Comprehensive Insights that Targeting PIM for Cancer Therapy: Prospects and Obstacles.

Proviral integration sitea for Moloney-murine leukemia virus (PIM) kinases are a family of highly conserved serine/tyrosine kinases consisting of three members, PIM-1, PIM-2, and PIM-3. These kinases regulate a wide range of substrates through phosphorylation and affect key cellular processes such as transcription, translation, proliferation, apoptosis, and energy metabolism. Several PIM inhibitors are currently undergoing clinical trials, such as a phase I clinical trial of Uzanserti (5) for the treatment of relapsed diffuse large B-cell lymphoma that has been completed. The current focus encompasses the structural and biological characterization of PIM, ongoing research progress on small-molecule inhibitors undergoing clinical trials, and evaluation analysis of persisting challenges in this field. Additionally, the design and discovery of small-molecule inhibitors targeting PIM in recent years have been explored, with a particular emphasis on medicinal chemistry, aiming to provide valuable insights for the future development of PIM inhibitors.

Large scale uniform Ni-P plated carbon fiber for boosting urea electro-oxidation and electro-detection.

Seeking an excellent electrocatalyst is the trickiest issue for the application of urea electro-oxidation and electro-detection. Phosphorus-doped nickel plating on carbon fibers (Ni-P/CF) is synthesized by simple electroless plating. SEM results exhibit that the Ni-P densely and uniformly grows onto the surface of carbon fibers (CF), forming carbon fibers-like nanoarchitectures. Benefiting from the carbon fibers-like nano architectures with abundant exposed active sites on the surface of CF, electron transfer can be synchronously facilitated, and Ni-P/CF displays superior urea electrooxidation (UOR) performance with potentials of 1.40 V to reach 100 mA cm-2. Impressively, it can maintain at 20 mA cm-2 for 48 h without evident activity attenuation, demonstrating robust durability. Cycle stability shows that the voltage has only increased by 10 mV at 300 mA cm-2 from the 10th to 20000th cycles. Most importantly, Ni-P/CF at a length of 100 cm with good reproducibility was successfully synthesized, denoting great potential for large-scale industrial production. Therefore, this work not only affords cost-effective tactics for urea-rich wastewater degradation but also can achieve practical medical applications.

Postmortem Brain Imaging in Alzheimer's Disease and Related Dementias: The South Texas Alzheimer's Disease Research Center Repository.

BACKGROUND: Neuroimaging bears the promise of providing new biomarkers that could refine the diagnosis of dementia. Still, obtaining the pathology data required to validate the relationship between neuroimaging markers and neurological changes is challenging. Existing data repositories are focused on a single pathology, are too small, or do not precisely match neuroimaging and pathology findings. OBJECTIVE: The new data repository introduced in this work, the South Texas Alzheimer's Disease research center repository, was designed to address these limitations. Our repository covers a broad diversity of dementias, spans a wide age range, and was specifically designed to draw exact correspondences between neuroimaging and pathology data. METHODS: Using four different MRI sequences, we are reaching a sample size that allows for validating multimodal neuroimaging biomarkers and studying comorbid conditions. Our imaging protocol was designed to capture markers of cerebrovascular disease and related lesions. Quantification of these lesions is currently underway with MRI-guided histopathological examination. RESULTS: A total of 139 postmortem brains (70 females) with mean age of 77.9 years were collected, with 71 brains fully analyzed. Of these, only 3% showed evidence of AD-only pathology and 76% had high prevalence of multiple pathologies contributing to clinical diagnosis. CONCLUSION: This repository has a significant (and increasing) sample size consisting of a wide range of neurodegenerative disorders and employs advanced imaging protocols and MRI-guided histopathological analysis to help disentangle the effects of comorbid disorders to refine diagnosis, prognosis and better understand neurodegenerative disorders.

Gas-Phase Preparation of 1-Germavinylidene (H2CGe; X1A1), the Isovalent Counterpart of Vinylidene (H2CC; X1A1), via Non-adiabatic Dynamics through the Elementary Reaction of Ground State Atomic Carbon (C; 3P) with Germane (GeH4; X1A1).

1-Germavinylidene (H2CGe; X1A1), the germanium analogue of vinylidene (H2CC; X1A1), was prepared via a directed gas-phase synthesis through the bimolecular reaction of ground state atomic carbon (C; 3P) with germane (GeH4; X1A1) under single-collision conditions. The reaction commences with the barrierless insertion of carbon into the Ge-H bond followed by intersystem crossing from the triplet to singlet surface and migration of atomic hydrogen to germylene (H2GeCH2), which predominantly decomposes via molecular hydrogen loss to 1-germavinylidene (H2CGe; X1A1). Therefore, the replacement of a single carbon atom in the acetylene-vinylidene system by germanium critically impacts the chemical bonding, molecular structure, and thermodynamic stability of the carbene-type structures favoring 1-germavinylidene (H2CGe) over germyne (HGeCH) by 160 kJ mol-1. Hence, the carbon-germane system represents a benchmark in the exploration of the chemistries of main group 14 elements with germanium-bearing systems showing few similarities with the isovalent carbon system.

Effectiveness and Accuracy of a Patient-Specific Instrumentation System for Total Hip Arthroplasty.

OBJECTIVE: Traditional total hip arthroplasty (THA) is often performed by visual inspection due to the lack of reliable reference, which results in inappropriate position of prosthesis and poor outcomes. This study attempts to introduce a novel patient-specific instrumentation (PSI) system and assess its effectiveness and accuracy compared with freehand operation and robot system through bone model experiments. METHODS: Equally divide 30 sawbone models into the freehand group, PSI group, and robot group. Ten sets of prosthesis parameters were randomly generated as planning, and the three groups underwent simulated THA depending on these parameters. After the placement of the femoral prosthesis, the acetabular anteversion plan was adjusted in the PSI and robot groups so that the combined anteversion was maintained before and after adjustment. After the surgery, the actual prosthesis parameters of all bone models were measured and analyzed statistically. RESULTS: No statistically significant difference was found in femoral anteversion error among the three groups (p = 0.951). The errors of acetabular cup anteversion, acetabular cup abduction, and combined anteversion in PSI group were 3.92° (2.94°, 4.62°), 5.65° (4.63°, 6.70°), and 3.93° (2.94°, 4.62°), respectively, which were significantly smaller than those in the freehand group [11.84° (9.92°, 13.87°), 13.54° (9.81°, 15.21°), 16.04° (8.18°, 19.25°), respectively, p < 0.05], but significantly larger than those in the robot group [1.34° (0.98°, 1.70°), 1.80° (1°, 2.02°), 1.34° (0.98°, 1.70°), respectively, p < 0.05]. CONCLUSION: Compared with the traditional freehand operation, the patient-specific instrumentation system is feasible in total hip arthroplasty because it improves the accuracy of prosthesis placement. In addition, the rapid measurement of intraoperative femoral prosthesis parameters can help surgeons optimize preoperative planning.

Association between paternal pre-pregnancy body mass index with preterm birth and low birth weight.

Background: With the current global epidemic of obesity, especially among men, there is a need to understand its impact on adverse pregnancy outcomes. This study aimed to assess whether paternal pre-pregnancy body mass index (BMI) was associated with preterm birth and low birth weight in offspring. Methods: Multinomial logistic regression model was used to analyze associations between paternal BMI and preterm birth and low birth weight in different subgroups, the final model was adjusted for confounding factors of mothers and fathers. Further subgroup analysis was conducted to explore the stability of the risk associations. Results: A total of 34,104 participants were included in this study, including 1,442 (4.2%) underweight, 13,930 (40.9%) overweight and 5,008 (14.7%) obese according to paternal BMI. The total incidence of preterm birth was 11.85% (4041/34104), and the incidence of low birth weight was 8.86% (3020/34104). In the total study population, compared with normal weight men, paternal pre-pregnancy overweight or obese was associated with a significantly increased risk of preterm birth [aOR; 95% CI respectively (1.34; 1.25-1.45 vs. 1.26; 1.14-1.40)] and low birth weight [aOR; 95% CI respectively (1.60; 1.46-1.74 vs. 1.40; 1.25-1.58)] in offspring. The results of subgroup analysis showed that the direction of the risk association was consistent, indicating good stability. Conclusion: Paternal pre-pregnancy overweight and obesity were associated with an increased risk of preterm birth and low birth weight in their offspring.

Association of methylenetetrahydrofolate reductase gene polymorphisms and maternal folic acid use with the risk of congenital heart disease.

Background: To systematically evaluate the association of MTHFR genetic polymorphisms, maternal folic acid intake, and the time when folic acid intake was started with the risk of congenital heart disease (CHD) and investigated the role of their interaction on infant CHD risk in Chinese populations. Methods: A case-control study involving 592 CHD cases, 617 health controls, and their mothers was performed. The exposures of interest were single nucleotide polymorphisms (SNPs) of the MTHFR gene, maternal folic acid use, and the time when folic acid use was started. We applied the logistic regression model to explore the strength of association. Results: Our findings showed that mothers lacking folic acid intake had a significantly higher risk of CHD in offspring (aOR = 2.00; 95%CI: 1.34-2.98). Mothers who started to use folic acid from the first trimester of the fetation (aOR = 1.65; 95% CI: 1.22-2.23) or from the second trimester of the fetation (aOR = 7.77; 95% CI: 2.52-23.96), compared with those starting to use folic acid from 3 months previous to the conception, were at a significantly higher risk of CHD in offspring. Genetic variants at rs2066470 (AA vs. GG: aOR = 5.09, 95%CI: 1.99-13.03), rs1801133 (AA vs. GG: aOR = 2.49, 95%CI: 1.58-3.93), and rs1801131 (TG vs. TT: aOR = 1.84, 95%CI: 1.36-2.50; GG vs. TT: aOR = 3.58, 95%CI: 1.68-7.63) were significantly associated with the risk of CHD based on the multivariate analysis. Additionally, statistically significant interactions between maternal folic acid intake and genetic variants of the MTHFR gene at rs1801133 and rs1801131 were observed. Conclusion: An association of maternal folic acid intake and the time when intake was started with the risk of CHD in offspring was found. What's more, maternal folic acid fortification may help counteract partial of the risks of CHD in offspring attributable to MTHFR genetic mutations. Registration number: http://www.chictr.org.cn/edit.aspx?pid=28300&htm=4, identifier: ChiCTR1800016635.

[Orthopedic robot based on 5G technology for remote navigation of percutaneous screw fixation in pelvic and acetabular fractures].

Objective: To investigate the accuracy and safety of percutaneous screw fixation for pelvic and acetabular fractures with remote navigation of orthopedic robot based on 5G technology. Methods: Between January 2021 and December 2021, 15 patients with pelvic and/or acetabular fractures were treated with percutaneous screws fixation which were placed by remote navigation of orthopedic robot based on 5G technology. There were 8 males and 7 females. The age ranged from 20 to 98 years, with an average of 52.1 years. The causes of trauma included traffic accident injury in 6 cases, falling from height injury in 6 cases, fall injury in 2 cases, and heavy object smashing injury in 1 case. The time from injury to operation ranged from 3 to 32 days, with an average of 10.9 days. There were 8 cases of simple pelvic fractures, 2 simple acetabular fractures, and 5 both pelvic and acetabular fractures. There were 7 cases of pelvic fractures of Tile type B2, 2 type B3, 1 type C1, and 3 type C2; 4 cases of unilateral anterior column fracture of the acetabulum, 2 bilateral anterior column fractures, and 1 anterior wall fracture. CT images within 5 days after operation were collected for screw position assessment. The screw planning time and guidewire placement time were recorded, as well as the presence of intraoperative adverse events and complications within 5 days after operation. Results: All patients achieved satisfactory surgical results. A total of 36 percutaneous screws were inserted (20 sacroiliac screws, 6 LC Ⅱ screws, 9 anterior column screws, and 1 acetabular apical screw). In terms of screw position evaluation, 32 screws (88.89%) were excellent and 4 screws (11.11%) were good; there was no screw penetrating cortical bone. The screw planning time ranged from 4 to 15 minutes, with an average of 8.7 minutes. The guidewire placement time ranged from 3 to 10 minutes, with an average of 6.8 minutes. The communication delayed in 2 cases, but the operation progress was not affected, and no serious intraoperative adverse events occurred. No delayed vascular or nerve injury, infection, or other complications occurred within 5 days after operation. No cases need surgical revision. Conclusion: The fixation of pelvic and acetabular fractures by percutaneous screw with remote navigation of orthopedic robot based on 5G technology is accurate, safe, and reliable.

Effect of Maternal Antidepressant Use During the Pre-pregnancy/Early Pregnancy Period on Congenital Heart Disease: A Prospective Cohort Study in Central China.

Background: With the increase in maternal antidepressant prescribing before/during pregnancy, concerns about the safety of antidepressants have come into focus. The purpose of this study was to explore the association between maternal antidepressant use before pregnancy/in early pregnancy and the risk of congenital heart disease (CHD) in children, and to provide a scientific basis for clinical safety of antidepressant use. Methods: The prospective cohort study ultimately included 34,104 singleton pregnancies. Modified Poisson regression model with robust error variances was used to evaluate RRs and 95% confidence intervals (CIs) for the risk of CHD in offspring exposed to maternal antidepressant in the 3 months before pregnancy and early pregnancy. In addition, sensitivity analysis was further performed to explore the robustness of the results. Results: In this study, the maternal antidepressant exposure rate was 2.83% in the 3 months before pregnancy, 2.42% in early pregnancy, and the incidence of CHD was 8.973 per 1,000 live births. We found that maternal antidepressant use in the 3 months before pregnancy and early pregnancy were all associated with an increased risk of CHD, ~2.54 times and 2.87 times, respectively, of non-use of antidepressants after adjusting for potential confounders. This association was also found in CHD specific phenotypic analysis. Of these, offspring whose mothers were exposed to antidepressants in the 3 months before pregnancy had the highest risk of transposition of the great arteries (aOR = 5.50, 95% CI: 1.91-15.88). The offspring of mothers exposed to antidepressants in early pregnancy had the highest risk of developing ventricular septal defect (aOR = 4.80, 95% CI: 2.50-9.24). Sensitivity analysis verified the stability of the results. Conclusions: Maternal antidepressant use in the 3 months before pregnancy and early pregnancy were all associated with an increased risk of CHD in their offspring. In order to reduce the risk of teratogenesis, we recommend that pregnant women prepare for pregnancy after their condition improves or receive the minimum effective dose of medication.

Assembly of bimetallic (Au-Ag)FON composite films at liquid/solid interfaces and their tunable optical properties.

The regular structure provided by two-dimensional (2D) structural colloidal crystals is widely accepted to provide an ideal template that ensures that plasmonic bimetallic composite nanostructures are uniform. Herein, we report an effective method for fabricating bimetallic Au-Ag composite films loaded on the surfaces of 2D polystyrene@polyacrylic acid (PS@PAA) colloidal crystals. PS@PAA particles coated with uniform Ag particle layers (AgFON) were produced by a simple and effective sputtering-deposition technique, after which the galvanic replacement (GR) reaction was used to produce a bimetallic (Au-Ag)FON composite film at the liquid/solid interface in aqueous HAuCl4. The morphology and relative contents of the bimetallic (Au-Ag)FON composite film can be regulated by changing the kinetic factors that control the GR reaction, including the concentration and pH of the HAuCl4 solution, and the reaction time. We demonstrated that the fabricated bimetallic (Au-Ag)FON composite has localized surface plasmon resonance (LSPR) properties that can be regulated by varying the composite structure and Ag/Au composition. On the one hand, the regular 2D colloidal crystal structure provides an ideal template for preparing Au-Ag composite films, which ensures that the optical signals of plasmonic Au-Ag composite films are reproducible. On the other hand, the synergy between Ag and Au in the bimetallic alloy composite film ensures stable and tunable LSPR performance. Furthermore, the prepared 2D ordered (Au-Ag)FON Au-Ag bimetallic material is expected to be used in sensing and catalysis applications.

Determinants for Perinatal Mortality in South China: A Prospective Cohort Study.

Objective: To estimate the association of selected maternal and fetal characteristics with the risk of perinatal mortality in South China. Methods: A prospective cohort study was conducted from March 2013 to December 2019. The exposures of interest were maternal sociodemographic characteristics, lifestyle and habits during early pregnancy, and complications of pregnancy. Their effects on the development of perinatal death were analyzed in our study. Results: A total of 44,048 eligible pregnant women were included in the analysis. Of these, 596 fetuses were perinatal deaths (perinatal mortality was 13.5 per 1,000 births). After adjustment, maternal obesity, being employed, history of gestational hypertension, taking antidepressants during early pregnancy, history of gestational diabetes mellitus, gestational diabetes mellitus, infertility drug treatment and assisted reproductive techniques, history of neonatal death, preterm birth, and congenital malformations all significantly increased the risk of perinatal death. Ethnic minority, income > 5,000, multiparous women, and cesarean section associated with reduced risk of perinatal death. Conclusion: Some factors of maternal sociodemographic characteristics, abnormal pregnancy history, lifestyle and habits during early pregnancy, and complications of pregnancy were associated with the risk of perinatal death.

Association Between First-Trimester Maternal Cytomegalovirus Infection and Stillbirth: A Prospective Cohort Study.

Background: Given that the time lag between cytomegalovirus (CMV) screening and diagnosed testing, a better knowledge of the association between pregnant women with CMV screening test positive and stillbirth in an epidemiological perspective was required to assist people being counseled reframe their pregnancy and birth plans based on the magnitude of the risk. Methods: This study recruited 44048 eligible pregnant women from March 13, 2013 to December 31, 2019. Serological tests including CMV-specific IgM and IgG, and IgG avidity index were used to screen for maternal CMV infection and were measured by automated chemiluminescence immunoassay. The association was assessed using the inverse probability of group-weighted multivariate-adjusted log-binomial models. Results: A total of 540 infants ended with a stillbirth (12.3 per 1000 pregnancies), and 2472 pregnancies with maternal CMV infection were screened out (56.1 per 1000 pregnancies) among all eligible pregnancies. In the comparison analysis, 326 infants ended with a stillbirth (86.6 per 1000 pregnancies) in the maternal CMV infection group compared with 214 infants (7.8 per 1000 pregnancies) in the group where mothers were not infected with CMV (RR 12.17; 95% CI 9.43-15.71). After excluding the pregnancies of stillbirth with birth defects, a strong association between the two groups was still observed (RR 9.38; 95% CI 6.92-12.70). Conclusion: Our findings quantified the risk of a woman having a baby with stillbirth if she had a positive serologic CMV screening test in her first trimester, and supported the value of using CMV serologic tests as part of regular testing in pregnant women. Trial registration: Registered in Chinese Clinical Trial Registry Center; registration number, ChiCTR1800016635; registration date, 06/14/2018 (Retrospectively registered); URL of trial registry record, https://www.chictr.org.cn/showproj.aspx?proj=28300.

Hypertensive Disorders in Pregnancy Are Associated With Congenital Heart Defects in Offspring: A Systematic Review and Meta-Analysis.

Background: Although research indicates an association between hypertensive disorders of pregnancy (HDP) and congenital heart defects (CHDs) in offspring, consistency is still lacking. Therefore, we aimed to synthesize the updated published epidemiologic evidence to estimate the association of maternal HDP with the risk of total CHDs and its phenotypes in offspring. Methods: A systematic search of Web of Science Database, PubMed, and Embase were searched from inception through April 30, 2021 based on a preprepared protocol, and the reference lists were also manually searched. The combined risk estimates were calculated using either the fixed-effect models or random-effect models. Possible heterogeneity moderators were detected by subgroup, sensitivity analyses, and Galbraith plot. Results: Twenty-four studies involving 477,839 CHDs cases among 40,394,699 participants were included in our meta-analysis. Mothers who had HDP exposure were significantly associated with an increased risk of total CHDs compared with non-exposure. When maternal HDP exposure was further subdivided into pre-eclampsia (OR = 1.79, 95% CI: 1.50-2.13), gestational hypertension (OR = 1.16, 95% CI: 1.02-1.31), and chronic hypertension (OR = 1.68, 95% CI: 1.49-1.89), a significantly increased risk of total CHDs were still presented. Furthermore, a statistically significant increased association was found between maternal HDP exposure and most CHD phenotypes. Besides, relevant heterogeneity moderators have been identified by subgroup and sensitivity analyses. Conclusion: Our study suggested that maternal HDP exposure may be associated with an increase in the risk of CHDs in offspring. These findings highlight the need for greater surveillance of pregnant women with HDP exposure to allow early prevention that may be good for reducing the risk of CHDs in offspring. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [CRD42021268093].

Pre-Pregnancy Body Mass Index and Risk of Macrosomia and Large for Gestational Age Births with Gestational Diabetes Mellitus as a Mediator: A Prospective Cohort Study in Central China.

This study aimed to examine the risk of macrosomia and large for gestational age (LGA) births in relation to maternal pre-pregnancy body mass index (BMI) status mediated through gestational diabetes mellitus (GDM). This prospective study included 34,104 singleton pregnancies at 8-14 weeks of gestation. The interesting outcomes were macrosomia (≥4000 g) and LGA (≥90th percentile). Mediation analyses were conducted using log-binomial regression adjusted for age, education, parity, fetal sex, and gestational weight gain. The proportion mediated was estimated based on the risk difference scale, and the E-value was utilized to assess potential confounders. Overall, 15.9% of women had GDM, and there were 4.0% macrosomia and 9.9% LGA births. The proportion mediated by GDM on macrosomia was up to 40% among obese women, and the estimate of the total effect was 6.18 (95% CI: 5.26-7.26), of the natural direct effect was 4.10 (95% CI: 3.35-4.99), and of the natural indirect effect was 1.51 (95% CI: 1.31-1.76). Likewise, among overweight women, the proportion mediated by GDM on macrosomia was up to 40%. Furthermore, consistent findings were evident for the outcome of LGA births. Pre-pregnancy overweight/obesity increased the risk of macrosomia and LGA births independently and partly mediated by GDM.

Association of MTHFD1 gene polymorphisms and maternal smoking with risk of congenital heart disease: a hospital-based case-control study.

BACKGROUND: MTHFD1 gene may affect the embryonic development by elevated homocysteine levels, DNA synthesis and DNA methylation, but limited number of genetic variants of MTHFD1 gene was focused on the association with congenital heart disease (CHD). This study examined the role of MTHFD1 gene and maternal smoking on infant CHD risk, and investigated their interaction effects in Chinese populations. METHODS: A case-control study of 464 mothers of CHD infants and 504 mothers of health controls was performed. The exposures of interest were maternal tobacco exposure, single nucleotide polymorphisms (SNPs) of maternal MTHFD1 gene. The logistic regression model was used for accessing the strength of association. RESULTS: Mothers exposed to secondhand smoke during 3 months before pregnancy (adjusted odds ratio [aOR] = 1.56; 95% confidence interval [CI]: 1.13-2.15) and in the first trimester of pregnancy (aOR = 2.24; 95%CI: 1.57-3.20) were observed an increased risk of CHD. Our study also found that polymorphisms of maternal MTHFD1 gene at rs1950902 (AA vs. GG: aOR = 1.73, 95% CI: 1.01-2.97), rs2236222 (GG vs. AA: aOR = 2.38, 95% CI: 1.38-4.12), rs1256142 (GA vs.GG: aOR = 1.57, 95% CI: 1.01-2.45) and rs11849530 (GG vs. AA: aOR = 1.68, 95% CI: 1.02-2.77) were significantly associated with higher risk of CHD. However, we did not observe a significant association between maternal MTHFD1 rs2236225 and offspring CHD risk. Furthermore, we found the different degrees of interaction effects between polymorphisms of the MTHFD1 gene including rs1950902, rs2236222, rs1256142, rs11849530 and rs2236225, and maternal tobacco exposure. CONCLUSIONS: Maternal polymorphisms of MTHFD1 gene, maternal tobacco exposure and their interactions are significantly associated with the risk of CHD in offspring in Han Chinese populations. However, more studies in different ethnic populations with a larger sample and prospective designs are required to confirm our findings. TRIAL REGISTRATION: Registration number: ChiCTR1800016635 .

High-Efficiency Capture of Cells by Softening Cell Membrane.

The capture of circulating tumor cells (CTCs) by nanostructured substrate surface is a useful method for early diagnosis of cancer. At present, most methods used to improve the cell capture efficiency are based on changing substrate surface properties. However, there are still some gaps between these methods and practical applications. Here, a method is presented for improving cell capture efficiency from a different perspective, that is, changing the properties of the cells. Concretely, the mechanical properties of the cell membrane are changed by adding Cytochalasin D to soften the cell membrane. Furthermore, a corresponding theoretical model is proposed to explain the experimental results. It is found that cell softening can reduce the resistance of cell adhesion, which makes the adhesion ability stronger. The high-efficiency capture of cells by softening the cell membrane provides a potential method to improve the detection performance of CTCs.

The ginger extract could improve diabetic retinopathy by inhibiting the expression of e/iNOS and G6PDH, apoptosis, inflammation, and angiogenesis.

Diabetic retinopathy is a complication of diabetes, caused by high blood sugar levels damaging the retina. It is the result of damage to the small blood vessels and neurons of the retina. Ginger and its phytochemical compounds can improve oxidative damage and inflammation. However, the effects of this plant on ocular expression G6PDH and e/iNOS, eye cell apoptosis, and angiogenesis are not well known in this tissue. Therefore, the aim of this study was to evaluate the therapeutic potential of ginger extract on rats with type 2 diabetic retinopathy. Thirty-two Wistar rats were randomly divided into four controlled and treated groups. The serum level of metabolic factors such as lipid profiles, insulin and glucose, and the level of oxidative biomarkers along with the TNF-α level in eye tissue were measured. The expression of NF-κB, VEGF, BAX, Bcl-2, caspase-3, e/iNOS, and G6PDH in eye tissue was measured. Serum levels of lipid profiles, glucose, and insulin, oxidative and inflammatory markers were significantly increased in the diabetic group compared to control. While, treatment with ginger extract could significantly improve these factors in diabetic rats. Moreover, the ocular expression of e/iNOS, G6PDH, VEGF, NF-κB, and genes involved in apoptosis was changed in diabetic rats. However, treatment with ginger extract could ameliorate these changes in the diabetic-treated group. It can be concluded that ginger extract could improve diabetic retinopathy by inhibiting oxidative damage, inflammation, iNOS, VEGF, apoptosis, and improving eNOS and G6PDH. PRACTICAL APPLICATIONS: Microvascular complications of diabetes such as retinopathy can be one of the main causes of disability in people with diabetes. Chronic hyperglycemia, oxidative stress, inflammation, and apoptosis cause diabetic retinopathy through retinal damage. Ginger, on the other hand, is an available, inexpensive, and uncomplicated medicinal plant that contains more than 20 different phytochemicals, such as gingerol and shogaol, which have anti-inflammatory, antioxidant, antihypertensive, hypoglycemic, and hypolipidemic properties. The results of our study showed well that the ginger extract could improve diabetic retinopathy by inhibiting the expression of e/iNOS and G6PDH and oxidative damage, apoptosis, inflammation, and angiogenesis. Therefore, ginger and its compounds can be a good option to improve the complications of diabetes.

Combination therapy with pioglitazone/exenatide/metformin reduces the prevalence of hepatic fibrosis and steatosis: The efficacy and durability of initial combination therapy for type 2 diabetes (EDICT).

AIM: To compare the efficacy of triple therapy (metformin/exenatide/pioglitazone) versus stepwise conventional therapy (metformin → glipizide → glargine insulin) on liver fat content and hepatic fibrosis in newly diagnosed, drug-naïve patients with type 2 diabetes. METHODS: Sixty-eight patients completed the 6-year follow-up and had an end-of-study (EOS) FibroScan to provide measures of steatosis (controlled attenuation parameter [CAP] in dB/m) and fibrosis (liver stiffness measurement [LSM] in kPa); 59 had magnetic resonance imaging-proton density fat fraction (MRI-PDFF) to measure liver fat. RESULTS: At EOS, HbA1c was 6.8% and 6.0% in triple and conventional therapy groups, respectively (P = .0006). Twenty-seven of 39 subjects (69%) receiving conventional therapy had grade 2/3 steatosis (CAP, FibroScan) versus nine of 29 (31%) in triple therapy (P = .0003). Ten of 39 (26%) subjects receiving conventional therapy had stage 3/4 fibrosis (LSM) versus two of 29 (7%) in triple therapy (P = .04). Conventional therapy subjects had more liver fat (MRI-PDFF) than triple therapy (12.9% vs. 8.8%, P = .03). The severity of steatosis (CAP) (r = 0.42, P < .001) and fibrosis (LSM) (r = -0.48, P < .001) correlated inversely with the Matsuda Index of insulin sensitivity, but not with percentage body fat. Aspartate aminotransferase (AST) to Platelet Ratio Index (APRI), non-alcoholic fatty liver disease fibrosis score (NFS), plasma AST, and alanine aminotransferase (ALT) all decreased significantly with triple therapy, but only the decrease in plasma AST and ALT correlated with the severity of steatosis and fibrosis at EOS. CONCLUSIONS: At EOS, subjects with type 2 diabetes treated with triple therapy had less hepatic steatosis and fibrosis versus conventional therapy; the severity of hepatic steatosis and fibrosis were both strongly and inversely correlated with insulin resistance; and changes in liver fibrosis scores (APRI, NFS, Fibrosis-4, and AST/ALT ratio) have limited value in predicting response to therapy.