Effects of vitamin D supplementation on liver fibrogenic factors, vitamin D receptor and liver fibrogenic microRNAs in metabolic dysfunction-associated steatotic liver disease (MASLD) patients: an exploratory randomized clinical trial.

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global metabolic problem which can lead to irreversible liver fibrosis. It has been shown that vitamin D and its receptors contribute to fibrogenic pathways in the liver. However, the effect of vitamin D supplementation on liver fibrosis related factors have not been examined. This double blinded placebo controlled clinical trial was designed to investigate the effects on vitamin D supplementation on serum levels of VDR, fibrogenic factors and fibrogenic MicroRNAs in MASLD patients. METHODS: Forty six MASLD patients after block matching for sex and BMI were randomly assigned to receive 4000 IU/d vitamin D or placebo for 12 weeks. Weight, height and waist circumference were measured. Serum fibrogenic microRNAs, laminin, collagen type IV, hyaluronic acid, vitamin D, VDR, PTH, blood fasting glucose, serum fasting insulin, lipid profile, ALT and AST were determined at the baseline and at the end of the trial. Insulin resistance and insulin sensitivity were calculated using the HOMA-IR and QUICKI equation. RESULTS: Supplementation with vitamin D for 12 weeks led to the significant increases in serum 25(OH) vitamin D, VDR and HDL-C compared to placebo (P < 0.001, P = 0.008 and P < 0.001). There were significant decreases in ALT, AST, FBS and LDL-C levels in the vitamin D group as compared to the placebo (P < 0.05). Laminin and hyaluronic acid concentrations were significantly decreased in the vitamin D group as compared to the placebo group, by -10.6 and - 28.7 ng/mL, respectively. Supplementation with vitamin D for 12 weeks resulted in a significant lower MiR-21 and MiR-122 gene expressions compared to the placebo group (P = 0.01 and P < 0.001, respectively). DISCUSSION: As the first randomized controlled trial on the effect of vitamin D supplementation on serum levels of VDR, fibrogenic factors and fibrogenic MicroRNAs in MASLD patients, we found a significant reduction in some liver fibrogenic factors, in liver transaminases and corresponding changes in some fibrosis-related MiRs and some metabolic factors. Further clinical trials with larger sample sizes and direct measures of liver fibrosis are needed to confirm these findings. TRIAL REGISTRATION NUMBER: (available at: http://www.irct.ir , identifier: IRCT201405251485N13), Registration date: 14-03-2017.

Effect of L-serine on oxidative stress markers in the kidney of streptozotocin-induced diabetic mice.

Oxidative stress is critical in the occurrence and development of diabetes and its related complications. L-serine has recently been shown to reduce oxidative stress, the incidence of autoimmune diabetes and improve glucose homeostasis. The aim of this study was to investigate the effects of daily L-serine administration on blood glucose, renal function and oxidative stress markers in the kidney of streptozotocin-induced diabetic mice. Eighteen C57BL/6 male mice were randomly divided into three groups (n = 6 per group). Streptozotocin was used to induce diabetes and a group of diabetic mice was treated with 280 mg/day of L-serine dissolved in drinking water for 4 weeks. The level of blood glucose, biochemical markers of renal function (total protein, urea, creatinine and albumin) and oxidative stress markers (protein carbonyls, malondialdehyde, glutathione peroxidase, superoxide dismutase and catalase) were measured using spectrophotometry. The results indicated that L-serine significantly decreased the glucose level in diabetic mice (188.6 ± 22.69 mg/dL, P = 0.02). Moreover, treatment of diabetic mice with L-serine reduced protein carbonyls (3.249 ± 0.9165 nmol/mg protein, P < 0.05) and malondialdehyde levels (1.891 ± 0.7696 µM/mg protein, P = 0.051). However, L-serine showed no significant effects on renal function, and a slight reduction in histopathological changes was observed in mice receiving L-serine. This study revealed that L-serine effectively ameliorates oxidative stress in kidney tissue and reduces the blood glucose concentration in diabetic mice.

Total Antioxidant Capacity and Total Oxidant Status and Disease Severity in a Cohort Study of COVID-19 Patients.

BACKGROUND: Previous reports have suggested the role of oxidative stress in progression of COVID-19 infection, but there is limited information regarding the effect of antioxidant capacity and total oxidant status of patients with COVID-19 on disease severity. In the present study, we aimed to investigate the relationship between total antioxidant capacity (TAC), total oxidant status (TOS), TAC/TOS levels, and disease severity in hospitalized patients with COVID-19. METHODS: This cohort study was carried out at Masih Daneshvari Hospital in Tehran, Iran, from September 2020 to October 2020. Clinical data of 331 patients with COVID-19 admitted to the hospital were analyzed and divided into mild, moderate, and severe groups (needed oxygen, intubation, and mechanical ventilation). The patients' TAC, TOS, and TAC/TOS levels were assessed using the serum samples by colorimetric assay kit. RESULTS: We found no significant difference in serum levels of TAC, TOS, and TAC/TOS in terms of the disease severity. CONCLUSIONS: These results indicated that total antioxidant capacity and total oxidant status may not be the determining factor on the disease severity.

Serum levels of Asprosin in patients diagnosed with coronary artery disease (CAD): a case-control study.

BACKGROUND: Coronary artery disease (CAD) is considered as a multi-faceted chronic inflammatory disease involving reduced blood supply to the myocardium as a result of accumulating lipids in the atrial walls. Visceral adiposity with disrupted release of adipokines play a key role in its pathogenesis. Asprosin is a newly identified fasting-induced glucogenic adipokine that has been related with metabolic disorders such as type II diabetes mellitus and polycystic ovary syndrome. The preset study sought to assess circulating asprosin in context of CAD. METHODS: In this study, serum levels of asprosin were determined in 88 CAD patients and 88 non-CAD healthy controls. Serum IL-6, TNF-α, asprosin and adiponectin were assessed using ELISA kits. RESULTS: Serum asprosin was found to be higher in CAD patients when compared to non-CAD subjects (7.84 ± 2.08 versus 5.02 ± 1.29 µg/mL, p <  0.001). Similarly, serum TNF-α, and IL-6 elevated in CAD group significantly (p <  0.001). However, circulating adiponectin diminished in CAD group when compared with non-CAD subjects (p < 0.001). Moreover, serum asprosin levels directly correlated with BMI, FBG, HOMA-IR, TG and TC. Logistic regression analyses showed that asprosin levels were associated with increased risk of developing CAD (odds ratio: 3.01, 95% CI: 2.16, 4.20 and p < 0.001), after adjusting for potential confounders (age, sex and BMI). CONCLUSIONS: The present study findings suggested a possible relation of serum asprosin with the pathogenesis of CAD, in particular through insulin resistance and dyslipidemia.

Circulating levels of C1q/TNF-α-related protein 6 (CTRP6) in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders affecting females of reproductive age. It has been associated with cardiometabolic disorders including diabetes mellitus and cardiovascular disorders, and increases the risk of developing fecundity pathologies including recurrent pregnancy loss (RPL) and infertility. C1q/tumor necrosis factor-α-related protein-6 (CTRP6) is a novel adipokine involved in glucose and lipid metabolism, host inflammation, and organogenesis. In the present study, we aimed to determine the association of serum CTRP6 levels with some components of metabolic syndrome in PCOS patients (infertile PCOS [inf-PCOS] and PCOS-RPL). This case-control study included 120 PCOS patients (60 inf-PCOS and 60 PCOS-RPL) and 60 healthy controls. Serum high-sensitivity C-reactive protein (hs-CRP) and homocysteine were measured using commercial kits, while adiponectin and CTRP6 levels were assessed using ELISA technique. Inf-PCOS and PCOS-RPL individuals had higher levels of serum CTRP6 than controls (546.15 ± 125.02 ng/ml and 534.04 ± 144.19 ng/ml vs. 440.16 ± 159.24 ng/ml; both p < .001). Moreover, serum adiponectin levels were significantly reduced, while fasting insulin, homeostasis model assessment of insulin resistance, free testosterone, and hs-CRP levels were significantly elevated in PCOS group, when compared with controls. Furthermore, serum CTRP6 positively associated with body mass index in all subjects. It showed an inverse correlation with adiponectin in PCOS group and subgroups. However, it had a direct association with hs-CRP in PCOS group and inf-PCOS subgroup, but not PCOS-RPL subgroup. These findings unravel a probable role of CTRP6 in PCOS pathogenesis, which poses a possibility to be a good diagnostic target. However, further investigation is needed.

Effects of DHA-enriched fish oil on gene expression levels of p53 and NF-κB and PPAR-γ activity in PBMCs of patients with T2DM: A randomized, double-blind, clinical trial.

BACKGROUND AND AIMS: Omega-3 polyunsaturated fatty acids (PUFAs) are natural peroxisome proliferator-activated receptor gamma (PPAR-γ) ligands. Activated PPAR-γ protects the cardiovascular system against atherosclerotic lesion formation and exerts its anti-inflammatory role by suppressing cytokines induced by nuclear factor kappa-B (NF-κB) in endothelial cells (ECs), and it is hypothesized that apoptosis and cell cycle arrest induced by PPAR-γ ligands may be mediated by the p53-dependent pathway. The aim of our study was to investigate the effects of docosahexaenoic acid (DHA)-enriched fish oil supplement on PPAR-γ activity and mRNA expression levels of p53 and NF-κB. METHODS AND RESULTS: Fifty patients with type 2 diabetes mellitus (T2DM) aged 30-70 years were randomly assigned to receive either 2400 mg/d DHA-rich fish oil or placebo for 8 weeks. Metabolic parameters were assessed at baseline and at the end of the intervention. PPAR-γ activity in the peripheral blood mononuclear cells (PBMCs) was measured using ELISA-based PPAR-γ Transcription Factor Assay Kit, and the gene expression levels of p53 and NF-κB were assessed using real-time quantitative reverse transcription polymerase chain reaction (RT-PCR). On the basis of our finding, 8 weeks of treatment with DHA-rich fish oil increased PPAR-γ activity in PBMCs of subjects with T2DM (p < 0.01) compared to that in placebo (p = 0.4). Between-group comparisons of mean PPAR-γ activity changes showed significant differences (p = 0.03), whereas mRNA expression levels of the p53 and NF-κB genes did not show significant differences between studied groups (p = 0.2 and p = 0.5, respectively). CONCLUSION: Our findings indicated that short-term DHA-rich fish oil supplementation may modulate PPAR-γ activity in PBMCs.

Evaluation of lipid ratios and triglyceride-glucose index as risk markers of insulin resistance in Iranian polycystic ovary syndrome women.

BACKGROUND: Insulin resistance has a vital role in the pathophysiology of polycystic ovary syndrome (PCOS). Previous investigations have shown that some lipid ratios could be a simple clinical indicator of insulin resistance (IR) in some disorders and ethnicities. The present study was conducted to evaluate the correlation between triglyceride to HDL-cholesterol (TG/HDL-C), total cholesterol to HDL-cholesterol (TC/HDL-C), as well as fasting triglyceride-glucose (TyG) indices with IR (as measured by homeostasis model assessment of IR (HOMA-IR), quantitative insulin sensitivity check index (QUICKI) and fasting glucose to insulin ratio (FGIR)) among the Iranian women diagnosed with PCOS. METHODS: In the current study, a total of 305 women with PCOS were evaluated. TG/HDL-C, TC/HDL-C, and TyG indices were calculated. Fasting insulin level was measured using ELISA technique. IR was defined as a HOMA-IR value of ≥2.63, FG-IR value of < 8.25, and QUICKI value of < 0.33. RESULTS: The insulin-resistant (IR) and insulin-sensitive (IS) groups, established by the HOMA-IR, FG-IR, and QUICKI values were different in terms of TG/HDL-C, TC/HDL-C, and TyG indices. These indices were associated with IR even after adjusting for age and BMI. ROC curve analyses showed that TyG, TG/HDL-C, and TC/HDL-C strongly predicted HOMA-IR with area under the curve (AUC) of 0.639, 0.619, and 0.623, respectively (P < 0.05). Further, TC/HDL-C was a good predictor of FG-IR with AUC of 0.614 (P = 0.04). CONCLUSION: TyG, TG/HDL-C, and TC/HDL-C indices might be good indicators of IR among Iranian women diagnosed with PCOS.

Does myoinositol supplement improve sperm parameters and DNA integrity in patients with oligoasthenoteratozoospermia after the freezing-thawing process?

Sperm cryopreservation is a routine method in andrology and IVF laboratory. However, the sperm quality and its fertilizing capacity have been decreased during this process. The purpose of this experiment was to determine the role of myoinositol as a supplement in amelioration of total and progressive sperm motility, DNA fragmentation, total antioxidant capacity (TAC), reactive oxygen species (ROS), and lipid peroxidation after the freezing-thawing process on patients with oligoasthenoteratozoospermia (OAT) syndrome. Semen samples obtained from 40 patients were divided into two aliquots and freezed with simple and 2 mg/mL myoinositol (MYO) supplemented freezing media. All samples were thawed and assessed after one month. Semen parameters were analyzed in terms of the motility by CASA, the level of total ROS by fluorimetry, TAC and MDA by colorimetric assay and finally DNA fragmentation by TUNEL assay. Our results clearly showed that MYO could improve total (37.46 vs. 12.91, p < 0.001) and progressive motility (21.92 vs. 6.49, p < 0.001) in experimental group compared to control group. A higher TAC level was observed in the MYO treated group in comparison to control group (1.11 vs. 0.91, p = 0.05). While MYO supplementation could not be effective on ROS level, it reduced DNA fragmentation of sperm after freeze-thaw process (p = 0.01). Therefore, MYO could be a good supplement for sperm freezing to reduce the detrimental effects of freezing process especially on DNA integrity, which is an important factor in the success of ART, in OAT suffered patients.

Niemann-Pick Disease, Type C1 Gene Expression in PBMCs is Associated with Interleukin 10 Serum Concentration: a Case-Control Study.

BACKGROUND: Recent studies showed that atherosclerosis is a lysosomal storage disease (LSD) and Niemann-Pick disease type C1 (NPC1) is the most important protein of the lysosomal membrane that is involved in the removal of FC from lysosomes. Whereas several in vitro and in vivo studies have described the crosstalk between lysosomal cholesterol accumulation and increased inflammation, there is no study addressing the correlation between NPC1 gene expression and an anti-inflammatory cytokine, interleukin 10 (IL-10) serum concentration in atherosclerotic patients. METHODS: IL-10 and 25-hydroxyvitamin D serum concentrations were quantified by enzyme-linked immunosorbent assay (ELISA) in atherosclerotic patients (n = 40) and a control group (n = 40). NPC1 gene expression analysis was performed by quantitative real-time PCR, and correlation between the two parameters was assessed. RESULTS: Mean IL-10 serum concentration and peripheral blood mononuclear cells' (PBMCs) gene expression of NPC1, adjusted for drug consumption, age, and BMI, was not significantly different between the patient and control groups (p = 0.6 and 0.67 respectively). However, NPC1 gene expression showed positive significant correlation with IL-10 serum concentration (p = 0.04, r = 0.29). We also observed lower serum concentration of IL-10 in the subjects with lower 25-hydroxyvitamin D serum concentration (p = 0.034). CONCLUSIONS: Our findings supported the previous observations showing the contribution of lysosomal lipid homeostasis of PBMCs to inflammation and pathogenesis of atherosclerosis.

Circulating Levels of IL-35 and Gene Expression of FoxP3 in Coronary Artery Disease: Is There Any Interplay Between Them and 25-Hydroxyvitamin D3?

BACKGROUND: We aimed to evaluate interleukin-35 (IL-35) serum levels and the forkhead box P3 (FoxP3) expression in peripheral blood mononuclear cells (PBMCs) of coronary artery disease (CAD) patients compared with the non-CAD group. Also, we examined the possible relationship between gene expression of FoxP3 and serum levels of IL-35 with several CAD-related clinical parameters. METHODS: This study was conducted on 40 men with CAD and 40 men with a normal coronary artery. The gene expression of FoxP3 was measured by real-time polymerase chain reaction (real-time PCR). The serum concentrations of IL-35 and 25-hydroxyvitamin D3 (25(OH)D3) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: FoxP3 gene expression was significantly decreased in patients compared to controls (p = 0.01). Serum concentrations of IL-35 and 25(OH)D3 were significantly reduced in patients in comparison with the control group (both, p < 0.001), and reduction of IL-35 showed an independent association with CAD. IL-35 levels had a significant positive correlation with serum 25(OH)D3 (r = 0.266, p = 0.044) in the whole population. Moreover, there was an inverse correlation between the FoxP3 expression and CAD severity in CAD patients (r = -0.372, p = 0.01). CONCLUSIONS: It appears that reduced mRNA expression of FoxP3 and circulating level of IL-35 are of significance in the context of CAD pathogenesis. However, more studies are required to elucidate underlying mechanisms.

mZD7349 peptide-conjugated PLGA nanoparticles directed against VCAM-1 for targeted delivery of simvastatin to restore dysfunctional HUVECs.

Endothelial dysfunction is initial and critical step of atherosclerosis. Impaired bioavailability of endothelial nitric oxide synthase (eNOS) is one of the main reasons of endothelial dysfunction. Improving bioavailability of eNOS by increasing its expression or activity using statins is an effective therapeutic strategy in restoring endothelial dysfunction. In this study, simvastatin (SIM) as a poorly water-soluble drug was loaded in poly (lactic-co-glycolic acid) (PLGA) nanoparticles (SIM-PLGA-NPs). NPs were then conjugated with mZD7349 peptide (mZD7349-SIM-PLGA-NPs) and directed against vascular cell adhesion molecule 1 (VCAM-1). In vitro evaluation of the NPs for targeted delivery of SIM was performed on activated Human Umbilical Cord Vascular Endothelial Cells (HUVECs) by tumor necrosis factor alpha (TNF-α). Effect of mZD7349-SIM-PLGA-NPs and SIM-PLGA-NPs was compared on eNOS phosphorylation (ser-1177). Results of western blot showed SIM post-treatment increased significantly phosphor-eNOS (Ser1177) expression but no total eNOS expression. The study showed that mZD7349-SIM-PLGA-NPs have particle size, zeta potential value, polydispersity index (PDI) and encapsulation efficacy % of 233±18nm, -9.6±1.1mV, 0.59±0.066 and 69±17.3%, respectively. Also phosphor-eNOS (Ser1177) expression in activated HUVECs treated with mZD7349-SIM-PLGA-NPs was significantly (p<0.05) better than treated cells with SIM-PLGA-NPs. The results suggest that mZD7349-SIM-PLGA-NPs may be usable as an appropriate drug carrier for restoring endothelial dysfunction.

PROTECTIVE EFFECTS OF GLUTATHIONE SUPPLEMENTATION AGAINST OXIDATIVE STRESS DURING CRYOPRESERVATION OF HUMAN SPERMATOZOA.

BACKGROUND: Freeze damage is one of the most important factors which impair the membrane and DNA integrity of sperm cells. OBJECTIVE: The present study aims to investigate glutathione (GSH) supplementation on human spermatozoa cryopreservation. We determined sperm motility and viability, sperm lipid peroxidation, DNA damage, and the amount of hydrogen peroxide (H(2)O(2)) and superoxide (O(2)(-)). MATERIALS AND METHODS: Twenty pooled semen samples were freeze with 5mM GSH for 10 minute (test) and without GSH as control and stored in liquid nitrogen. RESULTS: After thawing, cryovials supplemented with 5mM GSH led to higher sperm viability compared with control samples (p < 0.05). Furthermore, the addition of 5mM GSH decreased sperm lipid peroxidation, DNA fragmentation, and H(2)O(2) and O(2)(-) content compared with controls (p < 0.05). CONCLUSION: GSH can be a good free radical scavenger in the freezing media and can support function of sperm cell after a cycle of freezing and thawing.

Association of rs4588 polymorphism in vitamin D binding protein gene with polycystic ovarian syndrome in Iranian women: a case-control study.

OBJECTIVE: Vitamin D deficiency and variations in the vitamin D binding protein (VDBP) gene may play a role in the development of Polycystic ovary syndrome (PCOS). This study aims to investigate the association of the rs4588 polymorphism with PCOS in Iranian women, as well as its association with infertility and recurrent pregnancy loss (RPL) in these patients. RESULTS: The analysis revealed statistically significant differences in the distributions of genotypes and alleles of the rs4588 polymorphism among the three groups (p < 0.0001). The AC genotype and A allele showed an association with an elevated risk of PCOS and infertility. In this study, no association was found between genotypes and alleles of the rs4588 polymorphism and the risk of RPL in women with PCOS. Subjects with the AA or AC genotype exhibited significantly higher levels of LDL compared to those with the CC genotype.

The Role of the JAK-STAT Signaling Pathway in the Protective Effects of Hepatic Ischemia Post-conditioning Against the Injury Induced by Ischemia/Reperfusion in the Rat Liver.

Purpose: Hepatic ischemic post-conditioning (IPOC) is shown to protect the liver from injury induced by ischemia/reperfusion (IR). However, the mechanism underlying this protection has remained elusive. The present study aimed to investigate the role of the interleukin 6-Janus kinase-signal transducers and activators of transcription (IL-6-JAK-STAT) pathway in the protective effect of hepatic IPOC against the IR-induced injury in the liver. Methods: Twenty-five rats were randomly divided into 5 groups of (1) sham-operated, (2) IR, (3) IR+hepatic IPOC, (4) IR+tofacitinib (TOFA), and (5) IR+TOFA+hepatic IPOC. The changes induced by IR and the effects of different treatments were assessed by enzyme release, histopathological observations, the serum level of IL-6, and the occurrence of apoptosis detected via the expression of the Bax/Bcl-2 ratio. Results: The hepatic IPOC improved the liver injury induced by IR as shown by histological changes, reduction of IL-6 level, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) compared to the IR group (P<0.001, P<0.05, P<0.05, respectively). There was also downregulation of the Bax/Bcl2 ratio in the rats exposed to IR+hepatic IPOC compared with those in the IR group (P<0.05). However, TOFA, an inhibitor of JAK-STAT activity, inhibited the protective effect of hepatic IPOC. Conclusion: It suggests that the protective effect of hepatic IPOC against IR-induced injury may be mediated by activating the IL-6-JAK-STAT pathway.

Circulating levels of C1q/TNF-α-related protein 6 (CTRP6) in coronary artery disease and its correlation with inflammatory markers.

Introduction: Circulating levels of C1q/TNF-α-related protein 6 (CTRP6) is an adipokine that is involved in regulation of glucose and lipid metabolism, inflammation, and insulin sensitivity. However, the exact role of CTRP6 in metabolic processes remains unclear due to conflicting findings. To address current gap, we aimed to investigate the serum levels of CTRP6 in patients with coronary artery disease (CAD) and its association with inflammatory cytokines. Method: In this case-control study, the serum levels of CTRP6, interlukin-6 (IL-6), tumor necrosis factor- α (TNF-α), adiponectin, and fasting insulin were measured using enzyme-linked immunosorbent assay (ELISA) kits in a total of 176 participants, consisting of 88 CAD patients and 88 control subjects. Additionally, various anthropometric and biochemical measurements were measured and compared between cases and controls. Results: The present study found that serum levels of CTRP6 were significantly higher in the CAD group (561.3 ± 15.14) compared to the control group (429.3 ± 12.85, p < 0.001). After adjusting for age, sex, and body mass index (BMI), CTRP6 levels were found to be positively associated with the risk of CAD (p < 0.001). Correlation analysis in CAD subjects revealed a positive correlation between CTRP6 levels and BMI, systolic blood pressure (SBP), malondialdehyde (MDA), TNF-α, and IL-6, as well as a negative correlation with creatinine and total anti-oxidant capacity. Conclusion: The findings of this study provide novel evidence that elevated serum levels of CTRP6 are significantly associated with an increased risk of developing CAD. Moreover, our results indicate a correlation between CTRP6 and various risk factors for atherosclerosis. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01415-5.

Association between IL-6 -174 G/C (rs1800795) and IL-1A -889 C/T (rs1800587) cytokine variants with polycystic ovary syndrome in Iranian women: A case-control study.

BACKGROUND AND AIM: Infertility in women has various causes, one of which is ovulation disorders. Polycystic ovary syndrome (PCOS) affecting ovulation is a complex idiopathic disease in which genetic polymorphisms may be involved. This study aimed to investigate the relationship between IL-6 -174 G/C and IL-1A -889 G/A cytokine polymorphisms with polycystic ovary syndrome in a population of Iranian women. MATERIALS AND METHODS: In this case-control pilot study, 120 PCOS patients (60 infertile, LPI, and 60 women with recurrent pregnancy abortion, LPA) and 60 controls, CTRLs) participated. After genomic DNA extraction from peripheral blood, we investigated for the polymorphisms rs1800795 of the IL-6 -174 and rs1800587 of the IL-1A-889 using specific primers and PCR-RFLP followed by NlaIII enzyme digestion and PCR-ARMS techniques. RESULTS: There was a significant difference in the studied groups in terms of clinical characteristics (p-value < 0.05) except for the levels of HDL and LDL. Regarding demographic and clinical characteristics of patients, a significant correlation was observed between C/G and G/G genotypes of rs1800795 and FBS level (p value = 0.002). Also, rs1800587 showed a substantial relationship between CC and CT genotypes with the level of LH in LPI and the level of FBS in the LPAs (p value = 0.04). There was no significant difference between the frequencies of rs1800795 and frequencies of rs1800587 genotypes in the three studied groups (p value > 0.05).The studied variants were in Hardy-Weinberg equilibrium. CONCLUSION: The present work showed that rs1800795 and rs1800587 were not directly associated with PCOS in Iranian patients while the SNPs showed an indirect relationship with some factors affecting the disease. However, using genome-wide association analysis is a proper suggestion to obtain more reliable information about the disease's genetic view. To our knowledge, this is the first report that implicates the role of the examined SNPs in an Iranian PCOS population.

Adiponectin/leptin and HOMA/adiponectin ratios in Iranian women with polycystic ovary syndrome.

BACKGROUND: Insulin resistance and disrupted secretion of adipokines are the major contributors to the pathogenesis of polycystic ovary syndrome (PCOS). Previous research has indicated that adiponectin/leptin (A/L) and HOMA/adiponectin (H/A) ratios have a strong association with insulin resistance and metabolic syndrome. The current study aimed to assess the predictability of the A/L and H/A ratios for PCOS women infertility and recurrent pregnancy loss (RPL). In this study, we investigated the association of A/L and H/A ratios with PCOS, as well as infertility and RPL in Iranian women with PCOS. METHODS: This case-control study included 150 PCOS (60 infertile and 90 PCOS-RPL) and 50 non-PCOS women. Clinical, biochemical, and hormonal features were evaluated, and the A/L and H/A ratios were calculated. RESULTS: The A/L and H/A ratios were significantly decreased and increased in women with PCOS, respectively. A significant association was observed between the A/L and H/A ratios with PCOS, as well as PCOS-infertile and PCOS-RPL, even after adjusting for potential confounders. Although there was no significant difference between PCOS-infertile and PCOS-RPL subgroups, ROC curve analysis showed that A/L and H/A ratios could strongly predict PCOS with the area under the curve (AUC) of 0.867 and 0.861, respectively. CONCLUSION: The ratios of A/L and H/A may serve as biomarkers to distinguish women with PCOS from non-PCOS in the Iranian population. However, it seems that they are not discriminatory markers for PCOS-associated RPL and infertility.

Association of dietary total antioxidant capacity, alternative healthy eating index, and dietary inflammatory index with semen quality in men seeking infertility treatment.

Background: Since the association between dietary quality scores and semen quality remains unclear, we carried out a hospital-based cross-sectional study to investigate the association of Dietary Total Antioxidant Capacity (dTAC), Dietary Inflammatory Index (DII), and Alternative Healthy Eating Index (AHEI) scores with semen quality in men seeking infertility treatment. Methods: This study enrolled 210 men with unexplained or idiopathic infertility. Semen samples were collected and analyzed according to the WHO 2010 criteria. Dietary data was collected using a 168-item semi-quantitative food frequency questionnaire (FFQ) developed for Tehran Lipid and Glucose Study. Multivariable logistic regression models were used to estimate the relationship between dTAC, AHEI, and DII scores with abnormal semen in crude and adjusted models. Results: There were no significant differences across quartile categories of the dTAC, AHEI, and DII scores regarding semen parameters. There was a trend toward a significant direct association between DII and abnormal semen risk (p = 0.01). Infertile men in the highest quartile of DII had a 2.84 times higher risk of abnormal semen in the crude model (OR: 3.84; 95% CI: 1.64-8.95); such that remained after adjusting for several potential confounders. There was no significant association between dTAC or AHEI and the risk of abnormal semen in infertile men, either before or after adjusting for potential confounders. Total energy (p = 0.05), fat (p = 0.02), saturated fat (p = 0.02), mono-saturated fat (p = 0.009), Thiamine (Vitamin B1) (p = 0.02), Niacin (Vitamin B3) (p = 0.03), Calcium (p = 0.01), and Selenium (p = 0.01) were inversely associated with semen normality. Discussion: The study suggests that certain dietary factors may affect semen quality, and the mechanisms underlying the observed associations are likely multifactorial, involving complex interactions between diet, oxidative stress, inflammation, and hormone levels. Further research is required to confirm the results, fully elucidate the mechanisms underlying the associations, and identify specific dietary interventions that may improve male fertility outcomes.

Are lipid ratios and triglyceride-glucose index associated with critical care outcomes in COVID-19 patients?

Lipid ratios and the triglyceride and glucose index (TyG) could be a simple biochemical marker of insulin resistance (IR). The current study was carried out to examine the correlation between triglyceride to high-density lipoprotein-cholesterol (TG/HDL-C), total cholesterol to HDL-C (TC/HDL-C), low-density lipoprotein-cholesterol to HDL-C ratio (LDL-C/HDL-C), as well as TyG index with the severity and mortality of severe coronavirus disease 2019 (COVID-19). A total of 1228 confirmed COVID-19 patients were included in the current research. Regression models were performed to evaluate the correlation between the lipid index and severity and mortality of COVID-19. The TyG index and TG/HDL-C levels were significantly higher in the severe patients (P<0.05). TG/HDL-C, LDL-C/HDL-C, TC/HDL-C ratios, and TyG index were significantly lower in survivor cases (P<0.05). Multivariate logistic regression analysis demonstrated that predictors of the severity adjusted for age, sex and BMI were TyG index, TG/HDL-C ratio (OR = 1.42 CI:1.10-1.82, OR = 1.06 CI: 1.02-1.11, respectively). This analysis showed that TG/HDL-C, TC/HDL-C, LDL-C/HDL-C ratios, and TyG index statistically are correlated with COVID-19 mortality (OR = 1.12 CI:1.06-1.18, OR = 1.24 CI:1.05-1.48, OR = 1.47 CI:1.19-1.80, OR = 1.52 CI:1.01-2.31, respectively). In summary, the TyG index and lipid ratios such as TC/HDL-C, TG/HDL-C, LDL-C/HDL-C could be used as an early indicator of COVID-19 mortality. Furthermore, the study revealed that TyG index and TG/HDL-C indices are biochemical markers of COVID-19 severe prognosis.

Risk of embryo aneuploidy is affected by the increase in sperm DNA damage in recurrent implantation failure patients under ICSI-CGH array cycles.

This study investigates the relationship between sperm DNA damage in recurrent implantation failure (RIF) patients treated with comparative genomic hybridisation array-intracytoplasmic sperm injection (CGH array-ICSI) cycles and embryo aneuploidy screening. Forty-two RIF couples were selected. Sperm DFI was measured using TUNEL by flow cytometry. Two groups were defined as follows: (i) sperm with high DFI (> 20%); and (ii) low DFI (< 20%). Semen parameters, total antioxidant capacity (TAC), and malondialdehyde formation (MDA) were also measured in both groups. Following oocyte retrieval and ICSI procedure, blastomere biopsy was performed at the 4th day of development and evaluated with CGH-array. The high DFI group had a significant (p = 0.04) increase in the number of aneuploid embryos compared to the low one. According to Poisson regression results, the risk of aneuploidy embryos in the high DFI group was 55% higher than the low DFI group (RR = 1.55; 95% CI = 1.358-1.772). Moreover, chromosomal analysis showed an elevation of aneuploidy in chromosomes number 16 and 20 in the high DFI group compared to the low DFI group (p < 0.05). The high DFI in RIF patients may significantly affect the risk of aneuploidy embryos. Therefore, embryo selection by CGH-array should be considered for couples with high levels of sperm DNA fragmentation.