Exosomes Recovered From the Plasma of COVID-19 Patients Expose SARS-CoV-2 Spike-Derived Fragments and Contribute to the Adaptive Immune Response

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by beta-coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has rapidly spread across the globe starting from February 2020. It is well established that during viral infection, extracellular vesicles become delivery/presenting vectors of viral material. However, studies regarding extracellular vesicle function in COVID-19 pathology are still scanty. Here, we performed a comparative study on exosomes recovered from the plasma of either MILD or SEVERE COVID-19 patients. We show that although both types of vesicles efficiently display SARS-CoV-2 spike-derived peptides and carry immunomodulatory molecules, only those of MILD patients are capable of efficiently regulating antigen-specific CD4+ T-cell responses. Accordingly, by mass spectrometry, we show that the proteome of exosomes of MILD patients correlates with a proper functioning of the immune system, while that of SEVERE patients is associated with increased and chronic inflammation. Overall, we show that exosomes recovered from the plasma of COVID-19 patients possess SARS-CoV-2-derived protein material, have an active role in enhancing the immune response, and possess a cargo that reflects the pathological state of patients in the acute phase of the disease.

Features of the Clinical Course of Arterial Hypotension in Pregnant Women

A study was carried out of women with arterial hypotension against the background of the development of the pathological state of the fetus and newborns born to women living in two different climatic regions of Osh city and in the highlands of Chon-Alay district of Osh region. In the pathogenesis of pregnancy complications caused by arterial hypotension, the leading importance is attached to vascular disorders and microcirculation disorders, leading to systemic hemodynamic changes in the body of a pregnant woman. It was found that in mountainous terrain, arterial hypotension and exogenous hypoxia affect the “mother–placenta–fetus–newborn” system, increasing the load on the respiratory, circulatory and hematopoietic organs of the mother, and also leads to impaired placental function.

Striatal Syntaixin 1A Plays a Protective Role Against Iminodipropionitrile Induced Tic Disorder Through Interaction with Dopamine Transporter

An important mechanism of Tic disorder (TD) is dysfunction in the dopamine (DA) system. Our pilot observation found the expression of Syntaxin 1A (STX1A), a presynaptic SNARE complex, changed in the striatum of TD animals. The present study aimed to clarify the biological role of striatal STX1A in the pathological state of TD and the specific mechanism of its regulation of the dopaminergic system. The TD rat model was established using iminodipropionitrile (IDPN). Adenovirus was used to modulate the expression of STX1A and dopamine transporter (DAT) in vivo and vitro. Primary culture of striatal dopaminergic neurons was performed for in-vitro observation of the DA reuptake, CO-IP analysis of the interaction between STX1A and DAT. First, using immunofluorescence staining, Western blotting, and qPCR, we found that the IDPN induced TD model had reduced striatal STX1A expression. In vitro, the DA content in the supernatant was significantly lower in the STX1A overexpressed group, and the intracellular DA content was significantly higher. Overexpression of STX1A in vivo partially counteracts the IDPN-induced TD-like behaviors, including bite time and head shaking time. Meanwhile, in-vivo knockdown of STX1A can aggravates TD-like behaviors. Further, DAT was overexpressed in vivo, and the TD-like behavior was alleviated. Interestingly, overexpression of DAT in the striatum resulted in increased levels of STX1A. In order to clarify the interaction between DAT and STX1A, the CO-IP analysis was conducted based on the protein of purified striatal dopaminergic neurons. Compared to the IgG control, the blots of DAT and STX1A showed significant binding of each other. Striatal STX1A expression is decreased in TD development, and STX1A plays an anti-TD role possibly through interaction with DAT, which maintains the DA reuptake. The exorbitant DA signal caused by STX1A inhibition drives the pathological stereotyped behavior.

Gangliosides as Biomarkers of Human Brain Diseases: Trends in Discovery and Characterization by High-Performance Mass Spectrometry

Gangliosides are effective biochemical markers of brain pathologies, being also in the focus of research as potential therapeutic targets. Accurate brain ganglioside mapping is an essential requirement for correlating the specificity of their composition with a certain pathological state and establishing a well-defined set of biomarkers. Among all bioanalytical methods conceived for this purpose, mass spectrometry (MS) has developed into one of the most valuable, due to the wealth and consistency of structural information provided. In this context, the present article reviews the achievements of MS in discovery and structural analysis of gangliosides associated with severe brain pathologies. The first part is dedicated to the contributions of MS in the assessment of ganglioside composition and role in the specific neurodegenerative disorders: Alzheimer’s and Parkinson’s diseases. A large subsequent section is devoted to cephalic disorders (CD), with an emphasis on the MS of gangliosides in anencephaly, the most common and severe disease in the CD spectrum. The last part is focused on the major accomplishments of MS-based methods in the discovery of ganglioside species, which are associated with primary and secondary brain tumors and may either facilitate an early diagnosis or represent target molecules for immunotherapy oriented against brain cancers.

Lipidomic Profile and Enzymes Activity in Hepatic Microsomes of Rats in Physiological and Pathological Conditions

Among the risk factors affecting the development of cancer, nutritional factors occupy a significant place. Pomegranate seed oil (PSO) and bitter melon extract (BME), used for ages in folk medicine, are nowadays used in the prevention of many diseases and as ingredients of dietary supplements. Despite numerous publications on these raw materials or their active substances, their mechanism of action in various pathological states has not been recognized yet, nor has the safety of their simultaneous use been evaluated. The study aimed to assess how dietary supplementation with either PSO, with BME, or both, affects fatty acids’ profiles and their metabolism in hepatic microsomes, as well as the activity of selected microsomal enzymes (COX-2 and CYP1B1). Experimental animals (Sprague-Dawley rats) were divided into eight parallel experimental groups, differing in applied dietary modifications (control, PSO, BME and both PSO and BME) and introduction of chemical carcinogen—7,12-dimethylbenz[a]nthracene. Obtained results indicated the pronounced effect of the cancerous process on lipid metabolism and demonstrated the antagonistic effect of applied dietary supplements on the content of individual fatty acids and the activity of CYP1B1 and COX-2. The applied broad analytical approach and chemometric data analysis confirmed that raw materials, for which potential cancer prevention has been previously demonstrated, may differ in effects depending on the coexisting pathological state.

Efficiency of Experimental Allergic Encephalomyelitis Modeling as an Experimental Model of Multiple Sclerosis

The purpose of the study was the most adequate modeling of multiple sclerosis in the form of autoimmune allergic encephalomyelitis for further use in the study of experimental equivalents of neurodegenerative conditions. Materials and methods. The article highlights the results of the formation of experimental allergic encephalomyelitis, for the induction of which homologous brain homogenates were used, which in terms of encephalitogenicity ranks first among other drugs (homologous, heterogeneous brain and spinal cord homogenates). An encephalitogenic mixture was injected into the connective tissue of the base of the animal's tail at the rate of 0.1 ml per 100 g of body weight. Results and discussion. Experimental allergic encephalomyelitis reproducible by intradermal administration of a homogenate of the brain, spinal cord and peripheral nerves with a Freund's stimulator belongs to a true autoimmune disease of the nervous system and is an experimentally reproducible model of multiple sclerosis. According to the experimental data obtained, the state of the animals showed that the rats of the experimental group lost body weight, had a number of pathological neurological symptoms, which manifested on average from 10-12 days. The increase in symptoms continued for an average of 7 days and was not very stable. Experimental animals had paresis, manifestations of ataxia, walking disorders and urinary and fecal incontinence, lethargy, which corresponded to 1-2 degrees of the rating scale in 13 animals. In 7 rats, paresis of the hind limbs and loss of tail tone were expressed (grade 3). Most of the rats recovered spontaneously within 6-8 days after the onset of clinical manifestations (18-20 days after immunization). According to the requirements of the experiment, during the paralytic stage, the rats had free access to food and water. In addition, our experimental studies on the formation of experimental allergic encephalomyelitis were confirmed morphologically using electron microscopy. Conclusion. The use of this technique for the formation of experimental allergic encephalomyelitis made it possible to obtain a simulated pathological state of multiple sclerosis in the form of experimental allergic encephalomyelitis and can be used in further studies to identify the corresponding patterns, the degree and nature of changes in the immune and nervous systems of the body during the reproduction of an experimental pathological state. The data obtained can serve as a basis for further studies of drugs and their combinations in order to improve and rationalize the pharmacotherapy of multiple sclerosis

Molecular liver fingerprint reflects the seasonal physiology of the grey mouse lemur (Microcebus murinus) during winter

Grey mouse lemurs (Microcebus murinus) are a primate species exhibiting strong physiological seasonality in response to environmental energetic constraint. They notably store large amounts of lipids during early winter (EW), which are thereafter mobilized during late winter (LW), when food availability is low. In addition, they develop glucose intolerance in LW only. To decipher how the hepatic mechanisms may support such metabolic flexibility, we analyzed the liver proteome of adult captive male mouse lemurs, which seasonal regulations of metabolism and reproduction are comparable to their wild counterparts, during the phases of either constitution or use of fat reserves. We highlight profound changes that reflect fat accretion in EW at the whole-body level, however, without triggering an ectopic storage of fat in the liver. Moreover, molecular regulations would be in line with the lowering of liver glucose utilization in LW, and thus with reduced tolerance to glucose. However, no major regulation was seen in insulin signaling/resistance pathways, which suggests that glucose intolerance does not reach a pathological stage. Finally, fat mobilization in LW appeared possibly linked to reactivation of the reproductive system and enhanced liver detoxification may reflect an anticipation to return to summer levels of food intake. Altogether, these results show that the physiology of mouse lemurs during winter relies on solid molecular foundations in liver processes to adapt fuel partitioning while avoiding reaching a pathological state despite large lipid fluxes. This work emphasizes how the mouse lemur is of primary interest for identifying molecular mechanisms relevant to biomedical field.

Application of Electrospun Nanofiber Membrane in the Treatment of Diabetic Wounds

Diabetic wounds are complications of diabetes which are caused by skin dystrophy because of local ischemia and hypoxia. Diabetes causes wounds in a pathological state of inflammation, resulting in delayed wound healing. The structure of electrospun nanofibers is similar to that of the extracellular matrix (ECM), which is conducive to the attachment, growth, and migration of fibroblasts, thus favoring the formation of new skin tissue at the wound. The composition and size of electrospun nanofiber membranes can be easily adjusted, and the controlled release of loaded drugs can be realized by regulating the fiber structure. The porous structure of the fiber membrane is beneficial to gas exchange and exudate absorption at the wound, and the fiber surface can be easily modified to give it function. Electrospun fibers can be used as wound dressing and have great application potential in the treatment of diabetic wounds. In this study, the applications of polymer electrospun fibers, nanoparticle-loaded electrospun fibers, drug-loaded electrospun fibers, and cell-loaded electrospun fibers, in the treatment of diabetic wounds were reviewed, and provide new ideas for the effective treatment of diabetic wounds.

Research on Network Model of Dentate Gyrus Based on Bionics

As an important part of the brain, the dentate gyrus has an irreplaceable effect in the process of memory generation. Therefore, the study of the dentate gyrus model has important significance in the study of brain function. This paper, combined with the real anatomical structure of the dentate gyrus, is based on the existing calculation model for studying the pathological state of the dentate gyrus, a network model of dentate gyrus based on bionics. Then, a simulation experiment on the normal dentate gyrus model is performed on the NEURON platform, the output of each neuron in the model is observed, and a conclusion that the improved model can respond to stimuli, generate action potentials, and transmit them along with the neural network is made. At the same time, the output results are compared with the existing pathological models, and the characteristics of the stimulus response between neurons in the dentate gyrus under normal physiological conditions are obtained. Finally, according to the semiquantitative classification definition and quantitative classification definition of the small-world network, the model is analyzed, and it is concluded that the improved dentate gyrus network model has small-world characteristics. Therefore, the neurons in the improved dentate gyrus model are tightly connected and can simulate the real dentate gyrus to a certain extent.

Impact of Mobile Endoscopy Unit for Rendering Gastrointestinal Endoscopy Services at Two Community Health Centers in Western India

Background Patients with gastrointestinal (GI) symptoms in remote areas do not have access to standard medical care with the issues related to cost of medical care, transportation, health literacy, lack of healthcare insurance—all preventing healthcare access in a timely manner. To overcome this, we designed a mobile endoscopy van with the intent to provide free essential medical services to the rural population. Methods This is a retrospective study of patients with predominantly upper GI symptoms at two community health centers (each 2 days camp). This is an audit of endoscopy findings in a community set up using a Mobile Endoscopy Unit (MEU). Patients' details were collected in a pre-designed questionnaire. Only those patients with alarm symptoms and suspicion of any pathological state underwent esophagogastroduodenoscopy (EGD) in MEU. Data analysis was done using descriptive statistics. Results A total of 724 patients (424 [58.5%] males; mean [SD] age 48.5 [5.2] years) were included. The commonest presenting symptom was heartburn in 377 (52.1%) patients. The median duration of symptoms was 6.5 (range: 2–36) months. Gastroesophageal reflux disease was seen in 16 (6.8%) patients, ulceroproliferative growth was noted in the stomach in 3 (1.3%) patients. Eighteen (7.6%) patients had a positive rapid urease test and received Helicobacter pylori eradication therapy. The most commonly prescribed drugs were proton-pump inhibitors in 692 (95.6%) patients. Nine (1.2%) patients had chronic liver disease secondary to alcoholism and were counseled for abstinence. All procedures were safely performed without any immediate adverse events. Conclusions Community outreach strategies such as the use of mobile endoscopy unit were found to be very useful in the diagnosis of GI symptoms. More research is needed in low-income countries to treat complex pathological states in rural patients.