Influence of vitamin D supplementation on growth, body composition, pubertal development and spirometry in South African schoolchildren: a randomised controlled trial (ViDiKids).

OBJECTIVE: To determine whether weekly oral vitamin D supplementation influences growth, body composition, pubertal development or spirometric outcomes in South African schoolchildren. DESIGN: Phase 3 double-blind randomised placebo-controlled trial. SETTING: Socioeconomically disadvantaged peri-urban district of Cape Town, South Africa. PARTICIPANTS: 1682 children of black African ancestry attending government primary schools and aged 6-11 years at baseline. INTERVENTIONS: Oral vitamin D3 (10 000 IU/week) versus placebo for 3 years. MAIN OUTCOME MEASURES: Height-for-age and body mass index-for-age, measured in all participants; Tanner scores for pubertal development, spirometric lung volumes and body composition, measured in a subset of 450 children who additionally took part in a nested substudy. RESULTS: Mean serum 25-hydroxyvitamin D3 concentration at 3-year follow-up was higher among children randomised to receive vitamin D versus placebo (104.3 vs 64.7 nmol/L, respectively; mean difference (MD) 39.7 nmol/L, 95% CI 37.6 to 41.9 nmol/L). No statistically significant differences in height-for-age z-score (adjusted MD (aMD) -0.08, 95% CI -0.19 to 0.03) or body mass index-for-age z-score (aMD -0.04, 95% CI -0.16 to 0.07) were seen between vitamin D versus placebo groups at follow-up. Among substudy participants, allocation to vitamin D versus placebo did not influence pubertal development scores, % predicted forced expiratory volume in 1 s (FEV1), % predicted forced vital capacity (FVC), % predicted FEV1/FVC, fat mass or fat-free mass. CONCLUSIONS: Weekly oral administration of 10 000 IU vitamin D3 boosted vitamin D status but did not influence growth, body composition, pubertal development or spirometric outcomes in South African schoolchildren. TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov NCT02880982, South African National Clinical Trials Register DOH-27-0916-5527.

Cholestane-3ß,5α,6ß-triol Induces Multiple Cell Death in A549 Cells via ER Stress and Autophagy Activation.

Cholestane-3ß,5α,6ß-triol (CT) and its analogues are abundant in natural sources and are reported to demonstrate cytotoxicity toward different kinds of tumor cells without a deep probe into their mechanism of action. CT is also one of the major metabolic oxysterols of cholesterol in mammals and is found to accumulate in various diseases. An extensive exploration of the biological roles of CT over the past few decades has established its identity as an apoptosis inducer. In this study, the effects of CT on A549 cell death were investigated through cell viability assays. RNA-sequencing analysis and western blot of CT-treated A549 cells revealed the role of CT in inducing endoplasmic reticulum (ER) stress response and enhancing autophagy flux, suggesting a putative mechanism of CT-induced cell-death activation involving reactive oxygen species (ROS)-mediated ER stress and autophagy. It is reported for the first time that the upregulation of autophagy induced by CT can serve as a cellular cytotoxicity response in accelerating CT-induced cell death in A549 cells. This research provides evidence for the effect of CT as an oxysterol in cell response to oxidative damage and allows for a deep understanding of cholesterol in its response in an oxidative stress environment that commonly occurs in the progression of various diseases.

Prevalence of vitamin D deficiency and its association with cardiometabolic risk factors among healthcare workers in the Eastern Cape province, South Africa; cross-sectional study.

This study assesses the prevalence of Vitamin D deficiency and its potential association with cardiometabolic risk factors among South African adults residing in the Eastern Cape province. In this cross-sectional study, 1244 healthcare workers (HCWs) completed a self-administered questionnaire and venous blood samples were drawn at two academic hospitals in the Eastern Cape. History of hypertension and diabetes mellitus were self-reported. Participants were categorised as obese if their body mass index (BMI) ≥ 30 kg/m2. Participants were classified as having metabolic syndrome if they had hypertension, diabetes mellitus and obesity. Vitamin D [25(OH)D] deficiency was defined as venous blood concentrations < 50 nmol/L. Associations between vitamin D deficiency and participants' characteristics were assessed using multivariate logistic regression model analysis. The prevalence of vitamin D deficiency was 28.5% (n = 355), of whom 292 were female. Among the participants who were deficient in vitamin D, the prevalence of obesity, diabetes mellitus, hypertension, chronic kidney disease, and metabolic syndrome was 64.9% (n = 230), 9% (n = 32), 16.6% (n = 59), 2.3% (n = 8) and 18% (n = 64), respectively. In the adjusted multivariate logistic regression model, black Africans (AOR = 2.87; 95% CI 1.52-5.43) and individuals ≥ 42 years (AOR = 1.37; 95% CI 1.07-1.77) were more likely to exhibit vitamin D deficiency. However, there was no significant association by age, sex, and cardiometabolic markers. More than one in four healthcare workers was deficient in vitamin D among the study sample, especially the black Africans and older individuals. Further studies are needed at the population level to elucidate on the vitamin D status in the region.

Trodusquemine (MSI-1436) Restores Metabolic Flexibility and Mitochondrial Dynamics in Insulin-Resistant Equine Hepatic Progenitor Cells (HPCs).

Equine metabolic syndrome (EMS) is a significant global health concern in veterinary medicine. There is increasing interest in utilizing molecular agents to modulate hepatocyte function for potential clinical applications. Recent studies have shown promising results in inhibiting protein tyrosine phosphatase (PTP1B) to maintain cell function in various models. In this study, we investigated the effects of the inhibitor Trodusquemine (MSI-1436) on equine hepatic progenitor cells (HPCs) under lipotoxic conditions. We examined proliferative activity, glucose uptake, and mitochondrial morphogenesis. Our study found that MSI-1436 promotes HPC entry into the cell cycle and protects them from palmitate-induced apoptosis by regulating mitochondrial dynamics and biogenesis. MSI-1436 also increases glucose uptake and protects HPCs from palmitate-induced stress by reorganizing the cells' morphological architecture. Furthermore, our findings suggest that MSI-1436 enhances 2-NBDG uptake by increasing the expression of SIRT1, which is associated with liver insulin sensitivity. It also promotes mitochondrial dynamics by modulating mitochondria quantity and morphotype as well as increasing the expression of PINK1, MFN1, and MFN2. Our study provides evidence that MSI-1436 has a positive impact on equine hepatic progenitor cells, indicating its potential therapeutic value in treating EMS and insulin dysregulation.

Steroidal glycosides from Ornithogalum thyrsoides bulbs and their cytotoxicity toward HL-60 human promyelocytic leukemia cells and SBC-3 human small-cell lung cancer cells.

Ornithogalum thyrsoides Jacq belongs to the Asparagaceae family and is cultivated for ornamental purposes. The authors have previously reported several cholestane- and spirostan-type steroidal glycosides from O. thyrsoides. Conventional TLC analysis of the methanolic bulb extract of O. thyrsoides suggested the presence of unprecedented compounds; therefore, a detailed phytochemical investigation of the extract was performed and 35 steroidal glycosides (1-35), including 21 previously undescribed ones (1-21) were collected. The structures of 1-21 were determined mainly by analyses of their 1H and 13C NMR spectra with the aid of two-dimensional NMR spectroscopy. The isolated compounds were classified into three distinct groups: furostan-type (1, 2, 8-12, and 22), spirostan-type (3-7 and 23-26), and cholestane-type (13-21 and 27-35). Although the C/D-ring junction of the steroidal skeleton is typically trans-oriented, except for some cardiotonic and pregnane-type steroidal derivatives, 7 possess a cis C/D-ring junction. This is the first reported instance of such a configuration in spirostan-type steroidal derivatives, marking it as a finding of significant interest. Compounds 1-35 were evaluated for cytotoxicity against HL-60 human promyelocytic leukemia cells and SBC-3 human small-cell lung cancer cells. Compounds 3-6, 9, 17-21, 23-25, and 30-35 demonstrated cytotoxicity in a dose-dependent manner with IC50 values ranging from 0.000086 to 18 µM and from 0.00014 to 37 µM toward HL-60 and SBC-3 cells, respectively. Compound 19, which is obtained in a good yield and shows relatively potent cytotoxicity among the undescribed compounds, induces apoptosis in HL-60 cells, accompanied by arresting the cell cycle of HL-60 cells at the G2/M phase. In contrast, 19 causes oxidative stress-associated necrosis in SBC-3 cells. The cytotoxic mechanism of 19 is different between HL-60 and SBC-3 cells.

Vitamin D supplementation in a post-pandemic era: A narrative review.

Vitamin D is a fat-soluble molecule referring to the different isoforms, ergocalciferol (D2) and cholecalciferol (D3). Its physiological functions include increasing calcium serum concentrations. 25-hydroxyvitamin D3 (25(OH)D) (Calcifediol), a non-active, circulating instant precursor is seen as a pre-hormone. Studies have shown that a deficiency in calcifediol is related to chronic conditions such as cardiovascular, musculoskeletal, immune system, neurological, and anti-neoplastic functions. Vitamin D supplementation has shown its benefit as prophylaxis and treatment during the coronavirus disease 2019 (COVID-19) pandemic and an increase in the prescribing of vitamin D supplementation has been observed. The intention of this review article is to provide guidance on the recommended dosage regimen as a prophylactic measure during COVID-19 and its use as a supplement in general. From this review article, it is clear that vitamin D has an important role to play not only in COVID-19 but also in various other health aspects of the human body.Contribution: This review article highlighted the role of vitamin D in managing vitamin D deficiency and its role as a supplement in the management of respiratory tract infections, especially COVID-19. This overview can assist physicians in optimising healthcare by optimised dosing recommendations and indications.

Evaluation of the deficiency status of 25-hydroxyvitamin D and associated factors in Southwest China: A hospital-based retrospective cross-sectional analysis of a low-latitude, high-altitude, multiracial region.

Vitamin D deficiency is widespread in different populations and regions worldwide and has become a global health issue. The vitamin D status of the population in the Yunnan Province of Southwest China has not been evaluated to date. Therefore, in this study, we evaluated the vitamin D status according to the serum concentrations of 25-hydroxyvitamin D (25(OH)D) in individuals of Yunnan Province, a low-latitude, high-altitude and multiracial region in China. The data on 25(OH)D concentrations from October 2012 to December 2017 were retrospectively collected and assessed using the laboratory information system from 52 950 hospital-based participants (age, 1 day-96 years; females, 73.74%). The serum concentration of 25(OH)D was evaluated using a chemiluminescent immunoassay. The analysis was stratified by sex, age, sampling season, testing year, minority, residential district, latitude, altitude and meteorological factors. Vitamin D status was classified as follows: severe deficiency: <10 ng/mL; deficiency: <20 ng/mL; insufficiency: <30 ng/mL; and sufficiency: ≥30 ng/mL. The results showed that vitamin D deficiency is highly prevalent in Yunnan Province in a hospital-based cohort, with a deficiency and severe deficiency rate of 65.1% and a sufficiency rate of 5.30%. Significantly lower vitamin D levels and sufficiency rates were observed in females than in males (20.13 ± 7.22 ng/mL vs. 17.56 ± 6.66 ng/mL and 8.20% vs. 4.20%; p < 0.01, respectively); in spring and winter (16.93 ± 6.24 ng/mL; 2.97% and 16.38 ± 6.43 ng/mL; 3.06%, respectively) than in summer and autumn (20.23 ± 7.14 ng/mL; 8.02% and 19.10 ± 6.97 ng/mL; 6.61% [p < 0.01], respectively); and in older individuals (0-6 years: 28.29 ± 13.13 ng/mL vs. >60 years: 14.88 ± 8.39 ng/mL; p < 0.01). Relatively higher vitamin D levels were observed in individuals of Yi, Zhuang, Hani, Dai, Miao and Lisu minorities and lower levels in individuals of Hui and Zang minorities compared with those of the Han nationality (p < 0.01). The mean sunlight duration, mean air temperature, maximum ultraviolet value and latitude were significantly correlated with vitamin D levels (r = -0.53, 0.60, 0.31, -0.68, respectively; p < 0.05). These results suggest that vitamin D status is influenced by sex, age, minority, latitude and some meteorological factors in areas with high and low altitudes. Hence, new public health policies, such as advice on sunshine exposure, food fortification and nutrition education, as well as the implementation of vitamin D supplementation programmes must be considered to alleviate vitamin D deficiency in Yunnan province, Southwest China.

Exploration of Binding Affinities of a 3ß,6ß-Diacetoxy-5α-cholestan-5-ol with Human Serum Albumin: Insights from Synthesis, Characterization, Crystal Structure, Antioxidant and Molecular Docking.

The present study describes the synthesis, characterization, and in vitro molecular interactions of a steroid 3ß,6ß-diacetoxy-5α-cholestan-5-ol. Through conventional and solid-state methods, a cholestane derivative was successfully synthesized, and a variety of analytical techniques were employed to confirm its identity, including high-resolution mass spectrometry (HRMS), Fourier transforms infrared (FT-IR), nuclear magnetic resonance (NMR), elemental analysis, and X-ray single-crystal diffraction. Optimizing the geometry of the steroid was undertaken using density functional theory (DFT), and the results showed great concordance with the data from the experiments. Fluorescence spectral methods and ultraviolet-vis absorption titration were employed to study the in vitro molecular interaction of the steroid regarding human serum albumin (HSA). The Stern-Volmer, modified Stern-Volmer, and thermodynamic parameters' findings showed that steroids had a significant binding affinity to HSA and were further investigated by molecular docking studies to understand the participation of active amino acids in forming non-bonding interactions with steroids. Fluorescence studies have shown that compound 3 interacts with human serum albumin (HSA) through a static quenching mechanism. The binding affinity of compound 3 for HSA was found to be 3.18 × 104 mol-1, and the Gibbs free energy change (ΔG) for the binding reaction was -9.86 kcal mol-1 at 298 K. This indicates that the binding of compound 3 to HSA is thermodynamically favorable. The thermodynamic parameters as well as the binding score obtained from molecular docking at various Sudlow's sites was -8.2, -8.5, and -8.6 kcal/mol for Sites I, II, and III, respectively, supporting the system's spontaneity. Aside from its structural properties, the steroid demonstrated noteworthy antioxidant activity, as evidenced by its IC50 value of 58.5 µM, which is comparable to that of ascorbic acid. The findings presented here contribute to a better understanding of the pharmacodynamics of steroids.

Reduced High-Density Lipoprotein Cholesterol Is an Independent Determinant of Altered Bone Quality in Women with Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) is associated with an increased fracture risk. Our study aimed to explore differences in bone alterations between T2DM women and controls and to assess clinical predictors of bone impairment in T2DM. For this observational case control study, we recruited 126 T2DM female patients and 117 non-diabetic, age- and BMI-comparable women, who underwent clinical examination, routine biochemistry and dual-energy X-ray absorptiometry (DXA) scans for bone mineral density (BMD) and trabecular bone score (TBS) assessment-derived indexes. These were correlated to metabolic parameters, such as glycemic control and lipid profile, by bivariate analyses, and significant variables were entered in multivariate adjusted models to detect independent determinants of altered bone status in diabetes. The T2DM patients were less represented in the normal bone category compared with controls (5% vs. 12%; p = 0.04); T2DM was associated with low TBS (OR: 2.47, C.I. 95%: 1.19-5.16, p = 0.016) in a regression model adjusted for age, menopausal status and BMI. In women with T2DM, TBS directly correlated with plasma high-density lipoprotein cholesterol (HDL-c) (p = 0.029) and vitamin D (p = 0.017) levels. An inverse association was observed with menopausal status (p < 0.001), metabolic syndrome (p = 0.014), BMI (p = 0.005), and waist circumference (p < 0.001). In the multivariate regression analysis, lower HDL-c represented the main predictor of altered bone quality in T2DM, regardless of age, menopausal status, BMI, waist circumference, statin treatment, physical activity, and vitamin D (p = 0.029; R2 = 0.47), which likely underlies common pathways between metabolic disease and bone health in diabetes.

Non-alcoholic fatty liver disease is associated with decreased bone mineral density in upper Egyptian patients.

Nonalcoholic fatty liver disease (NAFLD) has been linked with a number of extra hepatic diseases and could be a potential risk factor of decreasing bone mineral density. To determine whether Upper Egyptian patients with NAFLD are at risk of developing osteoporosis. Cross sectional study was done on a total 100 individuals; 50 patients diagnosed with NAFLD (based on ultrasound imaging) crossed-matched with 50 individuals without NAFLD based on age, sex and body mass index. Bone mineral density, serum calcium and phosphorus levels, serum parathyroid hormone, serum vitamin D and fasting insulin level were assessed. Osteoporosis was prevalent in NAFLD patients versus to controls (19/50 vs. 0/50; P < 0.001). There was significant decrease in bone mineral density in NAFLD patients than controls (- 2.29 ± 0.4 vs. - 1.53 ± 0.1; P < 0.001). There was a statistical significance decrease in serum vitamin D and calcium levels in NAFLD patients than controls. Furthermore, vitamin D levels in the NAFLD group was a predictor for osteoporosis (OR 0.614; 95% CI 0.348-0.825). Patients with NAFLD tend to have a significant decrease in bone density, vitamin D, and serum calcium levels than controls.

Vitamin D Increases Irisin Serum Levels and the Expression of Its Precursor in Skeletal Muscle.

Irisin is a myokine synthesized by skeletal muscle, which performs key actions on whole-body metabolism. Previous studies have hypothesized a relationship between irisin and vitamin D, but the pathway has not been thoroughly investigated. The purpose of the study was to evaluate whether vitamin D supplementation affected irisin serum levels in a cohort of 19 postmenopausal women with primary hyperparathyroidism (PHPT) treated with cholecalciferol for six months. In parallel, to understand the possible link between vitamin D and irisin, we analyzed the expression of the irisin precursor, Fndc5, in the C2C12 myoblast cell line treated with a biologically active form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3). Our results demonstrate that vitamin D supplementation resulted in a significant increase in irisin serum levels (p = 0.031) in PHPT patients. In vitro, we show that vitamin D treatment on myoblasts enhanced Fndc5 mRNA after 48 h (p = 0.013), while it increased mRNAs of sirtuin 1 (Sirt1) (p = 0.041) and peroxisome proliferator-activated receptor γ coactivator 1α (Pgc1α) (p = 0.017) over a shorter time course. Overall, our data suggest that vitamin-D-induced modulation of Fndc5/irisin occurs through up-regulation of Sirt1, which together with Pgc1α, is an important regulator of numerous metabolic processes in skeletal muscle.

Novel Synthesis of IMC-48 and Affinity Evaluation with Different i-Motif DNA Sequences.

During the last decade, the evidence for the biological relevance of i-motif DNA (i-DNA) has been accumulated. However, relatively few molecules were reported to interact with i-DNA, and a controversy concerning their binding mode, affinity, and selectivity persists in the literature. In this context, the cholestane derivative IMC-48 has been reported to modulate bcl-2 gene expression by stabilizing an i-motif structure in its promoter. In the present contribution, we report on a novel, more straightforward, synthesis of IMC-48 requiring fewer steps compared to the previous approach. Furthermore, the interaction of IMC-48 with four different i-motif DNA sequences was thoroughly investigated by bio-layer interferometry (BLI) and circular dichroism (CD) spectroscopy. Surprisingly, our results show that IMC-48 is a very weak ligand of i-DNA as no quantifiable interaction or significant stabilization of i-motif structures could be observed, stimulating a quest for an alternative mechanism of its biological activity.

Fused Pyrroles in Cholestane and Norcholestane Side Chains: Acaricidal and Plant Growth-Promoting Effects.

Herein, we describe the synthesis and characterization of fused pyrroles in cholestane and norcholestane side chains derived from kryptogenin and diosgenin, respectively. Both conventional and microwave heating techniques were used to synthesize the steroidal pyrroles from primary amines, with the microwave method producing the highest yields. In particular, the norcholestane pyrroles were tested as acaricides against the two-spotted spider mite (Tetranychus urticae Koch) under laboratory conditions and as plant growth promoters on habanero pepper (Capsicum chinense Jacq) under greenhouse conditions.

Studying the trafficking of labeled trodusquemine and its application as nerve marker for light-sheet and expansion microscopy.

Trodusquemine is an aminosterol with a variety of biological and pharmacological functions, such as acting as an antimicrobial, stimulating body weight loss and interfering with the toxicity of proteins involved in the development of Alzheimer's and Parkinson's diseases. The mechanisms of interaction of aminosterols with cells are, however, still largely uncharacterized. Here, by using fluorescently labeled trodusquemine (TRO-A594 and TRO-ATTO565), we show that trodusquemine binds initially to the plasma membrane of living cells, that the binding affinity is dependent on cholesterol, and that trodusquemine is then internalized and mainly targeted to lysosomes after internalization. We also found that TRO-A594 is able to strongly and selectively bind to myelinated fibers in fixed mouse brain slices, and that it is a marker compatible with tissue clearing and light-sheet fluorescence microscopy or expansion microscopy. In conclusion, this work contributes to further characterize the biology of aminosterols and provides a new tool for nerve labeling suitable for the most advanced microscopy techniques.

Particulate matter may have a limited influence on maternal vitamin D levels.

Evidence for an association between the amount of particulate matter (PM) in the atmosphere and vitamin D status of pregnant women is limited. We aimed to examine the independent association between PM and maternal levels of serum 25-hydroxyvitamin D (25OHD) during the second trimester and to explore possible modifications to the association by meteorological factors. 27,768 pregnant women presenting for prenatal examination who were tested for serum 25OHD concentration during the second trimester between January 1, 2016, and December 31, 2020, were included in this retrospective analysis. Exposure to PM was evaluated based on daily average PM with an aerodynamic diameter of ≤ 2.5 µm (PM2.5) and PM with an aerodynamic diameter of ≤ 10 µm (PM10). Corresponding meteorological data for daily average atmospheric temperature, atmospheric pressure, relative humidity, sunshine duration, and wind speed were collected. The maximum cumulative effects of PM2.5 occurred at lag 45 days, and the maximum cumulative effects of PM10 occurred at lag 60 days. In crude models, 45-day moving daily average PM2.5 concentrations were negatively associated with 25OHD levels (ß, - 0.20; 95% CI - 0.21 to - 0.19), as were 60-day moving daily average PM10 concentrations (ß, - 0.14; 95% CI - 0.15 to - 0.14). After adjusting for temporal and meteorological factors, the effect values were drastically reduced (adjusted ß of PM2.5, - 0.032; 95% CI - 0.046 to - 0.018; adjusted ß of PM10, - 0.039; 95% CI - 0.049 to - 0.028). Our study showed there was a small, independent, negative association between PM in the atmosphere and maternal serum 25OHD levels during the second trimester of pregnancy after adjusting for temporal and/or meteorological factors, which indicates that PM may have a limited influence on maternal serum 25OHD levels. Besides taking vitamin D supplements, pregnant women should keep participating in outdoor activities while taking PM protection measures to improve their vitamin D levels when PM levels are high in winter and spring.

Parisfargosides A-E, five new cholestane glycosides from the rhizomes of Paris fargesii.

Five new cholestane glycosides, named parisfargosides A-E (1-5), were isolated from the rhizomes of Paris fargesii. Their structures were elucidated on the basis of UV, HR-ESI-MS, 1D and 2D NMR data as well as chemical methods. The structures of all compounds contained α, ß-unsaturated ketone unit. Compounds 3-5 possessed a 16,23-cyclocholest skeleton with 6/6/6/5/5 condensed ring, and the absolute configurations of C-16 and C-23 were confirmed according to ROESY spectra with pyridine­d5 and DMSO­d6 as solvents. In addition, the platelet aggregation activity and cytotoxic activity against five human cancer cell lines (HL-60, A549, SMMC-7721, MDA-MB-231, and SW480) of compounds 1-5 were evaluated.

From Marine Metabolites to the Drugs of the Future: Squalamine, Trodusquemine, Their Steroid and Triterpene Analogues.

This review comprehensively describes the recent advances in the synthesis and pharmacological evaluation of steroid polyamines squalamine, trodusquemine, ceragenins, claramine, and their diverse analogs and derivatives, with a special focus on their complete synthesis from cholic acids, as well as an antibacterial and antiviral, neuroprotective, antiangiogenic, antitumor, antiobesity and weight-loss activity, antiatherogenic, regenerative, and anxiolytic properties. Trodusquemine is the most-studied small-molecule allosteric PTP1B inhibitor. The discovery of squalamine as the first representative of a previously unknown class of natural antibiotics of animal origin stimulated extensive research of terpenoids (especially triterpenoids) comprising polyamine fragments. During the last decade, this new class of biologically active semisynthetic natural product derivatives demonstrated the possibility to form supramolecular networks, which opens up many possibilities for the use of such structures for drug delivery systems in serum or other body fluids.

Squalamine and trodusquemine: two natural products for neurodegenerative diseases, from physical chemistry to the clinic.

Covering: 1993 to 2021 (mainly 2017-2021)Alzheimer's and Parkinson's diseases are neurodegenerative conditions affecting over 50 million people worldwide. Since these disorders are still largely intractable pharmacologically, discovering effective treatments is of great urgency and importance. These conditions are characteristically associated with the aberrant deposition of proteinaceous aggregates in the brain, and with the formation of metastable intermediates known as protein misfolded oligomers that play a central role in their aetiology. In this Highlight article, we review the evidence at the physicochemical, cellular, animal model and clinical levels on how the natural products squalamine and trodusquemine offer promising opportunities for chronic treatments for these progressive conditions by preventing both the formation of neurotoxic oligomers and their interaction with cell membranes.