Artificial sweeteners promise sweetness with few or no calories, driving both their popularity and controversy. Recent studies have raised questions about their impact on the gut microbiome- a complex community of microorganisms vital for metabolism, immunity, and overall health. However, research findings remain inconsistent: some studies report significant microbial disruption, while others suggest minimal effects, even at high consumption levels. As regulators like the European Food Safety Authority (EFSA) and the United States Food and Drug Administration (FDA) reassess sweetener safety, nutrition science faces a pivotal moment- distinguishing genuine risks from exaggerated fears.1,2 Moreover, polyol sweeteners (e.g., xylitol, maltitol) can cause digestive issues like bloating and diarrhea at high consumption levels, although some may positively influence gut bacteria as prebiotics.2 Yet, some researchers caution that correlations between microbial patterns and specific health outcomes do not always imply causation. While personalized nutrition platforms promise diets tailored precisely to one's microbiota, evidence of consistent clinical benefits remains sparse.2 As startups invest in microbiome-driven dietary interventions, distinguishing genuine scientific advancement from commercial hype is crucial. Ultimately, while microbiome research holds great promise, careful interpretation and further studies are essential before fully embracing its purported health benefits.2,3 Sweeteners have become widely used as sugar substitutes due to their low-calorie content. Studies indicate that sweeteners can significantly alter gut flora, potentially leading to dysbiosis- a disruption associated with metabolic disorders like insulin resistance, obesity, and inflammation. Saccharin and sucralose specifically have been observed to impact gut microbiota composition in various studies consistently. Human studies corroborated these results, suggesting that saccharin can cause gut microbial imbalances linked to metabolic dysfunction.4 Animal studies report a decrease in beneficial groups like bifidobacteria, lactobacilli, and Clostridium clusters, while clinical trials have also highlighted its potential to disrupt microbial populations associated with gut health.2,4 Aspartame, rapidly metabolized in the small intestine, theoretically minimizes direct gut microbiota interactions. Human studies, however, report mixed results, suggesting that dietary habits and individual differences significantly influence outcomes.4 While some research shows minimal microbiota impact due to its rapid urinary excretion, other studies indicate changes in specific bacteria, particularly with prolonged high-dose intake.4 The scientific community emphasizes that responses can vary widely due to differences in study designs, dosages, duration of consumption, and individual microbiota profiles. Therefore, more controlled, longitudinal human trials are necessary to clarify these effects and establish safe consumption guidelines for sweeteners regarding gut microbiota health.2,4 Microbiome testing has become a transformative force within the nutrition industry, promising highly personalized diets that target gut health for optimal wellness. Artificial sweeteners, long celebrated as calorie-free sugar substitutes, have recently come under scrutiny for potentially disrupting gut bacteria. However, conflicting studies leave significant uncertainty about these effects, underscoring the complexity and variability of individual microbiomes.6 Personalized diets have emerged, with companies utilizing advanced microbiome analysis via at-home stool tests and genomic sequencing to provide customized dietary recommendations. These personalized approaches consider unique microbiome profiles, dietary habits, and physiological responses, enabling precise nutritional advice to optimize gut health. Despite this promise, challenges persist, as variability in microbiome composition makes universal conclusions about artificial sweeteners elusive. Personalized diets require extensive data collection, scientific validation, and consumer willingness to adopt tailored recommendations consistently.6 Future directions involve leveraging microbiome insights to formulate personalized dietary guidelines, develop targeted probiotic therapies, and create microbiota-specific treatments that counteract disruptions caused by artificial sweeteners. Additionally, sophisticated Artificial Intelligence (AI) algorithms integrating microbiome, metabolome, and genetic profiles will enhance predictions of individual metabolic reactions to sweeteners, significantly advancing precision nutrition. Concurrently, research into natural sweetener alternatives with microbiome-friendly characteristics is expanding, promising healthier consumer choices. As scientific understanding of artificial sweeteners deepens, microbiome-informed diets will likely become central to wellness strategies, offering unmatched accuracy in dietary management and health optimization.

The medicine kicked in and worked its magic while Mom and I waited in her cardiologist’s exam room. Thank goodness triptans are so effective for me. I popped into the grocery store for a few items after getting Mom back to her apartment. My thoughts moved ahead to the next items on the list, like writing a blog and catching up on laundry. One of my second cousins walked into the store while I was walking out. I looked up from my own agenda just in time to notice her. We’ve only spoken in person with each other a couple of times, but it felt like we knew each other well. We discovered our painful connection on social media and reached out a caring emoji to each other when times were difficult. I inherited episodic migraines from my dad’s side of the family. My cousin developed chronic migraines later in life.

In the project titled, "Automated acoustic voice screening techniques for comorbid depression and anxiety disorders," Mary Pietrowicz, along with colleagues from the University of Illinois Urbana-Champaign and UICOMP, explored how machine learning could effectively distinguish individuals with comorbid depression and anxiety disorders from healthy controls using acoustic and phonemic analysis of semantic verbal fluency data. Despite this high prevalence, treatment rates are low and, if left untreated, can lead to decreased productivity, poor functioning in society, erosion of cognitive abilities, strained relationships and suicide. This research demonstrates that analysis of short samples of acoustic voice, specifically one-minute verbal fluency tests, can be used in screening for anxiety and depression disorders, and can function online, at any time, addressing many of the barriers to screening and treatment. This work enables the development of clinical screening and tracking systems at scale. Researchers tested a custom dataset curated specifically for this study that included both healthy people and people with comorbid depression and anxiety across the spectrum of severity. People with other comorbid conditions known to affect speech and language were excluded from the study. Acoustic models using only data from one-minute verbal fluency tests discerned the presence of comorbid disorders at a highly successful rate. A primary benefit of these acoustic tests is that they're accessible. They may be administered either online, in-app or in-clinic, which directly addresses known barriers to screening, including factors such as stigma, low self-perception of need, costs, transportation issues and limited access to healthcare. "The development of an efficient, accurate and easy-to-use method for screening patients who may be suffering from depression or anxiety offers tremendous promise," said UICOMP Chair and Professor of Clinical Psychiatry Ryan Finkenbine. "The application of advanced machine learning models to the clinical setting provides a remarkable path for clinicians to screen for signs of mental illness in an adaptive and practical way.

Many intracellular pathways – series of signalling cascades within a cell – regulate these actions to avoid non-programmed growth that could lead to malformations or cancer. This may trigger the onset of different types of cancer, like breast and prostate, and when present in the germline cause several disorders. What scientists do know is that PI3K mutations affecting endothelial cells, the ones lining the inner layer of blood vessels, lead to vascular malformations. Not surprisingly, up to one in two PHTS patients also develop vascular malformations during early childhood. However, depending on the localization and extension, these strategies might not be possible, leaving patients without any other therapeutical option. The Endothelial Pathobiology and Microenvironment group at the Josep Carreras Institute, led by Dr. Mariona Graupera together with Dr. Sandra Castillo, former lab member and currently researcher at SDJ Pediatric Cancer Center Barcelona, and Dr. Eulàlia Baselga, head of the paediatric dermatology unit at Hospital Sant Joan de Deu, have investigated the genetic cause of PHTS-related vascular malformations. This genetic discovery, recently published at the high impact scientific journal Cancer Discovery, of the American Association for Cancer Research, has allowed them to generate the first mouse model of PHTS-related vascular malformations and use it as a benchmark to study the effects of two anticancer drugs known to counterbalance PI3K action, as PTEN would do if present. The studies have identified that blocking PI3K downstream effectors – down in the metabolic cascade – with rapamycin or capivasertib inhibitors significantly reduce vascular growth. However, the specific inhibition of PI3K with alpelisib gives no substantial benefit. Given these results, the team provides, as proof-of-concept for clinical activity, the off-label treatment with rapamycin of two patients with PHTS who indeed showed reduced vascular overgrowth and abrogated lesion-associated pain. These new findings are of paramount importance since the ability to stop PHTS effects from the very beginning would greatly improve patients' survival and quality of life. Also, PHTS is usually diagnosed when cancer has already grown in adults. This research has been funded by the PTEN Research Foundation, the Spanish Ministry of Science, Innovation and Universities of Spain and "la Caixa" Foundation.

A new artificial intelligence tool could aid in limiting or even prevent pandemics by identifying animal species that may harbor and spread viruses capable of infecting humans. Created by Washington State University researchers, the machine learning model analyzes host characteristics and virus genetics to identify potential animal reservoirs and geographic areas where new outbreaks are more likely to occur. Their findings could help scientists anticipate emerging zoonotic threats and, importantly, be adapted for other viruses. "Nearly three-quarters of emerging viruses that infect humans come from animals," said Stephanie Seifert, an expert in viral emergence and cross species transmission and an assistant professor in the WSU College of Veterinary Medicine's Paul G. Allen School for Global Health who helped to lead the project. These regions not only have high concentrations of potential hosts but also overlap with areas where smallpox vaccination rates are low. Katie Tseng, a veterinary medicine graduate student and the study's first author, noted the model not only demonstrated higher predictive accuracy than previous models, but it can be useful in predicting hosts for other viruses as well. While we used the model specifically for orthopoxviruses, we can also go in a lot of different directions and start fine tuning this model for other viruses." Katie Tseng, a veterinary medicine graduate student and study's first author Pilar Fernandez, a disease ecologist and assistant professor in the Allen School who helped to lead the project with Seifert, said previous machine learning models used to predict potential hosts for orthopoxviruses relied on the ecological traits of animals, such as habitat and diet, and other characteristics that influence their interactions with the environment, such as resource use and survival. Orthopoxviruses typically cause small, localized outbreaks, but recent events, including the global spread of mpox in 2022, have raised concerns about these viruses establishing new endemic areas and spreading through new animal reservoirs. Identifying possible reservoirs is key to anticipating spillover events, however, accomplishing that through traditional field sampling is a resource-intensive and impractical endeavor. The new model simplifies that task and can be used to target wildlife surveillance efforts. "If you are looking for the reservoir for mpox virus in Central Africa, that's one of the most biodiverse places on Earth, so where do you start?" "If we can use these machine learning models to help us prioritize sampling efforts, then that's going to be really beneficial in identifying where these viruses are coming from and in understanding the risks they pose." The research team also included Heather Koehler, an assistant professor in the School of Molecular Biosciences who has extensively studied mpox. Daniel J. Becker, University of Oklahoma; Rory Gibb, University College London; and Collin Carlson, Yale University, also contributed as members of the Viral Emergence Research Institute, a collaborative network of scientists studying host-virus interactions to predict virus spread on a global scale that is funded by the National Science Foundation.

Researchers have developed a virtual reality-based system that shows promise in improving the differentiation between common mental health conditions, potentially paving the way for earlier and more personalized treatment. Most psychiatric diagnoses rely on patients reporting their symptoms, but many mental health conditions share overlapping features. Now, a group of Danish scientists have combined virtual reality with physiological measurements (such as skin conductivity) to explore a more objective method for identifying different mental health conditions. Lead researcher Professor Kamilla Miskowiak (University of Copenhagen) said, "This is an important step forward. Until now, diagnosis has largely depended on self-reporting of symptoms, but our findings suggest that virtual reality scenarios combined with physiological measures may help differentiate between similar conditions. The researchers measured emotional responses and skin conductivity during these scenarios. Our initial findings are promising, but further large-scale research is needed to validate this approach and develop it into a practical clinical tool. We are now launching a follow-up study with 300 participants and implementing machine learning methods to improve individual-level diagnostic predictions. Our long-term goal is to improve early and personalised treatment for patients with mental health disorders." The European Neuropsychopharmacology paper has attracted attention since it was placed online, including a published commentary from Dr Sijia Liu at the Liaoning University of Traditional Chinese Medicine, Shenyang, China, stating: "This study offers a groundbreaking approach to addressing the persistent challenges in psychiatric diagnosis and treatment by leveraging virtual reality (VR) technology. I suggest that future research should consider integrating artificial intelligence algorithms to analyse the extensive data generated from these VR scenarios. I believe this work holds significant promise for advancing our understanding and clinical practices in mental health care". This project is a collaboration between the Copenhagen Mental Health Centre, Khora Virtual Reality and EXP360.

The Ateneo Laboratory for Intelligent Visual Environments (ALIVE) and international researchers have developed a deep learning model that aims to revolutionize dentistry, with the capability to identify tooth and sinus structures in dental X-rays with an accuracy of 98.2%. Using a sophisticated object detection algorithm, the system was specifically trained to help quickly and more accurately detect odontogenic sinusitis—a condition that is often misdiagnosed as general sinusitis and, if left unchecked, could spread infection to the face, eyes, and even the brain. Its symptoms—nasal congestion, foul-smelling nasal discharge, and occasional tooth pain—are nearly identical to those of ordinary general sinusitis. To make matters worse, only about a third of patients experience noticeable dental pain, meaning the condition is frequently overlooked by general practitioners. Traditional diagnosis requires collaboration between dentists and otolaryngologists, often leading to delayed treatment. By training deep learning models on dental panoramic radiograph (DPR) images, the researchers found a way to detect key anatomical relationships—such as the proximity of tooth roots to sinuses—with unprecedented accuracy. YOLO (You Only Look Once) is a state-of-the-art object detection algorithm known for its speed and accuracy. The YOLO 11n model, an improved version, is optimized for medical imaging tasks, enabling it to identify teeth and sinus structures with high precision in a single pass through the image. Unlike conventional diagnostic methods, which require multiple steps and expert interpretation, YOLO 11n rapidly pinpoints the affected areas in real time, making it an invaluable tool for dental professionals. It also provides a cost-effective screening tool, particularly useful in resource-limited areas where advanced imaging technology may not be available. This breakthrough highlights AI's growing role in medical diagnostics, bridging gaps where human expertise alone may fall short.

A newly developed blood test for Alzheimer's disease not only aids in the diagnosis of the neurodegenerative condition but also indicates how far it has progressed, according to a study by researchers at Washington University School of Medicine in St. Louis and Lund University in Sweden. Several blood tests for Alzheimer's disease are already clinically available, including two based on technology licensed from WashU. Current Alzheimer's therapies are most effective in early stages of the disease, so having a relatively easy and reliable way to gauge how far the disease has progressed could help doctors determine which patients are likely to benefit from drug treatment and to what extent. The new test can also provide insight on whether a person's symptoms are likely due to Alzheimer's versus some other cause. Analyzing blood levels of MTBR-tau243 from a group of people with cognitive decline, the researchers were able to distinguish between people with early- or later-stage Alzheimer's disease and separate both groups of Alzheimer's patients from people whose symptoms were caused by something other than Alzheimer's disease. In clinical practice right now, we don't have easy or accessible measures of Alzheimer's tangles and dementia, and so a tangle blood test like this can provide a much better indication if the symptoms are due to Alzheimer's and may also help doctors decide which treatments are best for their patients." Randall J. Bateman, MD, co-senior author, the Charles F. and Joanne Knight Distinguished Professor of Neurology at WashU Medicine The gold standard for staging Alzheimer's disease is positron emission tomography (PET) brain scans for amyloid plaques and tau tangles. Amyloid scans yield information about the presymptomatic and early symptomatic stages, while tau scans are useful for tracking later stages of the disease. PET brain scans are highly accurate but expensive, time-consuming and frequently unavailable outside of major research centers, so they are not widely used. Both are now used by doctors to aid diagnosis. But until now, there has been no blood test that reports on tau levels in the brain. In a previous study, Bateman and colleagues - including co-first authors Kanta Horie, PhD, a research associate professor of neurology at WashU Medicine, and Gemma Salvadó, PhD, then a postdoctoral researcher at Lund University, and co-senior author Oskar Hansson, MD, PhD, a professor of neurology at Lund University - showed that cerebrospinal fluid levels of MTBR-tau243 correlate closely with tau tangles in the brain. The researchers developed a technique to measure MTBR-tau243 levels in people's blood and compared it to the amount of tau tangles in their brains as measured by brain scans. They piloted the approach on data from two cohorts: volunteers at WashU Medicine's Charles F. and Joanne Knight Alzheimer Disease Research Center, which included 108 people, and a subset of 55 people from the Swedish BioFINDER-2 cohort. For comparison, cognitively healthy people with normal amyloid levels, and people with cognitive symptoms due to conditions other than Alzheimer's disease, were included. MTBR-tau243 levels in the blood were normal in asymptomatic people regardless of amyloid status, meaning that blood MTBR-tau243 levels do not change between healthy people and people in the presymptomatic stage of Alzheimer's disease with amyloid plaques. Among people with cognitive symptoms due to Alzheimer's disease, MTBR-tau243 levels were significantly elevated for people in the mild cognitive impairment phase of Alzheimer's disease and much higher - up to 200 times - for those in the dementia phase. Those differences translated into clear separation of people in early- and late-stage Alzheimer's disease. At the same time, MTBR-tau243 levels were normal in people with cognitive symptoms due to diseases other than Alzheimer's, meaning that the test effectively distinguished Alzheimer's dementia from other kinds of dementia. "I believe we will use blood-based p-tau217 to determine whether an individual has Alzheimer's disease, but MTBR-tau243 will be a highly valuable complement in both clinical settings and research trials," said Hansson. "When both of these biomarkers are positive, the likelihood that Alzheimer's is the underlying cause of a person's cognitive symptoms increases significantly, compared to when only p-tau217 is abnormal. Horie said the number and variety of available Alzheimer's medications may soon be expanding, as several experimental drugs that target tau or other aspects of Alzheimer's disease are in the pipeline. "We're about to enter the era of personalized medicine for Alzheimer's disease," Horie said. But after the onset of dementia with high tau tangles, anti-tau therapy or one of the many other experimental approaches may be more effective. Once we have a clinically available blood test for staging, plus treatments that work at different stages of the disease, doctors will be able to optimize their treatment plans for the specific needs of each patient."

Engineers working in the life sciences sector are facing increasing pressure to improve throughput and reduce total cost of ownership. Fluid Metering has developed the FENYX, a groundbreaking variable dispense pump that is able to increase throughput and decrease costs in the majority of syringe pump applications. Fluid Metering’s CeramPumps® have been used throughout the life sciences industry for more than 60 years, but until now, these pumps have been limited to precision dispensing with a fixed volume. The FENYX offers a number of advantages over traditional syringe pumps: Increase throughput by 10x-40x with the highest degree of accuracy and precision Depending on the pump’s duty cycle, this may involve sourcing replacement parts every few weeks or months. Recalibration could also be necessary, even in cases where the syringe pump is replaced entirely. The pump’s ceramic parts are both chemically inert and dimensionally stable, meaning that they will not stretch, distort, or change shape over time. For example, requiring separate pumps to prime, flush, and dispense requires extra lines of often frail tubing, additional risky leak points, and increased OEM machine size. The FENYX is valveless and able to self-prime 10x-40x faster than a syringe pump, helping OEMs eliminate unnecessary fluidic components such as flushing pumps, prime pumps, selector valves, and tubing. This air can only be removed through multiple priming cycles in small-volume syringe pumps, slowing down the priming process and creating problematic delays in time-sensitive applications. Syringe pumps also necessitate the use of a separate pump to prime. This removes any risk of bubble entrapment while addressing the priming issues common to smaller syringe barrel sizes. Syringe pumps work by exerting linear force on a plunger in order to dispense fluid. This means that highly viscous mediums cannot be handled because they tend to create more intense friction than the pump can accommodate. In these cases, throughput is fully dependent on the syringe diameter. The FENYX variable dispense pump has been developed with more robust components. It is able to accommodate more powerful motors, meaning that it can overcome the resistance required to accommodate a wider range of fluid viscosities with no performance degradation. The FENYX draws fluid from a reservoir as required, meaning that its flow rate can operate continuously at a wider range, spanning from 1 mL per minute at 1 rpm up to 400 mL per minute at 1000 rpm. Syringe pumps lack the capacity for non-contact dispensing, requiring life science OEMs to use touch-off or submersion methods in order to dispense single microliter volumes. This approach necessitates regular probe tip changes or washing in order to prevent cross-contamination, increasing costs and reducing throughput. This removes the need for washing or probe tip changes, reducing system costs and improving life science OEMs’ throughput. A calibratable flag, featuring updated home positioning and dispense options. An anti-backlash mechanism reduces dispensing variation when the linear actuator changes direction. The linear sensor is also dual-mounted, ensuring a stable home position that will not be impacted by manipulation of the pump during shipping. The FENYX can accommodate a much more diverse array of applications than a syringe pump, with Fluid Metering’s CeramPump® technology seeing routine use in the following applications: Fluid Metering, Inc. (FMI) is a worldwide leader in life science pumps and dispensers, having pioneered the first valve-less piston pump over 64 years ago. Committed to innovation through collaboration, Fluid Metering, Inc. advances health, sustainability, and quality of life. Sponsored Content Policy: AZoLifeSciences publishes articles and related content that may be derived from sources where we have existing commercial relationships, provided such content adds value to the core editorial ethos of AZoLifeSciences which is to educate and inform site visitors interested in life science news and information.

Under specific conditions, a liquid solution can form solid crystals, often due to environmental factors like temperature shifts, concentration changes, or air exposure. In life science OEM and laboratory research applications, crystallizing fluids pose a significant challenge, as conventional equipment often struggles to process them efficiently. That’s why selecting a pump designed to handle these fluids with ease is essential for maintaining reliable performance. Why You Need a Pump to Handle Crystallizing Fluids Pump users are increasingly experiencing crystallization concerns, not only with traditional high-salt fluids but also with more diluted solutions that do not typically produce deposits. As a precaution, many industry professionals utilize buffer solutions in their equipment to keep the fluid's pH steady while mixing it with the buffer. If crystallization occurs within the pump, it could cause a variety of issues: Temperature changes, pressure variations, contact with pump materials, air exposure, mechanical stress, and vibrations can all trigger fluid crystallization. This phenomenon is a frequent challenge across various applications. Dialysis instruments, for example, handle highly concentrated dialysate, which crystallizes easily. Similarly, hard water, salt water, and saline solutions used in industrial, environmental, and medical applications are especially prone to crystallization due to the strong ionic bonds in salt. While fluid crystallization may seem inevitable, there are effective strategies to minimize its occurrence and maintain smooth system operation. Fluid Metering has created some efficient techniques to avoid and reduce the problems produced by crystallizing fluids. Valveless Design – Avoids a common place for deposit buildup and blockages. – Avoids a common place for deposit buildup and blockages. Secondary Flush Ports - Users can flush viscous or crystallizing fluids through the second set of ports using gravity or pressure. - Corrosion-resistant ceramics and seals to fight abrasive wear. Optimized Internal Geometry - Reduces the amount of dead volume where crystalizing fluids might precipitate and collect. - Reduces the amount of dead volume where crystalizing fluids might precipitate and collect. These customized setups have a high success rate in reducing seepage and eliminating crystallization. Don’t allow crystallizing fluids to keep you from achieving your goals. Fluid Metering can assist you in troubleshooting current issues or getting a jump start on your new application. Fluid Metering, Inc. (FMI) is a worldwide leader in life science pumps and dispensers, having pioneered the first valve-less piston pump over 64 years ago. Committed to innovation through collaboration, Fluid Metering, Inc. advances health, sustainability, and quality of life. Sponsored Content Policy: AZoLifeSciences publishes articles and related content that may be derived from sources where we have existing commercial relationships, provided such content adds value to the core editorial ethos of AZoLifeSciences which is to educate and inform site visitors interested in life science news and information.

According to a recent study, superbugs could kill up to 40 million people by 2050.1 The World Health Organization has identified antimicrobial resistance (AMR) as one of the most serious global public health threats. The first way AMR develops is through intrinsic resistance, which refers to a microorganism’s natural ability to withstand antibiotics. "For example, an antibiotic that affects the wall-building mechanism of the bacteria, such as penicillin, cannot affect bacteria that do not have a cell wall. The second mechanism is acquired resistance, which occurs when antibiotic-susceptible bacteria gain the ability to resist the effects of an antibiotic, allowing them to survive and multiply under selective pressure. Acquired resistance can result from either modification to existing genetic material (gene mutation) or the acquisition of new genetic material from another source (horizontal gene transfer). These acquired resistance genes may enable bacteria to degrade or chemically modify antibiotics, rendering them ineffective. Bacteria may also produce or upregulate efflux pumps, which actively transport antibiotics out of the cell, preventing the drug from reaching its intracellular target. Mutation is a rare event, but due to the rapid growth rate of bacteria, it does not take long for resistance to develop within a population.3 Horizontal gene transfer (HGT) is the exchange of genetic information between organisms that are more or less closely related. Bacteria can acquire resistance by obtaining additional genetic material from resistant organisms. Transformation: Bacteria absorb extracellular, bare DNA from their surroundings. This DNA is typically found in the external environment because of another bacteria's death and lysis. Bacteria absorb extracellular, bare DNA from their surroundings. This DNA is typically found in the external environment because of another bacteria's death and lysis. Gram-positive bacteria, on the other hand, typically initiate conjugation by producing sex pheromones, which promote clumping of donor and recipient cells, facilitating DNA exchange. Conjugation refers to the direct transfer of DNA between cells. Gram-positive bacteria, on the other hand, typically initiate conjugation by producing sex pheromones, which promote clumping of donor and recipient cells, facilitating DNA exchange. Bacteriophages are viruses that infect bacterial cells and replicate within them. After replicating, these viruses assemble and may occasionally incorporate a fragment of the host bacterium’s DNA. When such a bacteriophage infects a new bacterial cell, the bacterial DNA can be integrated into the new host's genome. Many scientists use bacteriophages to transfer new genetic elements into different host cells.4 Norgen Biotek provides various kits for isolating high-quality bacterial DNA and RNA (both gram-positive and gram-negative) from a wide range of sample types, including stool, cell culture, sand, urine, plasma, tissue, and more. The role of biofilm in antimicrobial resistance Pathogens can also create a protective barrier around themselves, making treatment more difficult. This complex structure has been shown to significantly increase antibiotic resistance. Various bacteria exhibit resistance, each using unique strategies. These protein pumps are designed to remove hazardous compounds (such as antibiotics) from within the bacterial cell.6 They reduce the intracellular concentration of antibiotics, limiting their potency and ability to target essential cellular functions. β-lactams, known as penicillins, are among the most widely used antimicrobials. Bacteria have developed multiple resistance mechanisms against these drugs. Despite the development of β-lactamase inhibitors such as clavulanic acid and avibactam, newer and more resilient bacterial strains, like carbapenem-resistant Enterobacteriaceae (CRE), pose significant challenges.7 Bacteria also use other mechanisms to resist β-lactams. Gram-positive bacteria, for example, may modify the shape or number of penicillin-binding proteins (PBPs), reducing or entirely preventing antibiotic binding to the target.7 PBPs are bacterial cell membrane proteins involved in the formation of peptidoglycans (PG).8 Gram-negative bacteria are intrinsically resistant to drugs such as vancomycin, a glycopeptide that inhibits cell wall synthesis, and daptomycin, a lipopeptide that depolarizes the cell membrane. Some bacteria can develop resistance to glycopeptides by altering the structure of PG precursors, reducing glycopeptide binding. In other cases, gene mutations change the charge of the cell membrane, preventing calcium from binding, a step required for daptomycin activity. This reduces daptomycin's binding ability and its capacity to depolarize the cell membrane.7 Clinical bacterial isolates are collected from humans, animals, and the environment to track changes in resistance. Phenotypic testing, such as standard antibiotic susceptibility tests (for example, disk diffusion and broth microdilution), can be used to detect resistant organisms. Researchers may also use genotypic analysis, including molecular approaches such as PCR and whole-genome sequencing, to screen for known resistance genes and mutations.9 The most common molecular method used by clinical laboratories to study the mechanisms behind observed phenotypic resistance is PCR-based testing, including conventional PCR, real-time PCR, and qRT-PCR. This strategy involves amplifying and sequencing genes known to be involved in resistance. qRT-PCR can also be used to analyze and compare the expression levels of resistance genes between mutant strains with resistant phenotypes and wild-type strains.9 Functional genomics can help identify new antibiotic-resistance genes that encode enzymes based on their function. This approach involves extracting DNA fragments and creating a specific library of homogenous size. The library is then cloned into an expression vector, which is screened based on the antibiotic being studied. Moreover, cultivating harmful bacteria poses major risks to the scientists handling them and requires specialized equipment and strict safety protocols. Modern sequencing technologies offer significant potential in addressing the growing problem of antibiotic resistance. Metagenomic sequencing, in particular, has uncovered a vast reservoir of antibiotic resistance genes within the complex microbial communities found in the gastrointestinal systems of humans and animals, as well as in natural environments such as surface water and soil. This has been made possible by the rapid decrease in sequencing costs, which has led to the identification of an increasing number of resistance genes. Integrating genetic analysis with continuously updated databases is a powerful and expanding strategy. It enables access to large volumes of information and enhances our ability to investigate antibiotic resistance while offering deeper insights into bacterial behavior.10 The role of gene sequencing in AMR The prediction of new antimicrobial resistance through genome sequencing can be accelerated by prior knowledge of all variables that contribute to phenotypic resistance, such as inactivating enzymes, porin mutations, influx system alterations, binding site mutations, gene inactivation, and promoter mutations. Sequence-based identification of known resistance markers covers only a small portion of the resistance spectrum, whereas transcriptome analysis may provide a more comprehensive phenotypic profile. Transcriptome analysis is a promising alternative to genome sequencing for resistance gene identification. High-throughput RNA sequencing (RNA-Seq) is a cutting-edge technology that uses deep sequencing techniques to analyze an RNA population converted into a library of complementary DNA (cDNA) fragments. These sequences are then bioinformatically assembled to reconstruct the entire transcriptome and accurately measure gene expression levels.12 For example, recent research on colistin (a polymyxin antibiotic used to treat infections caused by susceptible gram-negative bacteria) has combined genome sequencing with transcriptional profiling via RNA-Seq. This approach led to the identification of crr genes, previously reported as uncharacterized histidine kinases, as additional regulators of colistin resistance. These discoveries expand the range of genes implicated in colistin resistance and highlight the many ways bacteria may respond to antimicrobial peptides.13 Pathogens continually evolve, finding new ways to become stronger and evade our treatments. As they become more resistant, the challenge of infection control intensifies. Scientists are developing new approaches to combat disease and protect global health by staying one step ahead of these clever microorganisms. That’s why Norgen is here to support you every step of the way. Phage therapy offers a promising alternative to antibiotics in the fight against AMR. Bacteriophages, commonly known as phages, are viruses that infect bacteria and replicate within them, causing cell lysis and, ultimately, bacterial death. Unlike traditional antibiotics, phages specifically target and destroy bacteria, offering a precise method of treatment that preserves beneficial microbes. Due to its targeted action, phage therapy is a valuable strategy for managing multidrug-resistant infections, where conventional treatments often fail. To advance phage therapy research, reliable technologies for isolating and studying bacteriophages are essential. Norgen Biotek’s Phage DNA Isolation Kit simplifies this process by providing a fast and efficient method for isolating high-quality phage DNA. Researchers at Bu-Ali Sina University studied a new lytic bacteriophage isolated from poultry slaughterhouse wastewater to evaluate its potential as an antibiotic alternative. The host range, environmental stability, genetic makeup, and bactericidal activity against 100 MDR-APEC bacteria were investigated. More importantly, they analyzed the phage genome using Norgen’s Phage DNA Isolation Kit and found that it lacks antibiotic resistance genes, mobile genetic elements, and E. coli virulence-associated genes. They also tested the phage’s stability and found it to be stable at temperatures ranging from 4 °C to 80 °C, pH levels between 4 and 10, and NaCl concentrations ranging from 1 % to 13 %. These findings support the potential of Escherichia phage AG-MK-2022 Basu as a safe biocontrol agent. The team stated that it “may safely be used as a biocontrol agent” but cautioned that "more work, such as whole genome sequencing of the isolated phage, is necessary to achieve more information regarding its safe use".14 The misuse and overuse of antibiotics, combined with natural microbial evolution, have created a problem that requires urgent attention. Innovative solutions like phage therapy offer hope, demonstrating that advanced research and cutting-edge technologies can help us outpace resistant infections. Norgen Biotek is committed to supporting researchers in this effort by providing reliable tools like the Phage DNA Isolation Kit, helping to drive progress in the fight against AMR. Through investment in research, responsible antibiotic use, and continued technological innovation, we can combat antimicrobial resistance. Global Burden of Bacterial Antimicrobial Resistance 1990–2021: a Systematic Analysis with Forecasts to 2050. Horizontal Gene Transfer of Antibiotic Resistance Genes in Biofilms. The Role of Bacterial Biofilms in Antimicrobial Resistance. Chemical tools for selective activity profiling of bacterial penicillin-binding proteins. The History of Colistin Resistance Mechanisms in Bacteria: Progress and Challenges. Next-generation approaches to understand and combat the antibiotic resistome. RNA signatures allow rapid identification of pathogens and antibiotic susceptibilities. Norgen Biotek: Advancing science with best-in-class, scientist-backed innovations Norgen Biotek is a fully integrated biotechnology company that focuses on providing complete workflows for molecular biology sample preparation and analysis. With a diverse portfolio of over 600 products, the company delivers high-performance, user-friendly, and cost-effective solutions. Our expert R&D team continuously develops cutting-edge technologies that set new industry standards for RNA, DNA, protein, and exosomal isolation, ensuring superior yield, purity, and integrity from even the most challenging sample types. At the heart of Norgen’s success is its patented Silicon Carbide (SiC) Technology. This proprietary resin exhibits uniform binding affinity for all RNA species, regardless of molecular weight or GC content. This ensures the full diversity of small and microRNA are captured while eliminating the need for phenol extraction. This innovative technology sets Norgen kits apart from others, positioning them as leaders in RNA purification. Norgen is committed to providing high-quality kits capable of processing a wide range of sample types, from ultra-low input samples such as liquid biopsies to highly impure samples like stool or soil. Our sample collection and preservation devices for stool and saliva simplify handling by rendering samples non-infectious by preventing microbial growth and inactivating viruses, while our blood and urine preservation solutions ensure the stability of highly vulnerable cell-free nucleic acids. To meet varying research demands, we offer multiple isolation methods including, but not limited to high-throughput and automation-ready magnetic bead-based formats. Additionally, our multiple-analyte kits enable the simultaneous purification of RNA, DNA, and proteins, maximizing data extraction from a single sample. Norgen offers an extensive variety of TaqMan qPCR kits designed for molecular diagnostic use, including lyophilized kits for easy shipping. Library preparation kits for both DNA and RNA samples are also available to support genomic applications. Norgen recently released their EXTRAClean technology, an innovative solution that minimizes background noise while providing high-purity RNA, significantly enhancing NGS performance. Scientist-Driven Innovation – Developed by leading experts in molecular biology Global Presence – We ship to over 150 countries and have a network of 60+ distributors Innovative Products – Hold more than thirty issued and pending patents for products presenting solutions for all research & clinical applications Driven by a mission to accelerate scientific discoveries, Norgen Biotek actively supports researchers by providing educational resources, technical workshops, and application notes. Their NorBlog serves as a hub for the latest scientific discoveries, protocol optimizations, and industry trends. Explore Norgen Biotek’s innovative solutions today and take your research to the next level. Sponsored Content Policy: News-Medical.net publishes articles and related content that may be derived from sources where we have existing commercial relationships, provided such content adds value to the core editorial ethos of News-Medical.Net which is to educate and inform site visitors interested in medical research, science, medical devices and treatments.

Cancer is the second most common cause of death in both men and women globally. In 2020, 1.41 million people were diagnosed with prostate cancer worldwide.1 With over 300,000 deaths caused by prostate cancer in 2022, early identification is critical for lowering mortality.2 Exosomal RNA has recently received significant attention as a potential biomarker for the early identification of cancers. It produces seminal fluid, which transports sperm. Prostate cancer is classified into several types, with adenocarcinoma being the most common. In its early stages, prostate cancer often progresses slowly and remains localized within the prostate.5 This makes early detection more difficult. However, if identified early, the cancer is highly treatable and can often be eradicated. This article will discuss the symptoms and risk factors of prostate cancer, as well as current screening methods. It will also highlight the significance of exosomal mRNA and present two studies exploring the potential of exosomal mRNAs as a non-invasive biomarker for early prostate cancer screening. Because prostate cancer grows slowly, there may be no signs or symptoms in its early stages. However, some symptoms may appear in the later stages of cancer progression. These can include difficulty urinating, increased urgency and frequency of urination, blood in the urine, blood in the semen, bone pain, decreased force of urine flow, erectile dysfunction, and weight loss. Like many other cancers, the exact cause of prostate cancer remains unclear. However, several risk factors have been identified. These include age (50 years or older), family history (a history of prostate cancer), and weight (obesity), all of which have been linked to an increased risk of developing the disease.6 Race is also associated with a higher risk of prostate cancer. A 2023 study found that black men have a greater risk of developing prostate cancer compared to non-Hispanic white men. This may be due to genetic factors, dietary differences, or increased levels of stress.7 The most common approach to diagnosing prostate cancer, according to the Centers for Disease Control and Prevention (CDC), is through biopsy.8 A prostate biopsy is a procedure that removes a small sample of prostate tissue for further investigation. A needle is inserted into the prostate to collect multiple samples of suspicious tissue. This method of diagnosis is highly invasive, painful, and uncomfortable. Before a prostate biopsy is performed, various preliminary screening procedures are typically conducted. Individuals with prostate cancer tend to have increased PSA levels. Although PSA blood tests are widely used, they can be unreliable because there are several other reasons why PSA levels may be elevated. Normal prostate cells also produce PSA, so benign (non-cancerous) conditions such as prostatitis (inflammation of the prostate) and benign prostatic hyperplasia (BPH), or an enlarged prostate, can raise PSA levels in the bloodstream.10 Strenuous exercise, ejaculation, or even a car accident could also increase PSA levels. The unreliability of PSA blood tests and the invasive nature of biopsies highlight the need for a more dependable, non-invasive method of prostate cancer screening. Exosomal mRNAs have recently gained attention from researchers as a potential biomarker for prostate cancer detection. Sample collection for exosomal mRNA is significantly less invasive, as exosomes are present in body fluids. Moreover, the specificity of exosomal mRNAs may allow for more accurate and reliable results compared to PSA blood tests. Messenger RNA (mRNA) is a single-stranded molecule involved in protein synthesis. mRNAs are transcribed from a DNA template and carry protein-coding information from the cell’s nucleus to the cytoplasm.11 mRNA research offers vital insights into gene expression, cellular function, and specific mutations associated with diseases such as cancer. Exosomes are extracellular vesicles (EVs) released by various cell types. They are found in physiological fluids such as plasma, urine, and saliva. These vesicles are enclosed by a lipid bilayer and carry a wide range of biomolecules, including nucleic acids and proteins, both inside and on their surface. Exosomes play essential roles in cell-to-cell communication, cellular maintenance, and tumor progression.12 They transport information from all cells, both healthy and diseased, making them valuable for understanding disease mechanisms and developing diagnostics or therapies. A 2021 study analyzed circulating exosomal mRNA to investigate its potential as a biomarker for prostate cancer. Exosomes can be found throughout the body and may carry different information depending on their location. To demonstrate that exosomal mRNAs can produce results as accurate as those from cancerous prostate tissue, the researchers used RNA sequencing to compare tissue-derived mRNA with circulating exosomal mRNA from blood samples. They found that both mRNA from prostate cancer tissue and circulating exosomal mRNA contained the same information. Samples were collected from 76 prostate cancer patients and 84 individuals with BPH. After a series of RNA sequencing analyses, the researchers identified six circulating exosomal mRNAs with significantly different expression levels among prostate cancer patients, BPH patients, and a control group.13 These findings showed strong potential for using circulating exosomal mRNA as a biomarker to detect prostate cancer. Blood samples were used in this study because exosomes can be detected in both blood and plasma. However, this method is not entirely noninvasive. Is there a truly noninvasive way to detect prostate cancer? Yes—a recent 2024 study explored the use of urinary exosomal mRNA for this purpose. Jiayin Yu et al. studied the use of urinary exosomal mRNAs as a potential biomarker for the early detection of prostate cancer. They selected urine because it allows for easy, noninvasive sample collection, making it suitable for large-scale screening and early detection. Exosomal mRNA was chosen due to its stability in the body. Key mRNA biomarkers identified for prostate cancer screening Subsequent qPCR and electrophoresis analysis showed that eight of these mRNAs (RAB5B, WWP1, HIST2H2BF, ZFY, MARK2, PASK, RBM10, and NRSN2) outperformed blood PSA as indicators of prostate cancer. The study concluded that their comprehensive model using urinary exosomal mRNAs outperformed existing PSA screening methods, with a sensitivity of 70–90 % and specificity of 20–40 %.14 Prostate cancer remains a leading cause of death among men. Although several screening methods exist, such as digital rectal exams (DRE) and blood PSA tests, they can be invasive and often lack reliability. This highlights the need for a non-invasive, more accurate, and reliable method for detecting prostate cancer. Current research on urinary exosomal mRNA shows promising potential for early diagnosis. However, further studies are needed to establish urinary exosomal mRNAs as a reliable diagnostic tool for prostate cancer. With that in mind, Norgen Biotek is committed to supporting continued research through its urine exosome kits, including the Urine Exosome RNA Isolation Kit and the Urine Exosome Purification and RNA Isolation Kit. Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis. Racism does not cause prostate cancer, it. Circulating exosomal mRNA profiling identifies novel signatures for the detection of prostate cancer. Unveiling potential: urinary exosomal mRNAs as non-invasive biomarkers for early prostate cancer diagnosis. Norgen Biotek: Advancing science with best-in-class, scientist-backed innovations Norgen Biotek is a fully integrated biotechnology company that focuses on providing complete workflows for molecular biology sample preparation and analysis. With a diverse portfolio of over 600 products, the company delivers high-performance, user-friendly, and cost-effective solutions. Norgen kits cover a broad range of applications from collection and preservation to isolation and purification. Our expert R&D team continuously develops cutting-edge technologies that set new industry standards for RNA, DNA, protein, and exosomal isolation, ensuring superior yield, purity, and integrity from even the most challenging sample types. At the heart of Norgen’s success is its patented Silicon Carbide (SiC) Technology. This proprietary resin exhibits uniform binding affinity for all RNA species, regardless of molecular weight or GC content. This ensures the full diversity of small and microRNA are captured while eliminating the need for phenol extraction. This innovative technology sets Norgen kits apart from others, positioning them as leaders in RNA purification. Norgen is committed to providing high-quality kits capable of processing a wide range of sample types, from ultra-low input samples such as liquid biopsies to highly impure samples like stool or soil. Our sample collection and preservation devices for stool and saliva simplify handling by rendering samples non-infectious by preventing microbial growth and inactivating viruses, while our blood and urine preservation solutions ensure the stability of highly vulnerable cell-free nucleic acids. To meet varying research demands, we offer multiple isolation methods including, but not limited to high-throughput and automation-ready magnetic bead-based formats. Additionally, our multiple-analyte kits enable the simultaneous purification of RNA, DNA, and proteins, maximizing data extraction from a single sample. Norgen offers an extensive variety of TaqMan qPCR kits designed for molecular diagnostic use, including lyophilized kits for easy shipping. Library preparation kits for both DNA and RNA samples are also available to support genomic applications. Norgen recently released their EXTRAClean technology, an innovative solution that minimizes background noise while providing high-purity RNA, significantly enhancing NGS performance. Scientist-Driven Innovation – Developed by leading experts in molecular biology Global Presence – We ship to over 150 countries and have a network of 60+ distributors Innovative Products – Hold more than thirty issued and pending patents for products presenting solutions for all research & clinical applications Driven by a mission to accelerate scientific discoveries, Norgen Biotek actively supports researchers by providing educational resources, technical workshops, and application notes. Their NorBlog serves as a hub for the latest scientific discoveries, protocol optimizations, and industry trends. Explore Norgen Biotek’s innovative solutions today and take your research to the next level. Sponsored Content Policy: News-Medical.net publishes articles and related content that may be derived from sources where we have existing commercial relationships, provided such content adds value to the core editorial ethos of News-Medical.Net which is to educate and inform site visitors interested in medical research, science, medical devices and treatments.

A new review uncovers how common natural supplements can both protect and endanger health, depending on dose, duration, and delivery—and points to next-gen technologies as the key to unlocking their full therapeutic power. Study findings reveal that while all evaluated nutraceuticals provide medically beneficial protective and therapeutic effects, each comes with its own side effects, particularly at higher dosages, highlighting the need for scientifically sound guidelines aimed at managing interactions and enhancing the benefits of nutraceuticals without subjecting patients to their adverse effects. The review further suggests innovations such as nanoencapsulation and AI-guided delivery systems that could help achieve these goals. However, a growing body of literature suggests that when taken out of context (without a prescription) or when consumed at higher dosages or in specific populations, bioactive nutraceuticals may pose medical challenges. “The growing interest in nutraceuticals stems from their potential to address chronic diseases, such as cardiovascular disorders, neurodegenerative conditions, and metabolic syndromes, which are often linked to oxidative stress and inflammation.” Unfortunately, given their relative novelty, the literature remains relatively scarce on the long-term effects of nutraceuticals, particularly their toxicity upon prolonged use, bioavailability, and interactions with conventional medical interventions. The review aims to guide clinicians, policymakers, researchers, and consumers in determining when and how to use nutraceuticals effectively, thereby maximizing their benefits while minimizing potential drawbacks. The review focuses on four widely used nutraceuticals: Resveratrol (RSV), a polyphenolic compound found in grapes and grape products; Curcumin (CUR), a bioactive obtained from turmeric (Curcuma longa); Piperine (PPR), obtained from black pepper; and Quercetin (QUE), a flavonoid found in several fruits and vegetables. Resveratrol may reshape gut bacteria populations, indirectly reducing systemic inflammation—a finding that links dietary habits to chronic disease management. RSV is gaining increasing scientific interest due to its wide-ranging therapeutic benefits, including cardiovascular, metabolic, neurological, pro-apoptotic, and anti-inflammatory. It has even been clinically validated to enhance cognitive function and delay Alzheimer’s disease (AD) progression. Chronobiological differences in RSV administration have also been observed, with some evidence suggesting time-of-day may influence lipid peroxidation and drug metabolism. Curcumin’s effects on thyroid function appear age-dependent, with studies showing altered hormone levels in older adults but minimal impact in younger populations. It also targets several oncological pathways and exhibits significant neuroprotective benefits. CUR’s interference with CVD drugs (e.g., amlodipine) occurs via modulation of CYP3A4 and P-glycoprotein (P-gp) pathways, underscoring the importance of complete health profile assessments before its use. Emerging evidence also notes potential impacts on thyroid hormone levels and reproductive function in animal models, particularly at high doses or via nanoparticle delivery systems. Piperine’s inhibition of the enzyme UDP-glucuronosyltransferase may prolong drug activity—a benefit for therapies but a risk for toxicity with medications like blood thinners. Emerging evidence also links prolonged high-dose PPR to impaired cognitive performance in animal models, highlighting the importance of understanding and educating the target patient before its prolonged consumption. Recent data also indicate tissue-level alterations and potential organ-specific toxicity in rodent models receiving higher doses. By inhibiting drug-metabolizing enzymes (e.g., cytochrome P450, UDP-glucuronosyltransferase) and enhancing intestinal absorption, PPR significantly inhibits P-glycoprotein (P-gp). Quercetin binds to heavy metals like lead and cadmium in lab studies, hinting at its potential as a detoxifying agent alongside its antioxidant properties. QUE is often obtained naturally, derived from the consumption of onions and apples. Its hallmark effects include free radical neutralization, oxidative stress mitigation, and enhancement of cellular integrity, making it a nutraceutical hailed as a potential treatment for cancer, cardiovascular disease (CVD), and aging. High-dose QUE supplements have been linked to pro-oxidant activity and organ damage in preclinical studies. The aglycone form found in supplements exhibits greater bioavailability but also a higher likelihood of interacting with drug-metabolizing enzymes and transporters. It further suggests emerging technologies, such as nanoencapsulation, to improve targeted delivery and bioavailability of these nutraceuticals, reducing off-target toxicity and ensuring that these bioactives reach their target organs or tissues, thereby maximizing their benefits and mitigating their costs. Additional innovations discussed include in silico molecular docking to predict drug-target interactions, nutrigenomic tools for personalizing interventions, and the Nutraceutical Interaction Risk Score (NIRS) to stratify patients by potential toxicity. “…while nutraceuticals represent a valuable tool in promoting health and preventing disease, their full potential can only be realized through rigorous scientific research, personalized dosing strategies, and a comprehensive understanding of both their benefits and potential risks. The investigational integration of nanotechnology and smart materials has emerged as a transformative approach to enhance the efficacy and safety of nutraceuticals.”

Swedish researchers have identified genetic variants that increase the risk of atherosclerosis. The aim is for these new findings to enable earlier detection of atherosclerosis and improved treatment of cardiovascular diseases such as heart attack and stroke. These accumulations of plaque grow over time and can form clots that cause a sudden stop in the blood supply. What sets SCAPIS apart is the highly detailed measurements of atherosclerosis using advanced diagnostic imaging, including both computed tomography and ultrasound. Twenty genetic variants were found to have a statistically significant association. When the coronary and carotid results were compared, several differences emerged, suggesting different underlying disease mechanisms. The lead researcher in the study is Anders Gummesson, Associate Professor of Molecular Medicine at the University of Gothenburg and Senior Physician in Clinical Genetics at Sahlgrenska University Hospital: We also hope to develop genetic tests to identify people at high risk of being affected," he explains. For many of those who suffer a heart attack or stroke, it comes without warning. Cardiovascular disease is the leading cause of death in Sweden and most other countries. The results provide us with important knowledge, and the entire dataset, containing results from millions of genetic variants, will be available to other researchers around the world to use in their research." Anders Gummesson, Associate Professor of Molecular Medicine at the University of Gothenburg and Senior Physician in Clinical Genetics at Sahlgrenska University Hospital SCAPIS (Swedish CArdioPulmonary BioImage Study) is led and conducted by six universities and six university hospitals across Sweden, in close collaboration with the Swedish Heart Lung Foundation, which is the main funder.

insights from industry Karl Box Chief Scientific Officer Pion Can you tell us about Pion’s Rainbow Dynamic Dissolution Monitor? The Rainbow Dynamic Dissolution Monitor is Pion's flagship product, a fiber optic UV spectrometer designed to integrate with various dissolution and permeation tools, both from Pion and other manufacturers. It comprises up to eight fiber optic probes that can be inserted into measurement vessels. Eliminating the need to remove samples for offline analysis provides real-time insights. The system typically captures data every 30 seconds, offering detailed information about a sample's behavior. How does the Rainbow Dynamic Dissolution Monitor integrate with Pion’s Dissolution-Absorption tools for assessing drug performance? For example, in early development, the MicroFLUXTM system uses Rainbow probes to measure drug permeability across a membrane separating donor and acceptor compartments. As we scale up to clinical development, tools like the MiniFLUX, BioFLUXTM, and MacroFLUXTM come into play. Can you explain the concept of particle drift and its impact on drug absorption? Numerous studies show that when an Active Pharmaceutical Ingredient (API) dose exceeds the intestinal solubility limits, oral absorption can increase more than expected. This suggests that undissolved particles can significantly influence the absorption process in vivo even when solubility is limited. This can lead to an increase in drug permeability, enabling enhanced absorption. This was a collaboration with Nanoform in Finland, and the work was first presented at the Controlled Release Society annual meeting in 2023. Experiments were conducted in pH5 acetate buffer at various drug loadings on the donor side. Flux was measured across Pion’s gastrointestinal tract membrane into acceptor sink buffer in the receiver. The results demonstrated a clear impact of particle size on Flux. We quantified how particle drift contributed to the total in vitro Flux, which has broader implications useful for the development of enabling formulations. The study highlights how reducing particle size not only improves dissolution rates but can also enhance drug permeability, particularly for compounds where the unstirred water layer permeability limits absorption. Particle size reduction can improve overall drug absorption in these cases. What are the implications of these findings for biopharmaceutical modeling and in vivo absorption? The findings have significant implications for both biopharmaceutical modeling and in vivo absorption. The human intestine’s large surface area is crucial in drug absorption. Related Stories Insights into drug absorption and predictive modeling with Professor Kiyohiko Sugano This is a game-changer because properly designed in vitro Flux assays allow scientists to estimate the relative improvement on in vivo absorption from nanosize reduction. Pion’s new PredictorTM software program is designed to handle data from Pion’s Rainbow instrument and enables the translation of in vitro results into in vivo-relevant predictions. These include correcting for in vivo absorption barrier properties such as unstirred water layer thickness, scaling the results based on the drug’s permeability and available intestinal surface area, accounting for dose clearance differences between in vitro and in vivo systems, and making necessary adjustments for intestinal transit time. Pion PredictorTM software uses the GUT framework to help model drug absorption. How can in vitro Flux be used within this framework? The Gastrointestinal Unified Theoretical (GUT) framework, as outlined in Kiyohiko Sugano’s book “Biopharmaceutical Modelling and Simulations: Theory, Practice, Method and Applications” published by Wiley in 2012, consists of a system of equations that model key processes such as dissolution, precipitation, and absorption. This framework requires input parameters, including specific measured physicochemical properties and constants, to make accurate predictions. While the equations may appear complex, an interesting aspect of this model is that in vitro Flux can serve as a surrogate for many of the dissolution and permeation processes involved. Using Flux results obtained from Pion’s Flux assays, many of the equations governing dissolution and permeation in the GUT framework can be replaced. Another case study was conducted in collaboration with researchers at Ritsumeikan University. How do the Celecox Flux assays' results demonstrate particle drift's impact on oral drug absorption prediction? Another study collaborated with Shiori Ishida and Kiyo Sugano at Ritsumeikan University in Japan. The marketed formulation, Celecox, contains a high percentage of nanosized particles, which can influence its pharmacokinetics. Our study, initially presented at the AAPS annual meeting in 2023, explored how these nanosized particles affect drug absorption. This adjustment makes predictions more aligned with published human oral fraction absorbed data. The comparison of predicted fraction absorbed values shows that ignoring particle drift results in increasingly inaccurate estimations at higher doses. This study demonstrates that Flux data can be used to estimate the absolute in vivo fraction of drug absorbed, determine the contribution of particle drift to the total Flux value, and adjust for its impact when scaling to in vivo conditions. Karl Box was appointed as the Chief Scientific Officer (Europe) at Pion (UK) in 2020. His expertise is in the field of physicochemical measurements, where he has forged a successful career in the development of new instrumentation and assays for supporting drug discovery and development. When data matters we apply out of the box problem solving abilities to help you reach a confident conclusion on your drug characterization challenges. Later in development, high-pressure homogenizers enable particle size reduction and ensure material consistency from bench- to production-scale.