Reduction in circulating vitamin D binding protein in patients with multiple sclerosis.

BACKGROUND: In this study, we aimed to determine the risk association between vitamin D binding protein (VDBP) polymorphism in patients with multiple sclerosis (MS) in a MS biobank and the difference in VDBP serum levels in MS patients who were recently diagnosed. METHOD: The current case-control study was performed on 296 MS patients and 313 controls. Thereafter, two common missense VDBP polymorphisms, named rs7041and rs4588, were evaluated in all the participants. Serum levels of vitamin D and vitamin D binding protein were assessed in 77 MS patients who were diagnosed since one year ago and in 67 healthy people who were matched in terms of age and sex. RESULT: The frequency distributions of VDBP genotypes and alleles of SNP rs7041 and rs4588 were observed to be similar in both the MS and control groups (p > 0.05). The VDBP haplotypes, as Gc2/Gc2, Gc1/Gc1, and Gc1/Gc2, were found to be similar in the MS and control groups (p > 0.05). In subgroup analysis, circulating VDBP was lower in MS patients (Ln-VDBP (µgr/ml): 3.64 ± 0.91 vs. 5.31 ± 0.77, p = 0.0001) even after adjusting for vitamin D levels, body mass index, and taking vitamin D supplement. There was no significant association between VDBP haplotypes and vitamin D levels in the two groups. CONCLUSION: The present study suggested an association between lower levels of circulating VDBP and multiple sclerosis in newly diagnosed patients. However, the VDBP causative role in the development of MS is still unclear, so it needs more studies.

The possible role of Interleukin-6 as a regulator of insulin sensitivity in patients with neuromyelitis optica spectrum disorder.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is associated with inflammatory mediators that may also trigger downstream signaling pathways leading to reduce insulin sensitivity. METHODS: We aimed to determine the risk association of hyperinsulinemia in NMOSD patients with seropositive AQP4-IgG and the serum levels of interleukin (IL)-6 and IL-17A compared with the control group. Serum levels of metabolic (Insulin, Fasting Blood Sugar (FBS), lipid profile) and inflammatory (IL-6 and IL-17) markers were assessed in 56 NMOSD patients and 100 controls. RESULTS: Hyperinsulinemia was more prevalent in NMOSD patients independent of age, sex and body mass index (BMI) (48.2% vs. 26%, p = 0.005) compared to control group. After adjusting age, sex and BMI, there was significant association between lower insulin sensitivity (IS) and NMOSD risk (95% CI: Beta = 0.73, 0.62 to 0.86, p = 0.0001). Circulating levels of IL-6 and IL-17 were higher in NMOSD patients, and only IL-6 had an effect modifier for the association between lower insulin sensitivity and NMOSD risk. CONCLUSIONS: Our data suggests that inflammatory pathogenesis of NMOSD leads to hyperinsulinemia and increases the risk of insulin resistance.

The gene expression of long non-coding RNAs (lncRNAs): MEG3 and H19 in adipose tissues from obese women and its association with insulin resistance and obesity indices.

BACKGROUND: There is evidence regarding the role of two lncRNAs: MEG3 and H19 the pathomechanism of obesity and related disorders. Here, we aimed to evaluate the expression of MEG3 and H19 in visceral adipose tissues (VAT) and subcutaneous adipose tissues (SAT) of obese women (n = 18), as compared to normal-weight women (n = 17). Moreover, we sought to identify the association of expression of MEG3 and H19 in SAT and VAT with obesity parameters, insulin resistance, and the mRNA expression of possible target genes involved in adipogenesis and lipogenesis including peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC). METHODS: Real-time PCR was performed to investigate the mRNA expression of the above-mentioned genes in VAT and SAT from all participants. RESULTS: The results showed lower mRNA levels of H19 in SAT of obese women, compared to normal-weight women, while MEG3 expression was significantly higher in the SAT of the obese group rather than controls. Correlation analysis indicated that the transcript level of H19 had an inverse correlation with obesity indices and HOMA-IR values. However, MEG3 expression displayed a positive correlation with all the indicated parameters in all participants. Interestingly, a positive correlation was found between transcript level of MEG3 in SAT with FAS and PPARγ. However, there was an inverse correlation between SAT expression of H19 and FAS. CONCLUSIONS: It appears that lncRNAs, MEG3 and H19, are involved in obesity-related conditions. However, more clinical studies are still required to clarify the relationships between lncRNAs with obesity and related abnormalities.

Detection of West Nile virus by real-time PCR in crows in northern provinces of Iran.

BACKGROUND & OBJECTIVES: West Nile virus (WNV) is a positive-sense, single-stranded RNA virion, that belongs to the Flaviviridae family. This virus is preserved in a bird-mosquito cycle that is capable of inducing diseases as a dead-end or endpoint host in humans as well as horses. In 2016, a suspicious case of crow population death was reported by the Department of Environment, Ministry of Health, Iran. Considering the mass migration of birds together with the WNV-related symptoms, including uncoordinated walking, ataxia, inability to fly, lack of awareness, and abnormal body posture, it was necessary to further investigate the possible causes of this incident. The objective of this study was molecular detection of WNV in crows utilizing the real-time PCR method in the northern provinces of Iran. METHODS: A total of 12 crows (8 dead, 4 alive) with a possible WNV infection, were collected from the northern provinces of Iran (Golestan, Mazandaran, and Guilan). A tissue sample of the liver, kidney, or lung was collected from all the crows, and RNA was isolated using an RNA extraction kit. A one-step real-time PCR method using a TaqMan probe was used for virus detection. RESULTS: All the infected crows were positive for WNV. The 132-bp real-time PCR amplicon of the genome was detected in all the samples. Comparative phylogenetic analysis revealed that WNV isolated from Iran clustered with strains from the USA, Hungary, and Culex pipiens. INTERPRETATION & CONCLUSION: The WNV genome sequence was detected in all the infected crows. The results confirmed the connection of this isolation with clade1a strains. Hence, determining the epidemiologic and prevalence characteristics of the WNV for transmission control is of critical importance in Iran.

HOMA-IR mean values in healthy individuals: a population-based study in iranian subjects.

Purpose: Homeostasis Model Assessment-estimated Insulin Resistance (HOMA-IR) is an important indicator of insulin resistance. In this population-based investigation, we sought to report the mean value of HOMA-IR in different subgroups of a large population-based database of Iranian healthy subjects. Methods: This study recruited adult healthy individuals between the ages of 18 to 70 years old to Massoud Medical Laboratory, Tehran, Iran. Fasting insulin was measured by using the Electro Chemiluminescence method using Roche Cobas 6000 e601/602 instrument. Results: The mean ± SD value of the HOMA-IR index in the studied population was 2.11 ± 0.99 (2.5-97.5% percentiles: 0.66-4.50). In addition, the mean ± SD of HOMA-IR index in male and female groups were 2.35 1.0 (2.5-97.5 percentile: 0.57-4.37) and 2.05 ± 1.0 (2.5-97.5 percentiles: 0.53-4.35), respectively. Interestingly, it was observed a significant increment for the HOMA-IR index in the male group compared with the female group in all age subgroups (P < 0.01). Conclusions: Our findings showed the mean value of 2.11 ± 0.99 HOMA-IR in the Iranian healthy population. Considering the large sample size in our study, more clinical investigations in terms of ethnicity should be done to provide a precise standardized HOMA-IR index in the Iranian population. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-022-01099-9.

Association between HDACs and pro-inflammatory cytokine gene expressions in obesity.

Histone deacetylases (HDACs) are important players in a variety of physiological and pathological conditions. Few studies have addressed HDAC expressions in human adipose tissue in obese individuals, and their association with pro-inflammatory cytokines. Here, we compared 20 non-obese and 20 obese women to investigate possible changes in gene expressions of HDAC2, 4, 5, and 6 in the subcutaneous adipose tissues (SAT) and visceral adipose tissues (VAT) of these individuals. Our findings showed decreased HDAC5 expression in SAT and elevated HDAC4 expression in VAT from the obese group compared with the non-obese group. Our analyses showed negative correlations between HDAC2, 5, and 6 and the obesity indices and positive correlations between HDAC4 and obesity indices. HDAC2 showed a positive correlation with pro-inflammatory cytokines whereas HDAC4, 5, and 6 were negatively correlated with pro-inflammatory cytokines. Our findings provide new evidence that implicates the important roles of HDACs in obesity and obesity-associated inflammation.

The circulating levels of CTRP1 and CTRP5 are associated with obesity indices and carotid intima-media thickness (cIMT) value in patients with type 2 diabetes: a preliminary study.

BACKGROUND: There is growing evidence that the C1qTNF-related protein (CTRP) family has a crucial role in the pathophysiology of metabolic disorders such as type 2 diabetes (T2D) and obesity. We sought to identify the association of CTRP1 and CTRP5 circulating levels with various obesity parameters such as visceral adipose tissue (VAT) thickness, visceral adiposity index (VAI), and with carotid intima-media thickness (cIMT) in patients with T2D and controls. METHODS: This preliminary study consisted of men with T2D (n = 42) and men without T2D (n = 42). The measurement of cIMT and VAT thickness was performed using an Accuvix XQ ultrasound. Circulating levels of CTRP1, CTRP5, and adiponectin were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: CTRP-1 and CTRP1/CTRP5 ratio were markedly higher in patients with T2D compared to controls (p < 0001 and p = 0004 respectively). Interestingly, binominal logistic regression revealed that a higher circulating level of CTRP1 was associated with the presence of T2D (odds ratio [OR]: 1.009 [95% CI: 1.004-1.015]; P = .001). CTRP1 circulating levels were correlated with WHR, VAT, and HOMA-IR in the whole population study. Also, we observed that the ratio of CTRP1 to CTRP5 in plasma (ß = 0.648, P = 0.005) and CTRP5 circulating levels (ß = 0.444, P = 0.049) are independently associated with cIMT value. CONCLUSIONS: Our results indicated that CTRP1 and CTRP5 concentrations were correlated with atherosclerosis in men with T2D and these adipokines might have a causal role for cardiometabolic risk in T2D.However, more studies in large sample sizes are required to clarify the role of CTRPs in T2D pathogenesis.

Increased mRNA Expression of CTRP3 and CTRP9 in Adipose Tissue from Obese Women: Is it Linked to Obesity-Related Parameters and mRNA Expression of Inflammatory Cytokines?

BACKGROUND: Obesity, a medical condition with impaired adipokine secretion and function, has a detrimental effect on insulin and glucose metabolism. CTRP3 and CTRP9 are adipokines with possible roles in energy homeostasis regulation. We sought to compare CTRP3, CTRP9, and inflammatory gene expression in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) from obese women who underwent bariatric surgery and non-obese women as controls. METHODS: For this study, the investigators recruited 20 morbidly obese women (BMI> 35) who qualified for bariatric surgery and 20 normal-weight women (BMI< 25) who underwent elective surgeries. Real-time PCR was performed to investigate mRNA expression of CTRP3, CTRP9, and the inflammatory genes IL1-ß, IL-6, MCP-1, and TNF-α in SAT and VAT from both obese patients and controls. RESULTS: We observed that CTRP3 mRNA levels were significantly greater in VAT from obese patients than from controls (P< 0.0003). Also, patient group had higher levels of CTRP9 that control group (P< 0.0026). Inflammatory cytokines were markedly increased in SAT of obese patients compared to controls (P< 0.05). In addition, our results revealed a positive correlation of CTRP9 with HOMA-IR and waist circumference in VAT and CTRP3 with IL-1ß, MCP-1, and TNF-α in SAT. CONCLUSION: Both CTRP3 and CTRP9 expression were significantly higher in VAT from obese patients than from controls, and CTRP3 expression positively correlated with inflammatory parameters. Our findings indicate that CTRP3 and CTRP9 might be important in regulating glucose metabolism and obesity-related conditions such as inflammation.

The C1q/TNF-related proteins (CTRPs) in pathogenesis of obesity-related metabolic disorders: Focus on type 2 diabetes and cardiovascular diseases.

The growing evidence has been tried to explain and characterize C1q/TNF- related proteins (CTRPs) family as the potential diagnostic or therapeutic targets of obesity-related metabolic disorders such as insulin resistance, type 2 diabetes (T2D), and cardiovascular disorders. However, the underlying mechanism is still obscure. Unraveling the signaling pathways downstream of CTRP family members is of great interest and could certainly be beneficial for finding new insights into therapeutic strategies for improving metabolic abnormalities. This review focused on the role of CTRP members in the initiation and development of obesity-related metabolic disorders with a focus on T2D and cardiovascular diseases. Here we summarize and discuss the role of CTRPs in the regulation of insulin signaling, inflammatory pathways, and energy metabolism, and other signaling pathways pertinent to the pathogenesis of T2D and cardiovascular diseases. We also review available clinical studies to better elucidate the roles of these potential molecules in the initiation and development of the afore-mentioned disorders.

The gene expression of CTRP12 but not CTRP13 is upregulated in both visceral and subcutaneous adipose tissue of obese subjects.

Obesity is a well-known chronic low-grade inflammation condition characterized by dysregulated adipokine secretion and function. Both CTRP12 and CTRP13 are adipokines that influence glucose and lipid metabolism. We aimed to investigate CTRP12, CTRP13, and inflammatory gene expressions in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) from obese women who underwent bariatric surgery in comparison with the normal weight women. This case-control study included 20 obese [body mass index (BMI) > 35-40 kg/m2] candidates for bariatric surgery and 20 normal-weight women (BMI <25 kg/m2) as control group, who underwent elective surgeries. Real-time PCR was used to evaluate mRNA expression levels of CTRP12, CTRP13, and inflammatory genes in SAT and VAT from both groups. We observed significantly higher mRNA expression of CTRP12 in SAT (p = 0.048) and VAT (p = 0.046) from obese patients compared to the controls. There was significantly greater expression of IL-6 and MCP-1 inflammatory genes in SAT (p = 0.013 and p = 0.005 respectively) and VAT (p = 0.000 and p = 0.001 respectively) of obese patients compared to the control group. IL-1ß (p = 0.015) and TNF-α (p = 0.014) expressions significantly increased in VAT from obese patients compared to the control group. Spearman correlation analysis showed that CTRP12 expression significantly correlated with obesity indices. Our findings showed that CTRP12 significantly increased in both VAT and SAT of obese group. More importantly, we observed a positive correlation between CTRP12 with inflammatory parameters. These results indicated that CTRP12 might be part of an intricate network for glucose metabolism and obesity-related inflammation processes.

Air pollution during pregnancy and placental adaptation in the levels of global DNA methylation.

BACKGROUND: Health in early life is crucial for health later in life. Exposure to air pollution during embryonic and early-life development can result in placental epigenetic modification and foetus reprogramming, which can influence disease susceptibility in later life. Objectives: The aim of this paper was to investigate the placental adaptation in the level of global DNA methylation and differential gene expression in the methylation cycle in new-borns exposed to high fine particulate matter in the foetal stage. STUDY DESIGN: This is a nested case-control study. We enrolled pregnant healthy women attending prenatal care clinics in Tehran, Iran, who were residents of selected polluted and unpolluted regions, before the 14th week of pregnancy. We calculated the regional background levels of particle mass- particles with aerodynamics diameter smaller than 2.5 µm (PM2.5) and 10 µm (PM10)-of two regions of interest. At the time of delivery, placental tissue was taken for gene expression and DNA methylation analyses. We also recorded birth outcomes (the new-born's sex, birth date, birth weight and length, head and chest circumference, gestational age, Apgar score, and level of neonatal care required). RESULTS: As regards PM2.5 and PM10 concentrations in different time windows of pregnancy, there were significantly independent positive correlations between PM10 and PM2.5 in the first trimester of all subjects and placental global DNA methylation levels (p-value = 0.01, p-value = 0.03, respectively). The gene expression analysis showed there was significant correlation between S-adenosylmethionine expression and PM2.5 (p = 0.003) and PM10 levels in the first trimester (p = 0.03). CONCLUSION: Our data showed prenatal exposures to air pollutants in the first trimester could influence placental adaptation by DNA methylation.