Morphological and histological kidney structure in diabetic rats model treated with ethanol extracts of jengkol fruit peel (Archidendron pauciflorum)

In a long term, diabetes mellitus (DM) leads to nephropathy due to glomerular hyperfiltration. One of the plant used as a diabetic drug by the community in Karangwangi Village, Cianjur Regency, West Java is the fruit peel of jengkol. Therefore, this study aims to determine the effect of the ethanolic extract of Jengkol fruit peel (EEJFP) toward the morphological and histological structure on the kidney of the diabetic rat model. The method adopted was the Randomized Design (CRD) with 6 treatments namely NC (Carboxyl Methyl Cellulose (CMC) 0.5%), PC (CMC 0.5%), Pb (Glibenclamide 5 mg/kg BW), P1, P2, and P3 (EEJFP 385; 770; and 1,540 mg/kg BW) with 4 replications for 14 consecutive days. Furthermore, the induction of diabetes with streptozotocin dose of 60 mg/Kg BW was performed intravenously in experimental animals except for the NC group. The parameters observed include relative weight, morphological, and histological structure of kidney which include glomerular diameter, Bowman space distance, and percentage of proximal tubular cell necrosis. The non-parametric and parametric data were tested by Kruskal Wallis and ANOVA test as well as Duncan's follow-up test, respectively. The results showed that there was no significant difference in the morphological structure of the kidney between treatment groups. Furthermore, the relative weights of kidney in the PC, Pb, P1, and P3 groups were larger and significantly different compared to NC and P2 also, the histological structure showed that the glomerular diameter (65.43 ± 0.7 m), Bowman space distance (4.19 ± 1.7 µm), and the percentage of proximal tubular cell necrosis (24.6 ± 5.5%) at P2 were not significantly different from NC. Based on this results, it was concluded that EEJFP has no effect on the kidney’s morphological structure, however, it decreases its relative weight and repair the kidney’s histological damage of the diabetic rat model with the optimum dose of 770 mg/kg BW.

Role of IL-33/ST2 Axis in Chronic Inflammatory Neurological Disorderss

Interleukin-33 (IL-33) is a member of IL-1 family of cytokines, produced constitutively by fibroblasts, endothelial cells, and epithelial cells. IL-33 can be released passively from cells during tissue damage and cell necrosis, suggesting that it may act as an alarmin. Function of IL-33 is mediated by its interaction with ST2 molecule that is expressed on many immune cells: Th2 lymphocytes, NK, NKT and mast cells, monocytes, dendritic cells and granulocytes. IL-33/ST2 pathway plays, often dual, roles in different physiological and inflammatory processes, mediating both, pathological immune responses and tissue repair. Expression of IL-33 in the central nervous system (CNS) is significantly enhanced during various pathological processes, indicating its important role in the pathogenesis of neurological inflammatory and degenerative diseases. In this review the biological features, expression of IL-33 and its ligand ST2 in CNS, and the role of IL- 33/ST2 pathway in development of Alzheimer’s disease and multiple sclerosis are discussed.

Aggregated Mycobacterium tuberculosis Enhances the Inflammatory Response

Mycobacterium tuberculosis (Mtb) bacilli readily aggregate. We previously reported that Mtb aggregates lead to phagocyte death and subsequent efficient replication in the dead infected cells. Here, we examined the transcriptional response of human monocyte derived macrophages to phagocytosis of aggregated Mtb relative to phagocytosis of non-aggregated single or multiple bacilli. Infection with aggregated Mtb led to an early upregulation of pro-inflammatory associated genes and enhanced TNFα signaling via the NFκB pathway. These pathways were significantly more upregulated relative to infection with single or multiple non-aggregated bacilli per cell. Phagocytosis of aggregates led to a decreased phagosome acidification on a per bacillus basis and increased phagocyte cell death, which was not observed when Mtb aggregates were heat killed prior to phagocytosis. Mtb aggregates, observed in a granuloma from a patient, were found surrounding a lesion cavity. These observations suggest that TB aggregation may be a mechanism for pathogenesis. They raise the possibility that aggregated Mtb, if spread from individual to individual, could facilitate increased inflammation, Mtb growth, and macrophage cell death, potentially leading to active disease, cell necrosis, and additional cycles of transmission.

Intra-articular injection of loaded sPL sustained-release microspheres inhibits osteoarthritis and promotes cartilaginous repairs

Background Osteoarthritis is a chronic inflammatory disease of the joints associated with significant morbidity and lower quality of life. Current treatment strategies focus on reducing cartilage degeneration but fail to restore their proliferative ability. Super-activated platelet lysate (sPL) is an enhanced form of platelet-rich plasma that can be easily inactivated. The purpose of this study is to evaluate whether sPL-loaded PLGA/chitosan/gelatin microspheres can prevent and treat osteoarthritis. Methods Features of biological microspheres were detected by SEM and ELISA. Osteoarthritis chondrocytes were co-cultured with hydrogel loaded with sPL. The effect of biological microspheres on chondrocyte proliferation was evaluated using a CCK-8 cell proliferation test. Cell morphology and cell necrosis were measured with a microscope. The gene expression levels of cartilage-related markers type 2 collagen, aggrecan (ACAN), and SRY type high mobility group box-9 (SOX9) were determined by real-time quantitative polymerase chain reaction (Rt-PCR). A rat osteoarthritis model was established. Micro-CT was used to characterize cartilaginous changes after the injection of biological microspheres. Histopathological HE staining, Safranin-O Fast Green staining and staining scores, type II collagen staining, and proteoglycan staining were used to evaluate the degree of cartilaginous repair. Results Biological microspheres were able to continuously release biological factors. Exposure to loading sPL microspheres significantly increased chondrocyte proliferation, reduced cell necrosis, and increased the expression of cartilage markers type 2 collagen, ACAN, and SOX9 in osteoarthritic chondrocytes. In vivo experiments found that biological microspheres also smoothen cartilage surfaces, promote the expression of proteoglycan and type 2 collagen while also increasing cartilaginous integrity as evaluated using Safranin-O Fast Green staining. Conclusions PLGA/chitosan/gelatin hydrogel loaded with sPL is a promising tool for effective and non-invasive articular cartilage repair in osteoarthritis. Graphic abstract Biological microspheres loaded with sPL release various biological factors to promote chondrocyte proliferation and upregulate chondrocyte functionalization genes (SOX9, CoX II, ACAN), leading to an overall enhanced cartilaginous matrix.

Staurosporine-induced cleavage of apoptosis-inducing factor in human fibrosarcoma cells is independent of matrix metalloproteinase-2

Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein which mediates staurosporine (STS)-induced cell death. AIF cleavage and translocation to the cytosol is thought to be calpain-1-dependent as calpain inhibitors reduced AIF proteolysis. However, many calpain inhibitors also inhibit matrix metalloproteinase-2 (MMP-2) activity, an intracellular and extracellular protease implicated in apoptosis. Here we investigated whether MMP-2 activity is affected in response to STS and if contributes to AIF cleavage. Human fibrosarcoma HT1080 cells were treated with STS (0.1 µM, 0.25-24 hr). A significant increase in cellular MMP-2 activity was seen by gelatin zymography after 6 hr STS treatment, prior to induction of cell necrosis. Western blot showed the time-dependent appearance of two forms of AIF (~60 and 45 kDa) in the cytosol which were significantly increased at 6 hr. Surprisingly, knocking down MMP-2 or inhibiting its activity with MMP-2 preferring inhibitors ARP-100 or ONO-4817, or inhibiting calpain activity with ALLM or PD150606, did not prevent the STS-induced increase in cytosolic AIF. These results show that although STS rapidly increases MMP-2 activity, the cytosolic release of AIF may be independent of the proteolytic activities of MMP-2 or calpain.

The Effects of Borax (NA2B4O710H2O) on Histopathology of Wistar Rats’ Cerebrum (Rattus norvegicus)

The present study aimed to determine the effects of borax (Na2B4O7.10H2O) addition on the changes of histological cerebrum imaging in the brains of white mice (Rattus norvegicus). The current research was an experimental study with randomization of 24 white mice that were divided into four treatment groups with five replications. Borax was dissolved for each treatment with a dose of 19 mg/mouse/day, 26 mg/mouse/day, and 37 mg/mouse/day, and it was administered orally for 14 days. Then, it was analyzed statistically using the Kruskal-Wallis test. The statistical analysis results suggested that there were significantly different results in each treatment group. The control treatment with an administration dose of 26 mg/rat/day had a significantly different result in the worst cloudy swelling degeneration of cerebrum in histopathology imaging on Wistar rats (Rattus norvegicus). Using the Mann-Whitney test, it was found that the dose of borax at 37 mg/rat/day led to significant difference, compared to the other treatment groups, which means that 37 mg/rat/day of borax caused the worst pyramidal cell necrosis in histopathology imaging of the cerebrum on white mice. Borax exposure on Wistar rats (Rattus norvegicus) can cause cloudy swelling at a dose of 26mg/head/day, and pyramidal cell necrosis at a dose of 37 mg/head/day.

Clinical Significance of Changes in the Subendocortical Volume of Wilson Disease

Wilson disease (WD) is a rare neurogenetic disease with a variety of clinical manifestations. The disorder of copper metabolism can lead to cell necrosis, while nerve cell necrosis can reduce the volume of the corresponding parts. This study quantifies the degree of nerve cell injury by studying the subcortical volume changes in WD patients, and discusses the correlation between nerve cell injury in different parts and clinical manifestations. The results showed that compared with the healthy control group, the subcortical volume of WD decreased significantly, and the decrease in different parts was related to clinical symptoms. This study shows that we can quantify the degree of nerve cell injury by measuring the change of subcortical volume. Predict possible clinical symptoms.

Deletion of Mocos induces xanthinuria with obstructive nephropathy and major metabolic disorders in mice

Background: Xanthinuria type II is a rare autosomal purine disorder. This recessive defect of purine metabolism remains an underrecognized disorder. Methods: Mice with targeted disruption of the molybdenum cofactor sulfurase (Mocos) gene were generated to enable an integrated understanding of purine disorders and evaluate pathophysiological functions of this gene found in large number of pathways and known to be associated with autism. Results: Mocos deficient mice die with 4 weeks of age due to renal failure of distinct obstructive nephropathy with xanthinuria, xanthine deposits, cystic tublular dilatation, Tamm Horsfall (uromodulin) protein deposits, tubular cell necrosis with neutrophils and occasionally hypdronephrosis with urolithiasis. Obstructive nephropathy is associated with moderate interstitial inflammatory and fibrotic responses, anemia, reduced detoxification systems and important alterations of the metabolism of purines, amino acids and phospholipids.Conversely, heterozygous mice expressing reduced MOCOS protein are healthy with no apparent pathology. Conclusions: Mocos deficient mice develop a lethal obstructive nephropathy associated with profound metabolic changes. Studying MOCOS functions may provide important clues about the underlying pathogenesis of xanthinuria and other diseases requiring early diagnosis