Defense Factors Research Articles

PREDICTION OF THE DYSBIOSIS DEVELOPMENT RISK ACCORDING TO HUMORAL IMMUNITY INDICATORS

Diseases associated with bacterial vaginosis lead to chronic inflammatory processes of the internal genitals, the development of adhesions of the pelvic organs, infertility, spontaneous abortion at different times, as well as the development of malignant neoplasms. Vaginal microflora is an indicator of a woman’s health, which can form changing in hormonal and immunological status during various pathological conditions. The aim of the study was to create a system for prediction of the dysbiosis development according to the levels of nonspecific humoral factor of immune defense. Materials and methods. The study was performed in 298 women aged 16 to 64 years, 53 of whom were diagnosed with normocenosis, and 245 have dysbiosis. Women were divided into 3 groups according to age. Regression analysis was used. Research results and their discussion. Our previous research have shown a correlation between increased levels of anti-inflammatory cytokines in the blood and vaginal secretions with the stage of dysbiosis. A logistic regression model was constructed during the study, which showed that the risk of developing dysbiosis in terms of normobiota increases with increasing levels of interleukin 2 in the blood, tumor necrosis factor α. Significant features of the three-factor model for predicting the risk of developing dysbiosis (IL2, IL4 and TNFα) were selected by the method of genetic algorithm. The levels of these indicators in the blood were related to the severity of dysbiosis according to the results of discriminant analysis. Conclusions. Thus, a linear neural network model was developed for determination of dysbiosis severity according to the levels of nonspecific humoral factors of immune defense such as the C4 component of the complement system and γ-interferon in vaginal secretions, as well as the amount of circulating immune complexes and tumor necrosis factor α in the blood. Kappa Cohen’s agreement for this model on the training set was 0.87 (95% CI 0.82-0.91), and on the confirmatory set was 0.89 (95% CI 0.77-1.00). These indicators show the adequacy of the constructed model. The interface of the expert system for the dysbiosis severity prediction has been created. Key words: normobiota, bacterial vaginosis, linear neural network model for determination of the dysbiosis severity, humoral factor of immune defense.

Impact of Oral Health on Rheumatoid Arthritis

This is a narrative review describing how oral infections and diseases associate with rheumatoid arthritis. From the voluminous oral microbiom, bacteria can get access to circulation through inflamed periodontal tissue, oral mucosa, and carious teeth. This results in upregulation of a number of chemokines and cytokines that often cause chronic, subclinical systemic inflammation with consequent organ pathology. The periodontal pathogen Porphyromonas gingivalis was observed to cause citrullination of proteins that play a role in the development of arthritis by generating of specific autoantibodies such as anti-citrullinated peptide antibody. These migrate and form immune complexes at the synovial membrane of joints. In general, patients with rheumatoid arthritis should have a healthy mouth. Dry mouth is a symptom seen among many patients with rheumatic diseases, also rheumatoid arthritis. Because saliva is one of the principal defense factors of the mouth, hyposalivation renders the patient liable to oral diseases. Consequently, the patients must drink enough daily and use saliva substitutes when necessary, and, above all, maintain good oral hygiene daily. In rheumatoid arthritis, manual dexterity may be impaired, however, causing cleaning the teeth difficult. Hence, patients with rheumatic diseases like rheumatoid arthritis need counseling and individual oral health care instructions by oral health care professionals for implementation at home. An electric toothbrush should be recommended. Regular oral health examinations by dentists are needed more often than among the healthy.

ПАРАДИГМА ВІЙСЬКОВО-МОРСЬКИХ СИЛ УКРАЇНИ ПІСЛЯ «МОРСЬКИХ ПРИЗІВ» «ЧОРТОВОЇ ДЮЖИНИ»

On the basis of open sources, the article analyzes the activities of the Naval Forces of the Armed Forces of Ukraine at sea from May 18 to September 21, 2022 (the date of the beginning of the Lend-Lease) and establishes the reasons for the decline of the so-called maritime prizes compared to the achievements of other types of the Armed Forces of Ukraine. Positive and negative factors are identified and ways of possible solution of problems are outlined (but not limited). Reference is made to examples of circumvention of the Montreux Convention to build up naval maneuver forces in the Black Sea during World War II. Examples of both foreign policy and internal defense factors are given, which in one way or another affect the tasks of the Naval Forces of the Armed Forces of Ukraine and their achievements according to the open quantitative criteria of the General Staff of the Armed Forces of Ukraine.

Manufacture and Characterization of Good Manufacturing Practice-Compliant SARS-COV-2 Cytotoxic T Lymphocytes.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 virus-specific cytotoxic T-cell lymphocytes (vCTLs) could provide a promising modality in COVID-19 treatment. We aimed to screen, manufacture, and characterize SARS-CoV-2-vCTLs generated from convalescent COVID-19 donors using the CliniMACS Cytokine Capture System (CCS). Donor screening was done by stimulation of convalescent COVID-19 donor peripheral blood mononuclear cells with viral peptides and identification of interferonγ (IFN-γ)+ CD4 and CD8 T cells using flow cytometry. Clinical-grade SARS-CoV-2-vCTLs were manufactured using the CliniMACS CCS. The enriched SARS-CoV-2-vCTLs were characterized by T-cell receptor sequencing, mass cytometry, and transcriptome analysis. Of the convalescent donor blood samples, 93% passed the screening criteria for clinical manufacture. Three validation runs resulted in enriched T cells that were 79% (standard error of the mean 21%) IFN-γ+ T cells. SARS-CoV-2-vCTLs displayed a highly diverse T-cell receptor repertoire with enhancement of both memory CD8 and CD4 T cells, especially in CD8 TEM, CD4 TCM, and CD4 TEMRA cell subsets. SARS-CoV-2-vCTLs were polyfunctional with increased gene expression in T-cell function, interleukin, pathogen defense, and tumor necrosis factor superfamily pathways. Highly functional SARS-CoV-2-vCTLs can be rapidly generated by direct cytokine enrichment (12 hours) from convalescent donors. NCT04896606.

RESULTS OF CYTOLOGICAL STUDY IN EXPERIMENTAL ANIMALS WITH AND WITHOUT TREATMENT OF ULCERATIVE NECROTIC GINGIVITIS WITH A COMPLEX OF DRUGS WITH ANTIOXIDANT PROPERTIES

Changes in the quantitative indicators of non-specific resistance systems of the body indicate a damage to homeostasis in the body and the development of a pathological process. The state of defense systems largely determines the course and provides a predictive characteristic of the intensity and effectiveness of treatment measures. In patients with inflammatory processes of periapical tissues, there is an imbalance of factors that characterize the state of local resistance of the oral cavity and the mucous membrane of the gums. Also, quantitative and qualitative changes in indicators of phagocytosis, chemotaxis of leukocytes, secretion of cytokines, immunoglobulins, and bactericidal activity of humoral factors of the body's defense were observed.
 Laboratory animals with experimental model of ulcerative-necrotic gingivitis by chemical burn were divided into three groups: intact, control, and experimental. Animals of the control group were not treated; in the experimental group, complex of drugs was applied to the ulcer surface, which included Thiotriazoline ointment, Zinc oxide, and 0.05% Chlorhexidine solution. In the selected periods of observation (3rd, 5th, 7th, and 10th days), cytological examination of smears was used to determine the adsorption reaction of microorganisms (ARM) by counting the number of bacteria adsorbed on the surface of each epithelial cell (based on 100 cells).
 At the beginning of the observation, sharp decrease in the number of highly differentiated cells was noted in the smears of animals of the control group, cells of the III stage of differentiation prevailed, and the IDC decreased to 67.52% of the level of intact animals. In all subsequent periods, animals of the control group showed a gradual increase in the IDC index due to an increase in cells in the V stage of differentiation on the surface of the ulcer. The CDI value was significantly different from the norm on the 5th day, with a value of 75.15% of the physiological level, and on the 7th day, with a value of 87.54%. Only on the 10th day was an unreliable difference from the average indicator with 99.13% to its value.
 In the experimental group, on the 3rd day, sharp and reliable decrease in the number of highly differentiated pools of epitheliocytes and the dominance of cells in the III stage of differentiation was observed, the number of which reached the value of 44.0±1.5%. As a result, at this time, the CDI value decreased relative to the indicator of intact animals to 69.85% of its level. At the end of the observation, the CDI value reliably exceeded the level of intact animals by 4.12%.
 The most significant decrease in the value of ARM in animals of the control group was detected on the 3rd day, which in percentage value was 76% of the value of intact animals. On the 5th day, the value of "ARM +" increased slightly (only by 4%) to 80% of the physiological norm, and on the 7th day by another 5.5% to 85.5%. Even at the end of the experiment, the "RAM +" indicator in the animals of the control group was significantly lower than that of the intact animals. It was equal to 90% of it.
 In the experimental group, unlike the control group, satisfactory state of local non-specific resistance in the area of the damaged mucosa was observed only on the 3rd and 5th days. The value of "ARM+" in these terms was only 79.46% and 83.6% of the value of intact animals, respectively. Due to the local effect of the developed complex of drugs, the state of non-specific resistance on the 7th day of observation reached a value corresponding to the "good" level. The "ARM +" percentage value increased to 93.6% of intact animals. At the end of the observation, it reached 97.87% of the physiological norm.
 Therefore, the cytological study's data coincided with the results of a visual examination of the course of healing of local gingivitis of chemical origin. Due to the additional local anti-inflammatory effect of the developed complex of drugs, it became possible to achieve the normalization of the damaged local non-specific reactivity of the oral mucosa faster (on average, for 3-4 days), and the stimulating regenerative effect promotes more rapid differentiation of epitheliocytes and complete restoration of the damaged area of the gums in a shorter time (on average, 2 -3 days) treatment terms.

Povezanost socijalne podrške i otpornosti osoba s invaliditetom sa zadovoljstvom životom i nadom u budućnost

The presented research explored the relationship of social support, the resilience of people with disabilities and the satisfaction with life and hope for the future. The aim of the research was to explore the possibility of predicting the quality of life and hope for the future among people with disabilities on the grounds of sociodemographic data as well as measurements of resilience and social support on 230 participants. The research was conducted via online survey form, consisting of a questionnaire exploring demographic characteristics, Brief scale of resilience, Scale of satisfaction with life, Scale of hope for the future and Scale of social support. The findings of this research imply several possible defence factors for satisfaction with life and hope for the future of people with disabilities and the role of all of us is to encourage and improve social support for people with disabilities.

Receiver Operator Characteristic (ROC) Analysis of Lipids, Proteins, DNA Oxidative Damage, and Antioxidant Defense in Plasma and Erythrocytes of Young Reproductive-Age Men with Early Stages of Type 1 Diabetes Mellitus (T1DM) Nephropathy in the Irkutsk Region, Russia.

Oxidative stress plays a leading role in the pathogenesis of diabetic nephropathy. However, many aspects of oxidative stress reactions in the initial stages of this disease are not fully understood. The men cohort is of particular interest because of the severe effects of diabetes on their urogenital system. The aim of this study is to assess the intensity of lipids, proteins, DNA oxidative damage, blood antioxidant defense enzymatic, and activity of non-enzymatic components in men with type 1 diabetes mellitus (T1DM) in the early stages of diabetic nephropathy using receiver operator characteristic (ROC) analysis. This study included eighty-nine reproductive-age men in the initial stages of diabetic nephropathy (DN) and thirty-nine age- and sex-matched individuals not suffering from glycemic disorders. The DN patients were divided into two subgroups: stage 1 patients (urinary albumin < 30 mg/day and albumin/creatinine ratio < 3 mg/mmol (n = 45)) and stage 2 patients (urinary albumin 30−300 mg/day and albumin/creatinine ratio 3−30 mg/mmol (n = 44)). Levels of oxidative damage products (conjugated dienes (CDs), thiobarbituric acid reactants (TBARs), methylglyoxal (MGO), and 8-hydroxy-2’-deoxyguanosine (8-OHdG)) and antioxidants (glutathione peroxidase (GPx), glutathione S-transferases π (GSTp), glutathione reductase (GR), copper and zinc-containing superoxide dismutase 1 (SOD-1), total antioxidant status (TAS), α-tocopherol, retinol, reduced glutathione (GSH), and oxidative glutathione (GSSG)) were estimated in plasma and erythrocytes. Oxidative damage to cellular structures (higher values of median CDs (1.68 µmol/L; p = 0.003), MGO (3.38 mg/L; p < 0.001) in the stage 1 group and CDs (2.28 µmol/L; p < 0.0001), MGO (3.52 mg/L; p < 0.001), 8-OHdG (19.44 ng/mL; p = 0.010) in the stage 2 group) and changes in the antioxidant defense system (lower values of TAS (1.14 units; p = 0.011), α-tocopherol (12.17 µmol/L; p = 0.009), GPx (1099 units; p = 0.0003) and elevated levels of retinol (1.35 µmol/L; p < 0.001) in the group with stage 1; lower values of α-tocopherol (12.65 µmol/L; p = 0.033), GPx (1029.7 units; p = 0.0001) and increased levels of GR (292.75 units; p < 0.001), GSH (2.54 mmol/L; p = 0.010), GSSG (2.31 mmol/L; p < 0.0001), and retinol (0.81 µmol/L; p = 0.005) in the stage 2 group) were identified. The ROC analysis established that the following indicators have the highest diagnostic significance for stage 1 diabetic nephropathy: CDs (AUC 0.755; p < 0.0001), TBARs (AUC 0.748; p = 0.0001), MGO (AUC 0.720; p = 0.0033), retinol (AUC 0.932; p < 0.0001), GPx (AUC 0.741; p = 0.0004), α-tocopherol (AUC 0.683; p = 0.0071), and TAS (AUC 0.686; p = 0.0052) and the following for stage 2 diabetic nephropathy: CDs (AUC 0.714; p = 0.001), TBARs (AUC 0.708; p = 0.001), 8-OHdG (AUC 0.658; p = 0.0232), GSSG (AUC 0.714; p = 0.001), and GSH (AUC 0.667; p = 0.0108). We conclude that changes in indicators of damage to lipids, proteins, DNA, and the insufficiency of antioxidant defense factors already manifest in the first stage of diabetic nephropathy in men with T1DM. The ROC established which parameters have the greatest diagnostic significance for stages 1 and 2 of diabetic nephropathy, which may be utilized as additional criteria for defining men with T1DM as being in the risk group for the development of initial manifestations of the disease and thus allow for substantiating appropriate approaches to optimize preventive measures.

Evaluation of osmoregulation and morpho-physiological responses of Borago officinalis under drought and salinity stress with equal osmotic potential

As the global demand for medicinal plants increases and the forthcoming climate change reveals itself, understanding the morpho-physiological behaviors of borage plants under salinity and drought stress can be significant. However, accurate comparison of these behaviors at different salinity and drought stress conditions requires a new approach to equalization at stress levels. This experiment was conducted in a greenhouse to identify the borage response to salinity (NaCl) and drought (PEG) stress conditions with equal osmotic potential (−0.371 and −0.742 MPa) with a post-stress recovery period. In general, both types of stress conditions caused plant damage, antioxidant defense, and increased osmolyte levels; however, the negative effect of drought stress on the growth and development of this plant was more than that of salinity stress. Borage had an acceptable capability to absorb and accumulate sodium in its leaves and considerably controlled the toxic effect of these ions on membrane destruction (malondialdehyde level) and potassium homeostasis and used the benefits of these ions for osmoregulation. In drought stress, the cause of significant damage to plant growth can be attributed to allocating a significant portion of plant energy to the synthesis of defense factors and osmo-protectants like proline. This damage delayed the reproductive growth and flowering of this plant and impaired the plant growth. The results of osmotic stress and the measurement of the growth potential of the plant in the recovery phase indicated that borage plant had better growth potential in salinity stress compared to dry stress by controlling the negative effect of salt ions, accumulating these ions in its organs, and allocating lower energy to osmoregulation.

Comparative Analysis of Immunological and Hematological Indices of Patients with Septic Arthritis after Intra-Articular Injection of Glycocorticoids

Summary. Subject of the research: immune status of 26 patients (main group) with septic complications after local application of glycocorticoids and 17 patients (comparative group) with septic arthritis, in which the purulent inflammatory process developed due to hematogenous spread of infection of the joint and was not a complication caused by local use of glycocorticoids.&#x0D; Objective: to evaluate the immune status of patients of the main and comparative groups, to study the dynamics of immunological indicators before and after surgical treatment, and to determine factors which are important to predict the disease course and treatment results.&#x0D; Research methods: an analysis of immunological (content of lymphocytes and their subpopulations – CD3+-, CD4+-, CD8+-cells; А, М and G classes of immunoglobulins; levels of circulating immune complexes) and hematological (levels of erythrocytes, leucocytes, thrombocytes, hemoglobin, as well as erythrocyte sedimentation rate) laboratory data of both groups was conducted.&#x0D; Results. Disorders concerning cellular and humoral factors of immune defense as well as hematological indices were revealed. It is shown that the improvement of immune status after clearing surgical intervention and the reduction of inflammatory response in patients of the main group is slower than in the comparative group.&#x0D; Conclusions. Assumption was made that glycocorticoids may be a factor that deepens and prolongs the immunosuppression that patients had before their local use.

Review of the unique and dominant lectin pathway of complement activation in agnathans

As the most primitive vertebrates, lampreys are significant in understanding the early origin and evolution of the vertebrate innate and adaptive immune systems. The complement system is a biological response system with complex and precise regulatory mechanisms and plays an important role in innate and adaptive immunity. It consists of more than 30 distinct components, including intrinsic components, regulatory factors, and complement receptors. Complement system is the humoral backbone of the innate immune defense and complement-like factors have also been found in cyclostomes. Our knowledge as such in lamprey has dramatically increased in the recent years. The searching for complement components in the reissner lamprey Lethenteron reissneri genome database, together with published data, has unveiled the existence of all the orthologues of mammalian complement components identified thus far, including the complement regulatory proteins and complement receptors, in lamprey. This review, summarizes the key themes and recent updates on the complement system of agnathans and discusses the individual complement components of lampreys, and critically compare their functions to that of mammalian complement components. Interestingly, the adaptive immune system of agnathans differs from that of gnathostomes. Lamprey complement components also display some distinctive features, such as lampreys are characterized by the variable lymphocyte receptors (VLRs)-based alternative adaptive immunity. This review may serve as important literature for deducing the evolution of the immune system from invertebrates to vertebrates.

PENGARUH INHALASI MINYAK KAYU PUTIH (Melaleuca leucadendron) TERHADAP GAMBARAN HISTOLOGI LAMBUNG MENCIT JANTAN (Mus musculus) YANG DIINDUKSI STRES AKUT

Damage on gastric mucosa is caused by an imbalance of defensive factors and aggressive factors. This can be due to various factors, one of which is stress. Cajuput oil as aromatherapy is proven to prevent stress because it contains 1,8 cineole, α-terpineol, and 4-terpineol which have a sedative-hypnotic effect. This study aims to determine the effect of inhalation of cajuput oil on the gastric histology of mice. This research is a true experimental with a post test only control group design. The research subjects were 16 adult male mice taken by simple random sampling and divided into normal group (KN), negative control group (K-), positive control group (K+), and cajuput oil inhalation group (P). Groups K+, K-, and P were given stress treatment with the Tail Suspension Test (TST) method for six minutes for 14 day. Surgery was perfomed on the 15th day and histology preparations were made. The average score of gastric mucosal damage in cajuput oil group was lower when compared to the stress group although the results of the Tukey test showed no significant results between these two group. It can be concluded that cajuput oil with an inhalation dose 0.5 mL has anti-stress effect that prevent gastric mucosal damage in mice which acute stress induced.

Integrated Transcriptome and Metabolome Analysis to Identify Sugarcane Gene Defense against Fall Armyworm (Spodoptera frugiperda) Herbivory.

Sugarcane is the most important sugar crop, contributing ≥80% to total sugar production around the world. Spodoptera frugiperda is one of the main pests of sugarcane, potentially causing severe yield and sugar loss. The identification of key defense factors against S. frugiperda herbivory can provide targets for improving sugarcane resistance to insect pests by molecular breeding. In this work, we used one of the main sugarcane pests, S. frugiperda, as the tested insect to attack sugarcane. Integrated transcriptome and metabolomic analyses were performed to explore the changes in gene expression and metabolic processes that occurred in sugarcane leaf after continuous herbivory by S. frugiperda larvae for 72 h. The transcriptome analysis demonstrated that sugarcane pest herbivory enhanced several herbivory-induced responses, including carbohydrate metabolism, secondary metabolites and amino acid metabolism, plant hormone signaling transduction, pathogen responses, and transcription factors. Further metabolome analysis verified the inducement of specific metabolites of amino acids and secondary metabolites by insect herbivory. Finally, association analysis of the transcriptome and metabolome by the Pearson correlation coefficient method brought into focus the target defense genes against insect herbivory in sugarcane. These genes include amidase and lipoxygenase in amino acid metabolism, peroxidase in phenylpropanoid biosynthesis, and pathogenesis-related protein 1 in plant hormone signal transduction. A putative regulatory model was proposed to illustrate the sugarcane defense mechanism against insect attack. This work will accelerate the dissection of the mechanism underlying insect herbivory in sugarcane and provide targets for improving sugarcane variety resistance to insect herbivory by molecular breeding.

Transcriptome Analysis of Human Glioblastoma Cells Susceptible to Infection with the Leningrad-16 Vaccine Strain of Measles Virus.

Glioblastoma multiforme (GBM) accounts for almost half of all primary malignant brain tumors in adults and has a poor prognosis. Here we demonstrated the oncolytic potential of the L-16 vaccine strain of measles virus (MV) against primary human GBM cells and characterized the genetic patterns that determine the sensitivity of primary human GBM cells to oncolytic therapy. MV replicated in all GBM cells, and seven out of eight cell lines underwent complete or partial oncolysis. RNA-Seq analysis identified about 1200 differentially expressed genes (FDR < 0.05) with at least two-fold expression level change between MV-infected and uninfected cells. Among them, the most significant upregulation was observed for interferon response, apoptosis and cytokine signaling. One out of eight GBM cell lines was defective in type I interferon production and, thus, in the post-interferon response, other cells lacked expression of different cellular defense factors. Thus, none of the cell lines displayed induction of the total gene set necessary for effective inhibition of MV replication. In the resistant cells, we detected aberrant expression of metalloproteinase genes, particularly MMP3. Thus, such genes could be considered intriguing candidates for further study of factors responsible for cell sensitivity and resistance to L-16 MV infection.

Evaluation of mechanism(s) of action underlying the antioxidant and antiulcer activity of Sesamum indicum leaves extract in experimental rats.

The current study aimed to estimate phytochemical screening, in vitro antioxidant activity, and gastroprotective activity of Sesamum indicum Linn ethanolic extract. The current study was held out by ulceration induced by pylorus ligation and indomethacin-induced ulcer screening models in Wister albino rats. The screening of antiulcer activity of ethanolic extract of S. indicum leaves (EESIL) at the different amounts (100, 200, and 400 mg/kg; per orally for 7 days) was compared with omeprazole as a usual antiulcer drug. Additional parameters such as gastric content, pH, total acidity, pepsin activity ulcer score, free acidity, ulcer index (UI), % inhibition of ulcers, mean mucin, pepsin content, and total protein content were observed. In the pylorus ligation model, the pepsin activity free acidity, pepsin content, UI, total acidity, ulcer score, total protein content, and percentage ulcer inhibition were considerably decreased (P < 0.05 and P < 0.01), and mean mucin and gastric content pH extensively elevated (P < 0.05 and P < 0.01) in EESIL tested groups in the comparison of the control group. Doses (100, 200, and 400 mg/kg p.o.) of EESIL showed dose-reliant gastro protective outcomes, a considerable (P < 0.05 and P < 0.01) decrease in gastric parameters as UI and ulcer score and induction in gastric pH and percentage inhibition of ulcer compared with the control group. Antioxidant, anti-Ulcer, EESIL, and EESIL show antioxidant activity at different concentration. The fallout of the study indicated that the EESIL had improved antiulcer potential due to the decrease in offensive factors and increase in defensive factors.

Kerjasama Internasional Korea Selatan Dengan Indonesia (Studi Kasus Peningkatan Status Kerjasama Dari Strategic Partnership Menjadi Special Strategic Partnership Tahun 2017)

This research analyzes the bilateral cooperation relationship between Indonesia and South Korea regarding the increase in the status of cooperation from Strategic Partnership to Special Strategic Partnership. In this case, the focus of research is on the factors that made Indonesia agree to increase the status of cooperation to become a Special Strategic Partnership with South Korea. In addition to the existence of a free and active policy which is the basis of Indonesia's foreign policy, which makes Indonesia free to make friends and establish cooperation with any country, there is also a foreign policy. During the reign of President Joko Widodo, that accelerated infrastructure development, which of course required investment from other countries, and South Korea became one of the countries that invested in Indonesia. By conducting qualitative research, namely by reviewing the literature, and by using the concept of international cooperation, this thesis finds the factors that made Indonesia agree to increase the status of cooperation with South Korea to become a Special Strategic Partnership, namely, economic factors, defense and security factors, and social culture factors.

Trim69 is a microtubule regulator that acts as a pantropic viral inhibitor

Through a screen that combines functional and evolutionary analyses, we identified tripartite motif protein (Trim69), a poorly studied member of the Trim family, as a negative regulator of HIV-1 infection in interferon (IFN)-stimulated myeloid cells. Trim69 inhibits the early phases of infection of HIV-1, but also of HIV-2 and SIVMAC in addition to the negative and positive-strand RNA viruses vesicular stomatitis virus and severe acute respiratory syndrome coronavirus 2, with magnitudes that depend on the combination between cell type and virus. Mechanistically, Trim69 associates directly to microtubules and its antiviral activity is linked to its ability to promote the accumulation of stable microtubules, a program that we uncover to be an integral part of antiviral IFN-I responses in myeloid cells. Overall, our study identifies Trim69 as the antiviral innate defense factor that regulates the properties of microtubules to limit viral spread and highlights the cytoskeleton as an unappreciated battleground in the host-pathogen interactions that underlie viral infections.

Defects in the expression of colonic host defense factors associate with barrier dysfunction induced by a high-fat/high-cholesterol diet.

The effect of Western diets in the gastrointestinal system is largely mediated by their ability to promote alterations in the immunity and physiology of the intestinal epithelium, and to affect the composition of the commensal microbiota. To investigate the response of the colonic epithelium to high-fat/high-cholesterol diets (HFHCDs), we evaluated the synthesis of host defense factors involved in the maintenance of the colonic homeostasis. C57BL/6 mice were fed an HFHCD for 3 weeks and their colons were evaluated for histopathology, gene expression, and microbiota composition. In addition, intestinal permeability and susceptibility to Citrobacter rodentium were also studied. HFHCD caused colonic hyperplasia, loss of goblet cells, thinning of the mucus layer, moderate changes in the composition of the intestinal microbiota, and an increase in intestinal permeability. Gene expression analyses revealed significant drops in the transcript levels of Muc1, Muc2, Agr2, Atoh1, Spdef, Ang4, Camp, Tff3, Dmbt1, Fcgbp, Saa3, and Retnlb. The goblet cell granules of HFHCD-fed mice were devoid of Relmβ and Tff3, indicating defective production of those two factors critical for intestinal epithelial defense and homeostasis. In correspondence with these defects, colonic bacteria were in close contact with, and invading the epithelium. Fecal shedding of C. rodentium showed an increased bacterial burden in HFHCD-fed animals accompanied by increased epithelial damage. Collectively, our results show that HFHCD perturbs the synthesis of colonic host defense factors, which associate with alterations in the commensal microbiota, the integrity of the intestinal barrier, and the host's susceptibility to enteric infections.

Elucidation and Application of Novel Action of Therapeutic Agents for Diabetic Neuropathy

Epalrestat is the only aldose reductase inhibitor that is currently available for diabetic peripheral neuropathy. Oxidative stress impairs endothelial cells, thereby leading to numerous pathological conditions. Increasing antioxidative ability is important to prevent cellular toxicity induced by reactive oxygen species. Epalrestat increases antioxidant defense factors such as glutathione and γ-glutamylcysteine ligase in vascular endothelial cells through activation of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). This increases suppression of oxidative stress-induced cellular toxicity. Cadmium is an industrial and environmental pollutant that targets the vascular endothelium. The vascular system is critically affected by cadmium toxicity. Therapeutic treatment against cadmium toxicity is chelation therapy that promotes metal excretion; however, cadmium chelators can cause renal toxicity. Therefore, safe and efficient therapeutic agents are required. Epalrestat suppresses cadmium-induced cytotoxicity in vascular endothelial cells through activation of Nrf2. In addition, epalrestat affects the intracellular levels of cadmium, cadmium transporter Zrt-Irt-like protein 8 (ZIP8), and metallothionein (MT). The upregulation of ZIP8 and MT may be involved in the suppression of cadmium-induced cytotoxicity by epalrestat. Drug repurposing is a new strategy for drug discovery in which the pharmacological action of existing medicines whose safety and pharmacokinetics have already been confirmed clinically and whose use has been approved is examined comprehensively at the molecular level. The results can be applied to the development of existing drugs for use as medicines for the treatment of other diseases. This review provides useful findings for future expansion of indications as research leading to drug repurposing of epalrestat.

S1834 Spontaneous Bacterial Peritonitis in a Postpartum Female Secondary to Necrotizing Pancreatitis

Introduction: SBP is an infection of the fluid that accumulates in the abdomen caused by translocation of bacteria without an obvious source, such as bowel perforation. Typically, this translocation represents a failure in defensive factors to contain pathogens to the bowel and can lead to seeding other extra-intestinal sites. Our patient is unique in that her SBP was characterized in the setting of a recent pregnancy. Her course was complicated by pre-eclampsia resulting in emergent c-section, further complicated by hypertriglyceridemia-induced pancreatitis. After significant intervention, necrotizing pancreatitis leading to retroperitoneal fat saponification and abscess formation was the likely etiology for SBP. Case Description/Methods: A 27-year-old female presented with diffuse abdominal pain, nausea, vomiting, and diarrhea. Past medical history is significant for recent emergency c-section due to pre-eclampsia complicated by hypertriglyceridemia-induced pancreatitis. On admission, she was hypotensive, tachycardic, tachypneic and febrile, with significant bilious emesis. CT revealed large volume ascites, peri-pancreatic fluid, small volume fluid and gas within the endometrial cavity. Peritoneal fluid analysis presented an SBP picture. Abdominal drains were placed to mitigate peritoneal fluid collection, which settled in the retro-peritoneal space. Cultures resulted in pan-sensitive E.coli growth and the patient was started on appropriate therapy. However, the patient continued to have persistent fevers and severe abdominal pain while on medical management. At this point, exploratory abdominal surgery was indicated revealing significant amounts of retroperitoneal saponified fat secondary to necrotizing pancreatitis, and extensive communicating abscesses which were subsequently drained. Discussion: SBP is an infection of fluid that accumulates within the abdomen, typically seen in patient's with chronic liver disease and can be managed with medical therapy. In our patient's case, there was no know history of liver disease. Our patient presented febrile, with diffuse abdominal pain. Imaging revealed significant ascites and cultures resulted in pan-sensitive E.coli. Multiple differentials were assessed including recurrent pancreatitis, C.difficile infection leading to bowel perforation and/or protein-losing enteropathy, endometritis given recent c-section amongst others. After surgical assessment, our likely diagnosis was necrotizing pancreatitis seeding pancreatic enzymes into the retroperitoneal cavity.

Spiritual Well-Being, Depression, Anxiety, and Stress in Indonesian Muslim Communities During COVID-19.

PurposeThis study investigated how spirituality as a defensive factor of psychological well-being reduces anxiety among Indonesian Muslims during the pandemic COVID-19.Patients and MethodsData were collected from 538 Indonesian Muslims through a survey using the spiritual well-being and depression, anxiety and stress (DAS-21) and examined using structural equation model (SEM) analysis.ResultsThe empirical results indicate that spirituality is a factor that increases happiness, psychological well-being and mental health among Indonesian Muslims.ConclusionThe study also concluded that spirituality positively and significantly reduces anxiety, depression, and stress. This finding confirms that the spiritual beliefs of Indonesian Muslims can play a significant role in improving mental health during pandemic. This study can control mental illness based on spirituality theory and practice.