Search

In the pathophysiology of COVID-19, immunomodulatory factors play a vital role. Viruses have epigenetic effects on various genes, particularly methylation. Explaining the changes in immunological factor methylation levels during viral infections requires substantial consideration. HLA-C is a crucial determinant of immune function and NK cell activity and is primarily implicated in viral infections. This research focused on studying HLA-C methylation in COVID-19 patients with different severity. Peripheral blood samples were collected from 470 patients (235 men and 235 women) with RT-qPCR-confirmed COVID-19 test and classified into moderate, severe, and critical groups based on WHO criteria. Also, one hundred (50 men and 50 women) healthy subjects were selected as the control group. Peripheral blood mononuclear cells were used for DNA extraction, and the methylation-specific PCR (MSP) method and gel electrophoresis were used to determine the methylation status of the HLA-C. Significant statistical differences in HLA-C methylation were observed among cases and controls and various stages of the disease. HLA-C methylation in men and women has decreased in all stages (

Innate immune receptors detect nucleic acids, such as viruses, and initiate an immune response by secreting interferon (IFN) and regulating IFN-stimulated genes (ISG). in autoimmune conditions, expression of ISGs funded, show the activation of nucleic acid sensory pathways. However, the nucleus-localized innate sensors are recently found to detect pathogenic nucleic acids for initiating innate response, demonstrating a complicated crosstalk with cytoplasmic sensors and signaling molecules to form an elaborate tiered innate signaling network between nucleus and cytoplasm. to sustain immune hemostasis, these innate immune sensors develop different strategies for discriminating between self or non-self-nucleic acid. We reviewed all the sensors involved in the innate immune system in the present study. A better understanding of these sensors can lead to new treatments for infections, cancer, and autoimmune and inflammatory disorders.

The prolactin hormone (PRL) is often secreted by lactotrophic cells of the anterior pituitary and has been shown to play a role in various biological processes, including breast feeding and reproduction. The predominant form of this hormone is the 23 kDa form and acts through its receptor (PRLR) on the cell membrane. This receptor is a member of the superfamily of hematopoietic/cytokine receptors. PRL also has a 16 kDa subunit with anti-angiogenic, proapoptotic, and anti-inflammatory effects which is produced by the proteolytic breakdown of this hormone under oxidative stress. Although the common side effects of hyperprolactinemia are exerted on the reproductive system, new studies have shown that hyperprolactinemia has a wide variety of effects, including playing a role in the development of autoimmune diseases and increasing the risk of cardiovascular disease, peripartum cardiomyopathy, and diabetes among others. The range of PRL functions is increasing with the discovery of multiple sites of PRL secretion as well as PRLR expression in various tissues. This review summarizes current knowledge of the biology of PRL and its receptor, as well as the role of PRL in human pathophysiology.

Graphical abstract, Introduction Hyper-inflammatory reactions play a crucial role in the pathogenesis of the severe forms of COVID-19. However, clarification of the molecular basis of the inflammatory-related factors needs more consideration. The aim was to evaluate the gene expression of two fundamental molecules contributing to the induction of inflammatory like CCR2 and DPP9 in cells from peripheral blood samples from patients with various patterns of COVID-19. Methods Peripheral blood samples were collected from 470 patients (235 male and 235 female) with RT-qPCR-confirmed COVID-19 test exhibiting moderate, severe, and critical symptoms based on WHO criteria. 100 healthy subjects (50 male and 50 female) were also enrolled in the study as a control group. The gene expression of DPP-9 and CCR-2 was assessed in the blood samples using real-time PCR method. Results The COVID-19 patients in severe stage expressed higher levels of CCR2 and DPP9 compared with healthy controls. In male and female patients, the levels of CCR2 and DDP9 expression significantly differed between moderate, severe, and critical patterns (p

In this study, we aimed to investigate the effect of paraoxonase 1 (PON1) rs662 polymorphism, arylesterase (ARE) activity, and the serum lipid profile in patients with coronavirus disease 2019 (COVID-19) in different stages of the disease considering post-COVID outcomes. A total of 470 COVID-19 patients (235 female and 235 male patients) were recruited into the study, and based on the World Health Organization (WHO) criteria, the patients were divided into three groups: moderate, severe, and critical. PON1 rs662 polymorphism was determined by the Alw 1 enzyme followed by agarose gel electrophoresis. Moreover, serum levels of triglycerides (TG), cholesterol (Chol), high-density lipoprotein–cholesterol (HDL-c), and low-density lipoprotein–cholesterol (LDL-c), as well as the level of the ARE activity of PON1 in the sera of patients were measured at the time of infection and one and three months after hospitalization. There was a significant relationship between the G allele and the severity of the disease. In addition, the probability of death in homozygous individuals (GG) was higher than in heterozygous patients (GA), and it was higher in heterozygous patients than in wild-type individuals (AA). There was also a significant relationship between the decrease in serum lipids and the intensity of COVID-19. On the contrary, at the onset of the disease, the HDL-c level and serum ARE activity were reduced compared to one and three months after COVID-19 infection. The findings of this study indicated the significant impact of PON1 rs662 polymorphism on ARE activity, lipid profiles, disease severity, and mortality in COVID-19 patients.

Wound healing is an inflammatory process. Chrysin, a natural flavonoid found in honey, has been recently investigated to have anti-inflammatory and antioxidant effects. In this work, the effects of chrysin-loaded nanofiber on the expressions of genes that are related to wound healing process such as P53, TIMPs, MMPs, iNOS, and IL-6 in an animal model study were evaluated. The electrospinning method was used for preparation the different concentrations of chrysin-loaded PCL-PEG nanofiber (5%, 10%, and 20% [w/w]) and characterized by FTIR and SEM. The wound healing effects of chrysin-loaded PCL-PEG nanofiber were in vivo investigated in rats, and the expressions of genes related to wound healing process were evaluated by real-time PCR. The study results showed chrysin-loaded PLC-PEG compared to chrysin ointment and control groups significantly increase IL-6, MMP-2, MMP-8, MMP-9, TIMP-1, and TIMP-2 (p

The aim of the present study was to produce chrysin-curcumin-loaded PCL-PEG nanofibres by an electrospinning technique and to evaluate the biological activity of the chrysin-curcumin-loaded PCL-PEG fibres for wound healing and its related genes using in vivo methods.The electrospinning method was carried out for the preparation of the chrysin, curcumin and chrysin-curcumin-loaded PCL-PEG nanofibres with different concentrations. FTIR and SEM were performed to characterize the chemical structures and morphology of the nanofibres. In vitro drug release, as well as in vivo wound-healing studies were investigated in male rats. The expressions of genes related to the wound-healing process were also evaluated by real-time PCR.Our study showed that the chrysin-curcumin-loaded nanofibres have anti-inflammatory properties in several stages of the wound-healing process by affecting the IL-6, MMP-2, TIMP-1, TIMP-2 and iNOS gene expression. Our results demonstrated that the effect of the chrysin-loaded nanofibre, the curcumin-loaded nanofibre and the chrysin-curcumin-loaded nanofibre in the wound-healing process is dose dependent and in accordance with the obtained results in that it might affect the inflammation phase more than the other stages of the wound-healing process.We have introduced chrysin-curcumin-loaded PCL-PEG nanofibres as a novel compound for shortening the duration of the wound-healing process.

Background Acute lymphoblastic leukemia (ALL) is characterized by excessive accumulation of lymphoblast and progenitors. Leukemia is the most common cancer in children and ALL is the most common subtype. Many studies have shown that the YKL-40 gene is one of the most widely expressed genes in tumors, including leukemia, but not in healthy blood cells. Clinical studies have shown that serum YKL-40 levels have a positive correlation with tumor expansion, in addition to being a prognostic agent independent of a short relapse-free interval, as well as a brief overall survival in patients with various cancers. The previous study shows that YKL-40 is closely related to the degree of pathology or degree of human leukemia pathology and plays an important role in cell proliferation. Hence, the YKL-40 can be an attractive target in designing anticancer therapies. Methods CCRF-CEM cells were treated with resveratrol and prednisolone. For analysis of YKL-40 expression changes under medication, real-time polymerase chain reaction (PCR) and Western blot techniques were used at resonating intervals of 24 and 48 hours. Results The effect of 15, 50, and 100 μM resveratrol and 700 μM of prednisolone on CCRF-CEM cells reduced YKL-40. The YKL-40 gene was quantitatively measured using RT-PCR. The Western blot method was used to evaluate changes in the expression of YKL-40 protein. Conclusion In this study, we first evaluated YKL-40 expression and resveratrol and prednisolone effect on YKL-40 in ALL. This finding supports the idea of targeting YKL-40 as a new drug treatment of ALL and extends the use of resveratrol in antileukemia research.

Despite the advances in medicine, cancer remains as one of the leading causes of the death worldwide. Through our previous study, the Chrysin loaded PGLA/PEG has been synthesized, and its physico-chemical properties were characterized. The aim of the present study was to evaluate the Chrysin loaded PGLA/PEG nanoparticle therapeutic effects on TIMP-1, TIMP-2, MMP-2, MMP-9 and PI3k expression in Mouse 4T1 breast tumor model.30 mice were enrolled in the current study, and the mice were randomly divided into 3 groups: untreated (n=10), Chrysin treatment (n=10) and Chrysin-loaded PLGA/PEG-based treatment (n=10). 1064T1 mammary carcinoma cells subcutaneously inoculated in the flank on mice orthotopically. After the treatments, the primary tumors were isolated from the Mice under anesthesia. For RNA extraction, the isolated tissues were frozen in -70°C. RNA extraction was performed by using RNA extraction kit. The expression of TIMP-1, TIMP-2, MMP-2 and MMP-9 were measured by the real time PCR.The study results showed the expression of TIMP-1 and TIMP-2 in Chrysin-loaded PLGA/PEG treatment groups was higher than Chrysin receiving one. Also, the results showed that the MMP-9 and MMP-2 expressions were reduced after Chrysin loaded PLGA/PEG treatment. The reduction of the mentioned genes was greater in Chrysin-loaded PLGA/PEG treatment group in comparison with Chrysin receiving group.According to our present study, expression of the mentioned genes after treatments, Chrysin; especially, Chrysin-loaded PLGA/PEG could be proposed as a new component in the cancer therapy for reducing the progression and metastasis.

Peripheral nerve injuries with a poor prognosis are common. Evening primrose oil (EPO) has beneficial biological effects and immunomodulatory properties. Since electrical activity plays a major role in neural regeneration, the present study investigated the effects of electrical stimulation (ES), combined with evening primrose oil (EPO), on sciatic nerve function after a crush injury in rats. In anesthetized rats, the sciatic nerve was crushed using small haemostatic forceps followed by ES and/or EPO treatment for 4 weeks. Functional recovery of the sciatic nerve was assessed using the sciatic functional index. Histopathological changes of gastrocnemius muscle atrophy were investigated by light microscopy. Electrophysiological changes were assessed by the nerve conduction velocity of sciatic nerves. Immunohistochemistry was used to determine the remyelination of the sciatic nerve following the interventions. EPO + ES, EPO, and ES obviously improved sciatic nerve function assessed by the sciatic functional index and nerve conduction velocity of the sciatic nerve at 28 days after operation. Expression of the peripheral nerve remyelination marker, protein zero (P0), was increased in the treatment groups at 28 days after operation. Muscle atrophy severity was decreased significantly while the nerve conduction velocity was increased significantly in rats with sciatic nerve injury in the injury + EPO + ES group than in the EPO or ES group. Totally speaking, the combined use of EPO and ES may produce an improving effect on the function of sciatic nerves injured by a crush. The increased expression of P0 may have contributed to improving the functional effects of combination therapy with EPO and ES as well as the electrophysiological and histopathological features of the injured peripheral nerve.