Natural products from plants targeting key enzymes for the future development of antidiabetic agents.

Covering: 2000 to January 2023Diabetes is a metabolic disease of serious concern nowadays, with a negative economic impact. In 2021, the International Diabetes Federation estimated that more than 537 million adults live with diabetes, causing over 6.7 million deaths in that year. Intensive scientific research on medicinal plants in the last 100 years reveals that herbal drugs have been an essential source of products for developing antidiabetic agents acting on different physiological targets. This review summarizes recent research from 2000 to 2022 on plant natural compounds affecting selected crucial enzymes (dipeptidyl peptidase IV, diacylglycerol acyltransferase, fructose 1,6-biphosphatase, glucokinase, and fructokinase) involved in glucose homeostasis. Enzyme-aimed treatments usually induce reversible inhibition, irreversible by covalent changes of the objective enzymes, or bind non-covalently but so tightly that their inhibition is irreversible. Depending on the binding site, these inhibitors could be orthosteric or allosteric; in any case, the desired pharmacological action is achieved. One crucial advantage of targeting enzymes in drug discovery is that the required assays are usually simple, using biochemical experiments capable of analyzing enzyme activity.

Habitat type drives the spatial distribution of Australian fish chorus diversitya).

Fish vocalize in association with life functions with many species calling en masse to produce choruses. Monitoring the distribution and behavior of fish choruses provides high-resolution data on fish distribution, habitat use, spawning behavior, and in some circumstances, local abundance. The purpose of this study was to use long-term passive acoustic recordings to obtain a greater understanding of the patterns and drivers of Australian fish chorus diversity at a national scale. This study detected 133 fish choruses from year-long recordings taken at 29 Australian locations with the highest fish chorus diversity identified at a site in the country's northern, tropical waters. A linear model fitted with a generalized least squares regression identified geomorphic feature type, benthic substrate type, and northness (of slope) as explanatory variables of fish chorus diversity. Geomorphic feature type was identified as the significant driver of fish chorus diversity. These results align with broad-scale patterns reported previously in fish biodiversity, fish assemblages, and fish acoustic diversity. This study has highlighted that passive acoustic monitoring of fish chorus diversity has the potential to be used as an indicator of fish biodiversity and to highlight habitats of ecological importance.

Anaerobic RSH-dependent tellurite reduction contributes to Escherichia coli tolerance against tellurite.

BACKGROUND: Tellurium is a rare metalloid that exerts high toxicity on cells, especially on bacteria, partly due to reactive oxygen species (ROS) generation. Moreover, it has also been observed that tellurite can target free cell thiols groups (RSH) (i.e. reduced glutathione (GSH)), enhancing the cellular redox imbalance. Additionally, in vitro experiments have suggested that several enzymes can reduce tellurite (IV) to its elemental form (0); where RSH present on their active sites may be responsible for the process. Nevertheless, the mechanisms implemented by bacteria for tellurite reduction and its role in resistance have not been evaluated in vivo. RESULTS: This work shows that tellurite reduction to elemental tellurium is increased under anaerobic conditions in E. coli cells. The in vivo tellurite reduction is related to the intracellular concentration of total RSH, in the presence and absence of oxygen. This metabolization of tellurite directly contributes to the resistance of the bacteria to the oxyanion. CONCLUSIONS: We demonstrated that in vivo tellurite reduction is related to the intracellular thiol concentration, i.e. large availability of cellular RSH groups, results in a more significant reduction of tellurite. Furthermore, we observed that, when the bacterium exhibits less resistance to the oxyanion, a decreased tellurite reduction was seen, affecting the growth fitness. Together, these results let us propose that tellurite reduction and the intracellular RSH content are related to the oxyanion bacterial resistance, this tripartite mechanism in an oxygen-independent anaerobic process.

The effect of protease inhibitor-based dual antiretroviral regimens on CD4/CD8 ratio during the first year of therapy in ART-naïve patients with HIV-infection.

OBJECTIVES: To assess the effect of protease inhibitor (PI)-based dual therapy on CD4/CD8 ratio during the first year of therapy in antiretroviral therapy (ART)-naïve patients using data from randomized controlled clinical trials. METHODS: We pooled data from the GARDEL and ANDES studies, both randomized controlled clinical trials that recruited ART-naïve people living with HIV and randomly assigned them to receive PI-based dual therapy (DT) or triple therapy (TT) aiming to compare viral efficacy. We compared median CD4/CD8 ratios and the proportion of patients with CD4/CD8 ratio > 1 at 48 weeks after ART initiation in both treatment arms using the Mann-Whitney U-test and the χ2 test. We performed subgroup analysis for patients > 50 years old, with baseline CD4 counts ≤ 200 cells/µL, viral load > 100 000 HIV RNA copies/mL, and ritonavir-boosted lopinavir-based therapy. RESULTS: We analysed data from 571 patients: 292 on DT and 279 on TT. No differences were observed in CD4/CD8 ratio (0.632 vs. 0.617, P = 0.729) or in the proportion of patients with CD4/CD8 ratio > 1 (17.9% vs. 19.3%, P = 0.678) 48 weeks after ART initiation. Subgroup analysis showed no further differences. CONCLUSION: The impact of PI-based DT regimens on the CD4/CD8 ratio during the first year of treatment for ART-naïve patients is similar to that of TT.

Understanding gold toxicity in aerobically-grown Escherichia coli.

BACKGROUND: There is an emerging field to put into practice new strategies for developing molecules with antimicrobial properties. In this line, several metals and metalloids are currently being used for these purposes, although their cellular effect(s) or target(s) in a particular organism are still unknown. Here we aimed to investigate and analyze Au3+ toxicity through a combination of biochemical and molecular approaches. RESULTS: We found that Au3+ triggers a major oxidative unbalance in Escherichia coli, characterized by decreased intracellular thiol levels, increased superoxide concentration, as well as by an augmented production of the antioxidant enzymes superoxide dismutase and catalase. Because ROS production is, in some cases, associated with metal reduction and the concomitant generation of gold-containing nanostructures (AuNS), this possibility was evaluated in vivo and in vitro. CONCLUSIONS: Au3+ is toxic for E. coli because it triggers an unbalance of the bacterium's oxidative status. This was demonstrated by using oxidative stress dyes and antioxidant chemicals as well as gene reporters, RSH concentrations and AuNS generation.

Influence of protamine shell on nanoemulsions as a carrier for cyclosporine-A skin delivery.

Novel protamine-based nanosystems have been studied for cyclosporine-A (CsA) skin delivery. Core-shell structure systems have been developed to this end. These vehicles have particles sizes of 200-300 nm, a low polydispersity index and a zeta potential which varies between -16 mV and +35 mV. The resulting four nanosystems efficiently encapsulated CsA in their oily nucleus (60-80%) and released this drug in a controlled manner. These formulations have shown a high stability in aqueous suspension in storage conditions at 4 °C (for at least 21 months) and in acetate buffer at a physiological temperature of 37 °C (for at least 24 h). Ex vivo transdermal diffusion experiments using Franz diffusion cells and 2- to 3-day-old pig skin as a biological barrier were performed. All nanoformulations designed produced an increase in CsA transdermal delivery and two of these nanosystems presented a marked promoting effect; the more relevant parameters were smaller particle size (200 ± 7 nm) and negative superficial charge. Finally, the ability of these nanosystems to enhance retention of CsA in the skin was also studied. The protamine disposition in the shell influenced CsA skin retention. Therefore, the incorporation of CsA into the nanosystems studied here makes them suitable vehicles for CsA transdermal administration.

Realized niche and spatial pattern of native and exotic halophyte hybrids.

Interspecific hybridization is an important and common evolutionary mechanism, but field-based evaluations of changes in realized niches and zonation patterns of native and exotic hybrids relative to those of their parental plant species are rare. Would native hybrids forming hybrid zones between their parental species show realized niches similar to that of their parents, whereas would exotic hybrids show larger realized niches than their parents, and alter zonation patterns of native species? To address these questions, we examined key sediment characteristics in plots representing realized niches of native Sarcocornia hybrids, invasive Spartina hybrids and parental species in 14 salt marshes from four estuaries in the Gulf of Cadiz, Southwest Iberian Peninsula. In one representative marsh, the presence of plant taxa relative to intertidal plant zonation was recorded. Results documented that native and fertile hybrids of Sarcocornia had similar realized niche dimensions as their parental species and co-occurred with other plant species, supporting community diversity. However, exotic sterile hybrids of Spartina had realized niche dimensions lower than those of their parental species and occurred in monocultures. The native hybrids played a community structuring role, whereas the exotic Spartina hybrids were a disruptive influence that changed native halophyte zonation pattern and decreased diversity. This negative functional role could intensify if the sterile hybrids evolve and become fertile. Our study suggests the ecological niche dimension concept is an important tool for understanding species roles in ecosystems, incorporating many ideas from the individual to ecosystem levels.

Comparison of boiling and chlorination on the quality of stored drinking water and childhood diarrhoea in Indonesian households.

We compared the impact of a commercial chlorination product (brand name Air RahMat) in stored drinking water to traditional boiling practices in Indonesia. We conducted a baseline survey of all households with children 1000 MPN/100 ml (RR 1·86, 95% CI 1·09-3·19) in stored water than in households without detectable E. coli. Although results suggested that Air RahMat water treatment was associated with lower E. coli contamination and diarrhoeal rates among children <5 years than water treatment by boiling, Air RahMat use remained low.

[Morbimortality associated to nutritional status and feeding path in children with cerebral palsy]. / Morbimortalidad asociada al estado nutricional y vía de alimentación en niños con parálisis cerebral.

INTRODUCTION: Children and adolescents with cerebral palsy (CP) have a high prevalence of malnutrition associated to poor prognosis. For an adequate nutritional assessment, new growth curves (Brooks, 2011) are available, in which precise cut-off points in Weight/Age index correlate to increased morbidity and mortality rate. OBJECTIVE: To evaluate risk of hospitalization and death in patients with CP, according to nutritional risk (NR). PATIENTS AND METHOD: Observational and prospective cohort study of patients with CP in an outpatient referral center. We registered demographic, socioeconomic data and nutritional assessment. During a one-year follow-up, hospitalizations and mortality were recorded. The correspondent committee extended an ethical approval. RESULTS: 81 CP patients were recruit, age 131.6 ± 60.4 months (25-313), 60 % male, 77.5 % without independent mobility. The 23 NR patients (28.4%) had lower muscle and fat mass (p = 0.000). During the follow-up, 29/81 patients required hospitalization (35.8%) and 4/81 died (4.9%). There was not an increased risk of hospitalization and/or mortality in NR group, but both were significantly higher in gastrostomy-fed children (RR: 2,98 CI 95%: 1.32-6.75 combining both variables). CONCLUSIONS: In this study, children and adolescents with severe CP and nutritional risk had similar morbidity and mortality during a one-year follow-up, compared to those with acceptable nutritional status. Both risks were higher in gastrostomy-fed than the orally fed children.

Multibacillary leprosy mimicking systemic lupus erythematosus: case report and literature review.

Leprosy is an infectious chronic disease with a wide range of clinical and serological manifestations. We report a case of a woman presenting with a malar rash, painless oral ulcers, photosensitivity, arthritis, positive antinuclear antibodies test and leuko-lymphopenia. Our case illustrates an unusual presentation of leprosy initially diagnosed as systemic lupus erythematosus (SLE). After the confirmation of multibacillary leprosy and multidrug therapy recommended by the World Health Organization, a good clinical response was observed. Recognition of rheumatic manifestations in leprosy is important as they may be confused with SLE. A literature review is presented to encourage clinicians to consider leprosy as a differential diagnosis. Specifically in patients with unusual rheumatic manifestations and persistent skin lesions, and when neurological symptoms are present. Leprosy has not been eradicated, so misdiagnosis can be frequent. It is necessary to increase medical practitioner awareness in order start proper treatment.

Filamentous bacteria existence in aerobic granular reactors.

Filamentous bacteria are associated to biomass settling problems in wastewater treatment plants. In systems based on aerobic granular biomass they have been proposed to contribute to the initial biomass aggregation process. However, their development on mature aerobic granular systems has not been sufficiently studied. In the present research work, filamentous bacteria were studied for the first time after long-term operation (up to 300 days) of aerobic granular systems. Chloroflexi and Sphaerotilus natans have been observed in a reactor fed with synthetic wastewater. These filamentous bacteria could only come from the inoculated sludge. Thiothrix and Chloroflexi bacteria were observed in aerobic granular biomass treating wastewater from a fish canning industry. Meganema perideroedes was detected in a reactor treating wastewater from a plant processing marine products. As a conclusion, the source of filamentous bacteria in these mature aerobic granular systems fed with industrial effluents was the incoming wastewater.

Use of DMPC and DSPC lipids for verapamil and naproxen permeability studies by PAMPA.

Verapamil and naproxen Parallel Artificial Membrane Permeability Assay (PAMPA) permeability was studied using lipids not yet reported for this model in order to facilitate the quantification of drug permeability. These lipids are 1,2-distearoyl-sn-glycero-3-phosphatidylcholine (DSPC), 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and an equimolar mixture of DMPC/DSPC, both in the absence and in the presence of 33.3 mol% of cholesterol. PAMPA drug permeability using the lipids mentioned above was compared with lecithin-PC. The results show that verapamil permeability depends on the kind of lipid used, in the order DMPC > DMPC/DSPC > DSPC. The permeability of the drugs was between 1.3 and 3.5-times larger than those obtained in lecithin-PC for all the concentrations of the drug used. Naproxen shows similar permeability than verapamil; however, the permeability increased with respect to lecithin-PC only when DMPC and DMPC/DSPC were used. This behavior could be explained by a difference between the drug net charge at pH 7.4. On the other hand, in the presence of cholesterol, verapamil permeability increases in all lipid systems; however, the relative verapamil permeability respect to lecithin-PC did not show any significant increase. This result is likely due to the promoting effect of cholesterol, which is not able to compensate for the large increase in verapamil permeability observed in lecithin-PC. With respect to naproxen, its permeability value and relative permeability respect lecithin-PC not always increased in the presence of cholesterol. This result is probably attributed to the negative charge of naproxen rather than its molecular weight. The lipid systems studied have an advantage in drug permeability quantification, which is mainly related to the charge of the molecule and not to its molecular weight or to cholesterol used as an absorption promoter.

Genetic identification of Theobroma cacao L. trees with high Criollo ancestry in Soconusco, Chiapas, Mexico.

Criollo-type cacao trees are an important pool of genes with potential to be used in cacao breeding and selection programs. For that reason, we assessed the diversity and population structure of Criollo-type trees (108 cultivars with Criollo phenotypic characteristics and 10 Criollo references) using 12 simple sequence repeat (SSR) markers. Cultivars were selected from 7 demes in the Soconusco region of southern Mexico. SSRs amplified 74 alleles with an average of 3.6 alleles per population. The overall populations showed an average observed heterozygosity of 0.28, indicating heterozygote deficiency (average fixation index F = 0.50). However, moderate allelic diversity was found within populations (Shannon index for all populations I = 0.97). Bayesian method analysis determined 2 genetic clusters (K = 2) within individuals. In concordance, an assignment test grouped 37 multilocus genotypes (including 10 references) into a first cluster (Criollo), 54 into a second (presumably Amelonado), and 27 admixed individuals unassigned at the 90% threshold likely corresponding to the Trinitario genotype. This classification was supported by the principal coordinate analysis and analysis of molecular variance, which showed 12% of variation among populations (FST = 0.123, P < 0.0001). Sampled demes sites (1- 7) in the Soconusco region did not show any evidence of clustering by geographic location, and this was supported by the Mantel test (Rxy = 0.54, P = 0.120). Individuals with high Criollo lineage planted in Soconusco farms could be an important reservoir of genes for future breeding programs searching for fine, taste, flavor, and aroma cocoa.

Factors related to non-adherence to cardiac rehabilitation in patients with heart failure.

INTRODUCTION: In heart failure, cardiac rehabilitation has been recommended as an intervention strategy that improves functional capacity, health-related quality of life and survival. However, adherence to these programs is low. The objective was to determine the factors related to non-adherence to cardiac rehabilitation in patients with heart failure in Colombia. METHOD: Observational and retrospective study. Patients with heart failure were linked in a clinic in Colombia, adherence to cardiac rehabilitation was measured with ≥80% of scheduled sessions. Sociodemographic and clinical variables, functional aerobic capacity (Sit to Stand and 6-minute walk test), Duke Activity Status Index (DASI), quality of life Minnesota Living with Heart Failure Questionnaire (MLFHQ) and depression Patient health questionnaire 9 (PHQ-9) were taken into account. RESULTS: 300 patients were linked with heart failure with age 63.16 ± 12.87 men 194 (64.7%). adherence to cardiac rehabilitation was 66.67%, there were statistically significant differences between the groups in arterial hypertension, LVEF, cholesterol, LDL, Triglycerides, SBP, DBP, distance traveled, VO2e, METs, DASI and PHQ-9 p-value =<0.05. The logistic regression model adjusted for sex and age showed OR for non-adherence to CR arterial hypertension 2.23[1.22-4.07], LDL outside of goals 2.15[1.20-3.88], triglycerides outside goals 2.34[1.35-4.07], DASI<4METs 2.38 [1.04-5.45] and PHQ-9 1.06[1.00-1.12]. CONCLUSION: High blood pressure, LDL, triglycerides, DASI and depression with the PHQ-9 questionnaire are related factors for not having adherence to cardiac rehabilitation in patients with heart failure.

Effects of the cycle distribution on the performance of SBRs with aerobic granular biomass.

The aerobic granular systems are mainly sequencing batch reactors where the biomass is submitted to feast-famine regimes to promote its aggregation in the form of granules. In these systems, different cycle distributions can be applied for the simultaneous removal of organic matter, nitrogen and phosphorus. In this work two strategies were followed in order to evaluate the effects of the cycle distribution. In the first experiment, the length of the operational cycle was decreased in order to maximize the treatment capacity and consequently the famine/feast ratio was also decreased. In the second experiment, an initial anoxic phase was implemented to improve nitrogen removal efficiency. The results obtained showed that to reduce the famine/feast ratio from 10 to 5 was possible by increasing the treated organic and nitrogen loading rates in the system to 33%, without affecting the removal efficiencies of organic matter (97%) and nitrogen (64%) and producing a slight detriment of the granules characteristics. On the other hand, the implementation of an anoxic phase of 30 min previous to the aerobic one with a pulse-fed mode increased the nitrogen removal of pig manure from 20 to 60%, while the cycle configuration comprising a continuous feeding simultaneous with an anoxic phase of 60 min did not enhance the nitrogen removal and even worsen the ammonia oxidation.

[Hepatitis C virus genotype 5 in Mexico: a case report with successful treatment and a literature review]. / Hepatitis C genotipo viral 5 en México: reporte de caso con tratamiento exitoso y revisión de la literatura.

Hepatitis C virus (HCV) genotype 5 is extremely rare and there is very little reported on its management in the medical literature. We present herein the case of a patient with HCV genotype 5 that presumably acquired the disease through a blood transfusion during infancy. Sustained virologic response was achieved after 24 weeks of treatment. According to the available information on HCV genotype 5 treatment, it has a similar response to that of HCV genotype 1. Our patient presented with various favorable outcome factors. There is much less reported on the treatment of HCV genotype 5 than there is regarding HCV genotypes 1, 2, 3, and 4. This is mainly due to the low prevalence of genotype 5 in the Mexican environment.

Meta-analysis of pre-clinical studies on the effects of opioid receptor ligands on food intake, motivation, and choice.

The opioid receptors (OR) regulate food intake. Still, despite extensive pre-clinical research, the overall effects and individual contribution of the mu (MOR), kappa (KOR), and delta (DOR) OR subtypes to feeding behaviors and food intake remain unclear. To address this, we conducted a pre-registered systematic search and meta-analysis of rodent dose-response studies to evaluate the impact of central and peripheral administration of non-selective and selective OR ligands on intake, motivation, and choice of food. All studies had a high bias risk. Still, the meta-analysis confirmed the overall orexigenic and anorexigenic effects of OR agonists and antagonists, respectively. Our results support a larger orexigenic role for central MOR agonists among OR subtypes and that peripheral OR antagonists reduce motivation for and intake of preferred foods. In binary food choice studies, peripheral OR agonists selectively increase the intake of fat-preferred foods; in contrast, they did not increase the intake of sweet carbohydrate-preferred foods. Overall, these data support that OR regulation of intake, motivation, and choice is influenced by food macronutrient composition.

Innovative multiple nanoemulsion (W/O/W) based on Chilean honeybee pollen improves their permeability, antioxidant and antibacterial activity.

Beehive derivatives, including honeybee pollen (HBP), have been extensively studied for their beneficial health properties and potential therapeutic use. Its high polyphenol content gives it excellent antioxidant and antibacterial properties. Today its use is limited due to poor organoleptic properties, low solubility, stability, and permeability under physiological conditions. A novel edible multiple W/O/W nanoemulsion (BP-MNE) to encapsulate the HBP extract was designed and optimized to overcome these limitations. The new BP-MNE has a small size (∼100 nm), a zeta potential greater than +30 mV, and efficiently encapsulated phenolic compounds (∼82%). BP-MNE stability was measured under simulated physiological conditions and storage conditions (4 months); in both cases, stability was promoted. The formulation's antioxidant and antibacterial (Streptococcus pyogenes) activity was analyzed, obtaining a higher effect than the non-encapsulated compounds in both cases. In vitro permeability was tested, observing a high permeability of the phenolic compounds when they are nanoencapsulated. With these results, we propose our BP-MNE as an innovative solution to encapsulate complex matrices, such as HBP extract, as a platform to develop functional foods.

Aerobic granular SBR systems applied to the treatment of industrial effluents.

Four lab scale sequencing batch reactors (SBRs) were operated to remove organic matter and nitrogen from four different industrial wastewaters. The biomass grew in the reactors in the form of aerobic granules characterized by good settling properties. The high biomass concentrations achieved inside the reactors allowed reducing the solids concentration in the effluent down to 0.2 g VSS L(-1). The organic loading rates (OLR) applied to reactors ranged between 0.7 and 5.0 g CODL(-1)d(-1) with removal efficiencies of 60-95%. The nitrogen loading rates (NLR) applied varied between 0.15 and 0.65 g NH(4)(+)-NL(-1)d(-1) with variable removal efficiencies in the four systems (between 15% and 76%).

Evaluation of natural zeolite as microorganism support medium in nitrifying batch reactors: influence of zeolite particle size.

An evaluation of natural zeolite as a microorganism carrier in nitrifying reactors operated in batch mode was carried out. Specifically, the influence of zeolite particle sizes of 0.5, 1.0 and 2.0 mm in diameter on microorganism adherence to zeolite, ammonium adsorption capacity and the identification of microbial populations were assessed. The greatest amount of total biomass adhered was observed for a zeolite particle size of 1 mm (0.289 g) which was achieved on the 12th day of operation. The highest ammonium adsorption capacity was observed for a zeolite particle size of 0.5 mm, which was 64% and 31% higher than that observed for particle sizes of 1.0 and 2.0 mm, respectively. The maximum de-sorption values were also found for a zeolite particle size of 0.5 mm, although when equilibrium was reached the ammonium concentrations were similar to those observed for a zeolite particle size of 1.0 mm. It was also found that the experimental data on ammonium adsorption fitted very well to the Freundlich isotherm for the three particle sizes studied. Finally, the nitrifying reactors showed similar microbial populations independently of the particle size used as microorganism carrier. The dominant bacterial community was Gammaproteobacteria making up 80% of the total population found. Betaproteobacteria were also identified and made up 12% approx. of the total population. Ammonium Oxidant Betaproteobacteria and Nitrobacter were also detected.