanistic insights into the neuroprotective potential of dietary polyphenols in treating AD. It also reviews the usability of dietary polyphenol as nanoformulation for AD treatment.