Proteobiotics as a new antimicrobial therapy.

Antibiotic resistance is a major concern for healthcare. The emergence of resistant bacteria has contributed to an increase in cost, morbidity, and mortality rates of patients. There is evidence to suggest that the inhibition of bacteria's virulence strategies would downregulate their pathogenesis and stop infections while also preventing more resistance. This concept became the backbone of many studies in the arena of human microbiome. Through probiotic studies, novel compounds were discovered that possessed antimicrobial activity. These have become labeled as proteobiotics, i.e. metabolites from probiotics. Proteobiotics have demonstrated the ability to interrupt bacteria cell-to-cell communication. Currently, there is one approved product containing proteobiotic technologies for swine showing positive outcomes.

Naringenin-Functionalized Multi-Walled Carbon Nanotubes: A Potential Approach for Site-Specific Remote-Controlled Anticancer Delivery for the Treatment of Lung Cancer Cells.

Multi-walled carbon nanotubes functionalized with naringenin have been developed as new drug carriers to improve the performance of lung cancer treatment. The nanocarrier was characterized by Transmission Electron Microscopy (TEM), Fourier-Transform Infrared Spectroscopy (FTIR), X-ray photoelectron spectroscopy, Raman Spectroscopy, and Differential Scanning Calorimetry (DSC). Drug release rates were determined in vitro by the dialysis method. The cytotoxic profile was evaluated using the MTT assay, against a human skin cell line (hFB) as a model for normal cells, and against an adenocarcinomic human alveolar basal epithelial (A569) cell line as a lung cancer in vitro model. The results demonstrated that the functionalization of carbon nanotubes with naringenin occurred by non-covalent interactions. The release profiles demonstrated a pH-responsive behavior, showing a prolonged release in the tumor pH environment. The naringenin-functionalized carbon nanotubes showed lower cytotoxicity on non-malignant cells (hFB) than free naringenin, with an improved anticancer effect on malignant lung cells (A549) as an in vitro model of lung cancer.

Assessment of the approved Risk Evaluation and Mitigation Strategy programs for New Drug Applications and Biologics Licensing Applications.

The Food and Drug Amendments Act of 2007, (FDAAA), granted the United States Food and Drug Administration to require drug manufacturers to develop a Risk Evaluation and Mitigation Strategy, (REMS). Implementation of the FDAAA required drug manufacturers to utilize risk minimization strategies beyond routine labeling for benefit-risk profiles of prescription drugs. The first full year of FDAAA implementation, 2008, through 2016, was reviewed to assess presence of differences in REMS requirements in Center for Drug Evaluation and Research (CDER) New Drug Applications, (NDAs), and Biologics License Applications, (BLAs). The risks present in the current unreleased approved REMS were reviewed to determine any difference in FDA requirements for safety risks identified in the NDA and BLA REMS programs.

Oncology's trial and error: Analysis of the FDA withdrawn accelerated approvals.

Launched in 1992, the FDA accelerated approval program grants drugs indicated in rare/life threatening diseases the ability to be marketed at a faster pace than through the traditional track. Each manufacturing company presents its drug to the FDA, and within 60 days it will determine if the drug is eligible for this path. Many drugs that were initially approved through this route, subsequently did not demonstrate their clinical benefits. With cancer being a leading cause of death, a vast majority of drugs that have been approved/withdrawn from this pathway are indicated within oncology. There are a wide variety of cancer subtypes and therapeutic target sites that these drugs have been evaluated for. Herein, is an overview of the 17 oncology drugs, spanning 22 cancer-related indications, that had been approved within the accelerated route and subsequently withdrawn.

Regulatory insights into nanomedicine and gene vaccine innovation: Safety assessment, challenges, and regulatory perspectives.

This analysis explores the principal regulatory concerns linked to nanomedicines and gene vaccines, including the complexities involved and the perspectives on how to navigate them. In the realm of nanomedicines, ensuring the safety of nanomaterials is paramount due to their unique characteristics and potential interactions with biological systems. Regulatory bodies are actively formulating guidelines and standards to assess the safety and risks associated with nanomedicine products, emphasizing the need for standardized characterization techniques to accurately gauge their safety and effectiveness. Regarding gene vaccines, regulatory frameworks must be tailored to address the distinct challenges posed by genetic interventions, necessitating special considerations in safety and efficacy evaluations, particularly concerning vector design, target specificity, and long-term patient monitoring. Ethical concerns such as patient autonomy, informed consent, and privacy also demand careful attention, alongside the intricate matter of intellectual property rights, which must be balanced against the imperative of ensuring widespread access to these life-saving treatments. Collaborative efforts among regulatory bodies, researchers, patent offices, and the private sector are essential to tackle these challenges effectively, with international cooperation being especially crucial given the global scope of nanomedicine and genetic vaccine development. Striking the right balance between safeguarding intellectual properties and promoting public health is vital for fostering innovation and ensuring equitable access to these ground-breaking technologies, underscoring the significance of addressing these regulatory hurdles to fully harness the potential benefits of nanomedicine and gene vaccines for enhancing healthcare outcomes on a global scale. STATEMENT OF SIGNIFICANCE: Several biomaterials are being proposed for the development of nanovaccines, from polymeric micelles, PLGA-/PEI-/PLL-nanoparticles, solid lipid nananoparticles, cationic lipoplexes, liposomes, hybrid materials, dendrimers, carbon nanotubes, hydrogels, to quantum dots. Lipid nanoparticles (LNPs) have gained tremendous attention since the US Food and Drug Administration (FDA) approval of Pfizer and Moderna's COVID-19 vaccines, raising public awareness to the regulatory challenges associated with nanomedicines and genetic vaccines. This review provides insights into the current perspectives and potential strategies for addressing these issues, including clinical trials. By navigating these regulatory landscapes effectively, we can unlock the full potential of nanomedicine and genetic vaccines using a range of promising biomaterials towards improving healthcare outcomes worldwide.

Detection technologies of volatile organic compounds in the breath for cancer diagnoses.

Although there are new approaches in both cancer treatment and diagnosis, overall mortality is a major concern. New technologies have attempted to look at breath volatile organic compounds (VOCs) detection to diagnose cancer. Gas Chromatography and Mass Spectrometry (GC - MS) have remained the gold standard of VOC analysis for decades, but it has limitations in differentiating VOCs between cancer subtypes. To increase efficacy and accuracy, new methods to analyze these breath VOCs have been introduced, such as Solid Phase Microextraction/Gas Chromatography-Mass Spectrometry (SPME/GC-MS), Selected Ion Flow Tube - Mass Spectrometry (SIFT-MS), Proton Transfer Reaction - Mass Spectrometry (PRT-MS), Ion Mobility Spectrometry (IMS), and Colorimetric Sensors. This article highlights new technologies that have been studied and applied in the detection and quantification of breath VOCs for possible cancer diagnoses.

A systematic review of various pKa determination techniques.

The pKa values of functional groups is crucial in determining the pharmacokinetic properties of a drug, affecting its absorption and thus bioavailability. This physicochemical property is also vital for the designing of drug excipients and vehicles. There are currently 13 known methods of determining a pKa value, namely: potentiometric titration, spectrometry, fluorometry, NMR, HPLC, conductometry, electrophoresis, voltammetry, solubility, partition coefficient, calorimetry, computational, and surface tension. Some of these techniques are more widely utilized and well-established compared to others, with each having their inherent advantages and disadvantages. This review discusses each of the aforementioned techniques with emphasis on their pros and cons.

Fake drugs: Using Baseline Spectral Fingerprinting and a sorting algorithm to infer quality of medications.

An estimated 30-70% of available medications in low-income countries and conflict states are of low quality or counterfeit. Reasons for this vary but most are rooted in regulatory agencies being poorly equipped to oversee quality of pharmaceutical stocks. This paper presents the development and validation of a method for point-of-care drug stock quality testing in these environs. The method is termed Baseline Spectral Fingerprinting and Sorting (BSF-S). BSF-S leverages the phenomena that all compounds in solution have nearly unique spectral profiles in the UV spectrum. Further, BSF-S recognizes that variations in sample concentrations are introduced when preparing samples in the field. BSF-S compensates for this variability by incorporating the ELECTRE-TRI-B sorting algorithm, which contains parameters that are trained in the laboratory using authentic, proxy low quality and counterfeit samples. The method was validated in a case study using fifty samples that include factually authentic Praziquantel and inauthentic samples prepared in solution by an independent pharmacist. Study researchers were blinded to which solution contained the authentic samples. Each sample was tested by the BSF-S method described in this paper and sorted to authentic or low quality/counterfeit categories with high levels of specificity and sensitivity. In combination with a companion device under development using ultraviolet light emitting diodes, the BSF-S method is intended to be a portable and low-cost method for testing medications for authenticity at or near the point-of-care in low income countries and conflict states.

Evaluation of a chiral cubane-based Schiff base ligand in asymmetric catalysis reactions.

Recently, a novel chiral cubane-based Schiff base ligand was reported to yield modest enantioselectivity in the Henry reaction. To further explore the utility of this ligand in other asymmetric organic transformations, we evaluated its stereoselectivity in cyclopropanation and Michael addition reactions. Although there was no increase in stereocontrol, upon computational evaluation using both M06L and B3LYP calculations, it was revealed that a pseudo six-membered ring exists, through H-bonding of a cubyl hydrogen to the copper core. This decreases the steric bulk above the copper center and limits the asymmetric control with this ligand.

Anti-obesity weight loss medications: Short-term and long-term use.

As obesity prevalence increases, more and more drugs that assist with weight loss have been developed. Numerous weight loss drugs had been approved, but many have also been withdrawn based on their lack of efficacy as well as safety concerns. Initial approaches in developing weight loss drugs was by increasing physiological energy expenditure and suppressing the appetite. Subsequently, as more physiological mechanisms for weight gain has been unearthed, drugs targeting newly discovered receptors and/or enzymes have been introduced with improved safety profiles and fewer psychological adverse events. Additionally, drugs targeting hunger or satiety signaling have been actively studied, and have shown increased adoption by physicians. Studies have also evaluated drugs that target metabolic tissues-such as adipose tissue or muscle-to promote weight loss, however to-date nothing has carried on into clinical practice. Starting with a brief history of early obesity treatments, this review evaluates current weight loss pharmaceutical options based on their duration of therapy status.

Impact of chronic obstructive pulmonary disease, lung infection, and/or inhaled corticosteroids use on potential risk of lung cancer.

Chronic obstructive pulmonary disease is the 3rd leading cause of death worldwide. It not only affects current and former smokers, but non-smokers as well. Chronic inflammatory response in this disease state leads to the production of genotoxic free radicals and reactive oxygen species that could result in tumorigenesis. Inhaled corticosteroids are used for the management of inflammation in patients experiencing frequent exacerbation and/or have a high eosinophil count. However, these steroids are often prescribed off-label for symptom management. Using inhaled corticosteroids to combat inflammation in chronic obstructive pulmonary disease patients is suggested to be protective against lung cancer. However, immunomodulatory effects of these medications can pre-dispose patients to develop respiratory infections such as tuberculosis or pneumonia. These lung infections have shown to also increase the risk of developing lung cancer. Since chronic obstructive pulmonary disease is an independent risk factor for developing lung cancer, a subsequent infection could have an additive effect. Additionally, the aforementioned chemo-preventive effects of inhaled corticosteroids are inconsistent due to there being limited data on the long term effects of using inhaled corticosteroids in patients who do not meet the treatment recommendation guidelines. Hence, it is necessary to recognize the indirect connection between inhaled corticosteroids and lung cancer possibly via lung infections in chronic obstructive pulmonary disease patients. The rationale behind this review is to better understand the mechanistic links that connect these multiple disease states which could aid in guiding treatment with inhaled corticosteroids in specific sub-groups. This review discusses possible pathways that could lead to the lung carcinogenesis and the cumulative impact of chronic obstructive pulmonary disease, inhaled corticosteroids use, and pulmonary infections on the risk of lung cancer.

Alzheimer's disease failed clinical trials.

Alzheimer's disease is a progressive neurodegenerative disease typically presenting with symptoms of memory loss and cognitive decline. Existing theories for the causation of this focuses on amyloid beta plaques and neurofibrillary tau tangles. Most US Food and Drug Administration approved therapies for Alzheimer's disease target cognitive function. A multitude of clinical trials, with a variety of different targets have been conducted over the decades which have focused on the two clinical signs, with the only success being the controversial 2021 approval of an IgG1 anti-Ab antibody targeting the clearance of the Aß plaques. Presented is a review of all previously failed Alzheimer's disease clinical trials and the rationale for their failures.

Non-Invasive Breath Analysis for Disease Screening and Diagnoses.

Lower respiratory infections are a deadly communicable disease ranked as the fourth leading cause of death globally, with nearly 2 [...].

Beneficial effects of non-herbal supplements on patients with diabetes.

BACKGROUND AND AIMS: Controlling glycemic levels is crucial for patients with diabetes mellitus to improve their disease management and health outcomes. Beyond lifestyle modification and pharmacotherapy, some supplements have been shown to lower blood glucose as well as mitigate diabetic complications. METHODS: Information was primarily gathered by employing various PubMed scholarly articles for real-world examples in addition to data extraction from supplementary manuscripts. Only original human trials were used, and those published within the past two decades were primarily chosen. However, background information may contains review articles. RESULTS: Some non-herbal supplements have been suggested to lower fasting blood glucose, postprandial glucose, glycated glucose (HbA1c), lipid profiles, oxidative stress, and inflammation, as well as improving body composition, insulin sensitivity, blood pressure, and nephropathy. CONCLUSION: This review discusses ten non-herbal supplements that have been reported to have beneficial effects among different types of patients with diabetes as well as potential future clinical application. However, more long-term studies with a larger amount and more diverse participants need to be conducted for a robust conclusion. Also, mechanisms of action of antidiabetic effects are poorly understood and need further research.

Non-invasive ways of administering insulin.

BACKGROUND AND AIMS: Insulin is crucial in the management of diabetes. However, requires injection which itself comes with some challenges. Alternative delivery routes have been investigated that are needle-free, with enhanced absorption and bioavailability. This review presents novel non-invasive insulin administration approaches that overcome some hurdles, as well as delineating their advantages and disadvantages. METHODS: Information was primarily gathered by employing various PubMed scholarly articles for real-world examples in addition to data extraction from supplementary manuscripts. Articles were evaluated between 1958 and 2022. An introductive approach was used to identify matters related to the concept of different ways of administering insulin. RESULTS: Approaches aim to administer insulin in a safe, stable, and easy to use form, whether via oral, buccal, intranasal, oral inhalation, transdermal, ocular, rectal, or vaginal routes. Some have been shown to clinically improve blood glucose levels, while others are still in the investigational stage. CONCLUSION: Many approaches have been taken in an attempt to overcome physical barriers of insulin delivery. Some of these systems discussed may reach the market in the future and assist the millions of people who currently take subcutaneous injections of insulin.

Biosensor-Integrated Drug Delivery Systems as New Materials for Biomedical Applications.

Biosensor-integrated drug delivery systems are innovative devices in the health area, enabling continuous monitoring and drug administration. The use of smart polymer, bioMEMS, and electrochemical sensors have been extensively studied for these systems, especially for chronic diseases such as diabetes mellitus, cancer and cardiovascular diseases as well as advances in regenerative medicine. Basically, the technology involves sensors designed for the continuous analysis of biological molecules followed by drug release in response to specific signals. The advantages include high sensitivity and fast drug release. In this work, the main advances of biosensor-integrated drug delivery systems as new biomedical materials to improve the patients' quality of life with chronic diseases are discussed.

The Ketogenic Diet: Breath Acetone Sensing Technology.

The ketogenic diet, while originally thought to treat epilepsy in children, is now used for weight loss due to increasing evidence indicating that fat is burned more rapidly when there is a low carbohydrate intake. This low carbohydrate intake can lead to elevated ketone levels in the blood and breath. Breath and blood ketones can be measured to gauge the level of ketosis and allow for adjustment of the diet to meet the user's needs. Blood ketone levels have been historically used, but now breath acetone sensors are becoming more common due to less invasiveness and convenience. New technologies are being researched in the area of acetone sensors to capitalize on the rising popularity of the diet. Current breath acetone sensors come in the form of handheld breathalyzer devices. Technologies in development mostly consist of semiconductor metal oxides in different physio-chemical formations. These current devices and future technologies are investigated here with regard to utility and efficacy. Technologies currently in development do not have extensive testing of the selectivity of the sensors including the many compounds present in human breath. While some sensors have undergone human testing, the sample sizes are very small, and the testing was not extensive. Data regarding current devices is lacking and more research needs to be done to effectively evaluate current devices if they are to have a place as medical devices. Future technologies are very promising but are still in early development stages.

Medical Devices for Tremor Suppression: Current Status and Future Directions.

Tremors are the most prevalent movement disorder that interferes with the patient's daily living, and physical activities, ultimately leading to a reduced quality of life. Due to the pathophysiology of tremor, developing effective pharmacotherapies, which are only suboptimal in the management of tremor, has many challenges. Thus, a range of therapies are necessary in managing this progressive, aging-associated disorder. Surgical interventions such as deep brain stimulation are able to provide durable tremor control. However, due to high costs, patient and practitioner preference, and perceived high risks, their utilization is minimized. Medical devices are placed in a unique position to bridge this gap between lifestyle interventions, pharmacotherapies, and surgical treatments to provide safe and effective tremor suppression. Herein, we review the mechanisms of action, safety and efficacy profiles, and clinical applications of different medical devices that are currently available or have been previously investigated for tremor suppression. These devices are primarily noninvasive, which can be a beneficial addition to the patient's existing pharmacotherapy and/or lifestyle intervention.

Retinol binding protein 4 antagonists and protein synthesis inhibitors: Potential for therapeutic development.

Retinol-binding protein 4 (RBP4) is a serum protein that transports Vitamin A. RBP4 is correlated with numerous diseases and metabolic syndromes, including insulin resistance in type 2 diabetes, cardiovascular diseases, obesity, and macular degeneration. Recently, RBP4 antagonists and protein synthesis inhibitors are under development to regulate the effect of RBP4. Several RBP4 antagonists, especially BPN-14136, have demonstrated promising safety profiles and potential therapeutic benefits in animal studies. Two RBP4 antagonists, specifically tinlarebant (Belite Bio) and STG-001 (Stargazer) are currently undergoing clinical trials. Some antidiabetic drugs and nutraceuticals have been reported to reduce RBP4 expression, but more clinical data is needed to evaluate their therapeutical benefits. As regulating RBP4 levels or its activities would benefit a wide range of patients, further research is highly recommended to develop clinically useful RBP4 antagonists or protein synthesis inhibitors.