Bioprinted 3D outer retina barrier uncovers RPE-dependent choroidal phenotype in advanced macular degeneration.

Age-related macular degeneration (AMD), a leading cause of blindness, initiates in the outer-blood-retina-barrier (oBRB) formed by the retinal pigment epithelium (RPE), Bruch's membrane, and choriocapillaris. The mechanisms of AMD initiation and progression remain poorly understood owing to the lack of physiologically relevant human oBRB models. To this end, we engineered a native-like three-dimensional (3D) oBRB tissue (3D-oBRB) by bioprinting endothelial cells, pericytes, and fibroblasts on the basal side of a biodegradable scaffold and establishing an RPE monolayer on top. In this 3D-oBRB model, a fully-polarized RPE monolayer provides barrier resistance, induces choriocapillaris fenestration, and supports the formation of Bruch's-membrane-like structure by inducing changes in gene expression in cells of the choroid. Complement activation in the 3D-oBRB triggers dry AMD phenotypes (including subRPE lipid-rich deposits called drusen and choriocapillaris degeneration), and HIF-α stabilization or STAT3 overactivation induce choriocapillaris neovascularization and type-I wet AMD phenotype. The 3D-oBRB provides a physiologically relevant model to studying RPE-choriocapillaris interactions under healthy and diseased conditions.

Single-cell-resolution map of human retinal pigment epithelium helps discover subpopulations with differential disease sensitivity.

Regional phenotypic and functional differences in the retinal pigment epithelium (RPE) monolayer have been suggested to account for regional susceptibility in ocular diseases such as age-related macular degeneration (AMD), late-onset retinal degeneration (L-ORD), and choroideremia (CHM). However, a comprehensive description of human topographical RPE diversity is not yet available, thus limiting the understanding of regional RPE diversity and degenerative disease sensitivity in the eye. To develop a complete morphometric RPE map of the human eye, artificial intelligence­based software was trained to recognize, segment, and analyze RPE borders. Five statistically different, concentric RPE subpopulations (P1 to P5) were identified using cell area as a parameter, including a subpopulation (P4) with cell area comparable to that of macular cells in the far periphery of the eye. This work provides a complete reference map of human RPE subpopulations and their location in the eye. In addition, the analysis of cadaver non-AMD and AMD eyes and ultra-widefield fundus images of patients revealed differential vulnerability of the five RPE subpopulations to different retinal diseases.

1D-Guided Differential Rescaling of a Contour Plot in Comprehensive 2D Gas Chromatography.

A 1D-guided differential rescaling algorithm for a contour plot is developed based on our recently proposed comprehensive two-dimensional gas chromatography (GC × GC) system with a first-dimensional (1D) detector added. Chromatograms obtained from 1D and second-dimensional (2D) detectors are both incorporated during the data processing. As compared to the conventional contour plot methods using only 2D data, our algorithm can significantly improve precision and consistency of GC × GC results in terms of retention times, peak widths, and peak areas or volumes, regardless of modulation time selection, modulation phase shift fluctuations, and modulation duty cycle. The peak identification, quantification, and capacity can therefore be enhanced. Furthermore, the 1D-guided differential rescaling method is shown to better handle the coelution and missing peak issues often encountered in the conventional methods. Finally, the new method exhibits high versatility in 1D and 2D detector selection, which greatly broadens GC × GC utility. Our method can easily be adapted to other two-dimensional chromatography systems that have direct access to 1D chromatograms.

Modeling the neuroimmune system in Alzheimer's and Parkinson's diseases.

Parkinson's disease (PD) and Alzheimer's disease (AD) are neurodegenerative disorders caused by the interaction of genetic, environmental, and familial factors. These diseases have distinct pathologies and symptoms that are linked to specific cell populations in the brain. Notably, the immune system has been implicated in both diseases, with a particular focus on the dysfunction of microglia, the brain's resident immune cells, contributing to neuronal loss and exacerbating symptoms. Researchers use models of the neuroimmune system to gain a deeper understanding of the physiological and biological aspects of these neurodegenerative diseases and how they progress. Several in vitro and in vivo models, including 2D cultures and animal models, have been utilized. Recently, advancements have been made in optimizing these existing models and developing 3D models and organ-on-a-chip systems, holding tremendous promise in accurately mimicking the intricate intracellular environment. As a result, these models represent a crucial breakthrough in the transformation of current treatments for PD and AD by offering potential for conducting long-term disease-based modeling for therapeutic testing, reducing reliance on animal models, and significantly improving cell viability compared to conventional 2D models. The application of 3D and organ-on-a-chip models in neurodegenerative disease research marks a prosperous step forward, providing a more realistic representation of the complex interactions within the neuroimmune system. Ultimately, these refined models of the neuroimmune system aim to aid in the quest to combat and mitigate the impact of debilitating neuroimmune diseases on patients and their families.

Serum hepcidin levels in chronic liver disease: a systematic review and meta-analysis.

OBJECTIVES: Dysregulation of hepcidin-iron axis is presumed to account for abnormal iron status in patients with chronic liver disease (CLD). Our aim is to determine the effect of specific etiologies of CLD and of cirrhosis on serum hepcidin levels. METHODS: PubMed, Embase, Web of Science were searched for studies comparing serum hepcidin levels in patients with CLD to that in controls using enzyme-linked immunosorbent assay. The study was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Guidelines. Statistical analysis was carried out with STATA using random effects model to calculate the mean difference (MD) between two groups. RESULTS: Hepcidin levels were significantly lower in subjects with hepatitis C virus (16 studies) [MD -1.6 (95 % CI: -2.66 to -0.54), p<0.01] and alcoholic liver disease (3 studies) [MD -0.84 (95 % CI: -1.6 to -0.07), p=0.03] than controls. Serum hepcidin was significantly higher in subjects with non-alcoholic fatty liver disease (12 studies) [MD 0.62 (95 % CI: 0.21 to 1.03), p<0.01], but did not differ in subjects with hepatitis B and controls (eight studies) [MD -0.65 (95 % CI: -1.47 to 0.16), p=0.12]. Hepcidin levels were significantly lower in patients with cirrhosis of any etiology (four studies) [MD -1.02 (CI: -1.59 to -0.45), p<0.01] vs. controls (CI: confidence interval). CONCLUSIONS: Serum hepcidin levels are altered in common forms of CLD albeit not in a consistent direction. Additional study is needed to determine how changes in hepcidin levels are related to dysregulation of iron metabolism in CLD.

Colorectal Cancer Diagnosis through Breath Test Using a Portable Breath Analyzer-Preliminary Data.

Screening methods available for colorectal cancer (CRC) to date are burdened by poor reliability and low patient adherence and compliance. An altered pattern of volatile organic compounds (VOCs) in exhaled breath has been proposed as a non-invasive potential diagnostic tool for distinguishing CRC patients from healthy controls (HC). The aim of this study was to evaluate the reliability of an innovative portable device containing a micro-gas chromatograph in enabling rapid, on-site CRC diagnosis through analysis of patients' exhaled breath. In this prospective trial, breath samples were collected in a tertiary referral center of colorectal surgery, and analysis of the chromatograms was performed by the Biomedical Engineering Department. The breath of patients with CRC and HC was collected into Tedlar bags through a Nafion filter and mouthpiece with a one-way valve. The breath samples were analyzed by an automated portable gas chromatography device. Relevant volatile biomarkers and discriminant chromatographic peaks were identified through machine learning, linear discriminant analysis and principal component analysis. A total of 68 subjects, 36 patients affected by histologically proven CRC with no evidence of metastases and 32 HC with negative colonoscopies, were enrolled. After testing a training set (18 CRC and 18 HC) and a testing set (18 CRC and 14 HC), an overall specificity of 87.5%, sensitivity of 94.4% and accuracy of 91.2% in identifying CRC patients was found based on three VOCs. Breath biopsy may represent a promising non-invasive method of discriminating CRC patients from HC.

A biologically validated mathematical model for decoding epithelial apical, basolateral, and paracellular electrical properties.

Epithelial tissues form selective barriers to ions, nutrients, waste products, and infectious agents throughout the body. Damage to these barriers is associated with conditions such as celiac disease, cystic fibrosis, diabetes, and age-related macular degeneration. Conventional electrophysiology measurements like transepithelial resistance can quantify epithelial tissue maturity and barrier integrity but are limited in differentiating between apical, basolateral, and paracellular transport pathways. To overcome this limitation, a combination of mathematical modeling, stem cell biology, and cell physiology led to the development of 3 P-EIS, a novel mathematical model and measurement technique. 3 P-EIS employs an intracellular pipette and extracellular electrochemical impedance spectroscopy to accurately measure membrane-specific properties of epithelia, without the constraints of prior models. 3 P-EIS was validated using electronic circuit models of epithelia with known resistances and capacitances, confirming a median error of 19% (interquartile range: 14%-26%) for paracellular and transcellular resistances and capacitances (n = 5). Patient stem cell-derived retinal pigment epithelium tissues were measured using 3 P-EIS, successfully isolating the cellular responses to adenosine triphosphate. 3 P-EIS enhances quality control in epithelial cell therapies and has extensive applicability in drug testing and disease modeling, marking a significant advance in epithelial physiology.NEW & NOTEWORTHY This interdisciplinary paper integrates mathematics, biology, and physiology to measure epithelial tissue's apical, basolateral, and paracellular transport pathways. A key advancement is the inclusion of intracellular voltage recordings using a sharp pipette, enabling precise quantification of relative impedance changes between apical and basolateral membranes. This enhanced electrochemical impedance spectroscopy technique offers insights into epithelial transport dynamics, advancing disease understanding, drug interactions, and cell therapies. Its broad applicability contributes significantly to epithelial physiology research.

Retinal Pigment Epithelium Replacement Therapy for Age-Related Macular Degeneration: Are We There Yet?

Pluripotent stem cells (PSCs) are a potential replacement tissue source for degenerative diseases. Age-related macular degeneration (AMD) is a blinding disease triggered by degeneration of the retinal pigment epithelium (RPE), a monolayer tissue that functionally supports retinal photoreceptors. Recently published clinical and preclinical studies have tested PSC-derived RPE as a potential treatment for AMD. Multiple approaches have been used to manufacture RPE cells, to validate them functionally, to confirm their safety profile, and to deliver them to patients either as suspension or as a monolayer patch. Since most of these studies are at an early regulatory approval stage, the primary outcome has been to determine the safety of RPE transplants in patients. However, preliminary signs of efficacy were observed in a few patients. Here, we review the current progress in the PSC-derived RPE transplantation field and provide a comparative assessment of various approaches under development as potential therapeutics for AMD.

Ultrathin Silica Integration for Enhancing Reliability of Microfluidic Photoionization Detectors.

Microfluidic photoionization detectors (µPIDs) based on silicon chips can rapidly and sensitively detect volatile compounds. However, the applications of µPID are limited by the manual assembly process using glue, which may outgas and clog the fluidic channel, and by the short lifetime of the vacuum ultraviolet (VUV) lamps (especially, argon lamps). Here, we developed a gold-gold cold welding-based microfabrication process to integrate ultrathin (10 nm) silica into µPID. The silica coating enables direct bonding of the VUV window to silicon under amicable conditions and works as a moisture and plasma exposure barrier for VUV windows that are susceptible to hygroscopicity and solarization. Detailed characterization of the silica coating was conducted, showing that the 10 nm silica coating allows 40-80% VUV transmission from 8.5 to 11.5 eV. It is further shown that the silica-protected µPID maintained 90% of its original sensitivity after 2200 h of exposure to ambient (dew point = 8.0 ± 1.8 °C), compared to 39% without silica. Furthermore, argon plasma inside an argon VUV lamp was identified as the dominant degradation source for the LiF window with color centers formation in UV-vis and VUV transmission spectra. Ultrathin silica was then also demonstrated effective in protecting the LiF from argon plasma exposure. Lastly, thermal annealing was found to bleach the color centers and restore VUV transmission of degraded LiF windows effectively, which will lead to future development of a new type of VUV lamp and the corresponding µPID (and PID in general) that can be mass produced with a high yield, a longer lifetime, and better regenerability.

Apoptin NLS2 homodimerization strategy for improved antibacterial activity and bio-stability.

The emergence of antibiotic resistance prompts exploration of viable antimicrobial peptides (AMPs) designs. The present study explores the antimicrobial prospects of Apoptin nuclear localization sequence (NLS2)-derived peptide ANLP (PRPRTAKRRIRL). Further, we examined the utility of the NLS dimerization strategy for improvement in antimicrobial activity and sustained bio-stability of AMPs. Initially, the antimicrobial potential of ANLP using antimicrobial peptide databases was analyzed. Then, ANLP along with its two homodimer variants namely ANLP-K1 and ANLP-K2 were synthesized and evaluated for antimicrobial activity against Escherichia coli and Salmonella. Among three AMPs, ANLP-K2 showed efficient antibacterial activity with 12 µM minimum inhibitory concentration (MIC). Slow degradation of ANLP-K1 (26.48%) and ANLP-K2 (13.21%) compared with linear ANLP (52.33%) at 480 min in serum stability assay indicates improved bio-stability of dimeric peptides. The AMPs presented no cytotoxicity in Vero cells. Dye penetration assays confirmed the membrane interacting nature of AMPs. The zeta potential analysis reveals effective charge neutralization of both lipopolysaccharide (LPS) and bacterial cells by dimeric AMPs. The dimeric AMPs on scanning electron microscopy studies showed multiple pore formations on the bacterial surface. Collectively, proposed Lysine scaffold dimerization of Apoptin NLS2 strategy resulted in enhancing antibacterial activity, bio-stability, and could be effective in neutralizing the off-target effect of LPS. In conclusion, these results suggest that nuclear localization sequence with a modified dimeric approach could represent a rich source of template for designing future antimicrobial peptides.

Recent advances in the concept of paraprobiotics: Nutraceutical/functional properties for promoting children health.

Probiotics consumption has been associated with various health promoting benefits, including disease prevention and even treatment by modulating gut microbiota. Contrary to this, probiotics may also overstimulate the immune system, trigger systemic infections, harmful metabolic activities, and promote gene transfer. In children, the fragile immune system and impaired intestinal barrier may boost the occurrence of adverse effects following probiotics' consumption. To overcome these health challenges, the key focus has been shifted toward non-viable probiotics, also called paraprobiotics. Cell wall polysaccharides, peptidoglycans, surface proteins and teichoic acid present on cell's surface are involved in the interaction of paraprobiotics with the host, ultimately providing health benefits. Among other benefits, paraprobiotics possess the ability to regulate innate and adaptive immunity, exert anti-adhesion, anti-biofilm, anti-hypertensive, anti-inflammatory, antioxidant, anti-proliferative, and antagonistic effects against pathogens, while also enhance clinical impact and general safety when administered in children in comparison to probiotics. Clinical evidence have underlined the paraprobiotics impact in children and young infants against atopic dermatitis, respiratory and gastrointestinal infections, in addition to be useful for immunocompromised individuals. Therefore, this review focuses on probiotics-related issues in children's health and also discusses the Lactobacillus and Bifidobacterium spp. qualities for qualifying as paraprobiotics and their role in promoting the children's health.

Advances in the concept of functional foods and feeds: applications of cinnamon and turmeric as functional enrichment ingredients.

Spices are a rich source of vitamins, polyphenols, proteins, dietary fiber, and minerals such as calcium, magnesium, iron, and zinc, all of which play an important role in biological functions. Since ancient times, spices have been used in our kitchen as a food coloring agent. Spices like cinnamon and turmeric allegedly contain various functional ingredients, such as phenolic and volatile compounds. Therefore, this review aims to summarize the current knowledge about the nutritional profiles of cinnamon and turmeric, as well as to analyze the clinical studies on their extracts and essential oils in animals and humans. Furthermore, their enrichment applications for food products and animal feed have also been investigated in terms of safety and toxicity. Numerous studies have shown that cinnamon and turmeric have various health benefits, including the reduction of insulin resistance and insulin signaling pathways in diabetic patients, the reduction of inflammatory biomarkers, and the maintenance of gut microflora in both animals and humans. The food and animal feed industries have taken notice of these health benefits and have begun to promote cinnamon and turmeric as healthy foods. This has resulted in the development of new food products and animal feeds that contain cinnamon and turmeric as primary ingredients, which have been deemed an effective means of promoting cinnamon and turmeric's health benefits.

Non-edible fruit seeds: nutritional profile, clinical aspects, and enrichment in functional foods and feeds.

Nowadays, fruits are gaining high demand due to their promising advantages on human health. Astonishingly, their by-products, that is, seeds and peels, account for 10-35% of fruit weight and are usually thrown as waste after consumption or processing. But it is neglected that fruit seeds also have functional properties and nutritional value, and thus could be utilized for dietary and therapeutic purposes, ultimately reducing the waste burden on the environment. Owing to these benefits, researchers have started to assess the nutritional value of different fruits seeds, in addition to the chemical composition in various bioactive constituents, like carotenoids (lycopene), flavonoids, proteins (bioactive peptides), vitamins, etc., that have substantial health benefits and can be used in formulating different types of food products with noteworthy functional and nutraceutical potential. The current review aims to comprehend the known information of nutritional and phytochemical profiling of non-edible fruits seeds, viz. apple, apricot, avocado, cherry, date, jamun, litchi, longan, mango, and papaya. Additionally, clinical studies conducted on these selected non-edible fruit seed extracts, their safety issues and their enrichment in food products as well as animal feed has also been discussed. This review aims to highlight the potential applications of the non-edible fruit seeds in developing new food products and also provide a viable alternative to reduce the waste disposal issue faced by agro-based industries.

Photoinduced Alkyl/Aryl Radical Cascade for the Synthesis of Quaternary CF3-Containing Oxindoles and Indoline Alkaloids.

Metal- and additive-free, photoinduced decarboxylative radical alkylation-cyclization of CF3-acrylamides with alkyl redox-active esters provided the corresponding quaternary CF3-oxindole derivatives in good yields. Notably, diaryliodonium salts also efficiently participated in the arylation-cyclization of CF3-acrylamides in environmentally benign H2O as a solvent. The present approach has been extended for the concise synthesis of CF3-attached indoline alkaloid analogues, i.e., CF3-(±)-desoxyeseroline, CF3-(±)-esermethole, and CF3-(±) progesterone receptor antagonists. The preliminary mechanistic studies revealed that the reaction is likely to proceed through initial photoexcitation of redox-active ester/diaryliodonium salts followed by the SET process with acrylamide.

Leveraging multiomics approaches for producing lignocellulose degrading enzymes.

Lignocellulosic materials form the building block of 50% of plant biomass comprising non-chewable agri-components like wheat straw, rice stubbles, wood shavings and other crop residues. The degradation of lignin, cellulose and hemicellulose is complicated and presently being done by chemical process for industrial application through a very energy intensive process. Lignin degradation is primarily an oxidative process where the enzyme lignin peroxidase digests the polymer into smaller fragments. Being a recalcitrant component, higher lignin content poses a challenge of lower recovery of product for industrial use. Globally, the scientists are working on leveraging fungal biotechnology for using the lignocellulose degrading enzymes secreted by actinomycetes and basidiomycetes fungal groups. Enzymes contributing to degradation of lignin are mainly performing the function of modifying the lignin and degrading the lignin. Ligninolytic enzymes do not act as an independent reaction but are vital to complete the degradation process. Microbial enzyme technology is an emerging green tool in industrial biotechnology for commercial application. Bioprocessing of lignocellulosic biomass is challenged by limitations in enzymatic and conversion process where pretreatment and separation steps are done to remove lignin and hydrolyze carbohydrate into fermentable sugars. This review highlights recent advances in molecular biotechnology, lignin valorization, sequencing, decipher microbial membership, and characterize enzyme diversity through 'omics' techniques. Emerging techniques to characterize the interwoven metabolism and spatial interactions between anaerobes are also reviewed, which will prove critical to developing a predictive understanding of anaerobic communities to guide in microbiome engineering This requires more synergistic collaborations from microbial biotechnologists, bioprocess engineers, enzymologists, and other biotechnological fields.

A thorny matter: Spur cell anemia.

Spur cell anemia (SCA) is an acquired form of non-autoimmune hemolytic anemia that occurs in advanced liver disease. It is characterized by the presence of acanthocytes or spur cells, spiculated erythrocytes whose shortened life span causes anemia that is unresponsive to transfusion. SCA has been regarded as a rare condition with an ominous prognosis for which the only known cure is liver transplantation, but recent prospective studies have demonstrated the existence of a milder form of SCA in which there are smaller numbers of acanthocytes, but which is nevertheless associated with hemolysis and poor outcomes. This form of SCA appears to be considerably more common than the severe classical variant. The conventional understanding of the pathogenesis of SCA is that abnormalities of lipid metabolism are the primary event driving the formation of spur cells. However, the studies that underpin this theory are based on small numbers of patients with heterogeneous clinical features and inconsistent use of nomenclature for dysmorphic red blood cells. In this review, we discuss the evolution of the current understanding of SCA and therapeutic strategies that have been employed based on this understanding. Our goal is to raise awareness of this understudied condition that has significant implications for patient outcomes. Furthermore, we highlight the need for rigorous, contemporary research into the underlying cause or causes of SCA in order to develop an effective therapy for this disorder.

Retention Time Trajectory Matching for Peak Identification in Chromatographic Analysis.

Retention time drift caused by fluctuations in physical factors such as temperature ramping rate and carrier gas flow rate is ubiquitous in chromatographic measurements. Proper peak matching and identification across different chromatograms is critical prior to any subsequent analysis but is challenging without using mass spectrometry. The purpose of this work was to describe and validate a peak matching and identification method called retention time trajectory (RTT) matching that can be used in targeted analyses free of mass spectrometry. This method uses chromatographic retention times as the only input and identifies peaks associated with any subset of a predefined set of target compounds. An RTT is a two-dimensional (2D) curve formed uniquely by the retention times of the chromatographic peaks. The RTTs obtained from the chromatogram of a sample under test and those pre-installed in a library are matched and statistically compared. The best matched pair implies identification. Unlike most existing peak-alignment methods, no mathematical warping or transformation is involved. Based on the experimentally characterized RTT, an RTT hybridization method was also developed to rapidly generate more RTTs and expand the library without performing actual time-consuming chromatographic measurements, which enables successful peak matching even for chromatograms with severe retention time drifts. Additionally, 3.15 × 105 tests using experimentally obtained gas chromatograms and 2 × 1012 tests using two publicly available fruit metabolomics datasets validated the proposed method, demonstrating real-time peak/interferent identification.

Barley-based probiotic food mixture: health effects and future prospects.

Consumers around the globe are increasingly aware of the relation between nutrition and health. In this sense, food products that can improve gastrointestinal health such as probiotics, prebiotics and synbiotics are the most important segment within functional foods. Cereals are the potential substrates for probiotic products as they contain nutrients easily assimilated by probiotics and serve as the transporters of Lactobacilli through the severe conditions of gastrointestinal tract. Barley is one of the important substrates for the probiotic formulation because of its high phenolic compounds, ß-glucans and tocols. The purpose of this review is to examine recent information regarding barley-based probiotic foods with a specific focus on the potential benefits of barley as a substrate for probiotic microorganisms in the development of dairy and nondairy based food products, and to study the effects of food matrices containing barley ß-glucans on the growth and features of Lactobacillus strains after fermentation.

Photo- and Electrocatalytic Reduction of CO2 over Metal-Organic Frameworks and Their Derived Oxides: A Correlation of the Reaction Mechanism with the Electronic Structure.

A Ce/Ti-based bimetallic 2-aminoterephthalate metal-organic framework (MOF) was synthesized and evaluated for photocatalytic reduction of CO2 in comparison with an isoreticular pristine monometallic Ce-terephthalate MOF. Owing to highly selective CO2 adsorption capability, optimized band gaps, higher flux of photogenerated electron-hole pairs, and a lower rate of recombination, this material exhibited better photocatalytic reduction of CO2 and lower hydrogen evolution compared to Ce-terephthalate. Thorough probing of the surface and electronic structure inferred that the reducibility of Ce4+ to Ce3+ was due to the introduction of an amine functional group into the linker, and low-lying Ti(3d) orbitals in Ce/Ti-2-aminoterephthalate facilitated the photoreduction reaction. Both the MOFs were calcined to their respective oxides of Ce1-xTixO2 and CeO2, and the electrocatalytic reduction of CO2 was performed over the oxidic materials. In contrast to the photocatalytic reaction mechanism, the lattice substitution of Ti in the CeO2 fluorite cubic structure showed a better hydrogen evolution reaction and consequently, poorer electroreduction of CO2 compared to pristine CeO2. Density functional theory calculations of the competitive hydrogen evolution reaction on the MOF and the oxide surfaces corroborated the experimental findings.

Phyto-Enrichment of Yogurt to Control Hypercholesterolemia: A Functional Approach.

Cholesterol is essential for normal human health, but elevations in its serum levels have led to the development of various complications, including hypercholesterolemia (HC). Cholesterol accumulation in blood circulation formsplaques on artery walls and worsens the individuals' health. To overcome this complication, different pharmacological and non-pharmacological approaches are employed to reduce elevated blood cholesterol levels. Atorvastatin and rosuvastatin are the most commonly used drugs, but their prolonged use leads to several acute side effects. In recent decades, the potential benefit of ingesting yogurt on lipid profile has attracted the interest of researchers and medical professionals worldwide. This review aims to give an overview of the current knowledge about HC and the different therapeutic approaches. It also discusses the health benefits of yogurt consumption and highlights the overlooked phyto-enrichment option to enhance the yogurt's quality. Finally, clinical studies using different phyto-enriched yogurts for HC management are also reviewed. Yogurt has a rich nutritional value, but its processing degrades the content of minerals, vitamins, and other vital constituents with beneficial health effects. The option of enriching yogurt with phytoconstituents has drawn a lot of attention. Different pre-clinical and clinical studies have provided new insights on their benefits on gut microbiota and human health. Thus, the yogurtphyto-enrichment with stanol and ß-glucan have opened new paths in functional food industries and found healthy andeffective alternatives for HC all along with conventional treatment approaches.