Egyptian Dynasties to Biologics: A Historical Review of Nasal Polyposis.

The history of nasal polyposis originates even before Hippocrates described a nasal mass that he likened to a sea polyp. References to sinonasal disease and treatment can be found in ancient texts, such as the Ebers Papyrus and the Edwin Smith Papyrus of Ancient Egypt, as well as in the foundational texts of Ayurvedic medicine. Greek philosophers marked a significant shift away from the belief that illness was a result of divine intervention and embraced medical theory. Over the subsequent millennia, the understanding of nasal polyposis expanded, resulting in notable progress in surgical procedures and medical treatments. However, the complex pathophysiology of this condition remained enigmatic until breakthroughs in basic science and immunology. This historical journey takes us from the tomb of the first rhinologist in 2500 BC to the development of immune-modulating biologics.

Nature's Toolbox for Alzheimer's Disease: A Review on the Potential of Natural Products as Alzheimer's Disease Drugs.

Numerous clinical trials involving natural products have been conducted to observe cognitive performances and biomarkers in Alzheimer's Disease (AD) patients. However, to date, no natural-based drugs have been approved by the FDA as treatments for AD. In this review, natural product-based compounds that were tested in clinical trials from 2011 to 2023, registered at www.clinicaltrials.gov were reviewed. Thirteen compounds, encompassing 7 different mechanisms of action were covered. Several observations were deduced, which are: i) several compounds showed cognitive improvement, but these improvements may not extend to AD, ii) compounds that are endogenous to the human body showed better outcomes, and iii) Docosahexaenoic acid (DHA) and cerebrolysin had the most potential as AD drugs among the 13 compounds. Based on the current findings, natural products may be more suitable as a supplement than AD drugs in most cases. However, the studies covered here were conducted in a relatively short amount of time, where compounds acting on AD pathways may take time to show any effect. Given the diverse pathways that these natural products are involved in, they may potentially produce synergistic effects that would be beneficial in treating AD. Additionally, natural products benefit from both physicochemical properties being in more favorable ranges and active transport playing a more significant role than it does for synthetic compounds.

Treating cancer through modulating exosomal protein loading and function: The prospects of natural products and traditional Chinese medicine.

Exosomes, small yet vital extracellular vesicles, play an integral role in intercellular communication. They transport critical components, such as proteins, lipid bilayers, DNA, RNA, and glycans, to target cells. These vesicles are crucial in modulating the extracellular matrix and orchestrating signal transduction processes. In oncology, exosomes are pivotal in tumor growth, metastasis, drug resistance, and immune modulation within the tumor microenvironment. Exosomal proteins, noted for their stability and specificity, have garnered widespread attention. This review delves into the mechanisms of exosomal protein loading and their impact on tumor development, with a focus on the regulatory effects of natural products and traditional Chinese medicine on exosomal protein loading and function. These insights not only offer new strategies and methodologies for cancer treatment but also provide scientific bases and directions for future clinical applications.

The Potential Pharmacological Effects of Natural Product Withaferin A in Cancer: Opportunities and Challenges for Clinical Translation.

Cancer is one of the biggest health concerns with a complex pathophysiology. Currently, available chemotherapeutic drugs are showing deleterious side effects, and tumors often show resistance to treatment. Hence, extensive research is required to develop new treatment strategies to fight against cancer. Natural resources from plants are at the forefront of hunting novel drugs to treat various types of cancers. Withaferin A (WA) is a naturally occurring withanolide, a biologically active component obtained from the plant Ashwagandha. Various in vitro and in vivo oncological studies have reported that Withaferin A (WA) has shown protection from cancer. WA shows its activity by inhibiting the growth and proliferation of malignant cells, apoptosis, and inhibiting angiogenesis, metastasis, and cancer stem cells (CSCs). In addition, WA also showed chemo- and radio-sensitizing properties. Besides the beneficiary pharmacological activities of WA, a few aspects like pharmacokinetic properties, safety, and toxicity studies are still lacking, hindering this potent natural product from entering clinical development. In this review, we have summarized the various pharmacological mechanisms shown by WA in in vitro and in vivo cancer studies and the challenges that must be overcome for this potential natural product's clinical translation to be effective.

Antiviral screening of natural, anti-inflammatory compound library against African swine fever virus.

BACKGROUND: African swine fever virus (ASFV) is a major threat to pig production and the lack of effective vaccines underscores the need to develop robust antiviral countermeasures. Pathologically, a significant elevation in pro-inflammatory cytokine production is associated with ASFV infection in pigs and there is high interest in identifying dual-acting natural compounds that exhibit antiviral and anti-inflammatory activities. METHODS: Using the laboratory-adapted ASFV BA71V strain, we screened a library of 297 natural, anti-inflammatory compounds to identify promising candidates that protected Vero cells against virus-induced cytopathic effect (CPE). Virus yield reduction, virucidal, and cell cytotoxicity experiments were performed on positive hits and two lead compounds were further characterized in dose-dependent assays along with time-of-addition, time-of-removal, virus entry, and viral protein synthesis assays. The antiviral effects of the two lead compounds on mitigating virulent ASFV infection in porcine macrophages (PAMs) were also tested using similar methods, and the ability to inhibit pro-inflammatory cytokine production during virulent ASFV infection was assessed by enzyme-linked immunosorbent assay (ELISA). RESULTS: The screen identified five compounds that inhibited ASFV-induced CPE by greater than 50% and virus yield reduction experiments showed that two of these compounds, tetrandrine and berbamine, exhibited particularly high levels of anti-ASFV activity. Mechanistic analysis confirmed that both compounds potently inhibited early stages of ASFV infection and that the compounds also inhibited infection of PAMs by the virulent ASFV Arm/07 isolate. Importantly, during ASFV infection in PAM cells, both compounds markedly reduced the production of pro-inflammatory cytokines involved in disease pathogenesis while tetrandrine had a greater and more sustained anti-inflammatory effect than berbamine. CONCLUSIONS: Together, these findings support that dual-acting natural compounds with antiviral and anti-inflammatory properties hold promise as preventative and therapeutic agents to combat ASFV infection by simultaneously inhibiting viral replication and reducing virus-induced cytokine production.

Marine-Derived Peptides with Anti-Hypertensive Properties: Prospects for Pharmaceuticals, Supplements, and Functional Food.

Hypertension, a major health concern linked to heart disease and premature mortality, has prompted a search for alternative treatments due to side effects of existing medications. Sustainable harvesting of low-trophic marine organisms not only enhances food security but also provides a variety of bioactive molecules, including peptides. Despite comprising only a fraction of active natural compounds, peptides are ideal for drug development due to their size, stability, and resistance to degradation. Our review evaluates the anti-hypertensive properties of peptides and proteins derived from selected marine invertebrate phyla, examining the various methodologies used and their application in pharmaceuticals, supplements, and functional food. A considerable body of research exists on the anti-hypertensive effects of certain marine invertebrates, yet many species remain unexamined. The array of assessments methods, particularly for ACE inhibition, complicates the comparison of results. The dominance of in vitro and animal in vivo studies indicates a need for more clinical research in order to transition peptides into pharmaceuticals. Our findings lay the groundwork for further exploration of these promising marine invertebrates, emphasizing the need to balance scientific discovery and marine conservation for sustainable resource use.

Seaweeds as Nutraceutical Elements and Drugs for Diabetes Mellitus: Future Perspectives.

Diabetes mellitus is a chronic metabolic condition marked by high blood glucose levels caused by inadequate insulin synthesis or poor insulin use. This condition affects millions of individuals worldwide and is linked to a variety of consequences, including cardiovascular disease, neuropathy, nephropathy, and retinopathy. Diabetes therapy now focuses on controlling blood glucose levels through lifestyle changes, oral medicines, and insulin injections. However, these therapies have limits and may not successfully prevent or treat diabetic problems. Several marine-derived chemicals have previously demonstrated promising findings as possible antidiabetic medicines in preclinical investigations. Peptides, polyphenols, and polysaccharides extracted from seaweeds, sponges, and other marine species are among them. As a result, marine natural products have the potential to be a rich source of innovative multitargeted medications for diabetes prevention and treatment, as well as associated complications. Future research should focus on the chemical variety of marine creatures as well as the mechanisms of action of marine-derived chemicals in order to find new antidiabetic medicines and maximize their therapeutic potential. Based on preclinical investigations, this review focuses on the next step for seaweed applications as potential multitargeted medicines for diabetes, highlighting the bioactivities of seaweeds in the prevention and treatment of this illness.

Innovative Bioactive Products with Medicinal Value from Microalgae and Their Overall Process Optimization through the Implementation of Life Cycle Analysis-An Overview.

Microalgae are being recognized as valuable sources of bioactive chemicals with important medical properties, attracting interest from multiple industries, such as food, feed, cosmetics, and medicines. This review study explores the extensive research on identifying important bioactive chemicals from microalgae, and choosing the best strains for nutraceutical manufacturing. It explores the most recent developments in recovery and formulation strategies for creating stable, high-purity, and quality end products for various industrial uses. This paper stresses the significance of using Life Cycle Analysis (LCA) as a strategic tool with which to improve the entire process. By incorporating LCA into decision-making processes, researchers and industry stakeholders can assess the environmental impact, cost-effectiveness, and sustainability of raw materials of several approaches. This comprehensive strategy will allow for the choosing of the most effective techniques, which in turn will promote sustainable practices for developing microalgae-based products. This review offers a detailed analysis of the bioactive compounds, strain selection methods, advanced processing techniques, and the incorporation of LCA. It will serve as a valuable resource for researchers and industry experts interested in utilizing microalgae for producing bioactive products with medicinal properties.

An update on the development on tubulin inhibitors for the treatment of solid tumors.

INTRODUCTION: Microtubules play a vital role in cancer therapeutics. They are implicated in tumorigenesis, thus inhibiting tubulin polymerization in cancer cells, and have now become a significant target for anticancer drug development. A plethora of drug molecules has been crafted to influence microtubule dynamics and presently, numerous tubulin inhibitors are being investigated. This review discusses the recently developed inhibitors including natural products, and also examines the preclinical and clinical data of some potential molecules. AREA COVERED: The current review article summarizes the development of tubulin inhibitors while detailing their specific binding sites. It also discusses the newly designed inhibitors that may be useful in the treatment of solid tumors. EXPERT OPINION: Microtubules play a crucial role in cellular processes, especially in cancer therapy where inhibiting tubulin polymerization holds promise. Ongoing trials signify a commitment to revolutionizing cancer treatment and exploring targeted therapies. Challenges in microtubule modulation, like resistance and off-target effects, demand focused efforts, emphasizing combination therapies and personalized treatments. Beyond microtubules, promising avenues in cancer research include immunotherapy, genomic medicine, CRISPR gene editing, liquid biopsies, AI diagnostics, and stem cell therapy, showcasing a holistic approach for future advancements.

Neighbour-induced changes in root exudation patterns of buckwheat results in altered root architecture of redroot pigweed.

Roots are crucial in plant adaptation through the exudation of various compounds which are influenced and modified by environmental factors. Buckwheat root exudate and root system response to neighbouring plants (buckwheat or redroot pigweed) and how these exudates affect redroot pigweed was investigated. Characterising root exudates in plant-plant interactions presents challenges, therefore a split-root system which enabled the application of differential treatments to parts of a single root system and non-destructive sampling was developed. Non-targeted metabolome profiling revealed that neighbour presence and identity induces systemic changes. Buckwheat and redroot pigweed neighbour presence upregulated 64 and 46 metabolites, respectively, with an overlap of only 7 metabolites. Root morphology analysis showed that, while the presence of redroot pigweed decreased the number of root tips in buckwheat, buckwheat decreased total root length and volume, surface area, number of root tips, and forks of redroot pigweed. Treatment with exudates (from the roots of buckwheat and redroot pigweed closely interacting) on redroot pigweed decreased the total root length and number of forks of redroot pigweed seedlings when compared to controls. These findings provide understanding of how plants modify their root exudate composition in the presence of neighbours and how this impacts each other's root systems.

Effects of natural extract interventions in prostate cancer: A systematic review and network meta-analysis.

BACKGROUND: Over years, there has been a widespread quest for effective dietary patterns and natural extracts to mitigate prostate cancer risk. However, despite numerous experimental studies conducted on various natural extracts, the evidence substantiating their efficacy remains largely insufficient. This dearth of compelling evidence presents a significant challenge in advocating for their widespread use as preventive measures against prostate cancer. OBJECTIVE: Our study endeavors to undertake a network meta-analysis to evaluate the influence of natural extracts on prostate cancer. METHODS: Researchers systematically searched through Embase, PubMed, Cochrane Library, and Web of Science databases until December 2023. The main focus was on assessing primary outcomes comprising prostate-specific antigen (PSA), insulin-like growth factor-binding protein-3 (IGFBP-3), insulin-like growth factor-1 (IGF-1). We conducted data analysis utilizing StataMP 15.0 software. Therapeutic effects were ranked based on the probability values derived from Surface Under the Cumulative Ranking curve (SUCRA). Additionally, cluster analysis was employed to assess the impacts of natural extracts on three distinct outcomes. RESULTS: Following screening procedures, the 28 eligible studies were incorporated, the selected studies encompassed 1,566 prostate cancer patients and evaluated 16 different natural extract treatments. Specifically, 24 trials included PSA indicators, 10 included IGF-1 indicators, and 8 included IGFBP-3 indicators. The findings revealed that, based on the SUCRA values, the combined therapy of silybin with selenium (74%) appears to be the most effective approach for reducing serum PSA levels. Simultaneously, silybin alone (84.6%) stands out as the most promising option for decreasing serum IGF-1 levels. Lastly, concerning IGFBP-3, silybin alone (67.7%) emerges as the optimal choice. Twelve studies provided comprehensive information on adverse drug reactions/events (ADR/ADE), whereas five articles did not report any significant ADR/ADE. CONCLUSION: The NMA suggests that, compared to placebo, utilizing silybin either alone or in combination with selenium has been shown to enhance therapeutic effects, offering potential benefits to patients with prostate cancer. This study can offer valuable insights for prostate patients considering natural extract treatments. Further evidence is required to confirm the safety profile of these treatments.

Natural products and derivatives for breast cancer treatment: From drug discovery to molecular mechanism.

BACKGROUND: Breast cancer stands as the most common malignancy among women globally and a leading cause of cancer-related mortality. Conventional treatments, such as surgery, hormone therapy, radiotherapy, chemotherapy, and small-molecule targeted therapy, often fall short of addressing the complexity and heterogeneity of certain breast cancer subtypes, leading to drug resistance and metastatic progression. Thus, the search for novel therapeutic targets and agents is imperative. Given their low toxicity and abundant variety, natural products and their derivatives are increasingly considered valuable sources for small-molecule anticancer drugs. PURPOSE: This review aims to elucidate the pharmacological impacts and underlying mechanisms of active compounds found in select natural products and their derivatives, primarily focusing on breast cancer treatment. It intends to underscore the potential of these substances in combating breast cancer and guide future research directions for the development of natural product-based therapeutics. METHODS: We conducted comprehensive searches in electronic databases such as PubMed, Web of Science, and Scopus until October 2023, using keywords such as 'breast cancer', 'natural products', 'derivatives', 'mechanism', 'signaling pathways', and various keyword combinations. RESULTS: The review presents a spectrum of phytochemicals, including but not limited to flavonoids, polyphenols, and alkaloids, and examines their actions in various animal and cellular models of breast cancer. The anticancer effects of these natural products and derivatives are manifested through diverse mechanisms, including induction of cell death via apoptosis and autophagy, and suppression of tumor angiogenesis. CONCLUSION: An increasing array of natural products and their derivatives are proving effective against breast cancer. Future therapeutic strategies can benefit from strategic enhancement of the anticancer properties of natural compounds, optimization for targeted action, improved bioavailability, and minimized side effects. The forthcoming research on natural products should prioritize these facets to maximize their therapeutic potential.

Targeting CD8+ T cells with natural products for tumor therapy: Revealing insights into the mechanisms.

BACKGROUND: Despite significant advances in cancer immunotherapy over the past decades, such as T cell-engaging chimeric antigen receptor (CAR)-T cell therapy and immune checkpoint blockade (ICB), therapeutic failure resulting from various factors remains prevalent. Therefore, developing combinational immunotherapeutic strategies is of great significance for improving the clinical outcome of cancer immunotherapy. Natural products are substances that naturally exist in various living organisms with multiple pharmacological or biological activities, and some of them have been found to have anti-tumor potential. Notably, emerging evidences have suggested that several natural compounds may boost the anti-tumor effects through activating immune response of hosts, in which CD8+ T cells play a pivotal role. METHODS: The data of this review come from PubMed, Web of Science, Google Scholar, and ClinicalTrials (https://clinicaltrials.gov/) with the keywords "CD8+ T cell", "anti-tumor", "immunity", "signal 1", "signal 2", "signal 3", "natural products", "T cell receptor (TCR)", "co-stimulation", "co-inhibition", "immune checkpoint", "inflammatory cytokine", "hesperidin", "ginsenoside", "quercetin", "curcumin", "apigenin", "dendrobium officinale polysaccharides (DOPS)", "luteolin", "shikonin", "licochalcone A", "erianin", "resveratrol", "procyanidin", "berberine", "usnic acid", "naringenin", "6-gingerol", "ganoderma lucidum polysaccharide (GL-PS)", "neem leaf glycoprotein (NLGP)", "paclitaxel", "source", "pharmacological activities", and "toxicity". These literatures were published between 1993 and 2023. RESULTS: Natural products have considerable advantages as anti-tumor drugs based on the various species, wide distribution, low price, and few side effects. This review summarized the effects and mechanisms of some natural products that exhibit anti-tumor effects via targeting CD8+ T cells, mainly focused on the three signals that activate CD8+ T cells: TCR, co-stimulation, and inflammatory cytokines. CONCLUSION: Clarifying the role and underlying mechanism of natural products in cancer immunotherapy may provide more options for combinational treatment strategies and benefit cancer therapy, to shed light on identifying potential natural compounds for improving the clinical outcome in cancer immunotherapy.

Expression of IL-4 in Tumors: A Safety Surrogate to Predict Cancer Survival Associated With Biologic Therapies.

Interleukin (IL)-4-targeted therapies have revolutionized management of inflammatory dermatoses.

Unravelling inulin molecules in food sources using a matrix-assisted laser desorption/ionization magnetic resonance mass spectrometry (MALDI-MRMS) pipeline.

Inulin, a polysaccharide characterized by a ß-2,1 fructosyl-fructose structure terminating in a glucosyl moiety, is naturally present in plant roots and tubers. Current methods provide average degrees of polymerization (DP) but lack information on the distribution and absolute concentration of each DP. To address this limitation, a reproducible (CV < 10 %) high throughput (<2 min/sample) MALDI-MRMS approach capable of characterizing and quantifying inulin molecules in plants using matched-matrix consisting of α-cyano-4-hydroxycinnamic acid butylamine salt (CHCA-BA), chicory inulin-12C and inulin-13C was developed. The method identified variation in chain lengths and concentration of inulin across various plant species. Globe artichoke hearts, yacón and elephant garlic yielded similar concentrations at 15.6 g/100 g dry weight (DW), 16.8 g/100 g DW and 17.7 g/100 g DW, respectively, for DP range between 9 and 22. In contrast, Jerusalem artichoke demonstrated the highest concentration (53.4 g/100 g DW) within the same DP ranges. Jerusalem artichoke (DPs 9-32) and globe artichoke (DPs 9-36) showed similar DP distributions, while yacón and elephant garlic displayed the narrowest and broadest DP ranges (DPs 9-19 and DPs 9-45, respectively). Additionally, qualitative measurement for all inulin across all plant samples was feasible using the peak intensities normalized to Inulin-13C, and showed that the ratio of yacón, elephant garlic and Jerusalem was approximately one, two and three times that of globe artichoke. This MALDI-MRMS approach provides comprehensive insights into the structure of inulin molecules, opening avenues for in-depth investigations into how DP and concentration of inulin influence gut health and the modulation of noncommunicable diseases, as well as shedding light on refining cultivation practices to elevate the beneficial health properties associated with specific DPs.

[Reflections on good manufacturing practice and quality control system of personalized traditional Chinese medicine preparations].

Personalized traditional Chinese medicine(TCM) preparations have entered a stage of rapid development. The key to the healthy development of this industry is to establish a sound manufacturing standard and quality control system. This paper analyzed the characteristics of personalized TCM preparations and drew reference from the quality management standards in the production of commissioned decoctions and oral pastes, on the basis of which the production quality management scheme and cautions for the safe production of personalized TCM preparations was put forward with consideration to various problems that may exist and occur in the production of such preparations. It provided references for formulating the production standards and quality management system of personalized TCM preparations. The production standards and quality control system should develop with the times. In the future, modern technologies such as big data and artificial intelligence should be employed to achieve the automated and intelligent production and establish a sound quality traceability system, online control strategy, and safety management mode of personalized TCM preparations, which will ensure the healthy development of this industry under requirement of good manufacturing practice(GMP).

[Traditional Chinese medicine preparations in medical institutions: current situation and inspirations on research and development of new traditional Chinese medicine preparations].

Traditional Chinese medicine(TCM) preparations in medical institutions embody the characteristics of TCM and are the source for the development of new TCM drugs. This study summarizes the current situation, existing problems, and development trends of the TCM preparations in medical institutions in 31 provinces across China. Furthermore, this paper puts forward the development path of new TCM preparations based on the requirements of registration and management regulations of TCM preparations, providing new ideas for promoting the inheritance, innovation, and development of TCM.

Adverse Effects of Natural Products in the Oral Mucosa and Face: A Scoping Review.

Objective: This scoping review aimed to map the adverse reactions in the oral mucosa and face caused by the use of natural products. Methodology: This review was performed according to the Joanna Briggs Institute Manual for Evidence Synthesis and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines, with a protocol registered in the Open Science Framework (DOI 10.17605/OSF.IO/R57D8). The search was carried out systematically using PubMed, Scopus, Web of Science, Embase, LILACS, and LIVIVO databases, as well as gray literature through Google Scholar and OpenGrey. Reports of clinical cases on the adverse effects of natural products on the oral mucosa or perioral region of the face resulted from inappropriate use or self-medication were included. Data from the included studies were described in a narrative form. Results: Seven hundred and six studies were identified, and after removing duplicates and applying the eligibility criteria, 28 studies were included. The year of publication ranged from 1976 to 2022. The studies were conducted in 19 countries. Fifty patients were mentioned in the included studies and 34 were female (68%). The natural products most related to adverse reactions were propolis (n = 17), with manifestations such as perioral eczema, edema, erosions, erythema, allergic contact dermatitis, and garlic (n = 9), with manifestations such as chemical burn, burning sensation, vesicles and blisters, crusts, and ulcerations. Conclusion: Propolis and garlic were the natural products with the most reported adverse effects on the oral mucosa and perioral region.

Spatial multi-omics in medicinal plants: from biosynthesis pathways to industrial applications.

With the rapid development of molecular sequencing and imaging technology, the multi-omics of medicinal plants enters the single-cell era. We discuss spatial multi-omics applied in medicinal plants, evaluate the special products' biosynthesis pathways, and highlight the applications, perspectives, and challenges of biomanufacturing natural products (NPs).