Diabetes mellitus and risk of incident dementia in APOE ɛ4 carriers: an updated meta-analysis.

BACKGROUND AND AIM: Diabetes raises the risk of dementia, mortality, and cognitive decline in the elderly, potentially because of hereditary variables such as APOE. In this study, we aim to evaluate Diabetes mellitus and the risk of incident dementia in APOE ɛ4 carriers. METHOD: We thoroughly searched PubMed (Medline), Scopus, and Google Scholar databases for related articles up to September 2023. The titles, abstracts, and full texts of articles were reviewed; data were extracted and analyzed. RESULT: This meta-analysis included nine cohorts and seven cross-sectional articles with a total of 42,390 population. The study found that APOE ɛ4 carriers with type 2 diabetes (T2D) had a 48% higher risk of developing dementia compared to non-diabetic carriers (Hazard Ratio;1.48, 95%CI1.36-1.60). The frequency of dementia was 3 in 10 people (frequency: 0.3; 95%CI (0.15-0.48). No significant heterogeneity was observed. Egger's test, which we performed, revealed no indication of publication bias among the included articles (p = 0.2). CONCLUSION: Overall, diabetes increases the risk of dementia, but further large-scale studies are still required to support the results of current research.

Effects of marine-derived n-3 PUFA supplementation on soluble adhesion molecules: A systematic review and dose-response meta-analysis of randomized controlled trials.

Long-chain n-3 poly unsaturated fatty acids have anti-inflammatory effects but their effects on serum levels of adhesion molecules are inconsistent and contradictory. In this updated systematic review and meta-analysis, marine sources of omega-3 fatty acids were pooled up to determine the effects of omega-3 supplementation on adhesion molecules. PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases (from inception to April 2023) were searched and all RCTs investigating the effects of marine sources of omega-3, on blood concentrations of adhesion molecules were included and a meta-analysis undertaken. Forty-two RCTs were included involving 3555 participants aged from 18 to 75 years. Meta-analysis of 38 arms from 30 RCTs reporting serum concentrations of vascular cell adhesion molecule-1 (VCAM-1) showed a significant reduction after omega-3 supplementation (WMD: -1.26, 95% CI: -1.88 to -0.64 ng/mL, P < 0.001). Meta-analysis of 40 arms from 30 RCTs reporting serum concentrations of intercellular adhesion molecule-1 (ICAM-1) revealed a reduction following omega-3 supplementation, although it was not significant (WMD: -1.76, 95%CI: -3.68 to 0.16 ng/mL, P = 0.07). Meta-analysis of 27 arms from 21 trials showed no effect on E-selectin (WMD: 0.01, 95%CI: -0.02 to 0.04 ng/mL, P = 0.62). Pooling 15 arms from 11 RCTs showed a marginally significant reducing effect on P-selectin concentrations (WMD: -2.67, 95%CI: -5.53 to 0.19 ng/mL, P = 0.06). A considerable decrease in VCAM concentration was observed after omega-3 supplementation in this meta-analysis with a trend to decreases in both ICAM and P-selectin levels, with effects that may be significant depending on study design, and there was no effect on E-selectin.

Mpox vaccination and treatment: a systematic review.

The Human monkeypox virus (mpox) belongs to the Poxviridae family, characterized by double-stranded DNA. A 2022 outbreak, notably prevalent among men who have sex with men, was confirmed by the World Health Organization. To understand shifting prevalence patterns and clinical manifestations, we conducted a systematic review of recent animal and human studies. We comprehensively searched PubMed, Scopus, Web of Science, Cochrane Library, and Clinicaltrials.gov, reviewing 69 relevant articles from 4,342 screened records. Our analysis highlights Modified Vaccinia Ankara - Bavarian Nordic (MVA-BN)'s potential, though efficacy concerns exist. Tecovirimat emerged as a prominent antiviral in the recent outbreak. However, limited evidence underscores the imperative for further clinical trials in understanding and managing monkeypox.

Association of serum omentin levels with microvascular complications of type 2 diabetes mellitus: a systematic review and meta-analysis.

Background and aims: Type 2 diabetes mellitus (T2DM) is a chronic condition associated with various microvascular complications, including neuropathy, retinopathy, and nephropathy. Recent studies have suggested a potential association between serum omentin levels and the risk of developing microvascular complications in patients with T2DM. However, the existing evidence remains inconclusive. Therefore, we conducted a systematic review and meta-analysis to examine the association between serum omentin levels and microvascular complications in T2DM patients. Methods: A comprehensive search was conducted in PubMed, Scopus, and Google Scholar databases to retrieve relevant articles published up to May 2023. Observational studies investigating omentin levels association with microvascular complications in T2DM patients were included. Data was extracted and hence analyzed. Results: A total of seven cross-sectional articles met the inclusion criteria, with a total population of 1587 participants. The meta-analysis revealed a significant association between serum omentin levels and microvascular complications in patients with T2DM. Serum omentin levels were lower in patients with microvascular complications than in those without complications (Mean difference, 95% confidence interval: -1.31 [-2.50, -0.13], I2 = 99.62%). Conclusion: This systematic review and meta-analysis provides evidence supporting an association between serum omentin levels and microvascular complications in patients with T2DM. The findings suggest that Omentin may be lower in T2DM patients with microvascular complications. Further research is warranted to elucidate the underlying mechanisms and explore the clinical implications of these findings. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01359-2.

Increased Protein Kinase A Activity Induces Fibrolamellar Hepatocellular Carcinoma Features Independent of DNAJB1.

Fibrolamellar hepatocellular carcinoma (FLC) is a rare liver cancer that is driven by a fusion of DNAJB1 and PRKACA, the catalytic subunit of protein kinase A (PKA). PKA activity is controlled through regulatory proteins that both inhibit catalytic activity and control localization, and an excess of regulatory subunits ensures PRKACA activity is inhibited. Here, we found an increase in the ratio of catalytic to regulatory units in FLC patient tumors driven by DNAJB1::PRKACA using mass spectrometry, biochemistry, and immunofluorescence, with increased nuclear localization of the kinase. Overexpression of DNAJB1::PRKACA, ATP1B1::PRKACA, or PRKACA, but not catalytically inactive kinase, caused similar transcriptomic changes in primary human hepatocytes, recapitulating the changes observed in FLC. Consistently, tumors in patients missing a regulatory subunit or harboring an ATP1B1::PRKACA fusion were indistinguishable from FLC based on the histopathological, transcriptomic, and drug-response profiles. Together, these findings indicate that the DNAJB1 domain of DNAJB1::PRKACA is not required for FLC. Instead, changes in PKA activity and localization determine the FLC phenotype.

The relationship between the intake of dietary fatty acids and minerals with sperm parameters in infertile men.

BACKGROUND & AIMS: Infertility has been increasing among Iranian couples. Some epidemiological studies have reported a relationship between infertility and lifestyle patterns, including dietary habits. Our objective was to evaluate the relationship between sperm parameters and the intake of dietary fatty acids and minerals among Iranian infertile men. METHODS: This cross-sectional was performed on 400 newly diagnosed infertile men at Yazd Reproductive Sciences Institute from July to December 2019. Men whose infertility was confirmed by an andrologist based on the World Health Organization (WHO) criteria were selected. They delivered a semen sample and answered a 168-item semi-quantitative food frequency questionnaire. All data were analyzed using SPSS and STATA software. A p-value of less than 0.5 was considered significant. RESULTS: In the adjusted model, a significant negative association between sperm motility and the 3rd quartile (Q) of poly-unsaturated fatty acids compared to the 1st quartile) P = 0.02). Also, in the adjusted model, total mobility was significantly increased in the second, third and last quartiles of omega-3 fatty acids compared to the first quartile (P < 0.001, P = 0.02, P < 0.001, respectively). Furthermore, omega-6 fatty acid intake in the last quartile were positively associated with sperm motility (P = 0.01). Moreover, there was a significant association between omega-3 fatty acid intake in the second, third, and last quartiles and sperm normal morphology (P = 0.003, P = 0.018, and P = 0.005, respectively) compared with the first quartile. Further, we observed a significant association between omega-6 fatty acid intake and sperm normal morphology in the last quartile compared with the reference quartile (P = 0.04). Also, the findings showed a significant negative association between the second quartile of sodium and calcium intake and sperm volume compared with the first quartile (P = 0.04, for both) in the adjusted model. CONCLUSIONS: We concluded that dietary polyunsaturated fatty acid, sodium, and calcium intake are related to sperm morphology, volume, and total motility in Iranian infertile men. However, more research is needed to confirm these relationships and provide evidence to exert these findings into clinical practice.

Disruption of proteome by an oncogenic fusion kinase alters metabolism in fibrolamellar hepatocellular carcinoma.

Fibrolamellar hepatocellular carcinoma (FLC) is a usually lethal primary liver cancer driven by a somatic dysregulation of protein kinase A. We show that the proteome of FLC tumors is distinct from that of adjacent nontransformed tissue. These changes can account for some of the cell biological and pathological alterations in FLC cells, including their drug sensitivity and glycolysis. Hyperammonemic encephalopathy is a recurrent problem in these patients, and established treatments based on the assumption of liver failure are unsuccessful. We show that many of the enzymes that produce ammonia are increased and those that consume ammonia are decreased. We also demonstrate that the metabolites of these enzymes change as expected. Thus, hyperammonemic encephalopathy in FLC may require alternative therapeutics.

The Relationship between Plant-Based Diet Index and Semen Parameters of Men with Infertility: A Cross-Sectional Study.

BACKGROUND: Infertility is a major clinical problem that affects people psychologically and medically. For the past 40 years, studies have linked nearly 50% of childlessness to male infertility. It is worth noting that unlike other factors contributing to infertility, diet is a tunable factor and can be applied in counseling infertile men. The goal of this study was to determine the relationship between plant diet index (PDI) and semen parameters in Iranian infertile men. MATERIALS AND METHODS: In this cross-sectional study, dietary intake was determined by a valid 168-item questionnaire (FFQ). In this study, four dependent semen parameters, including total sperm motility (TSM), sperm concentration (SC), normal sperm morphology (NSM), and semen volume (SV) were measured. RESULTS: Results of this study stated that greater adherence to the healthful plant-based diet index (hPDI), can significantly increase sperm density and motility in men, as well as greater adherence to the PDI dietary pattern is related to a lower risk of sperm volume deficiency, and ultimately more adherence to the unhealthful plant-based diet index (uPDI), can reduce the risk of sperm motility. CONCLUSION: In this study, for the first time, the relationship between PDI, hPDI, uPDI and male infertility was evaluated. Altogether, this study demonstrated that nutrition has an impact on semen quality and fertility of men.

The relationship between plant and animal based protein with semen parameters: A cross-sectional study in infertile men.

OBJECTIVE: Infertility is a global challenge, affecting 15% of non-contracepting couples that have intercourse. Recent studies have shown that diet can directly affect sperm quality. Protein is one of the most important components of an adequate diet that can regulate metabolic profile and send signals to the reproductive axis. This study aimed to determine the relationship between plant and animal protein intake and infertility in Iranian men. METHODS AND MATERIALS: In this cross-sectional study, 270 infertile men aged 18-55 years were selected from Isfahan Infertility clinic in 2018. Semen assessment was performed according to the fifth edition of the WHO laboratory manual and a 168-item questionnaire was used to determine the amount of dietary intakes of participants. Statistical analyses were carried out using SPSS for Windows software (version 20.0), SPSS Inc, and Chicago IL. P-value < 0.05 was considered statistically significant. RESULTS: There was significant association between concentration and plant protein tertiles in the crude model (OR = 0.38; 95% CI: 0.19, 0.75; P = 0.004), which became significant in the both adjusted model and participants in highest tertile had a lower risk (OR = 0.36; 95% CI: 0.18, 0.72; P = 0.003 and OR = 0.31; 95% CI: 0.14, 0.65; P = 0.002). Also, there was a significant association between sperm concentration and animal protein in the crude model, and participants in the highest tertile had a higher risk (OR = 2.32; 95% CI: 1.13, 4.76; P = 0.02). Participants in highest animal protein tertile had a higher risk (OR = 2.38; 95% CI: 1.16, 4.91; P = 0.02 and OR = 2.42; 95% CI: 1.13, 5.19; P = 0.02) in adjusted model. Furthermore, there was a significant association between morphology and animal protein in the crude model, and participants in the highest tertile had a higher risk (OR = 3.68; 95% CI: 0.97, 13.91; P = 0.04). CONCLUSION: In this cross-sectional study, the relationship between plant and animal protein with semen parameters was evaluated. Although this study demonstrated the relationship between plant and animal based protein with semen parameters, more researches need to be done in this area.

The association between healthy eating index score with semen parameters in infertile men: A cross-sectional study.

Background: Infertility has been a major problem for young couples in recent years. One way to assay the diet quality is the healthy eating index (HEI), related to infertility. Objective: This study aims to assess the association between the HEI score with semen parameters in Iranian infertile men. Materials and Methods: Two hundred and sixty eligible men (18-55 yr), were referred to the major infertility clinic in the summer of 2018 and entered this cross-sectional study. Based on the 5 th edition of the world health organization laboratory manual, semen parameters including sperm concentration, volume, motility, and morphology were analyzed, and to specify the dietary intake of individuals a 168-item questionnaire was used. Also, to calculate the total HEI score, all 13 components based on HEI-2015 components and scoring standards were summed up. Results: Participants in the highest tertile, had no difference in mean sperm parameters with those in the lowest tertile in the crude model. No significant association was found between sperm parameters and HEI score tertiles in the crude model, even after adjustment for potential confounders, except for concentration (OR: 0.39 and CI: 0.15, 0.99, p = 0.04). Participants in the highest tertile had a lower risk of abnormal concentration and motility in the crude model. The risk of abnormal concentration decreased, and motility increased in the adjusted model. Conclusion: In this cross-sectional study, there was no significant relationship between HEI and sperm indexes, except for sperm concentration. Therefore, more studies need to be done in the future.

The association between dietary fat and mineral intake with semen parameters: A cross-sectional study in infertile men.

Background: Infertility has been a significant problem for couples in recent decades, and the issue can often lie with the male rather than the female. Objective: This study aimed to investigate the effects of fats and minerals intake on semen parameters in infertile men. Materials and Methods: This cross-sectional study was performed on 260 infertile men referred to Isfahan Infertility Clinic, Isfahan, Iran in the summer of 2018. Semen parameters regarding sperm concentration, total motility, normal morphology, and sperm volume were considered. To assess dietary intakes, a validated food frequency questionnaire was used. Results: In the adjusted model, the prevalence of abnormal concentration was 5.23 times higher in the top quartile of calcium intake, compared with the bottom quartile (p = 0.03). Also, the prevalence of abnormal morphology was 68% lower in the third quartile of calcium intake (p = 0.03). Additionally, the prevalence of abnormal concentration was 84% lower in the top quartile of folate intake in comparison to the bottom quartile (p = 0.01) and the prevalence of abnormal morphology was 70% lower in the top quartile of folate intake (p = 0.03). Additionally, the prevalence of abnormal concentration was 72% lower in the top quartile of selenium intake in comparison to the bottom quartile (p = 0.04). Furthermore, in the crude model, the prevalence of abnormal volume was 64% lower in the second quartile of linoleic acid intake rather than the first quartile (p = 0.01). Conclusion: In conclusion, diets containing higher amounts of folate and selenium, and lower amounts of cholesterol, saturated fatty acid and calcium were associated with more favorable semen quality parameters.

DXS998-DXS548-FRAXAC1 represents a novel informative haplotype at the FMR1 locus in the Iranian population.

Fragile X syndrome, which is caused by mutation in the FMR1 gene region, is one of the most prevalent forms of mental retardation. Direct diagnosis of the disease is based on PCR and southern blot analysis, but because of technical problems, use of polymorphic DNA markers can be helpful for carrier detection and prenatal diagnosis in families with an affected individual. The polymorphic markers usually show a population-based haplotype frequency and heterozygosity. In the present study, genotyping and analysis of haplotype frequency of three microsatellite markers including DXS998, DXS548 and FRAXAC1 at the FMR1 gene region were carried out in 140 unrelated healthy women and 26 families from the Iranian population. The data indicated the presence of a novel allele for DXS998 in the Iranian population. Estimation of haplotype frequency using Arlequin program showed 50 different DXS998-DXS548-FRAXAC1 haplotypes for the input data of 5, 7 and 4 alleles, respectively. Among these haplotypes five of them showed relatively high frequencies (≥0.05). Analysis of linkage disequilibrium (LD) for the unrelated individuals using the PowerMarker computer program, showed that this haplotype combination can be an informative haplotype for linkage analysis in carrier detection and possible molecular diagnosis of fragile X in the Iranian population.

Peroxisome proliferator activated receptor gamma (PPARγ) as a therapeutic target for improvement of cognitive performance in Fragile-X.

Rare disorders leading to intellectual disability, such as Fragile X syndrome (FXS) alter synaptic plasticity. Ligand identification of orphan nuclear receptors has led to the discovery of many signaling pathways and has revealed a direct link of nuclear receptors with human conditions such as mental retardation and neurodegenerative diseases. PPARγ agonists can act as neuroprotective agents, promoting synaptic plasticity and neurite outgrowth. Therefore, selective PPARγ agonists are good candidates for therapeutic evaluation in intellectual disabilities. Preliminary results suggest that PPARγ agonists such as Pioglitazone, Rosiglitazone and synthetic agonist, GW1929, are used as the therapeutic agent in neurological disorders. These components interact with intracellular transduction signals (e.g. GSK3ß, PI3K/Akt, Wnt/ß-Catenin, Rac1 and MMP-9). It seems that interaction with these pathways can improve memory recognition in FXS animal models. The present hypothesis consists of enhancing synaptic plasticity that may then rescue the learning and memory in FXS. This will open many new therapeutic avenues for a variety of human diseases.