Molecular Mechanisms of Metabolic Syndrome.

Metabolic syndrome represents a cluster of conditions, such as abdominal obesity, hypertension, dyslipidemia, and hyperglycemia, that are highly prevalent in developed countries because of unhealthy lifestyles [...].

Exploring the Metabolic and Endocrine Preconditioning Associated with Thyroid Disorders: Risk Assessment and Association with Acne Severity.

Metabolic preconditioning, characterized by conditions like obesity and insulin resistance syndrome, disrupts hormonal balance. Elevated androgen levels stimulate excessive sebum production and follicular cell proliferation, leading to acne lesions. Similarly, thyroid hormone imbalances affect sebaceous gland activity, epidermal lipid composition, and skin cell turnover, impacting acne occurrence and severity. This study aimed to assess the potential contribution of metabolic and endocrine preconditions to acne development. A total of 389 patients diagnosed with acne were included and divided into three groups: the metabolic precondition group (MPG, N = 163, 41.9%), the endocrine precondition group (EPG, N = 162, 41.65%), and the control group (CG, N = 89, 22.88%). Data related to the degree of acne severity and comorbidities of interest were collected from the patients' medical records. In the groups with concomitant diseases, moderate and severe acne were significantly more prevalent (56.44% and 41.10% in MPG, and 35.80% and 61.11% in EPG) compared to the control group (5.61% and 4.89%). The most prevalent preconditions observed were insulin resistance syndrome in MPG (63.8%) and autoimmune thyroiditis in EPG (95.06%). Significant age-related differences in acne severity were found across all study groups (p < 0.05). In MPG, the age variable was significantly higher in the presence of mild acne, while in EPG, the age variable was significantly lower for the mild acne group. A positive association was observed between the severity of acne and insulin resistance syndrome, obesity, autoimmune thyroiditis, and hypothyroidism (p < 0.05). Risk analysis indicated a significantly higher risk (RR > 1, 95% CI RR > 1, p < 0.001) of developing moderate and severe acne in the presence of these preconditions. The presence of both metabolic and endocrine preconditions significantly increased the likelihood of developing severe acne, leading to the hypothesis that both conditions may be contributing factors to the development of acne.

Clinical Implications of Dietary Probiotic Supplement (Associated with L-Glutamine and Biotin) in Ulcerative Colitis Patients' Body Composition and Quality of Life.

Patients with ulcerative colitis (UC) are reported to have changes in body structure, with negative impact on the course of disease. This study explored the effects of a standardized nutritional supplement containing five bacterial strains of at least five billion bacteria (Bifidobacterium infantis, Bifidobacterium animalis, Lactobacillus bulgaricus, Lactobacillus helveticus, and Enterococcus faecium), L-glutamine, and biotin on the body composition and quality of life of patients with UC. Ninety-three patients over 18 years of age with a confirmed diagnosis of UC, for whom body composition could be accurately determined, were included in this observational follow-up randomized study. These patients were split into two groups: UC-P (44 patients with dietary counselling and supplement with probiotics) and UC-NP (49 patients with dietary counselling, without supplement). Body composition was assessed using the multifrequency bioelectrical impedance device, and the quality of life related to UC was evaluated by applying the short inflammatory bowel disease questionnaire (SIBDQ). The results showed that the average value of muscular mass (MM) and sarcopenic index (SMI) significantly increased (p = 0.043, respectively, p = 0.001) and a large fraction (p = 0.001) of patients had their SMI levels normalized in the UC-P group compared with UC-NP group. The extracellular water to total body water ratio (ECW/TBW) also had significantly different mean values (p = 0.022), favoring the UC-P group. By testing the differences between the average values of body composition parameters before and after treatment, we obtained significant results in body mass index (BMI) (p = 0.046), fat free mass (FFM) (p < 0.001), and ECW/TBW ratio (p = 0.048). The SIBDQ total score increased significantly (p < 0.001) in the UC-P group and was more strongly associated with changes in body parameters. Supplementation with probiotics associated with L-glutamine and biotin can improve body composition parameters, which in turn implies an increase in the overall quality of life of patients with UC.

In Vitro Studies Regarding the Effect of Cellulose Acetate-Based Composite Coatings on the Functional Properties of the Biodegradable Mg3Nd Alloys.

Magnesium (Mg) alloys are adequate materials for orthopedic and maxilo-facial implants due to their biocompatibility, good mechanical properties closely related to the hard tissues, and processability. Their main drawbacks are the high-speed corrosion process and hydrogen release. In order to improve corrosion and mechanical properties, the Mg matrix can be strengthened through alloying elements with high temperature-dependent solubility materials. Rare earth elements (RE) contribute to mechanical properties and degradation improvement. Another possibility to reduce the corrosion rate of Mg-based alloys was demonstrated to be the different types of coatings (bioceramics, polymers, and composites) applied on their surface. The present investigation is related to the coating of two Mg-based alloys from the system Mg3Nd (Mg-Nd-Y-Zr-Zn) with polymeric-based composite coatings made from cellulose acetate (CA) combined with two fillers, respectively hydroxyapatite (HAp) and Mg particles. The main functions of the coatings are to reduce the biodegradation rate and to modify the surface properties in order to increase osteointegration. Firstly, the microstructural features of the experimental Mg3Nd alloys were revealed by optical microscopy and scanning electron microscopy (SEM) coupled with energy-dispersive spectroscopy. Apart from the surface morphology revealed by SEM, the roughness and wettability of all experimental samples were evaluated. The corrosion behavior of the uncoated and coated samples of both Mg3Nd alloys was investigated by immersion testing and electrochemical testing using Simulated Body Fluid as the medium. The complex in vitro research performed highlights that the composite coating based on CA with HAp particles exhibited the best protective effect for both Mg3Nd alloys.

Antioxidant and Hypoglycemic Potential of Essential Oils in Diabetes Mellitus and Its Complications.

Since the earliest times, essential oils (EOs) have been utilized for medicinal and traditional purposes. However, in recent decades, an increasing interest has developed due to the need to rediscover herbal remedies and adjuvant therapies for the management of various diseases, particularly chronic ones. The present narrative review examines the potential for EOs to exert hypoglycemic and antioxidant effects in diabetes mellitus, analyzing the main publications having evaluated plant species with potentially beneficial effects through their phytocompounds in diabetes mellitus and its complications. Numerous species have shown promising characteristics that can be used in diabetes management. The hypoglycemic effects of these EOs are attributed to their capacity to stimulate glucose uptake, suppress glucose production, and increase insulin sensitivity. Moreover, EOs can alleviate the oxidative stress by manifesting their antioxidant effects via a variety of mechanisms, including the scavenging of free radicals, the regulation of antioxidant enzymes, and the decreasing of lipid peroxidation, due to their diverse chemical composition. These findings demonstrate the possible benefits of EOs as adjuvant therapeutic agents in the management of diabetes and its complications. The use of EOs in the treatment of diabetes shows good potential for the development of natural and effective strategies to enhance the health outcomes of people with this chronic condition, but additional experimental endorsements are required.

The Crucial Role of Diet Therapy and Selenium on the Evolution of Clinical and Paraclinical Parameters in Patients with Metabolic Syndrome.

Oxidative stress (OS) is associated with metabolic syndrome (MS) and represents a complex disease association that has become a major challenge in the field of public health. The aim of this study was to investigate the effectiveness of introducing selenium in the management of OS, while considering a balanced diet based on a healthy lifestyle and dietary therapy. A total of 206 individuals participated voluntarily in the study, divided into three groups: the control group with 35 individuals (17.0%) designated as control lot (LC), the group undergoing diet therapy with 119 individuals (57.8%) designated as diet therapy lot (LD), and the group undergoing diet therapy supplemented with selenium consisting of 52 individuals (25.2%) designated as diet therapy with selenium lot (LD + Se). The study assessed various clinical parameters (such as body mass index (BMI), body weight status, fat mass, visceral fat, and sarcopenic index), paraclinical parameters (including HOMA index, cholesterol, triglycerides, C-reactive protein, and glycosylated haemoglobin (HGS)), as well as OS parameters (measured using the FORD test, FORT test, and MIXED test). The LD + Se group demonstrated the most favourable results in terms of BMI reduction, decreased fat and visceral mass, reduced levels of C-reactive protein, and improved glycosylated haemoglobin levels. By implementing a balanced diet therapy and supplementing the diet with selenium, it was possible to achieve a reduction in adipose tissue and glycosylated haemoglobin levels, ultimately contributing to the reduction of OS in the body.

The Relationship Between Oxidative Stress, Selenium, and Cumulative Risk in Metabolic Syndrome.

BACKGROUND/AIM: Oxidative stress in association with metabolic syndrome represents a complex disease entity that has emerged as a significant public health challenge, and it is closely linked to an elevated risk of cardiovascular disease, type 2 diabetes, and even cancer. The objective of this study was to investigate the effectiveness of selenium supplementation in managing oxidative stress while considering a well-balanced diet based on a healthy lifestyle and diet therapy. PATIENTS AND METHODS: The study included a total of 206 participants divided into three groups: the control group consisting of 35 individuals (17.0%) named LC, the diet therapy group comprising 119 individuals (57.8%) named LD, and the diet therapy group supplemented with selenium consisting of 52 individuals (25.2%) named LD+Se. Various clinical parameters such as body mass index (BMI), weight status, fat mass, visceral fat, and sarcopenia index, as well as paraclinical parameters including the HOMA index, cholesterol, triglycerides, C-reactive protein, and HGZ, were evaluated. Additionally, oxidative stress parameters using the FORD, FORT and MIXT tests were measured. RESULTS: Selenium supplementation, along with FORD and FORT tests, demonstrated effectiveness in individuals with chronic venous disease, with a significantly greater decrease observed in those with chronic venous disease in the LD+Se group. CONCLUSION: Physiological aging has an important role in triggering or aggravating oxidative stress, and the use of antioxidant products such as selenium can reduce this process.

Emerging Insights into the Applicability of Essential Oils in the Management of Acne Vulgaris.

The occurrence of pustules, comedones, nodules, and cysts defines acne vulgaris, a prevalent chronic inflammatory dermatological condition. In the past few decades, essential oils extracted from varied natural sources have acquired recognition due to their potential medicinal applications in acne therapy. However, there is not yet sufficient medical data to fully characterize this interaction. Multiple factors contribute to the development of acne vulgaris, including excessive sebaceous production, inflammatory processes, hyperkeratinization, and infection with Cutibacterium acnes. Essential oils, including oregano, lavender, lemon grass, myrtle, lemon, thyme, eucalyptus, rosemary, and tea tree, have been found to possess anti-inflammatory, antioxidant, and antimicrobial properties, which may target the multifactorial causes of acne. Analytical methods for determining antioxidant potential (i.e., total phenolic content, diphenyl-1-picrylhydrazyl free radical scavenging assay, reducing power assay, ferrous ion chelating activity, thiobarbituric acid reactive species assay, ß-carotene bleaching assay, etc.) are essential for the evaluation of these essential oils, and their method optimization is crucial. Further studies could include the development of novel acne treatments incorporating essential oils and an assessment of their efficacy in large clinical trials. In addition, further research is necessary to ascertain the mechanisms of action of essential oils and their optimal doses and safety profiles for optimal implementation in the management of acne vulgaris.

Cardiometabolic Risk: Characteristics of the Intestinal Microbiome and the Role of Polyphenols.

Cardiometabolic diseases like hypertension, type 2 diabetes mellitus, atherosclerosis, and obesity have been associated with changes in the gut microbiota structure, or dysbiosis. The beneficial effect of polyphenols on reducing the incidence of this chronic disease has been confirmed by numerous studies. Polyphenols are primarily known for their anti-inflammatory and antioxidant properties, but they can also modify the gut microbiota. According to recent research, polyphenols positively influence the gut microbiota, which regulates metabolic responses and reduces systemic inflammation. This review emphasizes the prebiotic role of polyphenols and their impact on specific gut microbiota components in patients at cardiometabolic risk. It also analyzes the most recent research on the positive effects of polyphenols on cardiometabolic health. While numerous in vitro and in vivo studies have shown the interaction involving polyphenols and gut microbiota, additional clinical investigations are required to assess this effect in people.

Micropulse Laser Therapy as an Integral Part of Eye Disease Management.

Ocular diseases can significantly impact vision and quality of life through pathophysiological alterations to the structure of the eye. The management of these conditions often involves a combination of pharmaceutical interventions, surgical procedures, and laser therapy. Laser technology has revolutionized many medical fields, including ophthalmology, offering precise and targeted treatment options that solve some of the unmet needs of other therapeutic strategies. Conventional laser techniques, while effective, can generate excessive thermal energy, leading to collateral tissue damage and potential side effects. Compared to conventional laser techniques, micropulse laser therapy delivers laser energy in a pulsed manner, minimizing collateral damage while effectively treating target tissues. The present paper highlights the advantages of micropulse laser therapy over conventional laser treatments, presents the implications of applying these strategies to some of the most prevalent ocular diseases, and highlights several types and mechanisms of micropulse lasers. Although micropulse laser therapy shows great potential in the management of ocular diseases, further research is needed to optimize treatment protocols, evaluate long-term efficacy, and explore its role in combination therapies.

Effect of Fluoride Coatings on the Corrosion Behavior of Mg-Zn-Ca-Mn Alloys for Medical Application.

The most critical shortcoming of magnesium alloys from the point of view of medical devices is the high corrosion rate, which is not well-correlated with clinical needs. It is well- known that rapid degradation occurs when an implant made of Mg-based alloys is placed inside the human body. Consequently, the implant loses its mechanical properties and failure can occur even if it is not completely degraded. The corrosion products that appear after Mg-based alloy degradation, such as H2 and OH- can have an essential role in decreasing biocompatibility due to the H2 accumulation process in the tissues near the implant. In order to control the degradation process of the Mg-based alloys, different coatings could be applied. The aim of the current paper is to evaluate the effect of fluoride coatings on the corrosion behavior of magnesium alloys from the system Mg-Zn-Ca-Mn potentially used for orthopedic trauma implants. The main functional properties required for the magnesium alloys to be used as implant materials, such as surface properties and corrosion behavior, were studied before and after surface modifications by fluoride conversion, with and without preliminary sandblasting, of two magnesium alloys from the system Mg-Zn-Ca-Mn. The experimental results showed that chemical conversion treatment with hydrofluoric acid is useful as a method of increasing corrosion resistance for the experimental magnesium alloys from the Mg-Zn-Ca-Mn system. Also, high surface free energy values obtained for the alloys treated with hydrofluoric acid correlated with wettability lead to the conclusion that there is an increased chance for biological factor adsorption and cell proliferation. Chemical conversion treatment with hydrofluoric acid is useful as a method of increasing corrosion resistance for the experimental Mg-Zn-Ca-Mn alloys.

Assessment of Microstructural, Mechanical and Electrochemical Properties of Ti-42Nb Alloy Manufactured by Electron Beam Melting.

The ß-type Ti-42Nb alloy has been successfully manufactured from pre-alloyed powder using the E-PBF method for the first time. This study presents thorough microstructural investigations employing diverse methodologies such as EDS, XRD, TEM, and EBSD, while mechanical properties are assessed using UPT, nanoindentation, and compression tests. Microstructural analysis reveals that Ti-42Nb alloy primarily consisted of the ß phase with the presence of a small amount of nano-sized α″-martensite formed upon fast cooling. The bimodal-grained microstructure of Ti-42Nb alloy comprising epitaxially grown fine equiaxed and elongated equiaxed ß-grains with an average grain size of 40 ± 28 µm exhibited a weak texture. The study shows that the obtained microstructure leads to improved mechanical properties. Young's modulus of 78.69 GPa is significantly lower than that of cp-Ti and Ti-6Al-4V alloys. The yield strength (379 MPa) and hardness (3.2 ± 0.5 GPa) also meet the criteria and closely approximate the values typical of cortical bone. UPT offers a reliable opportunity to study the nature of the ductility of the Ti-42Nb alloy by calculating its elastic constants. XPS surface analysis and electrochemical experiments demonstrate that the better corrosion resistance of the alloy in SBF is maintained by the dominant presence of TiO2 and Nb2O5. The results provide valuable insights into the development of novel low-modulus Ti-Nb alloys, which are interesting materials for additive-manufactured implants with the desired properties required for their biomedical applications.

Oxidative stress and metabolic syndrome in acne vulgaris: Pathogenetic connections and potential role of dietary supplements and phytochemicals.

Acne vulgaris is a highly prevalent skin condition caused by androgen-induced elevated sebum secretion, abnormal keratinization, bacterial colonization, and inflammation. Current research indicates a link between acne vulgaris and the metabolic syndrome, a group of disorders that includes obesity, insulin resistance, hypertension, and dyslipidemia. This link is thought to be modulated by excessive concentrations of oxidative stress markers and chronic inflammation, which are included in the pathophysiological mechanisms shared by both conditions. Excessive generation of reactive oxygen species damages cellular components and initiates an inflammatory response, hence promoting the development of both disorders. The current narrative review focuses on the molecular implications of inflammatory, hormonal, and environmental factors in the acne-metabolic syndrome correlation. Furthermore, it outlines the current state of knowledge related to the phyto-therapeutic approach to these conditions as an adjuvant strategy to allopathic treatment, but future multicenter and larger-scale research studies are needed establish new algorithms to be included in the future management of patients with these conditions.

Plants-based medicine implication in the evolution of chronic liver diseases.

Hepatic disorders are considered major health problems, due to their high incidence, increased risk of chronicling or death and the costs involved in therapies. A large number of patients with chronic liver diseases use herbal medicines and dietary supplements in parallel with allopathic treatment. The current review provides a thorough analysis of the studies conducted on the most important species of medicinal plants used in this disease, bioactive compounds and on the activity of herbal medicines in the evolution of chronic liver diseases. However, a negative aspect is that there is frequently a lack of comprehensive data on the progression of the illness and the living standards of patients who are affected when evaluating the effects of these phytocomponents on the evolution of chronic liver disease, the patients' health, and their quality of life. It is essential to take this impairment into account when evaluating the long-term effects of herbal treatments on the health of individuals who suffer from liver illness. Bioactive phytocomponents may be a suitable source for the development of novel medications due to the correlation between traditional uses and medical advances. Additional high-quality preclinical examinations utilizing cutting-edge approaches are needed to assess safety and effectiveness and to detect, categorize, and standardize the active substances and their formulations for the most suitable therapeutic management of liver illnesses.

Novel Molecules in Diabetes Mellitus, Dyslipidemia and Cardiovascular Disease.

The purpose of this Special Issue is to present the impact in clinical practice as well as in medical research of novel molecules that have been introduced in the treatment of diabetes mellitus, dyslipidaemia, and cardiovascular disease [...].

Comorbidities, Associated Diseases, and Risk Assessment in COVID-19-A Systematic Review.

It is considered that COVID-19's pandemic expansion is responsible for the particular increase in deaths, especially among the population with comorbidities. The health system is often overwhelmed by the large number of cases of patients addressing it, by the regional limitation of funds, and by the gravity of cases at subjects suffering from this pathology. Several associated conditions including diabetes, cardiovascular illnesses, obesity, persistent lung condition, neurodegenerative diseases, etc., increase the mortality risk and hospitalization of subjects suffering from COVID-19. The rapid identification of patients with increased risk of death from the SARS-CoV-2 virus, the stratification in accordance with the risk and the allocation of human, financial, and logistical resources in proportion must be a priority for health systems worldwide.

Reviewing the Modern Therapeutical Options and the Outcomes of Sacubitril/Valsartan in Heart Failure.

Sacubitril/valsartan (S/V) is a pharmaceutical strategy that increases natriuretic peptide levels by inhibiting neprilysin and regulating the renin-angiotensin-aldosterone pathway, blocking AT1 receptors. The data for this innovative medication are mainly based on the PARADIGM-HF study, which included heart failure with reduced ejection fraction (HFrEF)-diagnosed patients and indicated a major improvement in morbidity and mortality when S/V is administrated compared to enalapril. A large part of the observed favorable results is related to significant reverse cardiac remodeling confirmed in two prospective trials, PROVE-HF and EVALUATE-HF. Furthermore, according to a subgroup analysis from the PARAGON-HF research, S/V shows benefits in HFrEF and in many subjects having preserved ejection fraction (HFpEF), which indicated a decrease in HF hospitalizations among those with a left ventricular ejection fraction (LVEF) < 57%. This review examines the proven benefits of S/V and highlights continuing research in treating individuals with varied HF characteristics. The article analyses published data regarding both the safeness and efficacy of S/V in patients with HF, including decreases in mortality and hospitalization, increased quality of life, and reversible heart remodeling. These benefits led to the HF guidelines recommendations updating and inclusion of S/V combinations a key component of HFrEF treatment.

Advanced two-stage cascade configurations for energy-efficient -80 °C refrigeration.

In response to the COVID-19 pandemic, some vaccines have been developed requiring ultralow-temperature refrigeration, and the number of these freezers has been increased worldwide. Ultralow-temperature refrigeration operates with a significant temperature lift and, hence, a massive decrease in energy performance. Therefore, cascade cycles based on two vapor compression single-stage cycles are traditionally used for these temperatures. This paper proposes the combination of six different cycles (single-stage with and without internal heat exchanger, vapor injection, liquid injection, and parallel compression with and without economizer) in two-stage cascades to analyze the operational and energy performance in ultralow-temperature freezers. All this leads to 42 different configurations in which the intermediate cascade temperature is optimized to maximize the coefficient of performance. Ultra-low global warming potential natural refrigerants such as R-290 (propane) and R-170 (ethane) for the cascade high- and low-temperature stage have been considered. From the thermodynamic analysis, it can be concluded that liquid and vapor injection cascade configurations are the most energy-efficient. More specifically, those containing a vapor injection in the low-temperature stage (0.89 coefficient of performance, 40 % higher than traditional configurations). Then, using an internal heat exchanger for such low temperatures is unnecessary in terms of energy performance. The optimum intermediate cascade temperature varies significantly among cycles, from -37 °C to 2 °C, substantially impacting energy performance. Parallel compression configuration improves energy performance over single-stage cycles, but not as much as multi-stage (between 20 % and 30 % lower coefficient of performance). For most of low-temperature cycles, the high-temperature stage can be based on a single-stage cycle while keeping the maximum coefficient of performance.

Some Mechanical Properties of Composite Materials with Chopped Wheat Straw Reinforcer and Hybrid Matrix.

Modern agriculture produces a very large amount of agricultural waste that remains unused. The use as a reinforcer of these renewable resources for the realization of composite materials, and the finding of useful industrial applications, constitutes or provokes the groups of researchers in this field. The study conducted in this article falls in this direction. Composites were fabricated with the chopped wheat straw reinforcement and epoxy resin matrix or hybrid resins with 50% and 70% Dammar volume proportions. Some mechanical properties of this type of composite materials were studied based on tensile strength, SEM analysis, water absorption/loss, vibration behavior and compression strength. The strength-strain and strain-strain diagrams, the modulus of elasticity, the breaking strength and the elongation at break were obtained. Compared to the epoxy resin composition, those with 50 and 70% Dammar, respectively, have a 47 and 55% lower breaking strength and a 30 and 84% higher damping factor, respectively. Because the values of these mechanical properties were limited, and in practice superior properties are needed, sandwich composites were manufactured, with the core of previously studied compositions, to which the outer faces of linen fabric were applied. These composites were applied to the bend (in three points), obtaining the force-deformation diagrams. The obtained properties show that they can be used in construction (paneling, shells, etc.), or in the furniture industry.

Reviewing the Traditional/Modern Uses, Phytochemistry, Essential Oils/Extracts and Pharmacology of Embelia ribes Burm.

OBJECTIVES: Embelia ribes Burm. (E. ribes, Myrsinaceae), also known as Vidanga in Ayurveda, has been shown to have significant therapeutic benefits on several disorders, and its main chemical bioactive constituent, embelin, has the therapeutic potential to be converted into innovative drugs, which is why it has recently received considerable interest. In the present work, we provide a higher level of comprehension, awareness, and extensive knowledge of the traditional uses, phytochemistry, and pharmacological characteristics of E. ribes throughout the last several decades (February 1965 to June 2021), emphasizing the importance of the study of essential oils extracted from E. ribes, which show a major potential for exerting antioxidant and anti-inflammatory activity. MATERIALS AND METHODS: Google Scholar, MEDLINE, EMBASE, Scifinder, Scopus, and ScienceDirect were used to conduct a thorough literature search. RESULTS: E. ribes is high in essential oils, alkaloids, flavonoids, steroids, and phenolics, all of which have medicinal benefits. The essential oils/extracts and isolated chemical constituents exhibited antioxidant activity, wound healing, antidiabetic, central nervous system (CNS)-related disease, antiviral, antiobesity, cardioprotective, antifungal, antibacterial, and antifertility activity, among other promising pharmacological effects. CONCLUSION: The translation between traditional applications and modern medicine may make E. ribes a promising target for the implementation of innovative medication. To investigate the efficacy and safety profile of E. ribes, further high-quality preclinical studies using advanced methodologies are required.