Engineered Probiotics for the Management of Congenital Metabolic Diseases: A Systematic Review.

Engineered probiotics (EPs) can be used to treat/manage chronic and congenital diseases. However, to the best of our knowledge, no systematic review has evaluated the effects of EPs on congenital metabolic disorders in murine models and human subjects. Thus, the present study systematically reviewed interventional studies that assessed the effects of EPs on congenital metabolic disorders. PubMed, Web of Science, and Scopus databases were searched up to February 2023 to retrieve related publications. Seventy-six articles were obtained in the primary step. After screening the titles/abstracts based on the inclusion and exclusion criteria, 11 papers were included. Finally, only seven articles were included after performing full-text evaluation. The included articles evaluated the effects of EPs on managing phenylketonuria (PKU, n=4) and hyperammonemia (n=3). Moreover, these studies examined mice and/or rats (n=6), monkeys (n=1), and humans (n=2). Studies on EPs and hyperammonemia revealed that some wild strains such as Lactobacillus plantarum have an innate ammonia-hyper-consuming potential; thus, there was no need to manipulate them. However, manipulation is needed to obtain a phenylalanine-metabolizing strain. In conclusion, EPs can be used to manage or treat congenital metabolic diseases including PKU.

Andrographolide induced heme oxygenase-1 expression in MSC-like cells isolated from rat bone marrow exposed to environmental stress.

BACKGROUND AND OBJECTIVES: Mesenchymal stem cells (MSC-like cells) are the most important stem cells that are used in transplantation clinically in various applications. The survival rate of MSC-like cells is strongly reduced due to adverse conditions in the microenvironment of transplantation, including environmental stress. Heme oxygenase-1 (HO-1) is a member of the heat shock protein, as well as a stress-induced enzyme, present throughout the body. The present study was conducted to investigate the effect of andrographolide, an active derivative from andrographolide paniculate, on HO-1 expression in mesenchymal stem cells derived from rat bone marrow. MATERIALS AND METHODS: The rat bone marrow-derived mesenchymal stem cells (BMSC-like cells) were extracted and proliferated in several passages. The identity of MSC-like cells was confirmed by morphological observations and differential tests. The flow cytometry method was used to verify the MSC-specific markers. Isolated MSC-like cells were treated with different concentrations of andrographolide and then exposed to environmental stress. Cell viability was assessed using the MTT colorimetric assay. A real-time PCR technique was employed to evaluate the expression level of HO-1 in the treated MSC-like cells. RESULTS: Isolated MSC-like cells demonstrated fibroblast-like morphology. These cells in different culture mediums differentiated into osteocytes and adipocytes and were identified using alizarin red and oil red staining, respectively. As well, MSC-like cells were verified by the detection of CD105 surface antigen and the absence of CD14 and CD45 antigens. The results of the MTT assay showed that the pre-treatment of MSC-like cells with andrographolide concentration independently increased the viability and resistance of these cells to environmental stress caused by hydrogen peroxide and serum deprivation (SD). Real-time PCR findings indicated a significant increase in HO-1 gene expression in the andrographolide-receiving groups (p < 0.01). CONCLUSION: Our results suggest that andrographolide creates a promising strategy for enhancing the quality of cell therapy by increasing the resistance of MSC-like cells to environmental stress and inducing the expression of HO-1.

Is collagen supplementation friend or foe in rheumatoid arthritis and osteoarthritis? A comprehensive systematic review.

Rheumatoid arthritis (RA) and osteoarthritis (OA) both are chronic diseases affecting joints. Immune response against collagen in both diseases may have a role in the initiation and progression of the disease. There is a hypothesis that suppression of immune response vs collagen could be a therapeutic approach in RA and OA. Exposure of gut immune system to collagen is a way to suppress immune response against collagen in the joints. So, the current systematic review is aimed to evaluate the effects of collagen supplementation in OA and RA patients. In the current systematic review, online electronic databases including PubMed/MEDLINE, Web of Sciences and Scopus were searched and finally 19 articles were included. The enrolled articles evaluated the effects of collagen supplementation on treatment of OA (n = 9) and RA (n = 10). Intact (n = 4) and hydrolyzed (n = 5) collagen were used to treat OA. All of the studies on RA used intact and type II collagen in their intervention. The last trials on collagen supplementation in RA and OA patients were performed in 2011 and 2016, respectively. High adverse effects of collagen supplementation and its low efficiency compared to routine treatments were reported by several included studies. Also, risk of bias assessment showed that most of the studies had poor quality. Therefore, it is not possible to definitely decide on the beneficial or detrimental effects of collagen supplementation on OA and RA patients. Further studies are needed to reach a final decision.

Ferulago angulata as a Good Radioprotector Against Genotoxicity.

INTRODUCTION: Natural products can be used as radioprotector agents because of containing phenolic compounds and several flavonoids with antioxidant properties. When the normal cells are exposed to ionizing radiation, they generate free radicals and reactive oxygen species that can cause damage in DNA, which leads to cellular dysfunction or even cell death. However, it is necessary to identify new radioprotective agents to protect normal cells. Ferulago angulata (F. angulata), a medicinal plant, can be used as a new radioprotective agent. PURPOSE: In this study, the radioprotective effect of F. angulata was evaluated against genotoxicity and oxidative stress induced by ionizing radiation in human blood lymphocytes. METHODS: The antioxidant activity of F. angulata was assayed using FRAP and DPPH methods. Then, the human blood samples were incubated with F. angulata at different concentrations (25, 50, 100, and 200 µM) and subsequently exposed to IR at a dose of 2Gy. The radioprotective effect of F. angulata on the exposed cells was assessed by the micronucleus (MN) method. Also, biomarkers of oxidative stress in the exposed cells were evaluated by malondialdehyde (MDA) and superoxide dismutase (SOD) methods. RESULTS: Our findings showed that F. angulata reduced the frequency of MN induced by IR in exposed cells. At a 200 µM concentration of F. angulata, the maximum reduction in the frequency of MN (63.11%) was observed that demonstrated a high degree of radioprotection. Afterward, pretreatment at 200 µM concentration of F. angulata inhibited oxidative stress in irradiated lymphocytes, leading to a reduction in MN frequency and MDA levels while SOD activity was enhanced in the exposed cells. CONCLUSION: F. angulata as a natural radioprotective agent can protect normal cells against reactive oxygen species and genetic damage induced by IR.

Piroxicam reduces acute and chronic pain response in type 1 diabetic rats.

OBJECTIVES: Pain associated with various underlying pathologies is a major cause of morbidity and diminished life quality in diabetic patients. Effective control of pain requires the use of analgesics with the best efficacy and with minimal side effects. Therefore, our aim in this study was to investigate the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on pain in diabetic rats. METHODS: In this study, we investigated the analgesic effects of drugs belonging to three different classes of NSAIDs in a rat model of diabetes. Four diabetic groups received normal saline, diclofenac, piroxicam and ketorolac, respectively, and four non-diabetic groups received normal saline, diclofenac, piroxicam and ketorolac. Type 1 diabetes was induced in rats by a single injection of streptozotocin (60 mg/kg bw). Formalin (50 µL of 2.5%) nociception assay was used to examine the effect of treatment with diclofenac, piroxicam and ketorolac on acute and chronic pain in healthy and diabetic rats. RESULTS: Piroxicam showed significant analgesic effects both in the acute phase of pain (5-10 min after injection of formalin into the left hind paw), and in the chronic phase (20-60 min after formalin injection) in healthy as well as diabetic rats. Diclofenac and ketorolac also reduced pain scores in healthy rats. However, these two drugs failed to diminish pain in diabetic rats. CONCLUSION: Our data point for better efficacy of piroxicam in controlling pain in diabetes.