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Studies have shown that decreased expression of glucose-6-phosphate dehydrogenase (G6PD) play an important role in DKD. However, the upstream and downstream pathways of G6PD downregulation leading to DKD have not been elucidated.We conducted a series of studies including clinical study, animal studies, and in vitro studies to explore this. Firstly, a total of 90 subjects were evaluated. The urinary G6PD activity and its association with the clinical markers were analyzed. Then, urine differentially microRNAs that can bind and degrade G6PD were screened and verified in DKD patients. After that, high glucose (HG)-cultured Human kidney cells (HK-2) and Zucker diabetic fatty (ZDF) rats were used to test the roles of miR-7977/G6PD/albumin-induced autophagy in DKD. The plasma and urinary G6PD activity were decreased significantly in patients with DKD, accompanied by increased urinary mir-7977 level. The fasting plasma glucose (FPG), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and urinary albumin excretion were independent predictors of urinary G6PD activity by multiple linear regression analysis.The increased expression of miR-7977 and decreased expression of G6PD were also found in the kidney of ZDF rats with early renal tubular damage.In HK-2 cells cultured with normal situation, low level of albumin could induce autophagy along with the stimulation of G6PD although this was impaired under high glucose. Overexpression of G6PD reversed albumin-induced autophagy in HK2 cells under high glucose.Inhibition mir-7977 expression led to significantly increased expression of G6PD and reversed the effects of high glucose on albumin induced autophagy.Our study supports a new mechanism of G6PD downregulation in DKD.

BACKGROUND: Testing for glucose-6-phosphate dehydrogenase (G6PD) deficiency is an important consideration regarding treatment for malaria. G6PD deficiency may lead to haemolytic anaemia during malaria treatment and, therefore, determining G6PD deficiency in malaria treatment strategies is extremely important.
METHODS: This report presents the results of a scoping review and evidence and gap map for consideration by the Guideline Development Group for G6PD near patient tests to support radical cure of Plasmodium vivax. This scoping review has investigated common diagnostic tests for G6PD deficiency and important contextual and additional factors for decision-making. These factors include six of the considerations recommended by the World Health Organization (WHO) handbook for guideline development as important to determining the direction and strength of a recommendation, and included \'acceptability\', \'feasibility,\' \'equity,\' \'valuation of outcomes,\' \'gender\' and \'human rights\'. The aim of this scoping review is to inform the direction of future systematic reviews and evidence syntheses, which can then better inform the development of WHO recommendations regarding the use of G6PD deficiency testing as part of malaria treatment strategies.
RESULTS: A comprehensive search was performed, including published, peer-reviewed literature for any article, of any study design and methodology that investigated G6PD diagnostic tests and the factors of \'acceptability\', \'feasibility,\' \'equity,\' \'valuation of outcomes,\' \'gender\' and \'human rights\'. There were 1152 studies identified from the search, of which 14 were determined to be eligible for inclusion into this review. The studies contained data from over 21 unique countries that had considered G6PD diagnostic testing as part of a malaria treatment strategy. The relationship between contextual and additional factors, diagnostic tests for G6PD deficiency and study methodology is presented in an overall evidence and gap, which showed that majority of the evidence was for the contextual factors for diagnostic tests, and the \'Standard G6PD (SD Biosensor)\' test.
CONCLUSIONS: This scoping review has produced a dynamic evidence and gap map that is reactive to emerging evidence within the field of G6PD diagnostic testing. The evidence and gap map has provided a comprehensive depiction of all the available literature that address the contextual and additional factors important for decision-making, regarding specific G6PD diagnostic tests. The majority of data available investigating the contextual factors of interest relates to quantitative G6PD diagnostic tests. While a formal qualitative synthesis of this data as part of a systematic review is possible, the data may be too heterogenous for this to be appropriate. These results can now be used to inform future direction of WHO Guideline Development Groups for G6PD near patient tests to support radical cure of P. vivax malaria.

BACKGROUND: Sirtuin 7 (SIRT7) is pivotal in diverse diseases progression. Importantly, SIRT7 is associated with melanin production. However, whether SIRT7 regulates vitiligo is unclear. Therefore, we aimed to investigate the effects of SIRT7 on pigmentation and the modification of glucose 6-phosphate dehydrogenase (G6PD).
METHODS: After knockdown SIRT7 and G6PD, pigmentation of melanocytes was evaluated using commercial kits, immunofluorescence, and Western blot analysis. The succinylation of G6PD mediated by SIRT7 was analyzed using co-immunoprecipitation, immunofluorescence, Western blot analysis, and cycloheximide-chase experiment.
RESULTS: We found that SIRT7 was highly expressed in vitiligo skin lesions. Knockdown of SIRT7 increased tyrosinase activity, melanin content, and the levels of α-melanocyte-stimulating hormone, MITF, TYR, TRP1, and TRP2. Additionally, SIRT7 directly interacted with G6PD. Silenced SIRT7 promoted the succinylation of G6PD and enhanced its protein stability. G6PD knockdown reversed the effect of reduced SIRT7 expression on melanin production.
UNASSIGNED: Silencing of SIRT7 promotes pigmentation of melanocytes by succinylating G6PD, suggesting that SIRT7-mediated G6PD desuccinylation may promote vitiligo progression.

Possible protective and therapeutic effects of nobiletin on kidney in a cisplatin-induced nephrotoxicity rat model were investigated. Forty male albino rats were divided into four groups: control, cisplatin (CIS), cisplatin+nobiletin (CIS+NOB), and nobiletin+cisplatin (NOB+CIS). At the end of the study, the rats were subjected to biochemical, histological and immunohistochemical analyzes. Compared to the control group, tGSH (p < 0.05) levels, and G6PD (p < 0.05) and GPx (p < 0.001) activities, were increased in the CIS group; while significant (p < 0.05) decreases occurred in the MDA and TOC levels. Histopathologically, the kidneys of the groups administered nobiletin (CIS+NOB, NOB+CIS) were significantly different from the CIS group, being closer to control group in terms of degeneration and hyaline cylinder formation in the tubules (p < 0.05). While dilatation in the tubules, protein-rich fluid and hyaline cylinder formation in the lumen were most common in the CIS group, a significant decrease (p < 0.05) of these parameters was seen in the nobiletin groups (CIS+NOB, NOB+CIS). This study suggests that nobiletin can be effective in preventing and ameliorating toxic effects of cisplatin on the kidney.

Chondrocytes, known for their metabolic adaptability in response to varying stimuli, play a significant role in osteoarthritis (OA) progression. Glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway, has recently been found to upregulate in OA chondrocyte. However, the exact role of G6PD in temporomandibular joint osteoarthritis (TMJOA) and its effect on chondrocyte function remains unclear. In present study, we induced OA-like conditions in the rat temporomandibular joint via occlusal disharmony (OD), noting a marked increase in G6PD expression in the condylar cartilage. Our data show that G6PD knockdown in mandibular condylar chondrocytes (MCCs) reduces the expression of catabolic enzymes (e.g., MMP3, MMP13) and inflammatory cytokines (e.g., IL6) induced by IL-1β. G6PD knockdown also mitigates IL-1β-induced upregulation of ERK, JNK, and p38 phosphorylation and reduces reactive oxygen species (ROS) levels by decreasing the nicotinamide adenine dinucleotide phosphate (NADPH) and NADPH oxidases 4 (NOX4) mRNA expression. In summary, G6PD appears to regulate the inflammatory state of condylar chondrocytes via the NOX-ROS-MAPK axis, highlighting its potential as a therapeutic target for TMJOA.

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.

Mice models of Alzheimer\'s disease (APP/PS1) typically experience cognitive decline with age. G6PD overexpressing mice (G6PD-Tg) exhibit better protection from age-associated functional decline including improvements in metabolic and muscle functions as well as reduced frailty compared to their wild-type counterparts. Importantly G6PD-Tg mice show diminished accumulation of DNA oxidation in the brain at different ages in both males and females. To further explore the potential benefits of modulating the G6PD activity in neurodegenerative diseases, triple transgenic mice (3xTg G6PD) were generated, overexpressing APP, PSEN1, and G6PD genes. The cognitive decline characteristic of APP/PS1 mice was prevented in 3xTg G6PD mice, despite similar amyloid-β (Aβ) levels in the hippocampus. This challenges the dominant hypothesis in Alzheimer\'s disease (AD) etiology and the majority of therapeutic efforts in the field, based on the notion that Aβ is pivotal in cognitive preservation. Notably, the antioxidant properties of G6PD led to a decrease in oxidative stress parameters, such as improved GSH/GSSG and GSH/CysSSG ratios, without major changes in oxidative damage markers. Additionally, metabolic changes in 3xTg G6PD mice increased brain energy status, countering the hypometabolism observed in Alzheimer\'s models. Remarkably, a higher respiratory exchange ratio suggested increased carbohydrate utilization. The relative failures of Aβ-targeted clinical trials have raised significant skepticism on the amyloid cascade hypothesis and whether the development of Alzheimer\'s drugs has followed the correct path. Our findings highlight the significance of targeting glucose-metabolizing enzymes rather than solely focusing on Aβ in Alzheimer\'s research, advocating for a deeper exploration of glucose metabolism\'s role in cognitive preservation.

Breast cancer is one of the most common malignant tumors in women and is a serious threat to women\'s health. The pentose phosphate pathway (PPP) is a mode of oxidative breakdown of glucose that can be divided into oxidative (oxPPP) and non-oxidative (non-oxPPP) stages and is necessary for cell and body survival. However, abnormal activation of PPP often leads to proliferation, migration, invasion, and chemotherapy resistance in breast cancer. Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme in PPP oxidation. Nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) produced by G6PD is the raw material for cholesterol and lipid synthesis and can resist the production of oxygen species (ROS) and reduce oxidative stress damage to tumor cells. Transketolase (TKT) is a key enzyme in non-oxPPP. Ribose 5-phosphate (R5P), produced by TKT, is a raw material for DNA and RNA synthesis, and is essential for tumor cell proliferation and DNA damage repair. In this review, we describe the role and specific mechanism of the PPP and the two most important enzymes of the PPP, G6PD and TKT, in the malignant progression of breast cancer, providing strategies for future clinical treatment of breast cancer and a theoretical basis for breast cancer research.

The pathogenesis of epilepsy remains unclear; however, a prevailing hypothesis suggests that the primary underlying cause is an imbalance between neuronal excitability and inhibition. Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway, which is primarily involved in deoxynucleic acid synthesis and antioxidant defense mechanisms and exhibits increased expression during the chronic phase of epilepsy, predominantly colocalizing with neurons. G6PD overexpression significantly reduces the frequency and duration of spontaneous recurrent seizures. Furthermore, G6PD overexpression enhances signal transducer and activator of transcription 1 (STAT1) expression, thus influencing N-methyl-d-aspartic acid receptors expression, and subsequently affecting seizure activity. Importantly, the regulation of STAT1 by G6PD appears to be mediated primarily through reactive oxygen species signaling pathways. Collectively, our findings highlight the pivotal role of G6PD in modulating epileptogenesis, and suggest its potential as a therapeutic target for epilepsy.