In vitro effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the expression of genes related to sperm motility and energy metabolism and intracytoplasmic sperm injection outcomes in obstructive azoospermic patients.

BACKGROUND: The presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and its receptor in various testicular cells and spermatozoa suggests a potential role in enhancing spermatogonial and postmeiotic cell development. Moreover, GM-CSF activates the pivotal pathways implicated in sperm motility regulation and glucose metabolism. However, the impact of GM-CSF on testicular biopsies from patients with obstructive azoospermia (OA) remains unexplored. Therefore, this study aimed to investigate the in vitro effects of GM-CSF on the expression of genes related to glucose transporters and signaling pathways, sperm motility, and viability in testicular biopsies. METHODS AND RESULTS: Following testicular sperm extraction from 20 patients diagnosed with OA, each sample was divided into two parts: the experimental samples were incubated with medium containing 2 ng/ml GM-CSF at 37 °C for 60 min, and the control samples were incubated with medium without GM-CSF. Subsequently, the oocytes retrieved from the partner were injected with sperm from the treatment and control groups. The sperm parameters (motility and viability), the expression levels of sperm motility-related genes (PIK3R1, PIK3CA, and AKT1), and the expression levels of sperm energy metabolism-related genes (GLUT1, GLUT3, and GLUT14) were assessed. Furthermore, the fertilization and day 3 embryo development rate and embryo quality were evaluated. Compared with those in the nontreated group, the motility parameters and the mRNA expression levels of PIK3R1, AKT1, and GLUT3 in testicular sperm supplemented with GM-CSF were significantly greater (p < 0.05). However, no significant differences in the mRNA expression of PIK3CA, GLUT1, or GLUT14 were detected. According to the ICSI results, compared with the control group, the GM-CSF treatment group exhibited significantly greater fertilization rates (p = 0.027), Day 3 embryo development rate (p = 0.001), and proportions of good-quality embryos (p = 0.002). CONCLUSIONS: GM-CSF increased the expression of genes related to motility and the energy metabolism pathway and effectively promoted the motility of testis-extracted spermatozoa, consequently yielding positive clinical outcomes.

Curcumin mitigates acrylamide-induced ovarian antioxidant disruption and apoptosis in female Balb/c mice: A comprehensive study on gene and protein expressions.

Curcumin is known for its antioxidant properties. This study aimed to investigate the impact of curcumin on acrylamide (ACR)-induced alterations in the first-line antioxidant defense of ovarian tissue. Female Balb/c mice were divided into control, ACR (50 mg/kg), ACR/CUR100 (received Acr + curcumin100 mg/kg), and ACR/CUR200 (Acr + curcumin 200 mg/kg) groups, and received oral treatments for 35 days. Evaluation of antioxidant enzyme expression (Sod, Cat, Gpx genes), pro-apoptotic gene expressions (Bax, Caspase 3), and anti-apoptotic gene expression (Bcl2l1) at mRNA and protein levels was done. Percentage of apoptotic cells using Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed. The model group (ACR) showed decreased mRNA expression of Sod, Cat, and Gpx genes compared with the control group. Treatment with two different doses of curcumin (CUR100 and CUR200) significantly increased Sod, Cat, and Gpx gene expression, with CUR200 demonstrating significant recovery. SOD, CAT, and GPX protein levels were similar to mRNA expression trends, significantly increased with curcumin administration. Acrylamide exposure significantly increased Bax and Caspase 3 expression and decreased Bcl2l1 gene expression leading to a notable rise in apoptosis in ACR group as compared to the control group. Conversely, curcumin administration, significantly reduced Bax and Caspase 3 expressions, with an increase in Bcl2l1expression, though not statistically significant. TUNEL assay revealed a substantial decrease in apoptosis in curcumin-received groups. In our study, ACR exposure adversely affected ovarian antioxidant defense thereby leading to increased pro-apoptotic markers. Notably, curcumin treatment effectively mitigated these effects, restored antioxidant potential, and reduced acrylamide-induced toxicity in female mouse ovaries.

The effects of two different fatigue protocols on movement quality during anticipated and unanticipated change of directions in female soccer players.

OBJECTIVE: This study compared neuromuscular control under two fatigue protocols during anticipated and unanticipated change of direction (COD) maneuvers and evaluated their effects on the risk of non-contact ACL injuries. METHOD: Forty-five female soccer players (mean age: 22.22 ± 2.24 years; mean height: 166.24 ± 3.33 cm; mean mass: 59.84 ± 5.03 kg) were divided into three groups: functional fatigue (Soccer specific fatigue ptotocol-SOFT90), non-functional fatigue (Bruce protocol), and control group. Before and after the implementation of neuromuscular control fatigue protocols were evaluated using the cutting motion assessment score tool (CMAS). Two-dimensional (2D) videos were recorded during anticipated and unanticipated COD trials for both dominant and non-dominant legs. RESULTS: Significant time effects (p < 0.05) and group-time interactions (p < 0.05) were observed in both anticipated and unanticipated conditions for both dominant and non-dominant legs after the fatigue protocols. The functional fatigue group exhibited higher CMAS changes, indicating poorer movement quality following fatigue. Notably, the non-dominant leg displayed amplified deficits during unanticipated COD maneuvers following the functional fatigue protocol. CONCLUSIONS: Fatigue significantly impairs neuromuscular control, particularly in unanticipated COD situations, which increases the risk of non-contact ACL injuries. To mitigate this risk, coaches, trainers, and medical professionals should prioritize targeted training and injury prevention strategies, focusing on the non-dominant leg during unanticipated COD maneuvers.

Leisure-time and occupational physical activity and risk of cardiovascular disease incidence: a systematic-review and dose-response meta-analysis of prospective cohort studies.

BACKGROUND AND OBJECTIVE: Physical activity has benefits for the cardiovascular system, however, what levels and types of activity provide optimal cardiovascular health is unclear. We aimed to determine the level of physical activity that has the most benefits against cardiovascular diseases (CVD). METHODS: PubMed, Scopus, and Web of Science were searched for prospective cohort studies on leisure-time (LTPA) or occupational physical activity (OPA) as the exposure and major types of CVD (total CVD, coronary heart disease [CHD], stroke, and atrial fibrillation [AF]) incidence as the outcome. Risk of bias of studies was evaluated using the ROBINS-I tool. Summary hazard ratios (HR) were calculated using random-effects pairwise model. RESULTS: A total of 103 studies were included in the analysis. The highest versus the lowest LTPA was associated with a lower risk of overall CVD (HR = 0.81; 95% CI: 0.77-0.86), CHD (HR = 0.83; 0.79-0.88), and stroke (HR = 0.83; 0.79-0.88), but not AF (HR = 0.98; 0.92-1.05). Linear dose-response analyses showed a 10%, 12%, 9%, and 8% risk reduction in CVD, CHD, stroke, and AF incidence, respectively, for every 20 MET-hours/week increase in LTPA. In nonlinear dose-response analyses, there were inverse associations up to 20 MET-hours/week with 19% and 20% reduction in CVD and CHD risk, and up to 25 MET-hours/week with 22% reduction in stroke, with no further risk reduction at higher LTPA levels. For AF, there was a U-shaped nonlinear association with the maximum 8% risk reduction at 10 MET-hours/week of LTPA. Higher levels of OPA were not associated with risk of CVD, CHD, stroke, or AF. CONCLUSIONS: Overall, results showed an inverse dose-response relationship between LTPA and risk of CVD, CHD, stroke, and AF. Running was the most beneficial LTPA but the risk was similar among various LTPA intensities. OPA showed no benefits in total or any type of CVD.

A 30-year trend of dairy consumption and its determinants among income groups in Iranian households.

Introduction: Milk and dairy products provide essential nutrients and have the potential to prevent chronic diseases, thus reducing healthcare costs. However, there is a lack of consistent and updated data on dairy consumption trends in Iran. This study aims to analyze the trends in dairy consumption among Iranian households from 1991 to 2021, focusing on household-level determinants across different expense groups. Methods: The study uses data from the Iranian Household Expenditure and Income Survey conducted annually from 1991 to 2021 to analyze households' dairy consumption. The data includes values and expenses of food and non-food items purchased in the previous month, as well as demographic characteristics of household members. The households were categorized into 10 deciles based on their gross expense. The econometric model used weighted mean per capita milk, yogurt, cheese, and total dairy consumption based on milk equivalent for each decile. The model takes into account changes in income, prices, household composition, education level, occupation, and residency area using panel data. Data preparation and model estimation were performed using RStudio and STATA17 software. Results: Based on the findings, in 1991, per capita milk, yogurt, and cheese consumption were 26.77 kg, 16.63 kg, and 2.42 kg, respectively. By 2021, these figures changed to 22.68 kg, 11.06 kg, and 3.79 kg, reflecting a decrease in milk and yogurt consumption but an increase in cheese consumption. Family size was positively correlated with yogurt consumption and head of the household spouse's job score were positively correlated with milk, yogurt and cheese consumption. Also, the presence of under five-year-old children and older adults members (over the age of 60) in the household was inversely related with yogurt and cheese consumption. Female-headed households tended to purchase more cheese, while their milk purchase level was significantly lower. Residing in urban areas was negatively related to milk, while cheese and total dairy consumption was higher in urban areas. Discussion: The findings highlight the importance of targeted dairy subsidy interventions and educational programs to improve dairy consumption in Iranian households, especially among vulnerable groups. This will require urging policymakers and food system stakeholders for effective strategies that address macro-level factors to promote dairy consumption.

Relationship between dietary glycemic index and glycemic load and sperm-quality parameters in Iranian men: a cross-sectional study.

BACKGROUND: Infertility is a major clinical problem with psychological, financial and medical costs. Male infertility has recently been linked to 50% of childless couples. It is worth mentioning that diet and its components can be manipulated and applied in counseling meetings of infertile men as a modifiable factor. The goal of this study was to determine the correlation of dietary glycemic index (GI) and glycemic load (GL) with sperm-quality parameters in Iranian men. MATERIALS AND METHODS: In this cross-sectional study which was carried from Aug to Nov 2023, after excluding smokers, 322 men who were attending the IVF clinic of Ayatollah Mousavi Hospital for seminal analysis were enrolled. Dietary intake was completed by an expert dietitian through face-to-face interviews with a validated 168-item food frequency questionnaire (FFQ). In the present study, sperm-quality parameters, including motility, concentration, normal morphology, vitality, DNA fragmentation index (DFI), and chromatin maturation of sperm, were analyzed. The relationship between dietary GI and CL and these parameters was assessed. RESULTS: Adjusting for the baseline variables, dietary GI and GL showed positive and negative associations with sperm progressive motility, respectively (p = 0.01 and p < 0.001). Higher dietary GI was associated with lower (p = 0.03); however, a higher dietary GL was associated with higher immotile sperm (p < 0.001). A higher dietary GI was associated with a 77% higher sperm count (p = 0.003). In contrast, higher dietary GL was associated with a lower count (p < 0.001). Higher dietary GI and GL were associated with higher and lower percentages of sperm with normal morphology by 70% and 40%, respectively (p < 0.001 in both). A higher dietary GL was associated with an increase in sperm vitality and DFI of 33% and 53%, respectively (p < 0.001). Higher dietary GI showed a significant negative effect on sperm DFI (p = 0.009). Dietary GI and GL showed significant positive and negative effects on SCMA, respectively (p = 0.002 and p < 0.001). CONCLUSION: A diet with a higher GI showed beneficial effects on more parameters of sperm; however, higher dietary GL showed deleterious effects, except sperm vitality and SCMA. More studies are needed to obtain a concise result.

A novel homozygote nonsense variant of MSH4 leads to primary ovarian insufficiency and non-obstructive azoospermia.

BACKGROUND: Both non-obstructive azoospermia (NOA) and primary ovarian insufficiency (POI) are pathological conditions characterized by premature and frequently complete gametogenesis failure. Considering that the conserved meiosis I steps are the same between oogenesis and spermatogenesis, inherited defects in meiosis I may result in common causes for both POI and NOA. The present research is a retrospective investigation on an Iranian family with four siblings of both genders who were affected by primary gonadal failure. METHODS: Proband, an individual with NOA, was subjected to clinical examination, hormonal assessment, and genetic consultation. After reviewing the medical history of other infertile members of the family, patients with NOA went through genetic investigations including karyotyping and assessment of Y chromosome microdeletions, followed by Whole exome sequencing (WES) on the proband. After analyzing WES data, the candidate variant was validated using Sanger sequencing and traced in the family. RESULTS: WES analysis of the proband uncovered a novel homozygote nonsense variant, namely c.118C>T in MSH4. This variant resulted in the occurrence of a premature stop codon in residue 40 of MSH4. Notably, the variant was absent in all public exome databases and in the exome data of 400 fertile Iranian individuals. Additionally, the variant was found to co-segregate with infertility in the family. It was also observed that all affected members had homozygous mutations, while their parents were heterozygous and the fertile sister had no mutant allele, corresponding to autosomal recessive inheritance. In addition, we conducted a review of variants reported so far in MSH4, as well as available clinical features related to these variants. The results show that the testicular sperm retrieval and ovarian stimulation cycles have not been successful yet. CONCLUSION: Overall, the results of this study indicate that the identification of pathogenic variants in this gene will be beneficial in selecting proper therapeutic strategies. Also, the findings of this study demonstrate that clinicians should obtain the history of other family members of the opposite sex when diagnosing for POI and/or NOA.

Methotrexate-induced Severe Pancytopenia in a Patient with Rheumatoid Arthritis: A Case Report and Review of Literature.

Toxicity associated with low doses of methotrexate (MTX) is low, but it may be fatal. Bone marrow suppression and mucositis are among the common side effects of low dose MTX toxicity. Different risk factors have been reported for toxicities associated with low doses of MTX, including accidental use of higher doses, renal dysfunction, hypoalbuminemia, and polypharmacy. In this paper, we present a female patient who had mistakenly used 7.5 mg of MTX daily instead of the same dose of MTX on Thursday and Friday. She was presented with mucositis and diarrhea to the emergency department. Moreover, we searched the databases Scopus and PubMed for available studies and case reports on toxicities associated with MTX dosing errors. The most frequently observed toxicities included gastrointestinal lesions, nausea, vomiting, skin lesions, and bone marrow suppression. Leucovorin, hydration, and urine alkalinization were among the most frequently used treatments. Finally, we summarize the data on the toxicities of low doses of MTX in different diseases.

Granulocyte-Macrophage Colony-Stimulating Factor Cytokine Addition After the Freeze-Thawing Process Improves Human Sperm Motility and Vitality in Asthenoteratozoospermia Patients.

The cryopreservation-thawing process of spermatozoa cells has negative impacts on their structure, function, and fertility parameters, which are known as cryoinjury. Asthenozoospermia patients are more susceptible to cryoinjury. Granulocyte-macrophage colony-stimulating factor (GM-CSF) increases sperm glucose uptake via the induction of glucose transporters, resulting in increased sperm motility. This study aimed to investigate the efficiency of GM-CSF supplementation of the cryopreservation media for semen samples of asthenoteratozoospermia patients. The study was carried out on 20 semen samples from infertile men referred to diagnosing semen analysis. To avoid subjective bias, two main sperm motility parameters, including velocity along the curvilinear path and velocity along the straight-line path were considered by the computer-assisted sperm analysis system. Afterward, each semen sample was divided into three equal aliquots and randomly assigned to one of the following groups: group I (control, freezing media only), group II (+GM-CSF, freezing medium supplemented with 2 µL/mL GM-CSF), or group III (GM-CSF added after thawing and washing). Following semen thawing, standard parameters, mitochondrial membrane potential (MMP), and the DNA Fragmentation Index were analyzed. Total sperm motility (progressive and non-progressive) improved significantly in group III samples after a 30-minute incubation with GM-CSF compared with the control group (26.5% ± 3.1% vs. 17.51% ± 2.59%). However, no differences in progressive motility or sperm morphology were found among the three thawed samples. The percentage of vitality was significantly higher in group III compared with the other two groups (28.38% ± 3.4% vs. 22.4% ± 3.08% and 22.14% ± 2.77%, respectively) (p < 0.05). JC-1 levels (a marker of MMP) were not significantly different between the examined groups (44.95% ± 8.26% vs. 36.61% ± 6.95% vs. 46.67% ± 7.7%, for control, group II, and group III, respectively) (p > 0.05). GM-CSF may be advantageous as an additive after freezing, improving total motility and viability after 30 minutes of post-thaw incubation; however, when supplied to the freezing media before cryopreservation, it is unable to protect against cryoinjury.

Correlation of Dietary Macro- and Micro-Mineral Intake with Seminal Plasma Quality/Quantity and Oxidant/Antioxidant Status in Infertile Compared to the Normal Men: a Case-Control Study.

Male infertility is a global public health issue, but studies on the correlation between the dietary components and sperm quality showed inconclusive results due to the heterogeneous population with different dietary habits and environmental stimuli. Herein, the correlation of dietary macro- and micro-mineral intake was evaluated with quality/quantity and oxidant/antioxidant status of seminal fluid in infertile compared to the healthy men. One hundred twenty men attending to the infertility clinic of Ayatollah Mousavi Hospital in Zanjan City were enrolled. Seminal fluid was extracted, and groups were categorized into the infertile (non-standard) and normal (standard) groups based on the WHO, 2020 criteria. Food frequency questionnaire was completed. Seminal malondialdehyde (MDA) and total antioxidant capacity (TAC) were measured by ELISA kit based on the manufacture's instruction. An independent sample t-test was used to determine differences between the two groups, and linear regression model was used to determine the effect of each dietary macro/micro mineral intake on these parameters. Adjusting for all parameters, dietary selenium increased 3.7-folds the seminal TAC level (p=0.04) and decreased sperm with non-progressive motility by 2.4-folds (p=0.04). Higher manganese intake increased the sperm count by 7.8-folds (p=0.005). Dietary copper decreased sperm vitality and increased sperm with slow motility (OR= -1.7, 95% CI= -59.8, -9.9; p=0.007). Dietary zinc (OR=1.24, p=0.01) and iron (OR=1.5, p=0.02) showed a positive effect on sperm vitality. None of macro and micro minerals showed a significant effect on the seminal MDA level. Daily intake of adequate amounts of micro and macro minerals improves sperm quality and increases the antioxidant capacity of the seminal fluid; however, copper showed a negative correlation that must be evaluated in future studies.

The test-retest reliability and limits of agreement of the balance evaluation systems test (BESTest) in young people with intellectual disability.

Clinical tests for the assessment of postural balance in people with intellectual disability have been the most commonly used single or multi-item tests, but some tests have been developed, such as the BESTest. The purpose of the study was to evaluate the test-retest reliability and limits of agreement of the Balance Evaluation Systems Test (BESTest) in young people with intellectual disabilities. A descriptive cross-sectional study was conducted with 65 young people (ages 16-25 years) with intellectual disability. The participants completed the BESTest (27 items) twice. Intraclass correlation coefficients (ICC), 95% confidence intervals (CIs), and standard error of measurement (SEM) were calculated to determine the test-retest reliability of the BESTest. The BESTest overall scores' test-retest reliability was rated as excellent (≥ 0.75). Stability limits/verticality and reactive are fair to good (≥ 0.40- < 0.75). Biomechanical constraints, transitions and anticipatory movements, sensory orientation, and gait stability were excellent (≥ 0.75). Current evidence shows that young people with intellectual disabilities have impaired postural balance. However, there appears to be a lack of assessment tools that reliably evaluate the postural balance of this population. The results from this investigation show that BESTest provides "excellent reliability" (≥ 0.75) to assess postural balance in young people with intellectual disability.

The Effect on Flexibility and a Variety of Performance Tests of the Addition of 4 Weeks of Soleus Stretching to a Regular Dynamic Stretching Routine in Amateur Female Soccer Players.

The purpose of this study was to investigate the effects of 4 weeks of soleus stretching on ankle flexibility and dynamic balance, as well as selected monitoring and performance tests in soccer. Forty-five healthy female soccer players were randomly divided into a regular stretching group, a regular stretching group with soleus stretching, and a control group. Dynamic stretching protocols were performed for 4 weeks during three sessions per week as part of routine exercises. The regular group stretched three muscle groups (i.e., gastrocnemius, quadriceps, and hamstrings), while the regular + soleus group also stretched the soleus muscle. Before and after the stretching intervention, the ankle range of motion test, Y-balance test, drop jump test, dynamic knee valgus test, and Illinois Agility Running Test were performed. Ankle ROM, Y-balance, and DJ significantly improved in both intervention groups compared to controls. Only the regular + soleus group showed improvement in the Illinois Agility Running Test. Additionally, athletes performing the additional soleus stretching had greater improvements in ankle ROM and DJ but not in DKV or Y-balance. The results showed that adding soleus stretching into regular protocols can provide benefits for female soccer players in terms of performance parameters.

Targeted Amino Acids Profiling of Human Seminal Plasma from Teratozoospermia Patients Using LC-MS/MS.

Identifying the metabolome of human seminal plasma (HSP) is a new research area to screen putative biomarkers of infertility. This case-control study was performed on HSP specimens of 15 infertile patients with teratozoospermia (defined as normal sperm morphology < 4%) and 12 confirmed fertile normozoospermic men as the control group to investigate the seminal metabolic signature and whether there are differences in the metabolome between two groups. HSPs were subjected to LC-MS-MS analysis. MetaboAnalyst5.0 software was utilized for statistical analysis. Different univariate and multivariate analyses were used, including T-tests, fold change analysis, random forest (RF), and metabolite set enrichment analysis (MSEA). Teratozoospermic samples contained seventeen significantly different amino acids. Upregulated metabolites include glutamine, asparagine, and glycylproline, whereas downregulated metabolites include cysteine, γ-aminobutyric acid, histidine, hydroxylysine, hydroxyproline, glycine, proline, methionine, ornithine, tryptophan, aspartic acid, argininosuccinic acid, α-aminoadipic acid, and ß-aminoisobutyric acid. RF algorithm defined a set of 15 metabolites that constitute the significant features of teratozoospermia. In particular, increased glutamine, asparagine, and decreased cysteine, tryptophan, glycine, and valine were strong predictors of teratozoospemia. The most affected metabolic pathways in teratozoospermic men are the aminoacyl-tRNA, arginine, valine-leucine, and isoleucine biosynthesis. Altered metabolites detected in teratozoospermia were responsible for various roles in sperm functions that classified into four subgroups as follows: related metabolites to antioxidant function, energy production, sperm function, and spermatogenesis. The altered amino acid metabolome identified in this study may be related to the etiology of teratozoospermia, and may provide novel insight into potential biomarkers of male infertility for therapeutic targets.

A conceptual model for empowering faculty members of third-generation universities of medical sciences.

Background and objectives: Despite the crucial role of university staff and especially faculty members in moving towards third-generation universities, as well as the necessity of staff empowerment, only a handful of studies have been carried out on staff (especially faculty member) empowerment. This study designed a conceptual model for empowering faculty members of universities of medical sciences and facilitating transition to third-generation universities. Methods: The grounded theory approach was adopted to conduct this qualitative study. A total of 11 faculty members with entrepreneurial experience were selected as the sample using purposive sampling. The data were collected using semi-structured interviews, and the obtained data were entered into qualitative software (MAXQDA 10) for analysis. Results: The concepts identified in the coding process were summarized and classified into five groups and seven main categories. Then the conceptual model was designed with a set of causal factors (including structure of the education system, recruitment, training, and investment), structure and context factors (including structure and relationship), intervening factors (including promotion and ranking systems in universities and lack of mutual trust between industry and university), a core category (characteristics of capable faculty members), and an outcome (third-generation university). Finally, the conceptual model was developed to empower faculty members of third-generation universities of medical sciences. Conclusions: Based on the designed conceptual model, the most important issue in moving towards third-generation universities is "characteristics of capable faculty members." The present findings will help policy makers better understand the major factors affecting faculty member empowerment.

Dietary Advanced Glycation End Products and Risk of Overall and Cause-Specific Mortality: Results from the Golestan Cohort Study.

Controversy exists regarding the association of dietary advanced glycation end products (dAGEs) with the risk of disease outcomes and mortality. We aimed to examine, prospectively, the association between dAGEs intake and the risk of overall and cause-specific mortality in the Golestan Cohort Study. The cohort was conducted between 2004 and 2008 in Golestan Province (Iran) recruiting 50,045 participants aged 40-75 years. Assessment of dietary intake over the last year was performed at baseline using a 116-item food frequency questionnaire. The dAGEs values for each individual were calculated based on published databases of AGE values of various food items. The main outcome was overall mortality at the time of follow-up (13.5 years). Hazard ratios (HRs) and 95% confidence intervals (CIs) for overall and cause-specific mortality were estimated according to the dAGEs quintiles. During 656, 532 person-years of follow-up, 5406 deaths in men and 4722 deaths in women were reported. Participants at the highest quintile of dAGE had a lower risk of overall mortality (HR: 0.89, 95% CI: 0.84, 0.95), CVD mortality (HR: 0.89, 95% CI: 0.84, 0.95), and death from other causes (HR: 0.89, 95% CI: 0.84, 0.95) compared to those in the first quintile after adjusting for confounders. We found no association of dAGEs with risk of mortality from cancer (all), respiratory and infectious diseases, and injuries. Our findings do not confirm a positive association between dAGEs and the risk of mortality in Iranian adults. There is still no agreement among studies investigating dAGEs and their health-related aspects. So, further high-quality studies are required to clarify this association.

Rescuing fertility during COVID-19 infection: exploring potential pharmacological and natural therapeutic approaches for comorbidity, by focusing on NLRP3 inflammasome mechanism.

The respiratory system was primarily considered the only organ affected by Coronavirus disease 2019 (COVID-19). As the pandemic continues, there is an increasing concern from the scientific community about the future effects of the virus on male and female reproductive organs, infertility, and, most significantly, its impact on the future generation. The general presumption is that if the primary clinical symptoms of COVID-19 are not controlled, we will face several challenges, including compromised infertility, infection-exposed cryopreserved germ cells or embryos, and health complications in future generations, likely connected to the COVID-19 infections of parents and ancestors. In this review article, we dedicatedly studied severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) virology, its receptors, and the effect of the virus to induce the activation of inflammasome as the main arm of the innate immune response. Among inflammasomes, nucleotide oligomerization domain-like receptor protein, pyrin domain containing 3 (NLRP3) inflammasome pathway activation is partly responsible for the inflicted damages in both COVID-19 infection and some reproductive disorders, so the main focus of the discussion is on NLRP3 inflammasome in the pathogenesis of COVID-19 infection alongside in the reproductive biology. In addition, the potential effects of the virus on male and female gonad functions were discussed, and we further explored the potential natural and pharmacological therapeutic approaches for comorbidity via NLRP3 inflammasome neutralization to develop a hypothesis for averting the long-term repercussions of COVID-19. Since activation of the NLRP3 inflammasome pathway contributes to the damage caused by COVID-19 infection and some reproductive disorders, NLRP3 inflammasome inhibitors have a great potential to be considered candidates for alleviating the pathological effects of the COVID-19 infection on the germ cells and reproductive tissues. This would impede the subsequent massive wave of infertility that may threaten the patients.

Maternal circulating leptin, tumor necrosis factor-alpha, and interleukine-6 in association with gestational diabetes mellitus: a systematic review and meta-analysis.

Background: Over the last decade, an emerging role of novel cytokines in the pathogenesis of gestational diabetes mellitus (GDM) has been proposed. The present study was implemented to provide a more accurate estimate of the effect size of the association between leptin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) and the risk of GDM.Methods: Online databases were looked up to January 2023 using the search string: (leptin OR TNF-α OR IL-6) AND "gestational diabetes." Observational studies investigating the association of selected cytokines and GDM risk were included. Odds ratios and their 95% confidence intervals (CIs) were extracted and random-effects models were used to estimate the pooled effect.Results: Twenty-four studies were included in the meta-analysis. A significant association was found between higher circulating leptin and the risk of GDM and the pooled estimate was 1.16 (95%CI: 1.07, 1.27). Higher circulating levels of IL-6 and TNF-α were associated with increased risk of GDM, and the pooled estimates were 1.35 (95%CI: 1.05, 1.73) and 1.28 (95%CI: 1.01, 1.62), respectively.Conclusions: The studied cytokines could be implicated in the GDM pathogenesis and used as potential biomarkers for assessing the GDM risk. Additional longitudinal studies with large sample sizes are needed for a further evaluation of these findings.

The relationship between major food sources of fructose and cardiovascular disease, cancer, and all-cause mortality: a systematic review and dose-response meta-analysis of cohort studies.

We aimed to summarize the associations between food sources of fructose and cardiovascular diseases (CVD), cancer, and all-cause mortality risk using a systematic review and meta-analysis. We searched PubMed, Scopus, and Web of Science up to November 2020. We included cohort studies that investigated the relationship between mortality risk (all-cause, CVD, specific CVD, and total and site-specific cancers) and intake of ≥1 food source of fructose (fruit, fruit juice, breakfast cereals, sugar-sweetened beverages (SSBs), sweets, and yogurt) in general adult population. Summary hazard ratios and 95% CIs were estimated using a random-effects model for linear and nonlinear relationships. Findings indicated that each 100 g/d increase in fruit intake was associated with 8-13% lower risk of CVDs, stroke, gastrointestinal, and lung cancer mortality. For all-cause mortality, there was a beneficial relationship up to 200 g/d fruit, and then plateaued. For ischemic heart disease and cancer mortality, there was a beneficial relationship up to 300 g/d followed by a slight increase. Ingestion of breakfast cereals and sweets was also associated with lower risk of all-cause mortality. For yogurt, a non-linear marginal decrease in all-cause mortality was found. Ingestion of each 200 g/d yogurt was associated with a 14% lower risk of CVD mortality. Every 60 g/d increase in sweet intake was linked to a 5% lower risk of all-cause mortality. Contrariwise, every 250 g/d increase in SSBs intake was associated with 7-10% higher risk of all-cause and CVD mortality. In conclusion, beneficial associations were found between fruit, breakfast cereals, sweets, and yogurt with all-cause and/or CVD mortality risk. Fruit intake had also an inverse link with cancer mortality. Conversely, SSBs had a harmful relationship with all-cause and CVD mortality.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2021.2000361 .Registry number: CRD42019144956.

The effects of fasting diets on nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. There is no confirmed treatment for NAFLD as yet. Recently, fasting regimens and their relationship to NAFLD have drawn a great deal of attention in the literature. We review the current evidence that supports fasting diets as an adjunctive therapeutic strategy for patients with NAFLD and address potential action mechanisms. We reason that the fasting diets might be a promising approach for modulating hepatic steatosis, fibroblast growth factors 19 and 21 signaling, lipophagy, and the metabolic profile.

Fasting diets: what are the impacts on eating behaviors, sleep, mood, and well-being?

Fasting diets (FDs) have drawn great attention concerning their contribution to health and disease over the last decade. Despite considerable interest in FDs, the effect of fasting diets on eating behaviors, sleep, and mood-essential components of diet satisfaction and mental health- has not been addressed comprehensively. Understanding the critical role that fasting plays in these elements will open up potential treatment avenues that have not yet been explored. The aim of the present paper was to conduct a comprehensive critical review exploring the effects of fasting on eating behaviors, sleep, and mood. There is currently a lack of clarity regarding which fasting option yields the most advantageous effects, and there is also a scarcity of consistent trials that assess the effects of FDs in a comparable manner. Similarly, the effects and/or treatment options for utilizing FDs to modify eating and sleep behaviors and enhance mood are still poorly understood. Further researches aiming at understanding the impacts of various fasting regimes, providing new insights into the gut-brain axis and offering new treatment avenues for those with resistant anxiety and depression, are warranted. Alteration of eating behaviors can have lasting effects on various physiological parameters. The use of fasting cures can underpin ancient knowledge with scientific evidence to form a new approach to the prevention and treatment of problems associated with co-morbidities or challenges pertaining to eating behaviors. Therefore, a thorough examination of the various fasting regimens and how they impact disease patterns is also warranted.