The twin challenges of longevity and climate change in controlling antimicrobial resistance.

Antimicrobial resistance (AMR) is one of the global health challenges of the 21st century that is faced with the twin threats of global climate change and greater longevity, which pose a synergistic risk to the management of AMR. Antimicrobial agents are in high demand due to the challenges faced by increasing life expectancy and the dynamic changes in disease ecology prompted by climate change. In light of global aging and climate change, the complexity and importance of addressing antibiotic resistance are further highlighted by this interplay of issues.

Healthy behaviors and gestational diabetes mellitus in an Iranian setting: A cross-sectional study.

The objective of this study is to determine the healthy behaviors of mothers with gestational diabetes mellitus (GDM) in Ardabil in 2020. An analytic cross-sectional study was conducted on 360 mothers with GDM in Ardabil in 2020. Self-reported data was collected using a sociodemographic and a lifestyle questionnaire (LSQ) with assistance from health staff. Univariate and multivariate linear regression tests were used to assess risk variables associated with health behaviors and GDM. The total score of the LSQ was 123.6 ±â€…9.9, which was considered fair or average. The participants' age had a significant relationship with physical health (beta = -.093, P = .004), weight control and nutrition (beta = .094, P = .010), and psychological health (beta = .081, P = .005). Higher educational level was associated with accident prevention (beta = .453, P = .001). Participants' occupation had a significant positive relationship with the prevention of diseases (beta = .925, P = .003). A gravida of the participants was associated with weight control and nutrition (beta = -.497, P = .016). Body mass index was associated with physical health (beta = -.179, P = .001), exercise and fitness (beta = -.149, P = .016), psychological health (beta = -.158, P = .001), accident prevention (beta = .098, P = .023), and total score of LSQ (beta = -.559, P = .006). The findings of this study showed that mothers with GDM had LSQ subscales scores considered fair or average, except for the prevention of diseases and avoidance of drugs, alcohol, and opiates subscales, which were considered good.

Role of micronutrients in the modulation of immune system and platelet activating factor in patients with COVID-19; a narrative review.

Background: Dietary micronutrients may play important roles in the improvement of the immune responses against SARS-CoV-2. This study aimed to assess the effect of micronutrients on platelet activating factor (PAF) and immunity with a special focus on the coronavirus disease 2019 (COVID-19). Methods: All paper published in English on the effects of micronutrients including fat soluble vitamins, water soluble vitamins, and minerals on PAF, immunity, and COVID-19 were collected from online valid databases. Results: Vitamin A may modulate the expression of PAF-receptor gene in patients with COVID-19. Vitamin D may modulate inflammatory response through influencing PAF pathway. Vitamin E may improve COVID-19 related heart injuries by exert anti-PAF activities. Vitamin C status may have PAF related anti-inflammatory and micro-thrombotic effects in SARS-CoV-2 patients. Furthermore, some trace elements such as copper, selenium, and iron may have key roles in strengthens immunity by inactivate PAF acetyl hydrolase. Conclusion: This narrative review study highlighted the importance of micronutrients in the improvement of immune function through modulation of PAF in patients with COVID-19. Further longitudinal studies are warranted.

Comparison of the duration of estradiol administration and the effect on pregnancy outcome of day 3 vitrified-warmed embryo transfer cycle: a randomized controlled trial.

Based on the fact that the follicular phase in the menstrual cycle has length variation, it has been assumed that the duration of oestrogen (E2) administration could also be variable; therefore, for the first time, this randomized clinical trial study was conducted to investigate and compare the duration of estradiol administration and the effect on pregnancy outcomes in the cleavage-stage frozen embryo transfer (FET) cycle. We included women aged 20-40 with a normal uterus on hysteroscopy between September and December 2022 and who were divided randomly into three groups: group A [n = 79; 8-11 days of oestrogen before progesterone (P4) supplementation], group B (n = 78; 12-14 days of oestrogen before P4 supplementation), and group C (n = 76; 15-18 days of estrogen before P4 supplementation). Serum levels for E2 on the initial progesterone day and P4 on the transfer day were measured. The effect of the duration of E2 administration on clinical pregnancy and pregnancy loss was investigated. We found no significant differences between the three groups in the clinical pregnancy rate (P = 0.696) and clinical abortion rate (P = 0.925) according to the duration of the E2. There was no significant difference in the E2, P4 levels, and endometrial thickness in pregnant vs. non-pregnant women. The mean of the E2 and P4 levels was 300.03 ± 22.21 and 25.36 ± 5.78, respectively. Our findings suggest that variation in the length of E2 administration (8-18 days) before progesterone initiation in day 3 FET cycles does not affect pregnancy outcome and transfer time can be flexibly arranged.

A Review of the Chemistry and Biological Activities of Natural Colorants, Dyes, and Pigments: Challenges, and Opportunities for Food, Cosmetics, and Pharmaceutical Application.

Natural pigments are important sources for the screening of bioactive lead compounds. This article reviewed the chemistry and therapeutic potentials of over 570 colored molecules from plants, fungi, bacteria, insects, algae, and marine sources. Moreover, related biological activities, advanced extraction, and identification approaches were reviewed. A variety of biological activities, including cytotoxicity against cancer cells, antioxidant, anti-inflammatory, wound healing, anti-microbial, antiviral, and anti-protozoal activities, have been reported for different pigments. Considering their structural backbone, they were classified as naphthoquinones, carotenoids, flavonoids, xanthones, anthocyanins, benzotropolones, alkaloids, terpenoids, isoprenoids, and non-isoprenoids. Alkaloid pigments were mostly isolated from bacteria and marine sources, while flavonoids were mostly found in plants and mushrooms. Colored quinones and xanthones were mostly extracted from plants and fungi, while colored polyketides and terpenoids are often found in marine sources and fungi. Carotenoids are mostly distributed among bacteria, followed by fungi and plants. The pigments isolated from insects have different structures, but among them, carotenoids and quinone/xanthone are the most important. Considering good manufacturing practices, the current permitted natural colorants are: Carotenoids (canthaxanthin, ß-carotene, ß-apo-8'-carotenal, annatto, astaxanthin) and their sources, lycopene, anthocyanins, betanin, chlorophyllins, spirulina extract, carmine and cochineal extract, henna, riboflavin, pyrogallol, logwood extract, guaiazulene, turmeric, and soy leghemoglobin.

The evaluation of chitosan hydrogel based curcumin effect on DNMT1, DNMT3A, DNMT3B, MEG3, HOTAIR gene expression in glioblastoma cell line.

BACKGROUND: Cancer is one of the most important causes of death worldwide. Some types of cancer, including glioblastoma, with a high potential for growth, invasion, and resistance to general treatments, chemotherapy, and radiotherapy, have a high potential for recurrence. Many chemical drugs have been used to treat it, but herbal drugs are more effective with fewer side effects; Therefore, this research aims to investigate the effect of curcumin-chitosan nano-complex on the expression of MEG3, HOTAIR, DNMT1, DNMT3A, DNMT3B genes in the glioblastoma cell line. METHODS: In this research, glioblastoma cell line, PCR and spectrophotometry techniques, MTT test and transmission, field emission transmission, and fluorescent electron microscopes were used. RESULTS: The morphological examination of the curcumin-chitosan nano-complex was without clumping, and the fluorescent microscope examination showed the nano-complex enters the cell and affects the genes expression. In its bioavailability studies, it was found that it significantly increases the death of cancer cells in a dose- and time-dependent manner. Gene expression tests showed that this nano-complex increased MEG3 gene expression compared to the control group, which is statistically significant (p < 0.05). It also decreased HOTAIR gene expression compared to the control group, which was not statistically significant (p > 0.05). It decreased the expression of DNMT1, DNMT3A, and DNMT3B genes compared to the control group, which is statistically significant (p < 0.05). CONCLUSION: By using active plant substances such as curcumin, the active demethylation of brain cells can be directed to the path of inhibiting the growth of brain cancer cells and eliminating them.

Potential of macronutrients and probiotics to boost immunity in patients with SARS-COV-2: a narrative review.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-COV-2) may cause inflammation and increased cytokine secretion. Dietary factors may play an important role in enhancing the immune responses against infectious diseases such as SARS-COV-2. This narrative review aims to determine the effectiveness of macronutrients and probiotics to improve immunity in SARS-COV-2 patients. Dietary proteins may boost pulmonary function in SARS-COV-2 patients through inhibitory effects on the Angiotensin-converting enzyme (ACE) and reduce Angiotensin (ANG-II). Moreover, omega-3 fatty acids may improve oxygenation, acidosis, and renal function. Dietary fiber may also produce anti-inflammatory effects by reducing the level of high-sensitivity C-Reactive Protein (hs-CRP), Interleukin (IL-6), and Tumor necrosis factor (TNF-α). In addition, some evidence indicates that probiotics significantly improve oxygen saturation which may enhance survival rate. In conclusion, the consumption of a healthy diet including adequate macronutrients and probiotic intake may decrease inflammation and oxidative stress. Following this dietary practice is likely to strengthen the immune system and have beneficial effects against SARS-COV-2.

Genetically engineered E. coli invade epithelial cells and transfer their genetic cargo into the cells: an approach to a gene delivery system.

PURPOSE: Despite advances in gene therapy, the lack of safe and efficient gene delivery systems limited the clinical effectiveness of gene therapy. Due to the inherent potential of bacteria, they can be considered as a good option for the gene transfer system. This study aimed to create a genetically engineered bacterium capable of entering epithelial cells and transferring its genetic cargo to the cell's cytoplasm, eventually expressing the gene of interest in the cell. METHODS: The invasin (inv) gene from Yersinia pseudotuberculosis and the listeriolysin (hlyA) gene from Listeria monocytogenes were isolated by PCR assay and inserted into a pACYCDuet-1 vector. The recombinant plasmid was then transformed into E. coli strain BL21. Subsequently, pEGFP-C1 plasmids containing a CMV promoter were transformed into the engineered bacteria. Finally, the engineered bacteria containing the reporter genes were incubated with the HeLa and LNCaP cell lines. Fluorescence microscopy, flow cytometry, and TEM were used to monitor bacterial entry into the cells and gene expression. We used native E. coli strain BL21 as a control. RESULTS: A fluorescence microscope showed that, in contrast to the control group, the manipulated E. coli were able to penetrate the cells and transport the plasmid pEGFP-C1 to the target cells. Flow cytometry also showed fluorescence intensity of 54.7% in HeLa cells and 71% in LNCaP cells, respectively. In addition, electron micrographs revealed the presence of bacteria in the cell endosomes and in the cytoplasm of the cells. CONCLUSION: This study shows that genetically engineered E. coli can enter cells, transport cargo into cells, and induce gene expression in the target cell. In addition, flow cytometry shows that the gene transfer efficiency was sufficient for protein expression.

Predictive factors for type A aortic dissection mortality based on electrocardiogram parameters and clinical presentations.

BACKGROUND: Aortic dissection is a rare but potentially lethal disorder and may be associated with electrocardiogram (ECG) changes. In this study, we aim to investigate ECG-related parameters alongside clinical presentations of type A aortic dissection to come up with the predictive factors for the severity of the disease and its mortality rate. METHODS: In this retrospective study, 201 patients with type A aortic dissection were studied between March 2015 and March 2020. Two expert cardiologists blinded to the diagnosis studied former and new patients' ECGs and recorded changes. RESULTS: Two-hundred and one patients, including 143 (71.1%) men and 58 (28.9%) women, presented with acute dissection of the aorta, were studied. Forty-four (21.8%) and 84 (41.7%) patients had ST-segment elevation and depression in ECG, respectively. Bivariate analysis revealed that higher heart rate (p = 0.006), longer QTc (p = 0.044), and ST-segment elevation in aVR lead (p = 0.044) were associated with mortality in the patients. Multivariate regression showed higher heart rate (OR = 1.022, CI = 1.003-1.041, p = 0.012) and ST-segment elevation in aVR (OR = 4.854, CI = 2.255-10.477, p < 0.001) were independently associated with increased odds of mortality in aortic dissection patients. ROC curve analysis showed heart rate equal to or >60 per minute (AUC = 0.625, sensitivity = 86%, specificity = 10%, p = 0.019) and ST-segment elevation in aVR >0.5 mm (AUC = 0.854, sensitivity = 75%, specificity = 92%, p < 0.001) were associated with a higher mortality rate. CONCLUSION: Heart rate equal or >60 and ST-segment elevation >0.5 mm in aVR lead can be used as predictive factors for mortality of patients with type A aortic dissection.

Effect of bread fortification with pomegranate peel powder on glycemic indicators, antioxidant status, inflammation and mood in patients with type 2 diabetes: study protocol for a randomized, triple-blind, and placebo-controlled trial.

Background: The oxidative stress caused by the creation and breakdown of reactive oxygen species affects glucose tolerance, B-cell function, insulin resistance, and metabolites containing free fatty acids. Functioning foods are therefore becoming increasingly popular because they provide health benefits and prevent oxidative stress. This research aims to assess strategies to alleviate oxidative stress and inflammation in patients with type 2 diabetes (T2DM). In the present study, the metabolic effect wheat bread fortified with pomegranate peel powder(PPP) will be assessed in participants with type 2 diabetes. Methods: A randomized, triple-blind, placebo-controlled, and parallel arms clinical trial will be conducted on 90 patients with T2DM. Run-in courses will last for two weeks. The intervention and control groups will receive wheat bread with and without PPP, respectively. Anthropometric data, fasting plasma glucose, hemoglobin A1C, lipid profile, insulin level, high-sensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA), Total antioxidant capacity(TAC), and mood state, will be measured at the baseline and three months post-intervention. Beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) will also be assessed. Discussion: This trial will provide novel data on the impact of fortified bread with PPP on metabolic profile and mood state of patients with type 2 diabetes. The results will demonstrate the potential of such intervention in glycemic indices, antioxidant status, inflammation and mood in these patients. Trial Registration: Trial is registered in the Iranian Registry of Clinical Trials (ID: IRCT20191209045672N1). Date of registration 21/09/2020. https://en.irct.ir/trial/48132.

Association between gene polymorphisms of IL-12, IL-12 receptor and IL-27 and organ involvement in Iranian endometriosis patients.

Endometriosis is an inflammatory disease characterized by the presence of ectopic endometrial tissue, immune cell dysfunction and abnormal cytokine secretion. In addition to immunological factors, genetic variations that influence endometriosis severity and cytokine expression levels play important roles in the pathogenesis of this disease. Interleukin-12 (IL-12), specifically its p40 subunit encoded by IL-12B gene and the interleukin-12 receptor ß1 (IL-12Rß2) chain of its receptor, as well as interleukin-27 (IL-27) are important in the establishment of endometriosis. So, in this study, we measured IL-12 and IL-27 serum levels and investigated the possible links between IL-12B rs3212227, IL-12Rß2 rs3790565 and IL-27 rs153109 polymorphisms and the risk of developing endometriosis in a group of Iranian women. In this case-control study, 162 endometriosis patients and 151 healthy women were included and tested for the aforementioned polymorphisms using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The enzyme-linked immunosorbent assay (ELISA) method was also used to measure IL-12 and IL-27 serum levels. Although there was no statistically significant association between the genotypes and alleles of the studied polymorphisms and the development of endometriosis in general, the AA genotype of IL-12B rs3212227 showed a significant association with uterine endometriosis when compared to AC+CC genotypes (p = .04, CI = 0.270-0.988, OR = 0.517). Indeed, the AA genotype of the IL-12B rs3212227 single nucleotide polymorphism (SNP) may be linked with a lower risk of developing uterine endometriosis. There was no significant difference in IL-27 levels between the two studied groups (p = .49), and IL-12 levels were undetectable in both groups. In conclusion, the AA genotype of IL-12B rs3212227 might be associated with a decreased risk of uterine involvement in endometriosis patients.

The effect of a web-based lifestyle intervention on nutritional status and physical activity on prevention of COVID-19: a randomized controlled trial in women's empowerment.

Background: Healthy dietary intake and physical activity affect the immune systems. The present study aimed to investigate the effects of a web-based lifestyle intervention on nutritional status, physical activity, and prevention of COVID-19. Methods: Three hundred-three women (30-60 years old), who did not have COVID-19 in the City of Ardabil, participated in this study. Participants were randomized into an intervention (n = 152) or control group (n = 151). The intervention group received eight online educational sessions focusing on a healthy diet and physical activity via the website. There was no educational session for the control group during the intervention, but they were placed on the waiting list to receive the intervention and given access to the website and educational content after the follow-up. Outcomes were nutritional status, physical activity, immunoglobulin G (IgG), and immunoglobulin M (Ig M) antibody titers against the virus. They were evaluated at the baseline, after 4 and 12 weeks. Results: Significant improvements in weight (P < 0.001), BMI (P < 0.001), total energy (P = 0.006), carbohydrate (P = 0.001), protein (P = 0.001), and fat (P < 0.001) were found for the intervention group compared to the control group during the study. MET-min/week for moderate physical activity increased during the time for the intervention and control groups (P < 0.001 and P = 0.007, respectively). MET-min/week for walking activity rose in the post-intervention and follow-up compared to that in the baseline in the groups (P < 0.001 for both groups). Total physical activity was increased during the study (P < 0.001) for both groups. The mean of serum IgG and IgM titers against the virus were increased during the study in both groups in time effect (P < 0.001). There was a significant time x group interaction for carbohydrate and fat intakes (P = 0.005 and P = 0.004, respectively). Conclusion: The web-based lifestyle intervention may improve nutritional status and physical activity, and have the potential to reduce the risk of contracting a COVID-19 infection.

A Review of Aspirin-exacerbated Respiratory Diseases and Immunological Efficacy of Aspirin Desensitization.

Aspirin-exacerbated respiratory disease (AERD) is a chronic inflammatory disease. It is defined by asthma, chronic rhinosinusitis with nasal polyposis, and a hypersensitivity reaction to aspirin or nonsteroidal anti-inflammatory drugs. Aspirin desensitization (AD) has been confirmed as an effective treatment to control AERD inflammation through the modulation of immune responses. We aimed to review AERD with an overview of the epidemiology, pathophysiology, and treatment. We also discussed the effect of AD on immunological markers involved in AERD pathogenesis. A search of electronic databases on AERD was performed. We included five randomized clinical trials (RCTs) on AD. We also searched databases for recent studies that investigated the effect of AD on the immunological mechanisms of AERD. RCTs have demonstrated the therapeutic effectiveness of AD on the patients' quality of life, asthma symptom score, inhaled and oral steroid use, forced expiratory volume in 1 sec (FEV1), and inflammatory mediators. The clinical benefits of AD can occur though the regulation of innate and adaptive immune responses that are involved in the pathogenesis of AERD. In addition to the valuable effects of AD in RCTs, some side effects such as gastrointestinal bleeding, asthma exacerbation, or rash have been reported that should be considered for reaching an optimal protocol for AD.

The Effects of Six Weeks of Endurance Training and CGRP Inhibition on Nrf2 and AKT Expression in the Hippocampal Tissue of Male Wistar Rats.

Purpose: To study the effects of a six-week endurance training protocol and calcitonin gene-related peptide (CGRP) inhibition on the nuclear factor erythroid 2-related factor 2 (Nrf2) and protein kinase B (PKB) or AKT expression in the hippocampal tissue of male Wistar rats. Main Methods. Building on a controlled experimental design with a posttest, 28 healthy Wistar male rats were randomly assigned to four groups (n = 7 per group), including control, control+CGRP inhibition, endurance training, and endurance training+CGRP inhibition groups. The training groups were trained for six weeks. Rats in the CGRP inhibition group received CGRP receptor antagonist daily (0.25 mg/kg) via intravenous (IV) injection. The Nrf2 and AKT (PKB) expression was measured using the real-time PCR technique. Results: In the endurance training group, Nrf2 expression in the hippocampal tissue was increased significantly more than in other groups (P < 0.05). There was also a significant increase in the AKT expression in the endurance training group compared to the control group (P = 0.048) and in the endurance training+CGRP inhibition compared to the control group (P = 0.012). In addition, there was no significant relationship between AKT (PKB) and Nrf2 (r = -0.27, n = 28, P = 0.16). Conclusion: Endurance training alone has been able to increase Nrf2 and AKT (PKB) mRNA levels in the hippocampal tissue, considering that endurance training had no significant effect on AKT and Nrf2 expression after adding to CGRP inhibition.

Effect of activity-based training versus strengthening exercises on upper extremity functions in Parkinson's patients; A randomized controlled, single blind, superiority trial.

BACKGROUND: Idiopathic Parkinson's disease is a neurodegenerative disease which is appeared by symptoms such as resting tremor, bradykinesia, rigidity, and postural instability. Such symptoms as tremor, bradykinesia, and rigidity significantly affect patients' upper extremity function. Rehabilitation programs should be implemented to improve the upper extremity functions of patients. OBJECTIVE: Activity-based training would improve dexterity and functional activities to a larger extent than strengthening exercises. This study aimed at evaluating the effect of activity-based training and strengthening exercises on upper extremity functions in Parkinson's disease and to compare the two methods. METHOD: 40 Parkinson's patients with mean of 64.45 ± 9.13 age were randomized and divided into two groups as activity-based training and strengthening exercise group. Patients were evaluated at the beginning and after 6 weeks of treatment with Unified Parkinson's Disease Rating Scale, Parkinson's Disease Questionnaire-39, Duruöz Hand Index, Jebsen Taylor Hand Function Test, Nine-Hole Peg Test, Jamar dynamometer, Jamar pinch meter, Semmes Weinstein Monofilament Test and two-point discrimination. RESULT: In both groups, upper extremity functions, handgrip strengths and quality of life of patients improved significantly. Tactile sense improved only in the activity-based training group. CONCLUSION: Activity-based training is not superior to strengthening exercise programs at improving upper extremity functions and dexterity of Parkinson's patients.

Reproductive health status of adolescent mothers in an Iranian setting: a cross-sectional study.

BACKGROUND: In low and middle-income countries (LMICs), where millions of women give birth before the age of 18, the reproductive health status of married adolescent mothers, including family planning, sexual, psychosocial, and maternal health, remains a significant and recurring phenomenon. As a result, the purpose of this study was to assess the reproductive health status of married adolescent mothers who sought treatment at Ardabil health care centers in 2019. METHODS: A cross-sectional study was carried out in five health centers in Ardabil, Iran. This research included 312 married adolescent mothers who were under 19 years old. Health workers who asked questions of each participant completed a demographic questionnaire and the Reproductive Health Assessment Scale for Married Adolescent Women, and all data were self-reported. Univariate and multivariate linear regressions were used to determine risk factors associated with reproductive health scores. The data was examined using statistical software (SPSS version 20). RESULTS: The mean age (years) of the respondents was 16.41 ± 0.85, the mean age of their husbands was 24.18 ± 2.29, and the mean age of their marriage was 15.06 ± 1.15. In this study, adolescent mothers had an average reproductive health score of 63.78 ± 11.06. There was a significant association between reproductive health status and age, education, husband's age and education, and contraceptive methods among married adolescent mothers (p < 0.05). CONCLUSION: The research findings indicated that adolescent mothers had an average level of reproductive health. Several socio-demographic characteristics, including age, education, gravida, and contraception, were linked to reproductive health scores. Programmers and policymakers should prioritize improving the reproductive health of adolescent mothers through education and increasing women's and spouses' knowledge and awareness.

In LMICs, the health status of adolescent mothers remains unstudied in a systematic way. This study aims to evaluate the reproductive health of married adolescent mothers. A cross-sectional study of adolescent mothers was conducted at five Ardabil health centers. A total of 312 adolescent mothers under the age of 19 were selected to complete a survey regarding their health and contraceptive awareness. The mothers' reproductive health status was rated as average. Age, education, husband's age and education, gravida, and contraceptive methods significantly impacted reproductive health. Increased education among women and their spouses, as well as pregnancy prevention, appear to be essential for safeguarding the health of adolescent mothers. This study recommends conducting qualitative research on reproductive health and contraception in the cultural context.

Antiviral activities of natural compounds and ionic liquids to inhibit the Mpro of SARS-CoV-2: a computational approach.

The recalcitrant spread of the COVID-19 pandemic produced by the novel coronavirus SARS-CoV-2 is one of the most destructive occurrences in history. Despite the availability of several effective vaccinations and their widespread use, this line of immunization often faces questions about its long-term efficacy. Since coronaviruses rapidly change, and multiple SARS-CoV-2 variants have emerged around the world. Therefore, finding a new target-based medication became a priority to prevent and control COVID-19 infections. The main protease (Mpro) is a salient enzyme in coronaviruses that plays a vital role in viral replication, making it a fascinating therapeutic target for SARS-CoV-2. We screened 0.2 million natural products against the Mpro of SARS-CoV-2 using the Universal Natural Product Database (UNPD). As well, we studied the role of ionic liquids (ILs) on the structural stabilization of Mpro. Cholinium-based ILs are biocompatible and used for a variety of biomedical applications. Molecular docking was employed for the initial screening of natural products and ILs against Mpro. To predict the drug-likeness features of lead compounds, we calculated the ADMET properties. We performed MD simulations for the selected complexes based on the docking outcomes. Using MM/PBSA approaches, we conclude that compounds NP-Hit2 (-25.6 kcal mol-1) and NP-Hit3 (-25.3 kcal mol-1) show stronger binding affinity with Mpro. The hotspot residues of Thr25, Leu27, His41, Met49, Cys145, Met165, and Gln189 strongly interacted with the natural compounds. Furthermore, naproxenate, ketoprofenate, and geranate, cholinium-based ILs strongly interact with Mpro and these ILs have antimicrobial properties. Our findings will aid in the development of effective Mpro inhibitors.

A case report of severe systemic infection with neurological HFMD symptoms followed by an accidental puncture of thumb during HFMD sample collection.

A 34-year-old female clinical virology assistant was punctured with a contaminated lancet used for sampling from a suspected Hand, Foot, and Mouth disease (HFMD) patient. Five days after a puncture, the disease symptoms manifested, including high fever, ague, and stiff neck. Skin rashes suddenly appeared after day 6. Stiff neck and fever were relieved two days after the rash appeared, and rashes disappeared gradually by the next five days. Samples for molecular detection and virus cultivation were taken from the patient. Real-time PCR found the enteroviral RNA in the throat swab and skin rashes. The specific CPE of Enteroviruses appeared on the Vero cell line after three days of incubation. In this case transmission occurs through needle injury and results in the systemic disease, so unusual and unexpected viral transmission should be considered when dealing with samples.

Effects of some cosmetic dyes and pigments on the proliferation of human foreskin fibroblasts and cellular oxidative stress; potential cytotoxicity of chlorophyllin and indigo carmine on fibroblasts.

INTRODUCTION: Fibroblasts and fibroblast-like cells (FLCs) are highly distributed in the dermis layer of the skin and gastrointestinal tract. A few studies have investigated the effects of color additives of cosmetic products on human fibroblasts. Therefore, this in vitro study was conducted to investigate the effects of 9 synthetic and natural dyes (indigo carmine, carmine, sunset yellow, tropaeolin, acid green 25, chlorophyllin, tartrazine, lissamine, and amaranth) on human foreskin fibroblast cells. METHODS: MTT assay was applied to investigate the effects of dyes on human normal fibroblast cells. For investigating the possible mechanism of cytotoxicity, the effect of dyes was evaluated on parameters of cellular oxidative stress including lipid peroxidation and reactive oxygen species (ROS) as well as lactate dehydrogenase. RESULTS: In the MTT assay, a significant reduction (p ≤ 0.05) was observed in the viability of fibroblast cells by chlorophyllin and indigo carmine at concentrations higher than 10 and 100 (µg/ml), respectively. Acid green 25 caused a significant reduction at very high concentrations (1000 and 2000 µg/ml), which was not toxic. The effect of other investigated dyes was not significant on the fibroblasts. A trend in increased cell proliferation by amaranth and carmine was observed, but this enhancement was not statistically significant. No significant changes were observed in lipid peroxidation or lactate dehydrogenase. Chlorophyllin caused a significant increase in the production of cellular ROS. CONCLUSIONS: Indigo carmine and chlorophyllin had cytotoxicity on human fibroblasts, and thus, further studies are required on their safety of use in cosmetics and pharmaceuticals.

Role of Cytomegalovirus in the Development of Posttransplant Lymphoproliferative Disorders With or Without Epstein-Barr Virus Infection.

OBJECTIVES: Many studies have revealed the role of Epstein-Barr virus infection, in combination with chronic immunosuppression, as the main factor in the development of posttransplant lymphoproliferative disorder malignancy. Although many studies have been published on other confounding factors involved in posttransplant lymphoproliferative disorders, the role of coinfection with both cytomegalovirus and Epstein-Barr virus has not been investigated. We evaluated the role of cytomegalovirus infection as a risk factor in transplant recipients who were simultaneously infected with Epstein-Barr virus. MATERIALS AND METHODS: In the current retrospective study, 143 recipients of various solid-organ transplants at Namazi Hospital from April 2018 to March 2019 were assessed for coinfection with cytomegalovirus and Epstein-Barr virus with the TaqMan real-time polymerase chain reaction assay. We collected clinical and pathology details from their medical records. RESULTS: Of the 143 patients, 81 (57%) were male. Children under 5 years old were the largest group with 32% prevalence, and the most common organ transplant in this study was liver transplant. The prevalence of cytomegalovirus and Epstein-Barr virus coinfection was 12.6% (18/143 patients), of whom 50% experienced posttransplant lymphoproliferative disorder (9/18 patients) during 18 months after transplant. The incidence of posttransplant lymphoproliferative disorder was significantly higher among patients coinfected with cytomegalovirus and Epstein-Barr virus than among patients without coinfection. We observed a significant correlation between cytomegalovirus viral loads, as well as Epstein-Barr virus genome load, in posttransplant lymphoproliferative disorder development. CONCLUSIONS: Coinfection with cytomegalovirus and Epstein-Barr virus, as well as the genome load of each virus, can serve as a strong predictive factor of posttransplant lymphoproliferative disorder in solidorgan transplant recipients.