Analysis of natural resistance-associated macrophage protein-1 (NRAMP-1) level based on death, comorbidities and severity of COVID-19 patients: a cross-sectional study.

An accurate diagnosis of COVID-19 is essential for pandemic control and for establishing adequate therapeutic strategies to reduce morbidity and mortality. COVID-19 infection replicates in macrophage cells and affects the immune system. Natural resistance-associated macrophage protein-1 (NRAMP-1) carries cation ions, such as Fe2+, Zn2+ and Mn2+, and plays an essential role in the immune system to infection with micro-organisms. In addition, the function of NRAMP-1 is to limit the replication of pathogens by changing the phagosomal environment. Levels of NRAMP-1 protein are based on death, comorbidities and clinical symptoms of COVID-19 patients and it is possible for the soluble protein NRAMP-1 level to be used as an additional biomarker for forensic and medicolegal related COVID-19 cases and prosecutions from patients and families. Methods: Determination of NRAMP-1 protein levels using the enzyme link-immunosorbent assay technique in death, had comorbidities and severity of clinical symptoms of COVID-19 patients. Results: Of the 62 patients who received treatment, 10 patients died with an average NRAMP-1 level of 650 ng/ml and 52 patients who survive with an average NRAMP-1 level of 1065.26 ng/ml. The results of the study also found that 34 patients had comorbidities with an average NRAMP-1 level of 838.82 ng/ml and 28 patients without comorbidities with an average NRAMP-1 level of 1191.92 ng/ml. Based on the severity of clinical symptoms in survive patients, 10 patients with mild were found with an average NRAMP-1 level of 984.31 ng/ml, with moderate in 31 patients with an average NRAMP-1 level of 1104.71 ng/ml and severe in 11 patients with an average NRAMP-1 level of 1027.71 ng/ml. Conclusions: NRAMP-1 protein levels were significantly lower in COVID-19 patients who died and had comorbidities.

The Role of Claudin-1 Expression in Follicular and Papillary Thyroid Neoplasm.

OBJECTIVE: This study evaluated differences in Claudin-1 expression between follicular adenoma (FA), follicular thyroid carcinoma (FTC), follicular variant papillary thyroid carcinoma (FV-PTC), and papillary thyroid carcinoma (PTC). MATERIAL AND METHODS: This study used a cross-sectional approach. Immunostaining using the polyclonal antibody Claudin-1 was performed on 75 samples divided into 20 samples for follicular adenoma, follicular thyroid carcinoma, papillary carcinoma, and 15 samples of follicular variant thyroid carcinoma, respectively. RESULTS: Claudin-1 expression is detected on the cytoplasmic membrane of tumor cells and appears to be varied among thyroid neoplasms. The claudin-1 expression score revealed a statistically significant difference between FA against FV-PTC, FA versus (vs) PTC, and FTC vs PTC, with median values of 4 vs 6 (p = 0.016), 4 vs 8 (p = 0.001), and 5 vs 8 (p = 0.002), respectively. However, there was no statistically significant difference in scores between the FA and the FTC (4 vs 5), or between the FTC and the FV-PTC groups (5 vs 6 (p=1,000). CONCLUSION: These results suggest that Claudin-1 may be capable of discriminating follicular adenoma from classic and follicular variant of papillary thyroid carcinoma. It can also differentiate follicular thyroid carcinoma and papillary thyroid carcinoma, especially for cases challenging to assess by hematoxylin and eosin staining. It still holds promise in providing targeted cancer therapy.

Expression of CD133 Cancer Stem Cell Marker in IDH-Mutant and IDH-wildtype (Isocitrate Dehydrogenase) Astrocytoma.

OBJECTIVE: This study evaluated the differences between IDH1-R132H and CD133 expression in different categories of  astrocytoma. MATERIAL AND METHODS: This study used a cross-sectional design.  Sixty-seven paraffin embedded block of Diffuse Astrocytoma (DA), Anaplastic Astrocytoma (AA) and Glioblastoma (GB) were assessed using using the monoclonal antibody IDH1-R132H and Rabbit polyclonal antibody CD133. RESULTS: It was found that there was a significant relationship between the expression of IDH1-R132H and CD133 in DA, AA and GB (p<0.001). Astrocytoma with IDH-mutant molecular status will express more markers of cancer stem cell CD133 than IDH-wildtype. CONCLUSION: The IDH1-R132H and CD133 can provide predictive value on treatment success, disease prognosis, recurrence and can be considered as target combination therapy with chemotherapy.

The role of MLC901 in reducing VEGF as a vascular permeability marker in rats with spinal cord injury.

Background: Damaged neural tissue caused by SCI could induce vascular endothelial growth factor (VEGF) that can worsen the condition in the late phase by increasing vascular permeability, thus inducing tissue oedema, which can worsen the infarction. MLC 901 has been widely used in Asia for stroke patients because its mechanism is known to down-regulate VEGF levels in ischemic tissue. Methods: Ten Sprague-Dawley rats were used in this experiment. To create a severe spinal cord injury in animal models. The animals were then randomly divided into two groups. MLC 901 was given to the first group, which was the intervention group, and placebo to the second group, which was the control group. Results: This study showed a decrease in the mean VEGF mRNA expression in the group given MLC 901 compared to the control group, which had a very high mean VEGF mRNA expression starting after 1 h of administration of MLC 901 until day 14 after spinal cord injury. In addition, there was a decrease in VEGF levels in the MLC 901 group compared to the control group from 3 h after spinal cord injury (1 h after MLC 901 administration) to 14 days after spinal cord injury. Conclusion: It can be concluded that administration of MLC 901 can reduce vascular permeability, one of the mechanisms that is thought to occur is to reduce VEGF levels. MLC 901 also maintains the neuroprotective effect provided by VEGF by maintaining this level above the basal level until day 14.

Doxorubicin induced immune abnormalities and inflammatory responses via HMGB1, HIF1-α and VEGF pathway in progressive of cardiovascular damage.

Background: Doxorubicin (DOX) is a commonly used treatment for cancer and the mechanism of DOX-induced cardiomyocyte damage in cardiovascular disease is not fully understood. High-mobility group box 1 (HMGB1), strong induce proinflammatory cytokines via damage associated molecular pattern (DAMP) which its interaction with the receptor of advanced glycation end products (RAGE), that affect cytokine release, and angiogenesis via the role of HMBG1, HIF-1α and VEGF as an important regulator in these cardiac failure processes. Hypoxia-inducible factor-1α (HIF-1α) is plays an important role in the cellular response to systemic oxygen levels of cells and VEGF is an angiogenic factor and can stimulate cellular responses on the surface of endothelial cells will be described. Objective: The aim of this article is to comprehensively review the role of HMGB1, HIF-1α, and VEGF in DOX-induced Cardiovascular Disease and its molecular mechanisms. Methods: The data in this study were collect by search the keyword combinations of medical subject headings (MeSH) of "HMGB1", "HIF-1 α", "VEGF", "DOX" and "Cardiovascular disease" and relevant reference lists were manually searched in PubMed, EMBASE and Scopus database. All relevant articles in data base above were included and narratively discussed in this review article. Results: Several articles were revealed that molecular mechanisms of the DOX in cardiomyocyte damage and related to HMGB1, HIF-1α and VEGF and may potential treatment and prevention to cardiovascular disease in DOX intervention. Conclusion: HMGB1, HIF-1α and VEGF has a pivotal regulator in DOX-induce cardiomyocyte damage and predominantly acts through different pathways. The role of HMGB1 in DOX-induced myocardial damage suggests that HMGB1 is a mediator of DOX-induced damage. In addition, DOX can inhibit HIF-1α activity where DOX can decrease HIF-1α expression and HIF-1α is also responsible for upregulation of several angiogenic factors, including VEGF. VEGF plays an important role in angiogenesis and anti-angiogenesis both in vitro and in vivo and reduces the side effects of DOX markedly. In addition, the administration of anti-angiogenesis will show an inhibitory effect on angiogenesis mediated by the VEGF signaling pathway and triggered by DOX in cells.

Systemic lidocaine administration influences NF-kß gene expression, NF-kß and TNF- α protein levels on BALB/c mice with musculoskeletal injury.

BACKGROUND: The immune system can produce various inflammatory mediators to protect the body from stress and surgical trauma. However, this excessive inflammatory response will interfere with the body's immune system, causing systemic inflammatory response syndrome and multi-organ failure if allowed to continue. Lidocaine as an anti-inflammatory is used to treat surgical pain and pain arising from the disease process and treat ventricular arrhythmias. This study aims to prove the efficacy of systemic lidocaine injection as an anti-inflammatory drug in BALB/c mice with sterile musculoskeletal injuries. METHODS: This study used a prospective experimental laboratory study on experimental animals of BALB/c mice using a simple randomized design. Sixteen adult white BALB/c mice (male, healthy, 10-12 weeks old, 35-40 g body weight, and no disability) were selected and randomly divided into two groups: the group given lidocaine (2 mg/kg body weight) and a group that was given sterile distilled water. NF-kß and TNF-α protein levels were detected by ELISA, while mRNA expression of NF-kß was analyzed and determined by quantitative real-time PCR. RESULTS: Musculoskeletal injury significantly increased the expression of both mRNA and protein levels of NF-kß and TNF-α protein level. In addition, the NF-kß (protein and mRNA) and TNF-α (protein) levels in rats experiencing inflammation due to musculoskeletal injury were significantly decreased in the lidocaine group (p < 0.001). CONCLUSIONS: The administration of systemic lidocaine injection was able to inhibit the expression of mRNA NF-kß, the protein levels of NF-kß, and protein levels of TNF-α in mice with musculoskeletal injuries.

Progesterone Receptor Expression and Score Differences in Determining Grade and Subtype of Meningioma.

Background Meningioma is the most common brain tumor in which therapy and monitoring depend on the histopathological grade (World Health Organization [WHO] Grade). Progesterone receptor (PR) expression was reported positive in meningothelial cells and meningiomas with various degrees of positivity. We evaluated PR expression to determine its correlation with WHO Grade and each subtype of meningioma. Materials and Methods This study used 70 samples of paraffin block that were diagnosed as meningioma and classified into WHO Grade I, II, and III. The paraffin blocks were sectioned in 5 µm thickness and immunohistochemically stained with the anti-PR antibody. Results PR expression was found positive in WHO Grade I and II groups, but negative in WHO Grade III group with the score of +2 found in clear cell and atypical subtype. These results were statistically significant with p -value < 0.05. Conclusion PR can be used as an additional marker to determine WHO Grade and subtype of meningioma.

Modification of the Marmarou model in developing countries.

INTRODUCTION: Head injury is an injury or wound of the brain tissue due to external forces; it can cause a decrease or change in the status of consciousness. Many head injury models have used mice as experimental animals; the Marmarou model is the most famous and the most widely-used diffuse brain injury model. In this study, we slightly modified the Marmarou model. The purpose of this study is to help researchers examining head injuries in mice, especially those in developing countries who have limited facilities and infrastructure. METHODS: This experimental research uses animals models (Rattus novergicus, strain Sprague Dawley) that fit several criteria, including male, aged 10-12 weeks, and body weight of 200-300 g. This study involves a slight modification on the tube used, with a 20 cm-long weight of 20 g. The blood samples for the following assays of ELISA and brain tissue samples were collected at 24 h and 4, 5, 6, and 7 days post-trauma. RESULTS: A significant effect on the brain was seen with the Marmarou model modification, at a mass weight of 20 g and height of 20 cm, with 0.04 J energy produced. Changes were also seen in the histological features of brain tissue and the serum levels of AQP-4, F2 IsoPs, MPO, and VEGF from 24 h until 7 days after trauma. CONCLUSION: This report describes the development of an experimental head injury approach modifying the Marmarou model that is able to produce a diffuse brain injury model in mice.

Impact of the Use of Ethanolic Extract of Propolis, Flavonoid and Non-Flavonoid Propolis for Direct Pulp Capping in Collagen Type I Density

Aim: To analysis collagen type I density on inflamed rat dental pulp after capping with propolis. Methods: Flavonoid and non-flavonoid substances were purified from propolis. Eighty male rats were divided into five groups, each group consisting of 16 rats. As a negative control (group I), rats were not conducted any treatment. A class I cavity was prepared on the occlusal surface of right maxillary first molar. Dental pulp was exposed and allowed in oral environment for 60 minutes, then dental pulp capping with ethanolic extract of propolis (group II), flavonoid propolis (group III), non-flavonoid propolis (group IV), or calcium hydroxide as positive control (group V). Rats were sacrificed at 6 hours, 2, 4 or 7 days, biopsy samples were obtained, stained and viewed by light microscope. Data was statistically analysis using Friedman and Kruskal-Wallis tests. Results: Except in group I, collagen type I density was increased in group II, III, and V with the longer of observation time periods. However, in group IV, collagen type I density increased only on day 7. No statistically significant differences of collagen type I density among the groups for each time period were found. Conclusions: Propolis and flavonoid propolis may increase collagen density on inflamed rat dental pulp (AU).

The neuropathological foundations for the restorative neurology of spinal cord injury.

An appreciation of the neuropathology of human spinal cord injury (SCI) is a basic requirement for all concerned with the medical treatment of patients with SCI as well as for the many neuroscientists devoted to finding a "cure". An understanding of the neuropathology of SCI is a necessary guide to those concerned at all levels of treatment, whether they are doctors or other health professionals. The underlying changes in the spinal cord are especially relevant to the restorative neurology (RN) of SCI. The new discipline of RN seeks to enhance the function of residual spinal cord elements which have survived the injury and so improve the patient's rehabilitative status. This is in contrast to the conventional approach in rehabilitation which works around the clinical neurological deficiencies. Following the injury a series of changes take place in the spinal cord and surrounding tissues which continue to evolve throughout the life of the patient. In flexion and extension injuries resulting from motor vehicle trauma, diving and sporting accidents the spinal cord is compressed and disrupted but usually with some continuity remaining in the white matter columns. The brunt of the injury is usually centrally placed where there is bleeding into the disrupted grey matter involving one two segments, usually cervical. The loss of central grey matter is nowhere near as important as is the tearing apart of the white matter tracts in determining the patient's clinical state. The central grey matter supplies one two overlapping segmental myotomes and sensory fields. In contrast loss of continuity in the long white matter tracts is catastrophic because all functions below the level of injury are affected, autonomic or voluntary either by paralysis or anaesthesia, usually both. It is important to determine the exact nature of the injury in every patient as a preliminary to treatment by RN. This assessment is both clinical and neurophysiological with special attention given to any part of the long white matter tracts which may have escaped the initial injury. It is these residual nerve fibres which provide the opportunity to improve the patient's neurological state by being re-activated, modulated and enhanced by stimulation or by other RN methods. The conversion of a clinically complete SCI patient to being incomplete and ambulant is a tremendous improvement in the patient's status. It is the purpose of this article to provide the reader with the essential neuropathology of SCI as a beginning point in planning treatment whether it is medical or ancillary, as well as to inform the neuroscientist about the condition being addressed in his or her research.