Time Course of Biochemical and Metabolic Parameters During and After COVID-19.

BACKGROUND: Long COVID is characterized by the persistence of symptoms among individuals who are infected with the SARS-CoV-2 virus. The enduring impact of these long-term effects on the health and well-being of those affected cannot be denied. METHOD: About 470 patients with SARS-CoV-2 were consecutively recruited in this longitudinal study. The participants were entered into moderate, severe, and critical groups. 235 out of 470 participants were female. The levels of fasting blood sugar (FBS), alanine transaminase (SGPT), aspartate aminotransferase (SGOT), alkaline phosphatase (ALP), creatinine (Cr), urea, uric acid (UA), and total protein (TP) were measured during hospitalization and again at one and three months after infection. The levels of Zn and hemoglobin A1c (HbA1c) were also measured only during hospitalization. RESULT: COVID-19 severity was associated with high levels of glucose, urea, Cr, ALT, AST, ALP, and HbA1c, and low levels of Zn, UA, and TP. There were significant sex differences for these markers at all three-time points. Glucose, urea, Cr, ALT, AST, and ALP all decreased three months after infection, whereas the levels of UA and TP returned towards normal. CONCLUSION: COVID-19 infection affects the levels of multiple biochemical factors in a gender-dependent manner. The biochemical changes become more tangible with increasing disease severity, and several of these predict mortality. Levels begin to return to normal after the acute phase of the disease, but in some individuals, at three months, several markers were still not within the normal range. Whether the trajectory of these changes can predict long COVID requires further testing.

Paraoxonase 1 rs662 polymorphism, its related variables, and COVID-19 intensity: Considering gender and post-COVID complications.

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.

Influence of Disease Severity and Gender on HLA-C Methylation in COVID-19 Patients.

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 (p < 0.05). In comparison with control, HLA-C methylation in both genders were as follows: moderate (women: 41.0%, men: 52.33%), severe (women: 43.42%, men: 64.86%), critical (women: 42.33%, men: 60.07%), and total patients (women: 45.52%, men: 56.97%). Furthermore, the methylation levels in men were higher than in women in all groups (p < 0.05). Significantly, among all groups, the severe group of men participants showed the highest methylation percentage (p < 0.05). No significant differences were detected for different disease severity in the women group (p > 0.1). This study found that HLA-C methylation was significantly lower in COVID-19 patients with different disease severity. There were also significant differences in HLA-C methylation between men and women patients with different severity. Therefore, during managing viral infections, particularly COVID-19, it is critical to consider patient gender and disease severity.

Recent findings on hyperprolactinemia and its pathological implications: a literature review.

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.

CCR2 and DPP9 expression in the peripheral blood of COVID-19 patients: Influences of the disease severity and gender.

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 < 0.0001) as well as between each COVID-19 form and control group (p < 0.0001). The male patients with severe COVID-19 expressed greater levels of CCR2 and DPP-9 than female with same disease form. The female patients with moderate and critical COVID-19 expressed greater levels of CCR2 and DPP-9 than male patients with same disease stage. CONCLUSION: We demonstrated that the expression of DPP-9 and CCR-2 was substantially increased in COVID-19 patients with different forms of disease. Considerable differences were also demonstrated between male and female with different patterns of disease. Therefore, we suggest to consider the gender of patients and disease severity for management of COVID-19.

The effect of chrysin-curcumin-loaded nanofibres on the wound-healing process in male rats.

AIM: 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. MATERIALS AND 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. RESULTS: 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. CONCLUSION: We have introduced chrysin-curcumin-loaded PCL-PEG nanofibres as a novel compound for shortening the duration of the wound-healing process.

The effect of chrysin-loaded nanofiber on wound healing process in male rat.

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 < .05). On the other hand, nanofibers containing chrysin significantly decreased p53 and iNOS expression compared to chrysin ointment and control groups (p < .05). According to the results, chrysin-loaded PCL-PEG-PCL nanofibers have positive effects on the expression of the genes that have pivotal role in wound healing.

The Effect of Chrysin Loaded PLGA-PEG on Metalloproteinase Gene Expression in Mouse 4T1 Tumor Model.

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.