Glucose-6-phosphate Dehydrogenase Research Articles

Biogenic selenium nanoparticles and selenium/chitosan-Nanoconjugate biosynthesized by Streptomyces parvulus MAR4 with antimicrobial and anticancer potential

BackgroundAs antibiotics and chemotherapeutics are no longer as efficient as they once were, multidrug resistant (MDR) pathogens and cancer are presently considered as two of the most dangerous threats to human life. In this study, Selenium nanoparticles (SeNPs) biosynthesized by Streptomyces parvulus MAR4, nano-chitosan (NCh), and their nanoconjugate (Se/Ch-nanoconjugate) were suggested to be efficacious antimicrobial and anticancer agents.ResultsSeNPs biosynthesized by Streptomyces parvulus MAR4 and NCh were successfully achieved and conjugated. The biosynthesized SeNPs were spherical with a mean diameter of 94.2 nm and high stability. Yet, Se/Ch-nanoconjugate was semispherical with a 74.9 nm mean diameter and much higher stability. The SeNPs, NCh, and Se/Ch-nanoconjugate showed significant antimicrobial activity against various microbial pathogens with strong inhibitory effect on their tested metabolic key enzymes [phosphoglucose isomerase (PGI), pyruvate dehydrogenase (PDH), glucose-6-phosphate dehydrogenase (G6PDH) and nitrate reductase (NR)]; Se/Ch-nanoconjugate was the most powerful agent. Furthermore, SeNPs revealed strong cytotoxicity against HepG2 (IC50 = 13.04 μg/ml) and moderate toxicity against Caki-1 (HTB-46) tumor cell lines (IC50 = 21.35 μg/ml) but low cytotoxicity against WI-38 normal cell line (IC50 = 85.69 μg/ml). Nevertheless, Se/Ch-nanoconjugate displayed substantial cytotoxicity against HepG2 and Caki-1 (HTB-46) with IC50 values of 11.82 and 7.83 μg/ml, respectively. Consequently, Se/Ch-nanoconjugate may be more easily absorbed by both tumor cell lines. However, it exhibited very low cytotoxicity on WI-38 with IC50 of 153.3 μg/ml. Therefore, Se/Ch-nanoconjugate presented the most anticancer activity.ConclusionThe biosynthesized SeNPs and Se/Ch-nanoconjugate are convincingly recommended to be used in biomedical applications as versatile and potent antimicrobial and anticancer agents ensuring notable levels of biosafety, environmental compatibility, and efficacy.

Tafenoquine following G6PD screening versus primaquine for the treatment of vivax malaria in Brazil: A cost-effectiveness analysis using a transmission model.

Malaria transmission modelling has demonstrated the potential impact of semiquantitative glucose-6-phosphate dehydrogenase (G6PD) testing and treatment with single-dose tafenoquine for Plasmodium vivax radical cure but has not investigated the associated costs. This study evaluated the cost-effectiveness of P. vivax treatment with tafenoquine after G6PD testing using a transmission model. We explored the cost-effectiveness of using tafenoquine after G6PD screening as compared to usual practice (7-day low-dose primaquine (0.5 mg/kg/day) without G6PD screening) in Brazil using a 10-year time horizon with 5% discounting considering 4 scenarios: (1) tafenoquine for adults only assuming 66.7% primaquine treatment adherence; (2) tafenoquine for adults and children aged >2 years assuming 66.7% primaquine adherence; (3) tafenoquine for adults only assuming 90% primaquine adherence; and (4) tafenoquine for adults only assuming 30% primaquine adherence. The incremental cost-effectiveness ratios (ICERs) were estimated by dividing the incremental costs by the disability-adjusted life years (DALYs) averted. These were compared to a willingness to pay (WTP) threshold of US$7,800 for Brazil, and one-way and probabilistic sensitivity analyses were performed. All 4 scenarios were cost-effective in the base case analysis using this WTP threshold with ICERs ranging from US$154 to US$1,836. One-way sensitivity analyses showed that the results were most sensitive to severity and mortality due to vivax malaria, the lifetime and number of semiquantitative G6PD analysers needed, cost per malaria episode and per G6PD test strips, and life expectancy. All scenarios had a 100% likelihood of being cost-effective at the WTP threshold. The main limitations of this study are due to parameter uncertainty around our cost estimates for low transmission settings, the costs of G6PD screening, and the severity of vivax malaria. In our modelling study that incorporated impact on transmission, tafenoquine prescribed after a semiquantitative G6PD testing was highly likely to be cost-effective in Brazil. These results demonstrate the potential health and economic importance of ensuring safe and effective radical cure.

Reference spectrophotometric values for glucose-6-phosphate dehydrogenase activity in two-to six-month-old infants on the Thailand-Myanmar border.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency represents a barrier to the full deployment of anti-malarial drugs for vivax malaria elimination and of first-line antibiotics. Lack of established reference ranges for G6PD activity in breast-fed infants puts them at risk of drug-induced haemolysis and restricts access to safe treatment of their mothers. The present work was undertaken to establish age-specific G6PD normal values using the gold standard spectrophotometric assay to support the future clinical use of tafenoquine in lactating women and safer antibiotic treatment in infants. Spectrophotometric results collected at the Thai-Myanmar border from 78 healthy infants between the ages of 2 and 6 months showed a trend of decreased enzymatic activity with increasing age (which did not reach statistical significance when comparing 2-3 months old against 4-6 months old infants) and provided a reference normal value of 100% activity for infants 2-6 months old of 10.18IU/gHb. Normal reference G6PD activity in 2-6-month-old infants was approximately 140% of that observed in G6PD normal adults from the same population. Age specific G6PD activity thresholds should be used in paediatric populations to avoid drug-induced haemolysis.

Vivax malaria: a possible stumbling block for malaria elimination in India.

Plasmodium vivax is geographically the most widely dispersed human malaria parasite species. It has shown resilience and a great deal of adaptability. Genomic studies suggest that P. vivax originated from Asia or Africa and moved to the rest of the world. Although P. vivax is evolutionarily an older species than Plasmodium falciparum, its biology, transmission, pathology, and control still require better elucidation. P. vivax poses problems for malaria elimination because of the ability of a single primary infection to produce multiple relapses over months and years. P. vivax malaria elimination program needs early diagnosis, and prompt and complete radical treatment, which is challenging, to simultaneously exterminate the circulating parasites and dormant hypnozoites lodged in the hepatocytes of the host liver. As prompt surveillance and effective treatments are rolled out, preventing primaquine toxicity in the patients having glucose-6-phosphate dehydrogenase (G6PD) deficiency should be a priority for the vivax elimination program. This review sheds light on the burden of P. vivax, changing epidemiological patterns, the hurdles in elimination efforts, and the essential tools needed not just in India but globally. These tools encompass innovative treatments for eliminating dormant parasites, coping with evolving drug resistance, and the development of potential vaccines against the parasite.

RORα inhibits gastric cancer proliferation through attenuating G6PD and PFKFB3 induced glycolytic activity

BackgroundGlycolysis is critical for harvesting abundant energy to maintain the tumor microenvironment in malignant tumors. Retinoic acid-related orphan receptor α (RORα) has been identified as a circadian gene. However, the association of glycolysis with RORα in regulating gastric cancer (GC) proliferation remains poorly understood.MethodsBioinformatic analysis and retrospective study were utilized to explore the role of RORα in cell cycle and glycolysis in GC. The mechanisms were performed in vitro and in vivo including colony formation, Cell Counting Kit-8 (CCK-8), Epithelial- mesenchymal transition (EMT) and subcutaneous tumors of mice model assays. The key drives between RORα and glycolysis were verified through western blot and chip assays. Moreover, we constructed models of high proliferation and high glucose environments to verify a negative feedback and chemoresistance through a series of functional experiments in vitro and in vivo.ResultsRORα was found to be involved in the cell cycle and glycolysis through a gene set enrichment analysis (GSEA) algorithm. GC patients with low RORα expression were not only associated with high circulating tumor cells (CTC) and high vascular endothelial growth factor (VEGF) levels. However, it also presented a positive correlation with the standard uptake value (SUV) level. Moreover, the SUVmax levels showed a positive linear relation with CTC and VEGF levels. In addition, RORα expression levels were associated with glucose 6 phosphate dehydrogenase (G6PD) and phosphofructokinase-2/fructose-2,6-bisphosphatase (PFKFB3) expression levels, and GC patients with low RORα and high G6PD or low RORα and high PFKFB3 expression patterns had poorest disease-free survival (DFS). Functionally, RORα deletion promoted GC proliferation and drove glycolysis in vitro and in vivo. These phenomena were reversed by the RORα activator SR1078. Moreover, RORα deletion promoted GC proliferation through attenuating G6PD and PFKFB3 induced glycolytic activity in vitro and in vivo. Mechanistically, RORα was recruited to the G6PD and PFKFB3 promoters to modulate their transcription. Next, high proliferation and high glucose inhibited RORα expression, which indicated that negative feedback exists in GC. Moreover, RORα deletion improved fluorouracil chemoresistance through inhibition of glucose uptake.ConclusionRORα might be a novel biomarker and therapeutic target for GC through attenuating glycolysis.

Evaluating the relationship between Clinical G6PD enzyme activity and gene variants.

Glucose-6-phosphate dehydrogenase (G6PD) is a the first and rate-limiting enzyme that plays a critical role in G6PD deficiency, the most common enzyme disorder worldwide, is related to intravascular hemolysis. To determine the clinical enzyme activity level in different G6PD variants, we evaluated 15 variant from 424 clinical blood samples by using multicolor melting curve analysis and DNA sequencing. The results showed that the enzyme activities of the hemizygous deficient were 1.5-2.4 U/gHb, which was significantly lower than those of the heterozygous (P < 0.001) and the compound heterozygous variants (P < 0.05). Since the hemizygous of c.1024C > T (Chinese-5) mutation affects the kinetic parameters of G6PD and increase utilization of analogues, its enzyme activity is more than those of other mutations that mutated in the β+α region of G6PD. The heterozygous enzyme levels ranged from 6.5-20.1 U/gHb; and there was no significant difference among different heterozygous variants (P > 0.05). The enzyme activity levels of the compound heterozygous mutation were mainly in the range of 1.7-3.8 U/gHb, which was much lower than that of the heterozygous mutation (P < 0.001). In summary, our findings revealed that the enzyme activity of G6PD in blood have a significant relationship with genotype of G6PD.

Glucose 6-phosphate dehydrogenase variants increase NADPH pools for yeast isoprenoid production.

Isoprenoid biosynthesis has a significant requirement for the co-factor NADPH. Thus, increasing NADPH levels for enhancing isoprenoid yields in synthetic biology is critical. Previous efforts have focused on diverting flux into the pentose phosphate pathway or overproducing enzymes that generate NADPH. In this study, we instead focused on increasing the efficiency of enzymes that generate NADPH. We first established a robust genetic screen that allowed us to screen improved variants. The pentose phosphate pathway enzyme, glucose 6-phosphate dehydrogenase (G6PD), was chosen for further improvement. Different gene fusions of G6PD with the downstream enzyme in the pentose phosphate pathway, 6-phosphogluconolactonase (6PGL), were created. The linker-less G6PD-6PGL fusion displayed the highest activity, and although it had slightly lower activity than the WT enzyme, the affinity for G6P was higher and showed higher yields of the diterpenoid sclareol in vivo. A second gene fusion approach was to fuse G6PD to truncated HMG-CoA reductase, the rate-limiting step and also the major NADPH consumer in the pathway. Both domains were functional, and the fusion also yielded higher sclareol levels. We simultaneously carried out a rational mutagenesis approach with G6PD, which led to the identification of two mutants of G6PD, N403D and S238QI239F, that showed 15-25% higher activity in vitro. The diterpene sclareol yields were also increased in the strains overexpressing these mutants relative to WT G6PD, and these will be very beneficial in synthetic biology applications.

Carrier frequency estimation of pathogenic variants of autosomal recessive and X-linked recessive mendelian disorders using exome sequencing data in 1,642 Thais

BackgroundPeople with autosomal recessive disorders often were born without awareness of the carrier status of their parents. The American College of Medical Genetics and Genomics (ACMG) recommends screening 113 genes known to cause autosomal recessive and X-linked conditions in couples seeking to learn about their risk of having children with these disorders to have an appropriate reproductive plan.MethodsWe analyzed the exome sequencing data of 1,642 unrelated Thai individuals to identify the pathogenic variant (PV) frequencies in genes recommended by ACMG.ResultsIn the 113 ACMG-recommended genes, 165 PV and likely PVs in 60 genes of 559 exomes (34%, 559/1642) were identified. The carrier rate was increased to 39% when glucose-6-phosphate dehydrogenase (G6PD) was added. The carrier rate was still as high as 14.7% when thalassemia and hemoglobinopathies were excluded. In addition to thalassemia, hemoglobinopathies, and G6PD deficiency, carrier frequencies of > 1% were found for Gaucher disease, primary hyperoxaluria, Pendred syndrome, and Wilson disease. Nearly 2% of the couples were at risk of having offsprings with the tested autosomal recessive conditions.ConclusionsBased on the study samples, the expanded carrier screening, which specifically targeted common autosomal recessive conditions in Thai individuals, will benefit clinical outcomes, regarding preconception/prenatal genetic carrier screening.

Prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency among the fulminant hepatitis A virus infection patients.

Hepatitis A is a widespread viral infection with significant public health implications. Assessing glucose 6-phosphate dehydrogenase (G6PD) deficiency in hepatitis A patients is essential for various reasons, including prognosis, disease severity evaluation, encephalopathy risk identification, tailored management, and advancing scientific understanding. This study aimed to investigate the prevalence and clinical implications of G6PD impairment in individuals with fulminant hepatitis A. A cross-sectional descriptive analysis was conducted, involving hospitalized patients with fulminant hepatitis A. Demographic data, prevalence rates, and clinical findings were recorded in a database. The diagnosis of hepatitis A infection was confirmed using an anti-HAV IgM antibody test, and G6PD enzyme activity was measured with a fluorescent spot assay. Out of 81 patients with hepatitis A, 57 (70.4%) were males, and 24 (29.5%) were females, with an average age of 24.6 years. Dark yellow urine and anorexia were the most common clinical symptoms. Notably, 30 (37%) patients lacked G6PD. The group with G6PD deficiency showed significantly higher rates of encephalopathy and mortality (P<0.01), along with elevated bilirubin (P=0.00), abnormal coagulation parameters, and low hemoglobin levels (P=0.00). In light of these findings, the present study proposes the implementation of routine G6PD level assessments and the evaluation of other relevant markers in regions where hepatitis A is endemic. Furthermore, the study underscores the need for vigilant monitoring of hemolysis and encephalopathy in affected patients to optimize clinical management and reduce morbidity and mortality associated with this condition.

Prevalence of Glucose-6-Phosphate Dehydrogenase deficiency among Hausa and Fulani ethnics in Kano, North-West Nigeria

Background: Glucose-6-phosphate dehydrogenase catalyzes the rate-determining step in the pentose phosphate pathway. Its activity is a key determinant of the reduced nicotinamide adenine dinucleotide phosphate to oxidized nicotinamide adenine dinucleotide phosphate (NADPH-to-NADP+) ratio in the cytoplasm and thus contributes to the replenishment of the antioxidant glutathione system. Glucose-6-phosphate dehydrogenase deficiency is a common X-linked human enzyme defect of red blood cells. Individuals with this gene defect appear normal until exposed to oxidative stress which induces haemolysis but it is infrequently taken into consideration in health practices. Aim: The present work was designed to determine the frequency of occurrence of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency among Hausa and Fulani ethnics. Material and methods: Cross-sectional comparative study in which 5 mL of venous blood samples were collected from 1000 individuals (596 males and 404 females) all of whom gave informed consent were screened for G-6-PD-deficiency by qualitative methaemoglobin reduction and quantitative enzyme activity measurement techniques. Results: Glucose-6-phoshate dehydrogenase deficiency was found in 194 (19.4%) of participants studied. Of these 10.3% were Fulani and 22.2% were Hausa with mean G-6-PD enzyme activity of 2.5 IU/gHb in a range from 1.4 to 2.4 IU/gHb. G-6-PD deficiency was found in 121 of 596 (20.3%) males and 73 of 404 (18.1%) females screened. Conclusions: These results suggest high occurrence of phenotypic G-6-PD deficiency in Hausa ethnics of Kano with lower enzyme status among males living with G-6-PD deficiency.

The global role of G6PD in infection and immunity.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy in humans. G6PD is an essential enzyme in the pentose phosphate pathway (PPP), generating NADPH needed for cellular biosynthesis and reactive oxygen species (ROS) homeostasis, the latter especially key in red blood cells (RBCs). Beyond the RBC, there is emerging evidence that G6PD exerts an immunologic role by virtue of its functions in leukocyte oxidative metabolism and anabolic synthesis necessary for immune effector function. We review these here, and consider the global immunometabolic role of G6PD activity and G6PD deficiency in modulating inflammation and immunopathology.

Glucose-6-phosphate dehydrogenase enzyme deficiency as a diagnostic factor of diabetes mellitus: An original study.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the most common genetic disorders affecting approximately 400 million people worldwide. Several recent studies have reported a relationship between G6PD deficiency and the incidence of diabetes. The aim of the present study was to evaluate and compare levels of G6PD deficiency in diabetes mellitus patients. G6PD activity and fasting glucose levels were measured in blood samples of 49 diabetic patients and 21 healthy controls. G6PD activity was decreased in patients with diabetes mellitus as compared to healthy controls and showed that overall G6PD deficiency was significantly associated with diabetes mellitus as compared to nondiabetics. The study concluded that G6PD deficiency is noted in diabetics than in nondiabetics and can be a biomarker of oxidative stress and poor glycemic control in diabetes mellitus.

Implementation of Glucose-6-Phosphate Dehydrogenase (G6PD) testing for Plasmodium vivax case management, a mixed method study from Cambodia.

Plasmodium vivax remains a challenge for malaria elimination since it forms dormant liver stages (hypnozoites) that can reactivate after initial infection. 8-aminoquinolone drugs kill hypnozoites but can cause severe hemolysis in individuals with Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency. The STANDARD G6PD test (Biosensor) is a novel point-of-care diagnostic capable of identifying G6PD deficiency prior to treatment. In 2021, Cambodia implemented the Biosensor to facilitate radical cure treatment for vivax malaria. To assess the Biosensor's implementation after its national rollout, a mixed-methods study was conducted in eight districts across three provinces in Cambodia. Interviews, focus group discussions, and observations explored stakeholders' experiences with G6PD testing and factors influencing its implementation. Quantitative data illustrative of test implementation were gathered from routine surveillance forms and key proportions derived. Qualitative data were analyzed thematically. The main challenge to implementing G6PD testing was that only 49.2% (437/888) of eligible patients reached health centers for G6PD testing following malaria diagnosis by community health workers. Factors influencing this included road conditions and long distances to the health center, compounded by the cost of seeking further care and patients' perceptions of vivax malaria and its treatment. 93.9% (790/841) of eligible vivax malaria patients who successfully completed referral (429/434) and directly presented to the health center (360/407) were G6PD tested. Key enabling factors included the test's acceptability among health workers and their understanding of the rationale for testing. Only 36.5% (443/1213) of eligible vivax episodes appropriately received primaquine. 70.5% (165/234) of female patients and all children under 20 kilograms never received primaquine. Our findings suggest that access to radical cure requires robust infrastructure and income security, which would likely improve referral rates to health centers enabling access. Bringing treatment closer to patients, through community health workers and nuanced community engagement, would improve access to curative treatment of vivax malaria.

In Situ Mapping of the Glucose Metabolism Heterogeneity in Atherosclerosis: Correlation With 2-Deoxyglucose Uptake

Objective 2-Deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is widely used for noninvasive imaging of atherosclerosis. However, knowledge about metabolic processes underlying [18F]FDG uptake is mostly derived from in vitro cell culture studies, which cannot recapitulate the complexities of the plaque microenvironment. Here, we sought to address this gap by in situ mapping of the activity of selected major dehydrogenases involved in glucose metabolism in atherosclerotic plaques. Methods In situ activity of lactate dehydrogenase (LDH), glucose-6-phosphate dehydrogenase (G6PD), succinate dehydrogenase (SDH), and isocitrate dehydrogenase (IDH) was assessed in plaques from murine aortic root and brachiocephalic arteries and human carotid arteries. High-resolution 2-deoxy-D-[1,2-3H]glucose ([3H]2-deoxyglucose) autoradiography of murine brachiocephalic plaques was performed. Results LDH activity was heterogeneous throughout the plaques with the highest activity in medial smooth muscle cells (SMCs). G6PD activity was mostly confined to the medial layer and to a lesser extent to SMCs along the fibrous cap. SDH and IDH activities were minimal in plaques. Plaque regions with increased [3H]2-deoxyglucose uptake were associated with a modestly higher LDH, but not G6PD, activity. Conclusions Our study reveals a novel aspect of the metabolic heterogeneity of the atherosclerotic plaques, enhancing our understanding of the complex immunometabolic biology that underlies [18F]FDG uptake in atherosclerosis.

Azo derivatives of monoterpenes as anti-Helicobacter pylori agents: from synthesis to structure-based target investigation.

Helicobacter pylori (Hp) infection affects nearly half of the global population. Current therapeutic options include the administration of a combination of antibiotics and proton pump inhibitors, although antimicrobial resistance rise remains a big concern. Phenolic monoterpenes, e.g., eugenol, vanillin, carvacrol, and thymol, have always attracted researchers for their multifaced biological activities and the possibility to be easily derivatized. Thereby, herein we present the functionalization of such compounds through the conventional aryl diazotization reaction, generating a series of mono- and bis-azo derivatives (1-28). Also, to continue previous studies, we investigated the role of the free phenolic moiety of thymol with eight compounds (29-36). The compounds were tested against four Hp strains including three clinical isolates, finding some potent and selective inhibitors of bacterial growth. Thus, the representative compounds underwent in vitro cytotoxicity evaluation on two normal cell lines and putative target investigation by performing a structure-based approach based on docking calculations on some of the most studied pharmacological targets for Hp, e.g., urease, β-hydroxyacyl-acyl carrier protein dehydratase, glucose 6-phosphate dehydrogenase, and inosine 5'-monophosphate dehydrogenase.

Oleuropein ameliorates hyperlipidemia, oxidative stress, inflammatory and liver dysfunction biomarkers, in streptozotocin-induced diabetic rats

Diabetes mellitus (DM) is a serious threat factor for chronic liver disorders and the development of nonalcoholic steatohepatitis into cirrhosis. However, numerous pharmacological actions of olive polyphenol have been discovered, with oleuropein being a primary phenolic substance found in olive leaves, olive oil, and olive fruit (Olea europaea). Our goal is to identify the impacts of oleuropein on lipid measurements, oxidative stress, serum leptin, adiponectin levels, inflammatory status, and hepatic dysfunctions in a male rat model with streptozotocin (STZ)-induced DM. Oleuropein was orally administered to diabetic rats at a 5 mg/kg bw/day dose for 15 days. Diabetic rats treated with oleuropein demonstrated improved hepatic function test results (ALT, AST, alkaline phosphatase, and bilirubin), while activity of the low liver glucose-6-phosphate dehydrogenase (G6PDH) increased. Moreover, serum triacylglycerol, very low-density lipoprotein, low-density lipoprotein, and total cholesterol (TC) were considerably reduced, while high-density lipoprotein increased markedly. In addition, serum antioxidative enzymes such as glutathione peroxidase, catalase, glutathione-S-transferase, and superoxide dismutase increased, as well as glutathione levels. Lipid peroxidation levels were lower than those in the STZ control group. Treating diabetic rats with oleuropein not only resulted in decreased serum leptin and increased adiponectin levels but also had a substantial inhibitory effect on the elevated COX-2 and TNF-α mRNA expression levels in the livers of the STZ group. In conclusion, oleuropein has shown promising results in mitigating hyperlipidemia, oxidative stress, inflammation, and hepatic dysfunction biomarkers in diabetic rats.

Oleic Acid and Succinic Acid: A Potent Nutritional Supplement in Improving Hepatic Glycaemic Control in Type 2 Diabetic Sprague–Dawley Rats

Nutritional supplements are gaining traction for their effects in mitigating the impacts of various health conditions. In particular, many supplements are being proposed to reduce the impacts of type 2 diabetes (T2D), a metabolic condition that has reached global epidemic proportions. Recently, a supplement of oleic acid (OA) and succinic acid (SA; 1 : 1, w/w) was reported to improve glycaemic control in type 2 diabetic (T2D) Sprague–Dawley (S‐D) rats through ameliorating insulin release and sensitivity. Here, we investigate the effects of the supplement (OA and SA) on hepatic and pancreatic function in T2D S‐D rats. Eighteen (18) S‐D rats were rendered diabetic and were divided into three equal groups: diabetic control, diabetic treatment, and diabetic glibenclamide. Another 12 S‐D rats were obtained and served as the normal groups. The animals were treated daily with the vehicle, OA and SA (800 mg/kg body weight (bw); 1 : 1), or glibenclamide (10 mg/kg bw) which served as the positive control. The findings indicated that treatment with the supplement resulted in a 35.69 ± 4.22% reduction (p = 0.006) in blood glucose levels (BGL). Analysis of hepatic enzymes depicted that the nutritional supplement reduced the activity of the gluconeogenesis enzyme, glucose‐6‐phosphatase (G6P) while improved the activity of catabolic enzymes such as glucose‐6‐phosphate dehydrogenase (G6PD) and pyruvate kinase (PK). Furthermore, the supplement attenuated oxidative stress through restoration of catalase (CAT) and superoxide dismutase (SOD), while reducing malondialdehyde (MDA) levels. Finally, the supplement showed no liver or kidney toxicity and improved the size and number of pancreatic islets of Langerhans, indicating its potential application in treating T2D. The study highlighted that a supplement of the two organic acids may be beneficial in reducing the rate of pathogenesis of type 2 diabetes. Therefore, it may offer therapeutic value as a dietary or nutritional supplement in the approach against diabetes and its complications.

Social Media Content Analysis of Public and Private Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency Facebook Groups

Social Media Content Analysis of Public and Private Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency Facebook Groups

Outcome of Expanded Newborn Screening Among 194 000 Neonates at Northeast México.

Objectives. To describe the results of a 16-year experience of a state-coverage expanded newborn screening program (NBSP) in Northeast México. Methods. Between 2002 and 2017, dried blood spots of newborns were screened for congenital hypothyroidism (CH), congenital adrenal hyperplasia (CAH), biotinidase deficiency, galactosemia, cystic fibrosis, and glucose-6-phosphate dehydrogenase (G6PD) deficiency via immunofluorescence and amino and fatty acid disorders and organic acidemias using tandem mass spectrometry. Frequency rates were determined. Results. Overall, 192 487 samples were processed; 99.4% had negative results, and 598 were diagnosed. The frequency was 3.01/1000 newborns. G6PD deficiency, CH, amino acidemia, organic acidemia, cystic fibrosis, CAH, fatty acid oxidation disorder, galactosemia, and biotinidase deficiency cases were 1:773, 1:962, 1:4277, 1:4476, 1:11,322, 1:10,693, 1:10,693, 1:38,497, and 1:64,162, respectively. Conclusion. Using different technologies in NBSP increased the number of conditions detected, facilitating infant morbidity and mortality prevention. The frequency of disorders depends on the population's genetic background and diagnostic capacity.

The dynamic relationship between inorganic polyphosphate and adenosine triphosphate in human non-small cell lung cancer H1299 cells.

Inorganic polyphosphate (polyP) plays a vital role in cellular energy metabolism and signaling, owing to its structure and high-energy phosphate bonds. Intracellular ATP functions both as a cellular energy source and a key factor in cell death, and ATP dynamics in tumor cells are crucial for advancing cancer therapy. In this study, we explored the interplay between polyP and ATP in cellular energy metabolism. Treatment with polyP did not affect cell proliferation of human non-small cell lung cancer H1299 and human glioblastoma T98G cell lines as compared to their respective control cells until 72 h post-treatment. The mitochondrial membrane potential (MMP) in polyP-treated cells was low, contrasting with the time-dependent increase observed in control cells. While the ATP content increased over time in untreated and Na-phosphate-treated control cells, it remained unchanged in polyP-treated cells. Furthermore, the addition of cyclosporine A, a mitochondrial permeability transition pore (mPTP) inhibitor, failed to restore ATP levels in polyP-treated cells. We performed lactate assays and western blot analysis to evaluate the effect of polyP on glucose metabolism and found no significant differences in lactate secretion or glucose-6-phosphate dehydrogenase (G6PD) activity between polyP-treated and control cells. Additional pyruvate restored MMP but had no effect on the cellular ATP content in polyP-treated cells. We observed no correlation between the Warburg effect and glucose metabolism during ATP depletion in polyP-treated cells. Further investigation is warranted to explore the roles of polyP and ATP in cancer cell energy metabolism, which might offer potential avenues for therapeutic interventions.