Guillain-Barré syndrome associated with COVID-19: a case report study.

Acute respiratory distress syndrome (ARDS) caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is spreading around the world. Patients with coronavirus disease 2019 (COVID-19) typically present fever, cough, and respiratory illnesses. It has been revealed that the comorbidities can turn it into severe types, and the managements meet unpredicted complications. Here, we report a case of coronavirus disease 2019 (COVID-19) coincidence with confirmed acute Guillain-Barré syndrome (GBS). Ten days after admission and therapeutic process, the patient developed autonomic dysfunction. Despite respiratory support and receiving intravenous immunoglobulin, the patient died due to cardiac arrest. Albeit it is yet scientifically doubtful, there are raising concerns toward a possible association between GBS and SARS-CoV-2 infection, demonstrating potential neurological symptoms of COVID-19.

A challenging choice of aptamer for the selective enrichment of ochratoxin A.

In a recent study, the adenosine monophosphate-specific aptamer has been applied for the rapid extraction of ochratoxin A. Although several publications have already reported the selection of adenosine monophosphate, adenosine triphosphate, and adenosine, there is no report on the detection of ochratoxin A using this aptamer. The data of the previous study are surprising since its aptamer-based magnetic metal-organic framework has shown a high selectivity with a very low detection limit for the selection of ochratoxin A. However, numerous studies have demonstrated that each aptamer can specifically bind to a target by folding into a unique structure and can differentiate molecules that differ by only one functional group. This study aimed to deal with the possibility of recognizing ochratoxin A and adenosine monophosphate by adenosine monophosphate-specific aptamer. The procedure was performed by determining structural similarity and alignment, docking adenosine monophosphate and ochratoxin A on aptamer, and monitoring the interactions between ochratoxin A and adenosine monophosphate specific aptamer complex. The results indicated not only the lack of structural similarity between adenosine monophosphate and ochratoxin A but also the little possibility for strong bonds between the ochratoxin A and aptamer.

Aptamers, the bivalent agents as probes and therapies for coronavirus infections: A systematic review.

The recently known coronavirus, SARS-CoV-2, has turn into the greatest global health challenge, affecting a large number of societies. The lack of specific treatment and gold-standard diagnostic system has made the situation more complicated. Efforts have led to production of several diagnostic kits that are associated with limitations such as inadequate sensitivity and accuracy. Aptamers as multipotent biological probes could be promising candidates to design sensitive and specific biosensors. Although few studies have introduced specific aptamer types of coronavirus, they may help us select the best approach to obtain specific aptamers for this virus. On the other hand, some of already-introduced aptamers have shown the inhibitory effects on coronavirus that could be applied as therapeutics. The present study has provided a systematic overview on use of aptamer-based biosensors and drugs to diagnose and treat coronavirus.

An investigation on the interaction modes of a single-strand DNA aptamer and RBP4 protein: a molecular dynamic simulations approach.

Type two diabetes is one of the primary health issues threatening public well-being worldwide. One of the pre-diagnosis biomarkers of this disease, retinol binding protein 4 (RBP4), has been demonstrated to be detected with a 76-mer ssDNA aptamer instead of conventional antibodies. However, there is no structural information on the RBP4 binding aptamer (RBA) and the mechanism of its binding to RBP4 still remains unexplored. The objective of the present study is to achieve a better understanding of specific binding interactions of the target protein (RBP4) and RBA, employing Molecular Dynamics simulations (MDs) to provide detailed information on fluctuations, conformational changes, critical bases and effective forces to develop regulated aptamers to be employed in designing new aptamers for many useful recognition applications. RBA was designed according to its reported base pair sequence and secondary structure. The HADDOCK on line docking program was used to predict a suitable RBP4-RBA mode of interaction to start MDs with. MDs methodology was used to analyze the final complex stability and detect interacting residues. Eventually, we conclude that single strand located bases are the key components that conduct the intercalation phenomenon with big targets rather than those involving loops and folded motifs, to encompass targets and probably inhibit their activity. Also, UV-visible, circular dichroism and fluorescence spectroscopy measurements confirmed the interactions between RBA and RBP4 and RBP4-RBA complex formation.

Ultrasensitive nano-aptasensor for monitoring retinol binding protein 4 as a biomarker for diabetes prognosis at early stages.

Prognosis of diabetes risk at early stages has become an important challenge due to the prevalence of this disease. Retinol binding protein 4 (RBP4), a recently identified adipokine, has been introduced as a predictor for the onset of diabetes type 2 in coming future. In the present report a sensitive aptasensor for detection of RBP4 is introduced. The immune sandwich was prepared by immobilizing biotinylated RBP4 aptamers on streptavidin coated polystyrene micro-wells and then incubation of RBP4 as target and finally addition of luminol-antibody bearing intercross-linked gold nanoparticles as reporter. The chemiluminescence intensity was recorded in the presence of hydrogen peroxide as oxidant agent and Au3+ as an efficient catalyst for luminol oxidation. The aptasensor responded to RBP4 in the linear concentration range from 0.001 to 2 ng/mL and detection limit was slightly less than 1 pg/mL. The proposed method has successfully applied to determine the RBP4 in patient real serums. By using the intercross-linked gold nanoparticles, it is possible to provide more accessible surface for immobilizing luminol and enhance the chemiluminescence signal. Therefore, the analytical parameters such as sensitivity, specificity, detection limit and linear range were improved in compare to the biosensors reported in the literature.

Recent advances in biosensor technology in assessment of early diabetes biomarkers.

Discovery of biosensors has acquired utmost importance in the field of healthcare. Recent advances in biological techniques and instrumentation involving nanomaterials, surface plasmon resonance, and aptasensors have developed innovative biosensors over classical methods. Integrated approaches provided a better perspective for developing specific and sensitive devices with wide potential applications. Type 2 diabetes mellitus is a complex disease affecting almost every tissue and organ system, with metabolic complications extending far beyond impaired glucose metabolism. Although there is no known cure for Type 2 diabetes, early diagnosis and interventions are critical to prevent this disease and can postpone or even prevent the serious complications that are associated with diabetes. Biomarkers for type 2 diabetes are useful for prediction and intervention of the disease at earlier stages. Proper selection of biomarkers that represent health and disease states is vital for disease diagnosis and treatment by detecting it before it manifests. In this respect, we provide an overview of different types of biosensors being used, ranging from electrochemical, fluorescence-based, nanomonitors, SPR-based, and field-effect transistor biosensors for early detection and management of diabetes with focus on prediabetes. In the future, novel non-invasive technologies combined with blood and tissue-based biomarkers will enable the detection, prevention, and treatment of diabetes and its complications long before overt disease develops.

Aptamer-Conjugated Calcium Phosphate Nanoparticles for Reducing Diabetes Risk via Retinol Binding Protein 4 Inhibition.

OBJECTIVES: Inhibition of the binding of retinol to its carrier, retinol binding protein 4, is a new strategy for treating type 2 diabetes; for this purpose, we have provided an aptamer-functionalized multishell calcium phosphate nanoparticle. METHODS: First, calcium phosphate nanoparticles were synthesized and conjugated to the aptamer. The cytotoxicity of nanoparticles releases the process of aptamer from nanoparticles and their inhibition function of binding retinol to retinol binding protein 4. RESULTS: After synthesizing and characterizing the multishell calcium phosphate nanoparticles and observing the noncytotoxicity of conjugate, the optimum time (48 hours) and the pH (7.4) for releasing the aptamer from the nanoparticles was determined. The half-maximum inhibitory concentration (IC50) value for inhibition of retinol binding to retinol binding protein 4 was 210 femtomolar (fmol). CONCLUSIONS: The results revealed that the aptamer could prevent connection between retinol and retinol binding protein 4 at a very low IC50 value (210 fmol) compared to other reported inhibitors. It seems that this aptamer could be used as an efficient candidate not only for decreasing the insulin resistance in type 2 diabetes, but also for inhibiting the other retinol binding protein 4-related diseases.

Distorted expression of dopamine receptor genes in systemic lupus erythematosus.

Several observations suggest that alterations in the neurotransmitter dopamine and/or its receptors could be associated with the pathophysiology of lupus. We therefore assessed expression of the five dopamine receptor genes in a cohort of patients. We found that all receptors are expressed in lupus peripheral blood cells. We also discovered that dopamine receptor 2 gene (DR2) was underexpressed, and that DR4 was overexpressed in lupus patients, as compared to controls. Cell sorting of peripheral T- and B-lymphocytes disclosed that the altered DR2 and DR4 expressions were borne by T-cells. These distorted expressions of DR2 and DR4 could influence immune functions in lupus through several mechanisms. Since DR2 can be effective in regulating the activation and differentiation of naive CD4⁺ cells by promoting polarization toward regulatory T-cells, the underexpression of DR2 we have observed may account, at least in part, for the reduction of regulatory T-cell function and/or numbers in lupus. In addition to providing novel insight into disease pathogenesis, our findings may have therapeutic implications. Because DR4 can be effective in triggering T-cell quiescence, its overexpression on lupus T cells suggests that inducing quiescence using DR4-specific agonists may represent a useful strategy in the treatment of lupus.

Combination of thrombophilic gene polymorphisms as a cause of increased the risk of recurrent pregnancy loss.

BACKGROUND: Recurrent pregnancy loss is (RPL) a heterogeneous condition. While the role of acquired thrombophilia has been accepted as an etiology for RPL, the contribution of specific inherited thrombophilic gene polymorphisms to the disorder has been remained controversial. METHODS: One hundred women with a history of two or more consecutive abortions and 100 women with at least two live births and no miscarriages were included in the study and evaluated for the presence of 11 thrombophilic gene polymorphisms (Factor V LEIDEN, Factor V 4070 A/G, Factor V 5279 A/G, Factor XIII 103 G/T, Factor XIII 614 A/T, Factor XIII 1694 C/T, PAI-1 -675 4G/5G, ITGB3 1565 T/C, ß-Fibrinogen -455G/A, MTHFR 677 C/T, MTHFR 1298 A/C) using PCR-RFLP technique. The data were statistically analyzed using Mann-Whitney test and logistic regression model. RESULTS: There was no relation between factor XIII 103G/T gene polymorphism with increased risk of RPL. However, the other 10 gene polymorphisms were found to be associated with increased/decreased risk of RPL. Multiple logistic regression model for analyzing the simultaneous effects of these polymorphisms on the risk of RPL showed that six of these 11 polymorphisms (Factor V 1691G/A, Factor V 5279A/G, Factor XIII 614A/T, ß-Fibrinogen -455G/A, ITGB3 1565T/C, and MTHFR 1298A/ C) were associated with RPL. CONCLUSION: It is possible to calculate the risk of abortion in a patient with RPL by determining only six of the 10 polymorphisms that are individually associated with RPL.

Analysis of plasminogen activator inhibitor-1, integrin beta3, beta fibrinogen, and methylenetetrahydrofolate reductase polymorphisms in Iranian women with recurrent pregnancy loss.

PROBLEM: To identify the associations of the plasminogen activator inhibitor-1 (PAI-1) -675 4G/5G, beta fibrinogen (BF) -455G/A, integrin beta 3 (ITGB3) 1565T/C, and methylenetetrahydrofolate reductase (MTHFR) 677C/T and 1298A/C polymorphisms with recurrent pregnancy loss (RPL). METHOD OF STUDY: Polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) were performed to assess the frequency of five candidate genetic risk factors for RPL, and the frequencies of the polymorphisms were calculated and compared between case and control groups. RESULTS: The BF -455G/A, MTHFR 677C/T, and 1298A/C polymorphisms were found to be positively, and ITGB3 1565T/C polymorphism negatively, associated with RPL. Homozygosity but not heterozygosity for PAI-1 -675 4G/5G polymorphism was significantly higher in patients with RPL than in the control group. The presence of both mutations of MTHFR genes highly increased the risk of RPL. CONCLUSION: The data highlight the importance of thrombophilia screening in patients with RPL.

Investigating Association of Three Polymorphisms of Coagulation Factor XIII and Recurrent Pregnancy Loss.

PROBLEM: among important suspected causes of thrombophilia in women with recurrent pregnancy loss (RPL) are the polymorphisms of coagulation factor XIII (FXIII) gene. We performed a case-control study on the association between three polymorphisms of factor XIII (FXIII G103T, FXIII A614T and FXIII C1694T) and RPL in Iranian women. METHOD OF STUDY: DNA samples from peripheral blood of 100 female patients with at least two recurrent abortions, as case group, and 100 healthy women with history of at least two successful deliveries were subjected to PCR-RFLP, and the frequencies of the polymorphisms were calculated and compared between the two groups. RESULTS: the prevalence of FXIII G103T polymorphism was 29% in the case group and 17% in the control group (P = 0.158). The frequencies of FXIII A614T and FXIII C1694T were 84% and 66% in the case group and 48% and 31% in the control group (P <0.001 and P < 0.001), respectively. The two latter polymorphisms are associated with RPL in Iranian women and increase the risk of RPL. A correlation was also found between FXIII A614T and FXIII C1694T polymorphisms (P < 0.001). CONCLUSION: we suggest the evaluation of FXIII A614T and FXIII C1694T polymorphisms in women with RPL.