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Understanding and Modulating Metalloenzymes with Unnatural Amino Acids, Non-Native Metal Ions, and Non-Native Metallocofactors.

Metalloproteins set the gold standard for performing important functions, including catalyzing demanding reactions under mild conditions. Designing artificial metalloenzymes (ArMs) to catalyze abiological reactions has been a major endeavor for many years, but most ArM activities are far below those of native enzymes, making them unsuitable for most pratical applications. A critical step to advance the field is to fundamentally understand what it takes to not only confer but also fine-tune ArM activities so they match those of native enzymes. Indeed, only once we can freely modulate ArM activi

Necrotizing Herpetic Retinopathy: A Case of Delayed Acute Retinal Necrosis Presentation in a Patient With Uncontrolled Diabetes Mellitus and Complications.

Necrotizing herpetic retinopathy is a term used to describe two similar yet different forms of retinopathy - acute retinal necrosis (ARN) and progressive outer retinal necrosis (PORN), which can both present similarly with eye pain and/or vision loss stemming from inflammatory and necrotic retinal changes caused by members of the Herpesviridae family. This case presentation involves a patient with ARN, which has a multifocal pathogenesis, creating diffuse necrosis that over time coalesces and increases the risk of rhegmatous retinal detachment. We report the case of a 56-year-old male with unc

AI-driven integration of Framingham Heart Study data with machine learning, deep learning, and explainable AI for enhanced pharmaceutical marketing.

AI algorithms, in drug discovery, support target identification by recognizing biological patterns and molecular interactions linked to disease mechanisms. They further aid in lead compound optimization, virtual screening of large chemical libraries, and do drug design, thereby reducing time and cost constraints traditionally associated with laboratory-based approaches. This research proposes a novel framework that integrates the Framingham Heart Study (FHS)—a gold standard longitudinal dataset in cardiovascular research—with advanced machine learning (ML), deep learning (DL), and explainable

The Safety, Clinical, and Neurophysiological Effects of Intranasal Ketamine in Patients Who Do Not Respond to Electroconvulsive Therapy: Protocol for a Pilot, Open-Label Clinical Trial.

BACKGROUND: Major depressive disorder is among the most disabling illnesses worldwide, with a lifetime prevalence of 16.2%. Research suggests that 20% to 40% of patients with depression do not respond to pharmacotherapy, developing treatment-resistant depression. Electroconvulsive therapy is the gold standard for treating individuals with treatment-resistant depression, with remission rates of approximately 75% to 90%. However, 10% to 25% of patients do not respond to electroconvulsive therapy, and many are unable to tolerate it due to the side effects. Both groups are considered to be patient

An update review on Commiphora molmol and related species.

The origins of myrrh and frankincense are traced to the Arabian Peninsula. According to Herodotus (5th century BC): "Arabia is the only country which produces frankincense, myrrh, cassia, and cinnamon.., the trees bearing the frankincense are guarded by winged serpents of small size and various colors." Diodorus Siculus wrote, in the second half of the first century BC, that "all of Arabia exudes a most delicate fragrance; even the seamen passing by Arabia can smell the strong fragrance that gives health and vigor." He also mentioned gold mines so pure that no smelting was necessary. The Magi,

Functional food science and defence against reactive oxidative species.

This paper assesses critically the science base that underpins the argument that oxidative damage is a significant causative factor in the development of human diseases and that antioxidants are capable of preventing or ameliorating these disease processes. The assessment has been carried out under a number of headings, and some recommendations for future research are made based on the present day knowledge base. The knowledge database (1) Consideration of the basic science that underlies understanding of the role of free radicals in causing cellular pathologies, and the role of antioxidants i

Collagen epineurial substitute-assisted neurorrhaphy is superior to conventional end-to-end neurorrhaphy in a rat model of peripheral nerve injury.

BACKGROUND: Peripheral nerve injuries (PNIs) are common and may result in profound and persistent functional deficits. Although end-to-end neurorrhaphy remains the gold standard for nerve repair, clinical outcomes are frequently suboptimal. This study aimed to validate a novel surgical method using a collagen epineurial substitute (CES) to minimize the number of sutures and reduce nerve tension at the coaptation site. METHODS: Finite element analysis (FEA) was performed to simulate stress distribution and guide suture configuration. Sprague-Dawley (SD) rats underwent sciatic nerve transection

Huntington's disease: a forensic risk factor in women.

The antioxidants are essential molecules in human system but are not miracle molecules. They are neither performance enhancers nor can prevent or cure diseases when taken in excess. Their supplemental value is debateable. In fact, many high quality clinical trials on antioxidant supplement have shown no effect or adverse outcomes ranging from morbidity to all cause mortality. Several Chochrane Meta-analysis and Markov Model techniques, which are presently best available statistical models to derive conclusive answers for comparing large number of trials, support these claims. Nevertheless none

The Road Ahead to Cure Alzheimer's Disease: Development of Biological Markers and Neuroimaging Methods for Prevention Trials Across all Stages and Target Populations.

Alzheimer's disease (AD) is a slowly progressing non-linear dynamic brain disease in which pathophysiological abnormalities, detectable in vivo by biological markers, precede overt clinical symptoms by many years to decades. Use of these biomarkers for the detection of early and preclinical AD has become of central importance following publication of two international expert working group's revised criteria for the diagnosis of AD dementia, mild cognitive impairment (MCI) due to AD, prodromal AD and preclinical AD. As a consequence of matured research evidence six AD biomarkers are sufficientl

Nanoparticle-Based Therapeutic Strategies in Respiratory Diseases: Current Approaches and Future Perspectives.

INTRODUCTION: Respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), lung cancer, tuberculosis, and acute respiratory distress syndrome (ARDS) remain major global health challenges, causing significant morbidity and mortality worldwide.1,2 Despite the availability of pharmacological treatments such as bronchodilators, corticosteroids, antibiotics, and chemotherapeutics, most conventional drug administration routes (oral or intravenous) are often associated with critical limitations. These systemic delivery methods lead to the widespread distribution of drugs through

Doxorubicin- and Trastuzumab-Modified Gold Nanoparticles as Potential Multimodal Agents for Targeted Therapy of HER2+ Cancers.

Recently, targeted nanoparticles (NPs) have attracted much attention in cancer treatment due to their high potential as carriers for drug delivery. In this article, we present a novel bioconjugate (DOX-AuNPs-Tmab) consisting of gold nanoparticles (AuNPs, 30 nm) attached to chemotherapeutic agent doxorubicin (DOX) and a monoclonal antibody, trastuzumab (Tmab), which exhibited specific binding to HER2 receptors. The size and shape of synthesized AuNPs, as well as their surface modification, were analyzed by the TEM (transmission electron microscopy) and DLS (dynamic light scattering) methods. Bi

Emergent Nanotechnological Strategies for Systemic Chemotherapy against Melanoma.

Melanoma is an aggressive form of skin cancer, being one of the deadliest cancers in the world. The current treatment options involve surgery, radiotherapy, targeted therapy, immunotherapy and the use of chemotherapeutic agents. Although the last approach is the most used, the high toxicity and the lack of efficacy in advanced stages of the disease have demanded the search for novel bioactive molecules and/or efficient drug delivery systems. The current review aims to discuss the most recent advances on the elucidation of potential targets for melanoma treatment, such as aquaporin-3 and tyrosi

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… Gold compounds as aquaporin inhibitors: New opportunities for therapy and imaging. Medchemcomm. 2014;5:1444–1453. doi: 10.1039/C4MD00265B. 52. Elechalawar C.K., Sridharan K., Pal A., Ahmed M.T., Yousuf M., Adhikari S.S., Banerjee R. … Gold compounds as anticancer agents: Chemistry, cellular pharmacology, and preclinical studies. Med. Res. Rev. 2010;30:550–580. doi: 10.1002/med.20168. 94. Ott I., Gust R. Non platinum metal complexes as anti-cancer drugs. Arch. Pharm. (Weinheim) 2007;340:117–126. doi: 10.1002/ardp.200600151. 95. …

Novel Strategies for Tumor Treatment: Harnessing ROS-Inducing Active Ingredients from Traditional Chinese Medicine Through Multifunctional Nanoformulations.

Reactive oxygen species (ROS) encompass a diverse group of chemically reactive molecules or ions distinguished by their substantial oxidative potential. Empirical studies have shown that the targeted administration of high toxic concentrations of ROS can effectively induce tumor cell death in various types. Numerous bioactive ingredients derived from traditional Chinese medicine (TCM), recognized for their ROS-inducing properties, have demonstrated significant anti-tumor activity. Nonetheless, their clinical application has been hindered by challenges such as low solubility, limited bioavailab

How to Treat Melanoma? The Current Status of Innovative Nanotechnological Strategies and the Role of Minimally Invasive Approaches like PTT and PDT.

Melanoma is the most aggressive type of skin cancer, the incidence and mortality of which are increasing worldwide. Its extensive degree of heterogeneity has limited its response to existing therapies. For many years the therapeutic strategies were limited to surgery, radiotherapy, and chemotherapy. Fortunately, advances in knowledge have allowed the development of new therapeutic strategies. Despite the undoubted progress, alternative therapies are still under research. In this context, nanotechnology is also positioned as a strong and promising tool to develop nanosystems that act as drug ca

What is the Reason That the Pharmacological Future of Chemotherapeutics in the Treatment of Lung Cancer Could Be Most Closely Related to Nanostructures? Platinum Drugs in Therapy of Non-Small and Small Cell Lung Cancer and Their Unexpected, Possible Interactions. The Review.

Over the course of several decades, anticancer treatment with chemotherapy drugs for lung cancer has not changed significantly. Unfortunately, this treatment prolongs the patient's life only by a few months, causing many side effects in the human body. It has also been proven that drugs such as Cisplatin, Carboplatin, Oxaliplatin and others can react with other substances containing an aromatic ring in which the nitrogen atom has a free electron group in its structure. Thus, such structures may have a competitive effect on the nucleobases of DNA. Therefore, scientists are looking not only for

Alternative Cancer Therapeutics: Unpatentable Compounds and Their Potential in Oncology.

Cancer remains a leading cause of death globally. Cancer patients often seek alternative therapies in addition to, or instead of, conventional treatments like chemotherapy, radiation, and surgery. The progress in medical advancements and early detection provides more treatment options; however, the development of cancer drugs requires a significant amount of time, demands substantial investments, and results in an overall low percent of regulatory approval. The complex relationship between patent protection and pharmaceutical innovation complicates cancer drug development and contributes to hi

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… Gold compounds exhibit anti-cancer effects through several mechanisms. They inhibit crucial enzymes like thioredoxin reductase, essential for maintaining cellular redox balance. … Gold compounds can inhibit angiogenesis by downregulating factors like VEGF, preventing the formation of new blood vessels necessary for tumor growth and metastasis [ 68 ]. …

Enhancing the Bioavailability of Resveratrol: Combine It, Derivatize It, or Encapsulate It?

Overcoming the limited bioavailability and extensive metabolism of effective in vitro drugs remains a challenge that limits the translation of promising drugs into clinical trials. Resveratrol, despite its well-reported therapeutic benefits, is not metabolically stable and thus has not been utilized as an effective clinical drug. This is because it needs to be consumed in large amounts to overcome the burdens of bioavailability and conversion into less effective metabolites. Herein, we summarize the more relevant approaches to modify resveratrol, aiming to increase its biological and therapeut

ЭРАДИКАЦИОННАЯ ТЕРАПИЯ HELICOBACTER PYLORI

Актуальность. Helicobacter pylori – бактерия, вызывающая хронический активный гастрит, пептическую язвенную болезнь, желудочную аденокарциному, МАЛТ-лимфому, атрофический гастрит. В последние годы в мире развилась устойчивость Helicobacter pylori к различным антибиотикам, что требует изучения вопроса и разработки новых схем терапии.) Цель: анализ современных подходов к эрадикационной терапии Helicobacter pylori по данным современной литературы. Стратегия поиска. Поиск научной литературы проводился в базах данных PubMed, Scopus, Web of Science и Cochrane Library за период с 2014 по 2024 год. Ис

Emerging Nanopharmaceuticals and Nanonutraceuticals in Cancer Management.

Nanotechnology is the science of nanoscale, which is the scale of nanometers or one billionth of a meter. Nanotechnology encompasses a broad range of technologies, materials, and manufacturing processes that are used to design and/or enhance many products, including medicinal products. This technology has achieved considerable progress in the oncology field in recent years. Most chemotherapeutic agents are not specific to the cancer cells they are intended to treat, and they can harm healthy cells, leading to numerous adverse effects. Due to this non-specific targeting, it is not feasible to a

An Overview of Polymeric Nanoparticles-Based Drug Delivery System in Cancer Treatment.

Cancer is recognized as one of the world's deadliest diseases, with more than 10 million new cases each year. Over the past 2 decades, several studies have been performed on cancer to pursue solutions for effective treatment. One of the vital benefits of utilizing nanoparticles (NPs) in cancer treatment is their high adaptability for modification and amalgamation of different physicochemical properties to boost their anti-cancer activity. Various nanomaterials have been designed as nanocarriers attributing nontoxic and biocompatible drug delivery systems with improved bioactivity. The present