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Scientifica 2024is well known for its medicinal properties. It has exhibited various pharmacological activities, such as antidiabetic, anti-inflammatory, and antimicrobial activities....
is well known for its medicinal properties. It has exhibited various pharmacological activities, such as antidiabetic, anti-inflammatory, and antimicrobial activities. Although this plant is used worldwide as a vegetable and medicinal ingredient in herbal medicines, its toxicity studies have not been conducted to date. This study attempts to understand its toxicity. The present study examined the activity of two enzymes, acetylcholinesterase and succinate dehydrogenase, as well as histopathological variations in the liver, intestine, and gills of zebrafish. The results of the acetylcholinesterase assay showed that the concentrations of 40 mg/L and 60 mg/L of the four extracts (leaf and fruit extracts of both varieties) exhibited increased enzyme activity. Interestingly, the leaves of the green fruit variety at a concentration of 60 mg/L showed the highest activity, with a value of 2.824 ± 0.0682 micromoles/min compared to the control value of 1.8347 ± 0.0046 micromoles/min. On the other hand, the succinate dehydrogenase assay revealed that the concentrations of 40 mg/L and 60 mg/L of the extracts decreased the enzyme activity. The highest inhibition was observed in the concentration of 60 mg/L of the leaves of the white-fruited variety and the green-fruited variety, with values of 1.884 ± 0.0482 micromoles/min compared to the control value of 2.747 ± 0.0046 micromoles/min. The studies on histopathological changes also demonstrated abnormalities in the brain, liver, intestine, and gills of zebrafish after the exposure to the extracts of . The severity of the damage varied from low to high concentraions. In general, this study sheds light on the safety profile of and highlights its potential toxicity in animal models. The findings suggest that more research is needed to fully understand the toxicity of this plant and its implications for human use.
PubMed: 38938544
DOI: 10.1155/2024/4689625 -
Journal of Cardiovascular Development... Jun 2024Trimethyl--oxide (TMAO) has been linked to peripheral artery disease (PAD). Taurisolo is a natural, balanced phytocomplex containing resveratrol, quercetin, catechins,...
Trimethyl--oxide (TMAO) has been linked to peripheral artery disease (PAD). Taurisolo is a natural, balanced phytocomplex containing resveratrol, quercetin, catechins, procianidins, gallic acid, and caffeic acid. Numerous studies have shown that Taurisolo reduces the damage of TMAO and exerts a protective effect on endothelial cells (ECs). The aim of this randomized, double-blind, single-center study was to evaluate the effects of Taurisolo on claudication in patients with PAD (Rutheford grade I, category II, Fontaine Classification: Stage IIA, American Medical Association Whole Person Impairment Classification: Class 0-WPI 0%) in two parallel groups of 31 patients. The primary outcomes were an increase in the pain-free walking distance and the ankle/brachial pressure index at the beginning and at the end of the treatment with Taurisolo. The secondary endpoint was the serum TMAO changes. The claudication distance improved by 14.1% in the Taurisolo group and by 2.0% in the placebo group, while the maximal distance increased by 15.8% and 0.6% only, respectively (both < 0.05). The TMAO plasma levels decreased from 3.97 ± 2.13 micromole/L to 0.87 ± 0.48 ( < 0.0001) in the treated group. All these changes were highly significant both in univariate mixed models as well as in the adjusted model. Ultimately, Taurisolo might be an effective intervention to ameliorate intermittent claudication.
PubMed: 38921674
DOI: 10.3390/jcdd11060174 -
Plants (Basel, Switzerland) Jun 2024Alpha-amylases are crucial hydrolase enzymes which have been widely used in food, feed, fermentation, and pharmaceutical industries. Methods for low-cost production of...
Alpha-amylases are crucial hydrolase enzymes which have been widely used in food, feed, fermentation, and pharmaceutical industries. Methods for low-cost production of α-amylases are highly desirable. Soybean seed, functioning as a bioreactor, offers an excellent platform for the mass production of recombinant proteins for its ability to synthesize substantial quantities of proteins. In this study, we generated and characterized transgenic soybeans expressing the α-amylase AmyS from . The α-amylase expression cassettes were constructed for seed specific expression by utilizing the promoters of three different soybean storage peptides and transformed into soybean via -mediated transformation. The event with the highest amylase activity reached 601 U/mg of seed flour (one unit is defined as the amount of enzyme that generates 1 micromole reducing ends per min from starch at 65 °C in pH 5.5 sodium acetate buffer). The optimum pH, optimum temperature, and the enzymatic kinetics of the soybean expressed enzyme are similar to that of the expressed enzyme. However, the soybean expressed α-amylase is glycosylated, exhibiting enhanced thermostability and storage stability. Soybean AmyS retains over 80% activity after 100 min at 75 °C, and the transgenic seeds exhibit no significant activity loss after one year of storage at room temperature. The accumulated AmyS in the transgenic seeds represents approximately 15% of the total seed protein, or about 4% of the dry seed weight. The specific activity of the transgenic soybean seed flour is comparable to many commercial α-amylase enzyme products in current markets, suggesting that the soybean flour may be directly used for various applications without the need for extraction and purification.
PubMed: 38891347
DOI: 10.3390/plants13111539 -
Nature Chemistry Apr 2024The importance of constructing Csp-Csp bonds has motivated the development of electrochemical, photochemical and thermal activation methods to reductively couple...
The importance of constructing Csp-Csp bonds has motivated the development of electrochemical, photochemical and thermal activation methods to reductively couple abundant aryl and alkyl electrophiles. However, these methodologies are limited to couplings of very specific substrate classes and require specialized sets of catalysts and reaction set-ups. Here we show a consolidation of these myriad strategies into a single set of conditions that enable reliable alkyl-aryl couplings, including those that were previously unknown. These reactions rely on the discovery of unusually persistent organonickel complexes that serve as stoichiometric platforms for C(sp)-C(sp) coupling. Aryl, heteroaryl or vinyl complexes of Ni can be inexpensively prepared on a multigram scale by mild electroreduction from the corresponding C(sp) electrophile. Organonickel complexes can be isolated and stored or telescoped directly to reliably diversify drug-like molecules. Finally, the procedure was miniaturized to micromole scales by integrating soluble battery chemistries as redox initiators, enabling a high-throughput exploration of substrate diversity.
PubMed: 38684816
DOI: 10.1038/s41557-024-01528-7 -
Autophagy Apr 2024Lyssaviruses are well-known worldwide and often cause fatal encephalitis. Previous studies have shown that autophagy is beneficial for the replication of rabies virus...
Lyssaviruses are well-known worldwide and often cause fatal encephalitis. Previous studies have shown that autophagy is beneficial for the replication of rabies virus (RABV), the representative lyssavirus, but the detailed mechanism remains obscure. In this study, we showed that the rabies virus matrix protein (RABV-M) used its PPxY motif to interact with the E3 ubiquitin-protein ligase NEDD4. NEDD4 then recruited MAP1LC3/LC3 via its LC3-interacting region (LIR). Interestingly, after binding to the ubiquitinated RABV-M, NEDD4 could bind more LC3 and enhance autophagosome accumulation, while NEDD4 knockdown significantly reduced M-induced autophagosome accumulation. Further study revealed that RABV-M prevented autophagosome-lysosome fusion and facilitated viral budding. Inhibition of RABV-M-induced autophagosome accumulation reduced the production of extracellular virus-like particles. We also found that M proteins of most lyssaviruses share the same mechanism to accumulate autophagosome by hijacking NEDD4. Collectively, this study revealed a novel strategy for lyssaviruses to achieve efficient viral replication by exploiting the host autophagy system. ABLV: Australian bat lyssavirus; ATG5: autophagy related 5; Baf A1:bafilomycin A;co-IP: co-immunoprecipitation; CQ: chloroquine; DAPI:4',6-diamidino-2'-phenylindole; DMSO: dimethyl sulfoxide; EBLV:European bat lyssavirus; GFP: green fluorescent protein; GST:glutathione S-transferase; hpi: hours post-infection; hpt: hourspost-transfection; LIR: LC3-interactingregion;MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; mCherry:red fluorescent protein; MOI: multiplicity of infection; NC: negativecontrol; MVB: multivesicular body; NEDD4: neural precursorcell-expressed developmentally down-regulated 4; RABV: rabies virus;SQSTM1/p62: sequestosome 1; VLP: virus-like particle; VPS4B: vacuolarprotein sorting 4B; TEM: transmission electron microscopy; WB:western blotting; WT: wild-type; μm: micrometer; μM: micromole.
PubMed: 38566321
DOI: 10.1080/15548627.2024.2338575 -
BMC Medical Genomics Mar 2024PKU is an autosomal recessive hereditary inborn error of metabolism caused by a lack of phenylalanine hydroxylase enzyme activity. Pegvaliase (PALYNZIQ®) treatment has...
BACKGROUND
PKU is an autosomal recessive hereditary inborn error of metabolism caused by a lack of phenylalanine hydroxylase enzyme activity. Pegvaliase (PALYNZIQ®) treatment has been approved to reduce blood Phe concentrations in adult phenylketonuria patients with uncontrolled blood Phe concentrations greater than 600 micromol/L on current management. However, data regarding individuals under the age of 16 is still unavailable.
CASE REPORT
We report a 12-year-old Saudi girl who underwent pegvaliase therapy and was closely monitored for one year. Remarkably, a positive therapeutic response became apparent six months after commencing pegvaliase treatment. Phenylalanine (Phe) levels showed significant improvement, stabilising within the < 5 to 14 µmol/L range on a regular diet without any restriction. At her current age of 12, the patient maintains an unrestricted dietary regimen, consuming a diverse selection of foods, including poultry, meat, and protein sources, all while consistently maintaining normal Phe levels with no change in mental status after treatment. The parents gave their written, informed consent in allowing the research study to be carried out and clinical data to be published.
CONCLUSIONS
This report addresses the potential broader applications of Pegvaliase in children, as well as its safety and tolerability in this age group. However, larger sample sizes and robust methodologies are required to validate such findings.
Topics: Child; Female; Humans; Food; Phenylalanine; Phenylalanine Ammonia-Lyase; Phenylketonurias; Recombinant Proteins
PubMed: 38515136
DOI: 10.1186/s12920-024-01847-1 -
Journal of the American Chemical Society Mar 20242'-Deoxynucleosides and analogues play a vital role in drug development, but their preparation remains a significant challenge. Previous studies have focused on...
2'-Deoxynucleosides and analogues play a vital role in drug development, but their preparation remains a significant challenge. Previous studies have focused on β-2'-deoxynucleosides with the natural β-configuration. In fact, their isomeric α-2'-deoxynucleosides also exhibit diverse bioactivities and even better metabolic stability. Herein, we report that both α- and β-2'-deoxynucleosides can be prepared with high yields and stereoselectivity using a remote directing diphenylphosphinoyl (DPP) group. It is particularly efficient to prepare α-2'-deoxynucleosides with an easily accessible 3,5-di-ODPP donor. Instead of acting as a H-bond acceptor on a 2-(diphenylphosphinoyl)acetyl (DPPA) group in our previous studies for syn-facial -glycosylation, the phosphine oxide moiety here acts as a remote participating group to enable highly antifacial -glycosylation. This proposed remote participation mechanism is supported by our first characterization of an important 1,5-briged -heterobicyclic intermediate via variable-temperature NMR spectroscopy. Interestingly, antiproliferative assays led to a α-2'-deoxynucleoside with IC values in the low micromole range against central nervous system tumor cell lines SH-SY5Y and LN229, whereas its β-anomer exhibited no inhibition at 100 μM. Furthermore, the DPP group significantly enhanced the antitumor activities by 10 times.
Topics: Humans; Neuroblastoma; Glycosylation; Phosphines
PubMed: 38483318
DOI: 10.1021/jacs.4c01780 -
Analytical Chemistry Mar 2024The oxygen isotope composition of phosphate is a useful tool for studying biogeochemical phosphorus cycling. However, the current AgPO method is not only tedious in PO...
The oxygen isotope composition of phosphate is a useful tool for studying biogeochemical phosphorus cycling. However, the current AgPO method is not only tedious in PO extraction and purification but also requires a large-sized sample at the micromole level, thereby limiting its application. Here, we present an approach to measuring the oxygen isotope composition, δO, of dissolved phosphate at the nanomole level using electrospray ionization Orbitrap mass spectrometry (ESI-Orbitrap-MS). We compared the reproducibility of δO measurements using the HPO ions (/ = 97 and 99 for HPO and HPOO, respectively) and using the PO fragment ions (/ = 79 and 81 for PO and POO, respectively) generated by source fragmentation and by higher-energy collisional dissociation, respectively. The results demonstrate that phosphate δO can be more reliably measured by the PO ions than by the HPO ions. PO generated by source fragmentation at 40 V achieved the highest reproducibility for δO based on precision tests. Furthermore, the mass spectrum for a 50:50 μM mixed solution of phosphate and sulfate revealed that PO ions resulting from source fragmentation at 40 V are the predominant species in the Orbitrap analyzer. Notably, PO ions (/: 79) are not interfered with by SO (/: 80) ions. This is in contrast to the case for HPO ions, which share the same / value with HSO ions and exhibit much lower signal intensity than HSO ions. Using the PO fragment method and six phosphate standards with a wide range of δO values, we obtained a calibration line with a slope of 0.94 ( = 0.98). The overall uncertainty for ESI-Orbitrap-MS phosphate δO measurement was 0.8‰ ( = 30; 1 SD). With much room for improvement, the PO fragment method presents a better approach to measuring the phosphate oxygen isotope composition, applicable to nanomole sample sizes in a liquid phase.
PubMed: 38447031
DOI: 10.1021/acs.analchem.3c03070 -
Brazilian Journal of Biology = Revista... 2024The consumption of products with high nutritional value and antioxidant capacity has increased notably in recent years. Due to health problems such as triglycerides and...
The consumption of products with high nutritional value and antioxidant capacity has increased notably in recent years. Due to health problems such as triglycerides and cardiovascular problems, its use is becoming reduced. So that, chia (Salvia hispánica) and sachatomate (Cyphomandra betacea) have gained interest as an alternative to develop nutraceutical products, compared to conventional products. The objective of the study was to determine the effect of the partial substitution of mango (Mangifera indica) and ground chia (Salvia hispánica) on the antioxidant capacity in the elaboration of nectar based on Sachatomate. The physicochemical characteristics were determined where sample 11 complies with the established parameters: 13.4° Brix, pH 4.323, 0.354 of C6-H8-O7 and viscosity 3967.3 mPas, according to the NTP 203.110 standard. Regarding the antioxidant capacity, sample 12 was the most optimal, according to the DPPH method, it has been determined 104.3 micromoles Trolox equivalents; according to the ABTS method, it was determined with an antioxidant content of 187.4 micromoles Trolox equivalents. Regarding the proximal chemical evaluation, sample 12 was determined to be the most suitable with a moisture percentage of 87.45%, ash 0.32%, crude fiber 0.09%, fat 0.10%, protein 0.45% and carbohydrates 11.59%. Concluding that substituting sachatomate and ground chia significantly influences the antioxidant capacity, increasing to 104.3 and 187.4 micromoles Trolox equivalents, determined by both methods, indicates that nectar consumption can be used to improve the health of consumers.
Topics: Antioxidants; Mangifera; Plant Nectar; Dietary Supplements; Seeds
PubMed: 38422270
DOI: 10.1590/1519-6984.277515 -
Pakistan Journal of Biological Sciences... Jan 2024<b>Background and Objective:</b> Diabetic foot ulcer (DFU) is a well-recognized vascular complication of uncontrolled diabetes mellitus. Unless immediate...
<b>Background and Objective:</b> Diabetic foot ulcer (DFU) is a well-recognized vascular complication of uncontrolled diabetes mellitus. Unless immediate measures are taken some patients end up with amputation. The hallmarks of DFU are hyperglycemia, neuropathy, ischemia and infection (Andrew). Recent studies confirmed the role of low serum arginine in the development of foot ulcer in diabetic patients. The current study aimed to investigate the relationship between low serum magnesium and diabetic foot ulcer and to identify the incidence of low plasma arginine levels in diabetic patients with DFU in Sudan. <b>Materials and Methods:</b> A total of 120 subjects were recruited in this study and were divided into three groups, namely, diabetic with foot ulcer (group-I), diabetic without foot ulcer (group-II) and non-diabetic healthy subjects (group-III). These subjects were investigated for FBS, HbA1c and serum arginine. Data were analysed using SPSS (28th release). <b>Results:</b> Analysis of the results obtained showed significantly marked reduced plasma arginine levels in group I than the other two groups where mean plasma arginine level was 12.08, 49.25 and 94.1 micromole/L, respectively. There was no statistical difference between the duration of diabetes and DFU in diabetic patients with DFU and diabetic patients without DFU, as well as levels of HbA1c (p-value 0.457, 0.89) respectively. <b>Conclusion:</b> The low serum arginine levels were significantly associated with foot ulcers in diabetic patients and play an important role in the development of diabetic foot ulcers.
Topics: Humans; Diabetic Foot; Glycated Hemoglobin; Hyperglycemia; Amputation, Surgical; Incidence; Risk Factors; Diabetes Mellitus
PubMed: 38413397
DOI: 10.3923/pjbs.2024.46.51