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Cancer is one of the most complicated and prevalent diseases in the world, and its incidence is growing worldwide. Natural products containing pharmacological activity are widely used in the pharmaceutical industry, especially in anticancer drugs, due to their diverse structures and distinctive functional groups that inspire new drug results by means of synthetic chemistry. Terrestrial medicinal plants have traditionally been the primary source for developing natural products (NPs). However, over the past thirty years, marine organisms such as invertebrates, plants, algae, and bacteria have revealed many new pharmaceutical compounds known as marine NPs. This field constantly evolves as a discipline in molecular targeted drug discovery, incorporating advanced screening tools that have revolutionised and become integral to modern antitumor research. This review discusses recent studies on new natural anticancer alkaloids obtained from marine organisms. The paper illustrates the structure and origin of marine alkaloids and demonstrates the cytotoxic action of new alkaloids from several structural families and their synthetic analogs. The most recent findings about the potential or development of some of them as novel medications, together with the status of our understanding of their current mechanisms of action, are also compiled.
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Skin cancer is the most common type of cancer among white people, according to the World Health Organisation. The incidence of melanoma and non-melanoma skin cancers has increased to epidemic levels, making them the most widespread type of skin cancer. Melanoma is a very aggressive form of cancer, characterized by limited treatment choices due to multidrug resistance and an extremely low probability of patient survival. This article explores the various impediments and limitations associated with conventionally available treatments. Chemotherapy, radiation, immunotherapy, and targeted therapy are among the conventional treatments for melanoma; however, each of these approaches has several adverse reactions. Recently, there has been a focus on biological and pharmacological research on developing alternative, site-specific therapy approaches. Nanotechnology offers several benefits in this regard, with the potential to enhance the longevity of melanoma patients while minimizing adverse effects. Nanoparticles serve as effective drug carrier systems due to their capacity to improve the solubility of medications with low water solubility, modify pharmacokinetics, prolong drug half-life by reducing immunogenicity, boost bioavailability, and decrease drug metabolism. This article highlights recent advancements in utilizing several nanotechnological techniques, including solid lipid nanoparticles, nanostructured lipid carriers, liposomes, transferosomes, ethosomes, and nanoemulsion polymeric mixed micelles.
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Chlorogenic acid (CHA) is a phenolic substance found in various edible plants, such as tea and green coffee extracts. This chemical has demonstrated significant efficacy in reducing the probability of many diseases in preclinical and clinical environments. Chlorogenic acid (CHA) possesses several pharmacological attributes, such as anticancer, hepatoprotective, antimicrobial, immune-suppressant, antioxidant, and antidiabetic activities. Its applications extend to multiple industries, such as food, chemicals, medicine, and healthcare. Studies have shown that CHA can exert its anticancer effects through numerous mechanisms. It can hinder the process of cell division, trigger cell apoptosis, and suppress an increase in cancerous cell growth. The literature research conducted for this study revealed a variety of molecular and cellular processes influencing distinct signaling pathways. These mechanisms include angiogenesis, invasion and migration, oxidative stress, inflammation, cell cycle arrest, and proliferation.However, significant issues surround the use of CHA, primarily due to its limited bioavailability in animal models. This review focuses on the chemistry, natural sources, pharmacokinetics, and underlying mechanisms of action of CHA and its clinical utility in treating life-threatening diseases, such as cancer. The manuscript provides insight into novel formulation approaches.
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Lignans, a group of naturally occurring compounds abundant in various plant-based foods, are becoming increasingly popular due to their potential health benefits. The literature suggests that these bioactive substances can reduce the risk of certain types of cancer, such as postmenopausal colon and breast cancer. Moreover, the significance of lignans for improving cardiovascular health has been recognized, as studies have revealed a potential correlation between the intake of lignans and a decreased risk of cardiovascular disease. These complex molecules possess diverse bioactive capabilities, rendering them potential alternatives for preventing chronic diseases. Further research is needed to examine the mechanisms responsible for their beneficial outcomes. Recent research has emphasized the pharmacological properties of lignans as effective substances for human health. Incorporating foods rich in lignans into the diet may be a practical approach to enhancing protection against life-threatening ailments, such as cardiovascular diseases and malignancies.
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Cancer is a prevalent and potentially fatal disease worldwide. The proliferation of abnormal cells and uncontrolled cellular growth characterizes cancer. Cancerous tumors exhibit distinct microenvironments characterized by a deficient lymphatic drainage system and aberrant blood supply. Various medications and diagnostic systems exist for cancer treatment, but they all have inherent limitations and undesirable consequences. Consequently, the achievement of effective cancer detection and treatment remains challenging. Theranostics nanoparticles are becoming increasingly popular in nano drug delivery systems. These nanoparticles can diagnose and treat tumors, making them a promising approach in the field. They are designed to be small in size, allowing them to be effective in delivering drugs to targeted areas. Furthermore, these nanoparticles can fundamentally transform the identification and management of several ailments, including cardiovascular disorders and infectious diseases. Such nanoparticles possess dual capabilities, functioning as therapeutic agents and diagnostic tools. They can transport medicinal substances, such as medications, nucleic acids, or therapeutic proteins, and include substances that can be used for imaging, such as contrast agents or fluorescent dyes, to enable non-invasive diagnostics and monitoring of the effectiveness of the treatment. These techniques can be employed for diagnostic purposes to identify, locate, and determine the extent of disorders using imaging modalities such as magnetic resonance imaging, computed tomography, positron emission tomography, and fluorescence imaging. These nanoparticles can deliver therapeutic compounds to specific locations accurately during therapy. This leads to improved effectiveness of the treatment, decreased adverse effects, and better patient outcomes. They offer a potential nanomedicine approach by providing diagnostic and therapeutic capabilities for disease diagnosis and treatment. Theranostics nanoparticles have distinct characteristics and adaptability, which can transform the healthcare sector by facilitating personalized and precise medical treatments.
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Flavonoids are a class of polyphenolic compounds that can be classified into six distinct categories, namely isoflavonoids, flavanones, flavanols, flavonols, flavones, and anthocyanidins. These compounds are naturally occurring and can be found in a diverse range of plant species. Flavonoids, a class of bioactive compounds, are mostly obtained through the consumption of vegetables, fruits and plant-derived beverages such as wine, cocoa-based products and green tea. Flavonoids have been demonstrated to exhibit a diverse range of anticancer properties. These include the modulation of activities of enzymes involved in scavenging reactive oxygen species, involvement in cell cycle arrest, induction of apoptosis and autophagy, as well as suppression of cancer cell proliferation and invasiveness. Flavonoids exhibit a dual role in maintaining reactive oxygen species balance. They function as antioxidants in regular physiological conditions, while also demonstrating significant pro-oxidant properties in cancer cells. This prooxidant activity induces apoptotic pathways and downregulates pro-inflammatory signalling pathways. The paper explores the biochemical characteristics, bioavailability, anticancer efficacy, and modes of action of flavonoids.
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Primary care physicians (PCPs) are well suited to manage patients with non-alcoholic fatty liver disease (NAFLD), but the limited, existing research suggests inadequate knowledge about the natural history, diagnostic methods, and management of NAFLD. The purpose of this qualitative study is to further understand the knowledge and practices for the diagnosis and management of NAFLD among PCPs. We conducted in-depth interviews with PCPs in the Greater Houston area, addressing current clinical practices used for diagnosing and managing NAFLD, as well as the perceptions of the PCPs regarding the burden of NAFLD on patients. We recorded interviews, transcribed them, coded transcripts, and identified patterns and themes. The interviewed PCPs (n = 16) were from internal or family medicine, with a range of experience (1.5-30 years). We found variations in NAFLD diagnosis and management across practices and by insurance status. Patients with abnormal liver imaging who had insurance or were within a safety-net healthcare system were referred by PCPs to specialists. Uninsured patients with persistently elevated liver enzymes received lifestyle recommendations from PCPs without confirmatory imaging or specialist referral. The role of PCPs in NAFLD management varied, with some helping patients set dietary and physical activity goals while others provided only general recommendations and/or referred patients to a dietitian. The diagnosis and management of NAFLD vary widely among PCPs and may be impacted by patients' insurance status and clinic-specific practices. The increasing burden of NAFLD in the U.S. medical system highlights the need for more PCPs involvement in managing NAFLD.
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Hepatopatia Gordurosa não Alcoólica , Médicos de Atenção Primária , Humanos , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/terapia , Pesquisa QualitativaRESUMO
Heat stress impacts plant growth at all phases of development, although the particular threshold for heat tolerance varies significantly across different developmental stages. During seed germination, elevated temperatures can either impede or completely halt the process, contingent upon the plant type and the severity of the stress. During advanced stages, high temperatures can have a negative impact on photosynthesis, respiration, water balance, and membrane integrity. Additionally, they can also influence the levels of hormones and primary and secondary metabolites. In addition, during the growth and development of plants, there is an increased expression of various heat shock proteins, as well as other proteins related to stress, and the generation of reactive oxygen species (ROS). These are significant plant responses to heat stress. Plants employ several strategies to deal with heat stress, such as maintaining the stability of their cell membranes, removing harmful reactive oxygen species (ROS), producing antioxidants, accumulating and adjusting compatible solutes, activating mitogen-activated protein kinase (MAPK) and calcium-dependent protein kinase (CDPK) cascades, and, crucially, signaling through chaperones and activating transcription. These molecular-level systems boost the ability of plants to flourish in heat stress. Potential genetic methods to enhance plant heat stress resistance encompass old and modern molecular breeding techniques and transgenic approaches, all of which rely on a comprehensive comprehension of these systems. Although several plants exhibit enhanced heat tolerance through traditional breeding methods, the effectiveness of genetic transformation techniques has been somewhat restricted. The latter results from the current constraints in our understanding and access to genes that have known impacts on plant heat stress tolerance. However, these challenges may be overcome in the future. Besides genetic methods, crops' heat tolerance can be improved through the pre-treatment of plants with various environmental challenges or the external application of osmoprotectants such as glycine betaine and proline. Thermotolerance is achieved through an active process in which plants allocate significant energy to maintain their structure and function to avoid damage induced by heat stress. The practice of nanoparticles has been shown to upgrade both the standard and the quantity of produce when crops are under heat stress. This review provides information on the effects of heat stress on plants and explores the importance of nanoparticles, transgenics, and genomic techniques in reducing the negative consequences of heat stress. Furthermore, it explores how plants might adapt to heat stress by modifying their biochemical, physiological, and molecular reactions.
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Plantas , Plantas/metabolismo , Resposta ao Choque Térmico , Espécies Reativas de Oxigênio/metabolismo , Termotolerância , Adaptação Fisiológica , Fenômenos Fisiológicos Vegetais , Temperatura AltaRESUMO
Meralgia paresthetica is a neurological disorder characterized by a symptom complex of numbness, burning, tingling, aching, or stabbing in the anterolateral portion of the upper thigh. Typically, this disorder is seen in patients with diabetes mellitus, obesity, and pregnancy. Also, it may result from a wide array of surgical interventions involving the region of the anterior superior iliac spine. Underlying pathophysiology concentrates on entrapment neuropathy of the lateral femoral cutaneous nerve (LFCN). Due to its location and wide anatomic variation, the LFCN is susceptible to compression, scarring, and injury during surgery. It is important to understand the regional anatomy. In addition, the plastic surgeon must have a working knowledge of the most common variations that can precipitate entrapment and increase susceptibility to injury during surgery. Surgeons lacking a substantial background on the numerous risk factors, origins, and anatomic variations of the LFCN may place patients at an even higher risk of damage to the nerve. An extensive knowledge of the anatomy and careful technique may be utilized by surgeons to prevent iatrogenic neuropathy of the LFCN.
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The inflammasome NLRP3 comprises a caspase recruitment domain, a pyrin domain containing receptor 3, an apoptosis-linked protein like a speck containing a procaspase-1, and an attached nucleotide domain leucine abundant repeat. There are a wide variety of stimuli that can activate the inflammasome NLRP3. When activated, the protein NLRP3 appoints the adapter protein ASC. Adapter ASC protein then recruits the procaspase-1 protein, which causes the procaspase- 1 protein to be cleaved and activated, which induces cytokines. At the same time, abnormal activation of inflammasome NLRP3 is associated with many diseases, such as diabetes, atherosclerosis, metabolic syndrome, cardiovascular and neurodegenerative diseases. As a result, a significant amount of effort has been put into comprehending the mechanisms behind its activation and looking for their specific inhibitors. In this review, we primarily focused on phytochemicals that inhibit the inflammasome NLRP3, as well as discuss the defects caused by NLRP3 signaling. We conducted an in-depth research review by searching for relevant articles in the Scopus, Google Scholar, and PubMed databases. By gathering information on phytochemical inhibitors that block NLRP3 inflammasome activation, a complicated balance between inflammasome activation or inhibition with NLRP3 as a key role was revealed in NLRP3-driven clinical situations.
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INTRODUCTION: Sepsis affects 25.2 million children per year globally and causes 3.4 million deaths, with an annual cost of hospitalisation in the USA of US$7.3 billion. Despite being common, severe and expensive, therapies and outcomes from sepsis have not substantially changed in decades. Variable case definitions, lack of a reference standard for diagnosis and broad spectrum of disease hamper efforts to evaluate therapies that may improve sepsis outcomes. This landscape analysis of community-acquired childhood sepsis in Australia and New Zealand will characterise the burden of disease, including incidence, severity, outcomes and cost. Sepsis diagnostic criteria and risk stratification tools will be prospectively evaluated. Sepsis therapies, quality of care, parental awareness and understanding of sepsis and parent-reported outcome measures will be described. Understanding these aspects of sepsis care is fundamental for the design and conduct of interventional trials to improve childhood sepsis outcomes. METHODS AND ANALYSIS: This prospective observational study will include children up to 18 years of age presenting to 12 emergency departments with suspected sepsis within the Paediatric Research in Emergency Departments International Collaborative network in Australia and New Zealand. Presenting characteristics, management and outcomes will be collected. These will include vital signs, serum biomarkers, clinician assessment of severity of disease, intravenous fluid administration for the first 24 hours of hospitalisation, organ support therapies delivered, antimicrobial use, microbiological diagnoses, hospital and intensive care unit length-of-stay, mortality censored at hospital discharge or 30 days from enrolment (whichever comes first) and parent-reported outcomes 90 days from enrolment. We will use these data to determine sepsis epidemiology based on existing and novel diagnostic criteria. We will also validate existing and novel sepsis risk stratification criteria, characterise antimicrobial stewardship, guideline adherence, cost and report parental awareness and understanding of sepsis and parent-reported outcome measures. ETHICS AND DISSEMINATION: Ethics approval was received from the Royal Children's Hospital of Melbourne, Australia Human Research Ethics Committee (HREC/69948/RCHM-2021). This included incorporated informed consent for follow-up. The findings will be disseminated in a peer-reviewed journal and at academic conferences. TRIAL REGISTRATION NUMBER: ACTRN12621000920897; Pre-results.
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Sepse , Criança , Humanos , Austrália/epidemiologia , Nova Zelândia/epidemiologia , Sepse/diagnóstico , Sepse/epidemiologia , Sepse/terapia , Projetos de Pesquisa , Hospitalização , Estudos Observacionais como AssuntoRESUMO
Neurodegeneration causes premature death in the peripheral and central nervous system. Neurodegeneration leads to the accumulation of oxidative stress, inflammatory responses, and the generation of free radicals responsible for nervous disorders like amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and Huntington's disorders. Therefore, focus must be diverted towards treating and managing these disorders, as it is very challenging. Furthermore, effective therapies are also lacking, so the growing interest of the global market must be inclined towards developing newer therapeutic approaches that can intercept the progression of neurodegeneration. Emerging evidences of research findings suggest that antioxidant therapy has significant potential in modulating disease phenotypes. This makes them promising candidates for further investigation. This review focuses on the role of oxidative stress and reactive oxygen species in the pathological mechanisms of various neurodegenerative diseases, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and Huntington's disorders and their neuroprotection. Additionally, it highlights the potential of antioxidant-based therapeutics in mitigating disease severity in humans and improving patient compliance. Ongoing extensive global research further sheds light on exploring new therapeutic targets for a deeper understanding of disease mechanisms in the field of medicine and biology targeting neurogenerative disorders.
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Antioxidantes , Doenças Neurodegenerativas , Estresse Oxidativo , Humanos , Estresse Oxidativo/efeitos dos fármacos , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/metabolismo , Antioxidantes/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Animais , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/químicaRESUMO
On April 5, 2022, FDA granted accelerated approval to alpelisib for the treatment of adult and pediatric patients 2 years of age and older with severe manifestations of PIK3CA-related overgrowth spectrum (PROS) who require systemic therapy. Efficacy was evaluated using real-world data (RWD) from EPIK-P1 (NCT04285723), a single-arm clinical study in patients 2 years of age and older with severe or life-threatening PROS who received alpelisib as part of an expanded access program (EAP) for compassionate use. The primary endpoint was confirmed radiologic response rate at week 24 as determined by blinded independent central review (BICR), using volumetric-based criteria given the atypical growth pattern and irregular shape of PROS lesions. Radiologic response was defined as a ≥20% reduction from baseline in the sum of measurable target lesion volume in up to three lesions. Of the 37 patients in the efficacy population, 27% [95% confidence interval (CI), 14-44] had a radiologic response at week 24. Duration of response (DOR) was an additional efficacy outcome measure, and among responders, 60% had a response lasting ≥12 months. Furthermore, supportive clinical documentation suggested early signals of clinical benefit (i.e., improvement in PROS-related signs and symptoms). The most common (≥10%) adverse reactions were diarrhea, stomatitis, and hyperglycemia.
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Tiazóis , Adulto , Humanos , Criança , Proliferação de Células , Classe I de Fosfatidilinositol 3-Quinases/genéticaRESUMO
Chemical probes are essential for academic research and target validation for disease identification. They facilitate drug discovery, target function investigation, and translation studies. A chemical probe provides starting material that can accelerate therapeutic values and safety measures for identifying any biological target in drug discovery. Essential read outs depend on their versatility in biochemical testing, proving the hypothesis, selectivity, specificity, affinity towards the target site, and valuable in new therapeutic approaches. Disease management will depend upon chemical probes as a primitive tool to ascertain the physicochemical stability for in vivo and in vitro studies useful for clinical trials and industrial application in the future. For cancer research, bacterial infection, and neurodegenerative disorders, chemical probes are integrated circuits which are on pipeline for the drug discovery process Furthermore, pharmacological modulators incorporate activators, crosslinkers, degraders, and inhibitors. Reports accessed depend on their structural, mechanical, biochemical, and pharmacological characterization in drug discovery research. The perspective for designing any chemical probes concludes with the utilization of drug discovery and identification of the potential target. It focuses mainly on evidence-based studies and produces promising results in successfully delivering novel therapeutics to treat cancers and other disorders at the target site. Moreover, natural product pharmacophores like rapamycin, cephalosporin, and ß-lactamase are utilized for drug discovery. Chemical probes revolutionize computational-based study design depending on identifying novel targets within the database framework. Chemical probes are the clinical answers for drug development and goforward tools in solving other riddles for scientists and researchers working in this industries.
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Recent advancements in biomedicine have seen a significant reliance on nanoengineering, as traditional methods often fall short in harnessing the unique attributes of biomaterials. Nanoengineering has emerged as a valuable approach to enhance and enrich the performance and functionalities of biomaterials, driving research and development in the field. This review emphasizes the most prevalent biomaterials used in biomedicine, including polymers, nanocomposites, and metallic materials, and explores the pivotal role of nanoengineering in developing biomedical treatments and processes. Particularly, the review highlights research focused on gaining an in-depth understanding of material properties and effectively enhancing material performance through molecular dynamics simulations, all from a nanoengineering perspective.
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Bioactive compounds found in various natural sources, such as fruits, vegetables, and herbs, have been studied for their potential benefits in managing obesity and diabetes. These compounds include polyphenols, flavonoids, other antioxidants, fiber, and certain fatty acids. Studies have found that these compounds may improve insulin sensitivity, regulate blood sugar levels, and promote weight loss. However, the effects of these compounds can vary depending on the type and amount consumed, as well as individual factors, such as genetics and lifestyle. Nutraceutical substances have multifaceted therapeutic advantages, and they have been reported to have disease-prevention and health-promoting properties. Several clinically used nutraceuticals have been shown to target the pathogenesis of diabetes mellitus, obesity, and metabolic syndrome and their complications and modulate various clinical outcomes favorably. This review aims to highlight and comment on some of the most prominent natural components used as antidiabetics and in managing obesity.
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Despite the improvements in HIV care outcomes in the United States (US), non-US-born persons continue to be disproportionately affected by HIV. We analyzed National HIV Surveillance System (NHSS) data on HIV diagnoses, stage 3 (AIDS) at diagnosis, linkage to medical care, and viral suppression for non-US-born persons by region of birth (RoB) reported to the (NHSS) in 2020 to determine care outcomes among this population. Overall, a larger proportion of non-US-born persons received a late-stage diagnosis [stage 3 (AIDS)] classification. Among all non-US-born persons, African-born males, Asian-born females, and persons aged 55 + years had the highest proportions of late-stage diagnosis. Despite a late-stage of diagnosis, a higher proportion of non-US-born persons were linked to medical care and were virally suppressed compared to US-born persons. HIV care outcomes varied by RoB and selected characteristics. Knowing the RoB of non-US-born persons is necessary to identify culturally sensitive approaches for prevention planning and increasing testing activities to ultimately increase early diagnosis in this population.
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In recent years, nanotechnology has been the focus of study for the cure of different diseases, among which nanosponge delivery system is one of a kind. Nano sponges are tiny, highly porous, three-dimensional nanostructures with a size range of 250nm-1µm in an amorphous or crystalline structure. Nanosponges usually act as an excipient or carrier of a drug in the different delivery systems. The type of polymers and cross-linkers, along with their concentration ratio, causes variation in nanosponges's dimension and encapsulation efficiency. Nanosponges have gained prominence in recent times due to their distinct ability to encapsulate both hydrophilic and lipophilic drugs within their internal cavity, thereby improving the solubility of drugs that have low water solubility. Virus-like size helps the nanosponges to circulate within the body without getting eliminated by the immune system until they stick to the targeted part of the body, which makes it the perfect candidate for a targeted drug delivery system and controlled delivery system as well because of its slow drug release property for a more extended period. Cyclodextrin-based nanosponges are the best choice for anticancer drug delivery as their small virus-like diameter helps them in passive targeting by enhancing the enhanced permeability and retention effect, allowing the anticancer drug to stay inside the tumour cell to show more significant therapeutic action on cancer, while for active targeting to the cancerous cell, nanosponges are attached with a ligand on it for receptor binding purpose. It can be used for drug delivery in many major diseases like brain-related diseases, diabetes, cancer, fungal, hypertension, etc., in different dosage forms, like oral, topical, hydrogel, parenteral, etc.
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Viruses are the cause of many human pathogenesis-related conditions. A serious hazard to public health has been created because of the increase in worldwide travel, fast urbanization, and infectious epidemics. At the same time, no preventative vaccines or antiviral treatments are currently available. Resources for developing new antiviral medications can be found in enhanced natural products and herbal medicines. These natural substances have aided the research on developing preventive vaccines and antiviral treatments. Based primarily on in vitro and in vivo searches, this review aims to explore the antiviral properties of plant extracts and some isolated plant natural products. Only a few antiviral medications have been given clinical approval, while numerous viruses continue to elude adequate immunization. Therefore, developing novel antiviral medicines is crucial, and natural substances make excellent sources for these new drugs. This review highlights various natural herbal drugs possessing antiviral properties.
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Nanosponges are porous solid cross-linked polymeric nanostructures. This study focuses on cyclodextrin-based nanosponges. Nanosponges based on cyclodextrin can form interactions with various lipophilic or hydrophilic compounds. The release of the entrapped molecules can be altered by altering the structure to obtain either a longer or faster release kinetics. The nanosponges might increase the aqueous solubility of weakly water-soluble compounds, develop long-lasting delivery systems, or construct novel drug carriers for nanomedicine. CD-NS (cyclodextrin-based nanosponges) are evolving as flexible and promising nanomaterials for medication administration, sensing, and environmental cleanup. CD-NS are three-dimensional porous structures of cyclodextrin molecules cross-linked by a suitable polymeric network, resulting in a large surface area. This overview covers CD-NS synthesis methods and applications.