Prevalence and clinical significance of incidental findings in chest and abdominopelvic CT scans of trauma patients; A cross-sectional study.

BACKGROUND: Imaging may inadvertently reveal pathologies unrelated to their performing purpose, known as incidental findings (IF). This study aimed to assess the prevalence, clinical significance, and documentation of IFs in chest and abdominopelvic computed tomography (CT) scans of trauma patients. METHODS: This observational study was conducted at two urban level-1 trauma centers from March 2019 through April 2022. Official radiology reports of trauma patients who underwent chest and/or abdominopelvic CT scans at the emergency department (ED) were explored, and IF were extracted. Predictive factors of the presence of IFs and their documenting were investigated. RESULTS: Out of 656 chest and 658 abdominopelvic CT scans, 167 (25.37%) and 212 (32.31%) scans harbored at least one IF, respectively. Patients with IFs tended to be of higher age and female in both chest (age: 48 [IQR: 35-62] vs. 34 [IQR: 25-42.5]; female: 31.14% vs 14.66%, p < 0.001 for both) and abdominopelvic CT scans (age: 41 [IQR: 30-57.5] vs 33 [IQR: 25-43], female: 26.42% vs. 13.96%, p < 0.001 for both). As for documentation of significant IFs, only 49 of 112 chest IFs (43.8%) and 55 of 176 abdominopelvic IFs (31.3%) were documented. Investigating factors associated with documentation of clinically significant IFs, shorter length of hospital stay (1.5 (IQR: 0-4) vs. 3 (IQR: 2-8), p = 0.003), and discharging by ED physicians (documentation rate: 13.2% vs 42.6%, p < 0.001) were associated with poorer documentation of IFs only in abdominopelvic scans. CONCLUSION: CT imaging in ED trauma patients often reveals incidental findings, especially in older patients. Over 50% of these findings are clinically significant, yet they are frequently ignored and not documented. Physicians need to be more vigilant in recognizing and documenting these incidental findings and informing patients of the need for further evaluation.

Effects of kisspeptin on the maturation of human ovarian primordial follicles in vitro.

At this time, with advances in medical science, many cancers and chronic diseases are treatable, but one of their side effects is infertility. Some women also want to delay pregnancy for personal reasons. There has been some evidence that kisspeptin activates broad signals by binding to its receptor, suggesting that the role of kisspeptin in direct control of ovarian function includes follicle growth and steroid production. In this study, the effect of kisspeptin on improving the quality and results for human ovarian follicles was investigated. A section of ovary was removed laparoscopically from women between 20 and 35 years of age (n = 12). Pieces were divided randomly into two groups, control and treatment (with 1 µM kisspeptin). Real-time PCR was performed for GDF9, BMP15 and mTOR gene expression assessments. Western blotting was carried out to measure AKT and FOXO3a protein expression. Data were analyzed using one-way analysis of variance (ANOVA) and Tukey's test; means were considered significantly different at a P-value < 0.05. During treatment with the kisspeptin group, maturity genes are expressed. Therefore, kisspeptin is an effective substance to improve the quality of the human ovarian medium as it increases the maturity of follicles.

Utilization of smartphones for the evaluation of Gr/Ni nanostructures magnetically controlled based on optical fibers surface plasmons.

In the suggested optical fiber-based magnetoplasmonic system, we investigated the magnetic properties of graphene/nickel nanostructures. The plasmonic mode changes under the magnetic field observed in the intensity diagrams over time. To be accessible, cheap, and portable, we used a smartphone as a detector and processor. Considering the ambient noise and the light source, it was reported that the intensity of the changes improved up to 5 times. Further, the clad corrosion experiment carried out by pure dimethyl ketone in an intensity modulation by a smartphone camera and 10 seconds suggested removing fluorine polymer clad.

Incidence, accuracy, and barriers of diagnosing healthcare-associated infections: a case study in southeast Iran.

BACKGROUND: Healthcare-associated infections (HAIs) are a threat to patients. Accurate surveillance is required to identify and prevent HAIs. To estimate the incidence rate, report the accuracy and identify the barriers of reporting HAIs using a mixed-method study. METHODS: In this quantitative study, we externally evaluated the incidence rate and accuracy of the routine surveillance system in one of the main hospitals by an active follow-up of patients from September to December 2021. We used in-depth interviews with 18 experts to identify the barriers of the routine surveillance system. RESULTS: Among 404 hospitalized patients, 88 HAIs were detected. The estimated rate of HAIs was 17.1 (95% Confidence Intervals 95: 14.1, 21.1) per 1000 patient-days follow-up. However, in the same period, 116 HAIs were reported by the routine surveillance system, but the agreement between the two approaches was low (sensitivity = 61.4%, specificity = 82.6%, negative predictive value = 89.7%, and positive predictive validity = 46.5%). The minimum and maximum positive predictive values were observed in urinary tract infection (32.3%) and surgical site infection (60.9%). The main barrier of reporting HAIs was lack of cooperation in reporting HAIs by infection control link nurses and laboratory supervisors. CONCLUSIONS: The discrepancy between the longitudinal study findings and the routine surveillance might be related to the inaccessibility of the surveillance system to clinical information of patients. In this regard, decreasing the barriers, increasing the knowledge of infection control nurses and other nurses, as well as the development of hospital information systems are necessary.

Ocular Trauma in Children: An Epidemiological Study.

OBJECTIVES: This study aimed to determine the epidemiology of eye injuries in children and the influential factors involved. METHODS: Eighty cases of confirmed ocular trauma were included in this cross-sectional study. Data were obtained via a checklist containing demographic information, site of the insult, the interval between the injury and physician visit, trauma mechanism, and medical history, including previous history of ocular trauma. RESULTS: Among 80 children with ocular trauma, 72.5% (n = 58) were boys. A marked preponderance (46.2%) of injuries was seen in the age group younger than 6 years. The youngest patient was a 1-year-old, and the oldest was aged 17. Most (76.25%) of the incidents occurred indoors. A total of 67.5% of accidents were induced by sharp objects (knife and glass). Most accidents occurred in spring, whereas the least number of accidents occurred in winter. The corneoscleral laceration was the most common manifestation, followed by the laceration of the iris, uveal prolapse, hyphema, and cataracts. Furthermore, rare cases of retinal detachment, hypopyon, and corneal epithelial defects were seen. CONCLUSIONS: The highest incidents of ocular trauma occurred in boys, especially those younger than 6 years. The high number of sharp object injuries is also concerning. These findings provide us with evidence that further educational interventions and supervision are required in these groups to minimize the possible devastating injuries before the opportunity even arises.

Barriers and Problems in Implementing Health-Associated Infections Surveillance Systems in Iran: A Qualitative Study.

Background: Healthcare-associated infections (HAIs) are among the most critical challenges for patients and healthcare providers. To achieve the goals of the surveillance system, it is necessary to identify its barriers and problems. This study aimed to identify the barriers and problems of the surveillance system for HAIs. Methods: This qualitative study was conducted using the content analysis method to investigate the challenges of this surveillance system from the perspective of 18 infection control nurses from hospitals in different cities of Iran with work experience of 1 to 15 years. Data were collected through semi-structured interviews and analyzed using the Lundman and Graneheim qualitative content analysis method. Results: In this study, we found 2 categories and 7 subcategories. Two categories were barriers related to human resources and organizational barriers to infection control. The 7 subcategories included weakness of medical staff in adherence to health principles, obstacles related to patients, high workload and insufficient motivation, lack of staff knowledge, lack of human resources, functional and logistical weaknesses, and weaknesses in the surveillance system. Conclusion: To reduce problems and improve HAIs reporting, the HAIs surveillance system needs the support of health system officials and managers. This administrative and support focus can establish the framework for removing and lowering other barriers, such as the number of reported cases, physician and staff noncooperation, and the prevalence of HAIs. It can also bring HAIs cases closer to reality.

Retrobulbar Injection of Amphotericin B in Patients With COVID-19 Associated Orbital Mucormycosis: A Systematic Review.

PURPOSE: Following COVID-19 infection a rising count of rhino-orbito-cerebral mucormycosis is observed, requiring orbital exenteration, a disabling lifetime affecting surgery. One of the potential interventions for globe salvage in these patients is retrobulbar injections of amphotericin B. This study was conducted to review protocols, outcomes, and side effects of retrobulbar injection of amphotericin B in patients with COVID-19 associated rhino-orbito-cerebral mucormycosis (CAM). METHODS: The PubMed, Scopus, Web of Science, and Embase databases were searched using a comprehensive string of relevant keywords. All English studies with the confirmed diagnosis of CAM infection were included. We excluded all studies in which retrobulbar injection of amphotericin B was not implemented in any of the patients or there was a lack of clarified and detailed data about this procedure among participants. RESULTS: A total of 647 cases had a history of retrobulbar injection(s) of amphotericin B in 13 reviewed studies with 3,132 subjects of CAM. The most common protocol was the retrobulbar injection of 1 ml of 3.5 mg/ml liposomal amphotericin B for 3 doses daily or on alternate days. We discerned that the globe salvage rate was 95.0% in eyes with a history of retrobulbar injection(s). The total rate of orbital exenteration was 14.9%, regardless of the history of retrobulbar injection of the drug. Other outcomes of this intervention were vision salvage and reduced major ophthalmic complaints, including pain, swelling, chemosis, ptosis, and ophthalmoplegia. The side effects of this intervention were not serious, and most of them were transient. They included swelling at the injection site, restriction of ocular motilities, exacerbation of orbital inflammation, and even intensification of visual impairment in a few cases. CONCLUSIONS: Retrobulbar injection of amphotericin B should be considered a nearly safe and protective intervention against orbital exenteration in patients with CAM. It may also be effective in saving vision. Since the effectiveness of orbital exenteration in the survival of patients is not ascertained, retrobulbar injections can be considered an alternative intervention.

Dual l-Carnosine/Aloe vera Nanophytosomes with Synergistically Enhanced Protective Effects against Methylglyoxal-Induced Angiogenesis Impairment.

Microvascular complications are among the major outcomes of patients with type II diabetes mellitus, which are the consequences of impaired physiological functioning of small blood vessels and angiogenic responses in these patients. Overproduction and accumulation of methylglyoxal (MGO), a highly reactive dicarbonyl byproduct of glycolysis pathway, has been acclaimed as the main inducer of impaired angiogenic responses and microvascular dysfunction in diabetic patients with uncontrolled hyperglycemia. Hence, an effective approach to overcome diabetes-associated microvascular complications is to neutralize the deleterious activity of enhanced the concentration of MGO in the body. Owing to the glycation inhibitory activity of Aloe vera whole extract, and capability of l-carnosine, an endogenous dipeptide, in attenuating MGO's destructive activity, we examined whether application of a combination of l-carnosine and A. vera could be an effective way of synergistically weakening this reactive dicarbonyl's impaired angiogenic effects. Additionally, overcoming the poor cellular uptake and internalization of l-carnosine and A. vera, a nanophytosomal formulation of the physical mixture of two compounds was also established. Although l-carnosine and A. vera at whole studied combination ratios could synergistically enhance viability of human umbilical vein endothelial cells (HUVECs) treated with MGO, the 25:1 w/w ratio was the most effective one among the others (27 ± 0.5% compared to 12 ± 0.3 to 18 ± 0.4%; F (4, 15) = 183.9, P < 0.0001). Developing dual nanophytosomes of l-carnosine/A. vera (25:1) combination ratio, we demonstrated superiority of the nanophytosomal formulation in protecting HUVECs against MGO-induced toxicity following a 24-72 h incubation period (17.3, 15.8, and 12.4% respectively). Moreover, 500 µg/mL concentration of dual l-carnosine/A. vera nanophytosomes exhibited a superior free radical scavenging potency (63 ± 4 RFU vs 83 ± 5 RFU; F (5, 12) = 54.81, P < 0.0001) and nitric oxide synthesizing capacity (26.11 ± 0.19 vs 5.1 ± 0.33; F (5, 12) = 2537, P < 0.0001) compared to their physical combination counterpart. Similarly, 500 µg/mL dual l-carnosine/A. vera nanophytosome-treated HUVECs demonstrated a superior tube formation capacity (15 ± 3 vs 2 ± 0.3; F (5, 12) = 30.87, P < 0.001), wound scratch healing capability (4.92 ± 0.3 vs 3.07 ± 0.3 mm/h; F (5, 12) = 39.21, P < 0.0001), and transwell migration (586 ± 32 vs 394 ± 18; F (5, 12) = 231.8, P < 0.001) and invasion (172 ± 9 vs 115 ± 5; F (5, 12) = 581.1, P < 0.0001) activities compared to the physical combination treated ones. Further confirming the proangiogenic activity of the dual l-carnosine/A. vera nanophytosomes, a significant shift toward expression of proangiogenic genes including HIF-1α, VEGFA, bFGF, KDR, and Ang II was reported in treated HUVECs. Overall, dual l-carnosine/A. vera nanophytosomes could be a potential candidate for attenuating type II DM-associated microvascular complications with an impaired angiogenesis background.

Protective effect of hydralazine on a cellular model of Parkinson's disease: a possible role of hypoxia-inducible factor (HIF)-1α.

Parkinson's disease (PD) is a neurodegenerative disease accompanied by a low expression level of cerebral hypoxia-inducible factor (HIF-1α). Hence, activating the hypoxia-signaling pathway may be a favorable therapeutic approach for curing PD. This study explored the efficacy of hydralazine, a well-known antihypertensive agent, for restoring the impaired HIF-1 signaling in PD, with the aid of 6-hydroxydopamine (6-OHDA)-exposed SH-SY5Y cells. The cytotoxicity of hydralazine and 6-OHDA on the SH-SY5Y cells were evaluated by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and apoptosis detection assays. The activities of malondialdehyde, nitric oxide (NO), ferric reducing antioxidant power (FRAP), and superoxide dismutase (SOD) were also measured. Expression levels of HIF-1α and its downstream genes at the protein level were assessed by Western blotting. Hydralazine showed no toxic effects on SH-SY5Y cells, at the concentration of ≤50 µmol/L. Hydralazine decreased the levels of apoptosis, malondialdehyde, and NO, and increased the activities of FRAP and SOD in cells exposed to 6-OHDA. Furthermore, hydralazine up-regulated the protein expression levels of HIF-1α, vascular endothelial growth factor, tyrosine hydroxylase, and dopamine transporter in the cells also exposed to 6-OHDA, by comparison with the cells exposed to 6-OHDA alone. In summary, hydralazine priming could attenuate the deleterious effects of 6-OHDA on SH-SY5Y cells by increasing cellular antioxidant capacity, as well as the protein levels of HIF-1α and its downstream target genes.

Control of Hyperglycemia Using Differentiated and Undifferentiated Mesenchymal Stem Cells in Rats with Type 1 Diabetes.

Due to their ability in self-renewing and differentiation into a wide variety of tissues, mesenchymal stem cells (MSCs) exhibit outstanding potential for regenerative medicine. This study was aimed at investigating different aspects of MSC therapy in controlling hyperglycemia in streptozotocin-induced diabetes rats. Using an islet cell differentiation protocol, bone marrow (BM) MSCs were differentiated into insulin-producing cells (IPCs). The differentiation process was evaluated by immunocytochemistry, reverse transcriptase PCR, and dithizone staining. Diabetic animals in 4 diabetic individual groups received normal saline, BM-MSCs, coadministration of BM-MSCs with supernatant, and IPCs. Blood glucose and insulin levels were monitored during the experiment. Immunohistochemical analysis of the pancreas was performed at the end of the experiment. Administration of BM-MSCs could not reverse glucose and insulin levels in experimental animals as efficiently as cotransplantation of BM-MSCs with supernatant. The effect of coadministration of BM-MSCs with supernatant and transplantation of IPCs on controlling hyperglycemia is comparable. Immunohistochemical analysis showed that number and size of islets per section were significantly increased in groups receiving IPCs and BM-MSC-supernatant compared to the MSC group of animals. In conclusion, coadministration of BM-MSCs with supernatant could be used as efficiently as IPC transplantation in controlling hyperglycemia in diabetic rats.

A new chromogenic and fluorescent chemosensor based on a naphthol-bisthiazolopyridine hybrid: a fast response and selective detection of multiple targets, silver, cyanide, sulfide, and hydrogen sulfide ions and gaseous H2S.

A novel chemosensor 1 based on a naphthol-bisthiazolopyridine hybrid was synthesized and characterized. Among the various screened cations and anions, chemosensor 1 selectively recognized Ag+ and CN- ions by relying on the color change and distinct absorption and emission changes. Moreover, the probe 1·Ag+ was well operable for the selective monitoring of S2-, HS- and H2S as evidenced by the different color and optical changes. The selective detection of all the anions was simply based on the breakage of the intramolecular hydrogen bonding of 1, followed by the protonation or deprotonation mechanism. In general, chemosensor 1 is a promising indicator in terms of its ease-of-use, selectivity, sensitivity, and rapid response (<1 s). Moreover, the visual detection and concentration determination of these analytes by solution or solid kits are the advantages for the practical applications of this sensor.

Nitroepoxide ring opening with thionucleophiles in water: synthesis of α-xanthyl ketones, ß-keto sulfones and ß-keto sulfonic acids.

Nitroepoxide ring opening with thionucleophiles such as potassium xanthates, sodium aryl sulfinates and sodium bisulfite in water is investigated. It provides a direct and green route for the synthesis of α-xanthyl-α-aryl-2-propanones (P2P-xanthate derivatives), ß-keto sulfones and ß-keto sulfonic acids. High to excellent yields, performing the reaction in water under catalyst-free conditions, and easy work-up are the main advantages of this protocol.

Distinct Tie2 tyrosine phosphorylation sites dictate phenotypic switching in endothelial progenitor cells.

Angiogenesis is a regulated process involving the proliferation, migration, and remodeling of different cell types particularly mature endothelial and their progenitor cells, nominated as endothelial progenitor cells (EPCs). Tie2/Tek is a tyrosine kinase receptor expressed by endothelial cells that induces signal transduction pathways involved in endothelial biology. To address the potential importance of the various tyrosine residues of Tie2 in EPC development, we generated a series of Tie2 tyrosine mutated (Y1106F, Y1100F, and Y1111F) EPCs and then assess the biological features of these cells. Clonogenic, tubulogenic, proliferative, migratory, and functional properties of these cells were analyzed. Next, GFP-positive EPCs containing Tie2 tyrosine mutations were systemically transplanted into sublethaly irradiated mice to analyze the potency of these cells for marrow reconstitution. We found that mutation in the Tie2 tyrosine 1106 residue directed EPCs toward a mature endothelial phenotype, which was associated with augmented tubulogenic and migratory properties, and increased phosphorylation of the active site (tyrosine 992) as well as increased vascular perfusion in the in vivo Matrigel plug assay. Moreover, transplantation of 1106 Tie2 mutant EPCs failed to reconstitute the bone marrow after myeloablation, whereas transplantation of EPCs with the 1100 or 1111 Tie2 tyrosine mutation resulted in bone marrow engraftment, leading to improved survival of recipient mice. Our findings demonstrate that the tyrosine 1106 residue in Tie2 plays a key role to maintain the stemness features of EPCs.

Protective effects of atorvastatin against high glucose-induced nuclear factor-κB activation in cultured C28I2 chondrocytes.

Aims: A number of epidemiological and experimental documents emphasizes a close relation between type 2 diabetes mellitus (T2DM) and the progression of osteoarthritis (OA). In order to understand the underlying mechanisms of atorvastatin (ATO) in OA, we sought to explore the effect of ATO on high glucose (HG)-mediated NF-κB activation in cultured C28I2 chondrocytes. Methods: The effects of various concentrations of ATO on C28I2 human chondrocytes viability were assessed to obtain the non-cytotoxic concentrations of drug by MTT-assay. The cells were pretreated with 0.01 and 0.1 µM ATO for 6 h, followed by incubation with HG (75 mM) for 72 h. The protein expressions of IκBα (np), IκBα (p), NF-κB (p), and NF-κB (np) were analyzed by western blotting. The effects of ATO on the mRNA expressions of chondrogenic specific markers including SOX9, aggrecan, collagen type 2, and COMP were evaluated by reverse transcription-polymerase chain reaction. Results: ATO in determined concentrations had no cytotoxic effect on C28I2 cells after 72 h. ATO pretreatment exerted remarkable protective effects against HG-induced cytotoxicity. Moreover, ATO decreased IκBα phosphorylation and NF-κB nuclear translocation. It was also able to improve the gene expression of chondrogenic-specific markers in C28I2 cells compared to the control group. Conclusion: ATO could significantly decrease HG-induced inflammation in the cultured C28I2 chondrocytes through the activation of canonical NF-κB signaling pathway. These beneficial effects of ATO may be owing to its anti-inflammatory properties. Therefore, treatment with ATO may provide an effective approach to prevent HG-induced cartilage destruction in clinical setting.

From individual Fuzzy Cognitive Maps to Agent Based Models: Modeling multi-factorial and multi-stakeholder decision-making for water scarcity.

Policy making for complex Social-Ecological Systems (SESs) is a multi-factorial and multi-stakeholder decision making process. Therefore, proper policy simulation in a SES should consider both the complex behavior of the system and the multi-stakeholders' interventions into the system, which requires integrated methodological approaches. In this study, we simulate impacts of policy options on a farming community facing water scarcity in Rafsanjan, Iran, using an integrated modeling methodology combining an Agent Based Model (ABM) with Fuzzy Cognitive Mapping (FCM). First, the behavioral rules of farmers and the causal relations among environmental variables are captured with FCMs that are developed with both qualitative and quantitative data, i.e. farmers' knowledge and empirical data from studies. Then, an ABM is developed to model decisions and actions of farmers and simulate their impacts on overall groundwater use and emigration of farmers in this case study. Finally, the impacts of different policy options are simulated and compared with a baseline scenario. The results suggest that a policy of facilitating farmers' participation in management and control of their groundwater use leads to the highest reduction of groundwater use and would help to secure farmers' activities in Rafsanjan. Our approach covers four main aspects that are crucial for policy simulation in SESs: 1) causal relationships, 2) feedback mechanisms, 3) social-spatial heterogeneity and 4) temporal dynamics. This approach is particularly useful for ex-ante policy options analysis.

Restoring the IL-1ß/NF-κB-induced impaired chondrogenesis by diallyl disulfide in human adipose-derived mesenchymal stem cells via attenuation of reactive oxygen species and elevation of antioxidant enzymes.

Strategies based on mesenchymal stem cell (MSC) therapy for restoring injured articular cartilage are not effective enough in osteoarthritis (OA). Due to the enhanced inflammation and oxidative stress in OA microenvironment, differentiation of MSCs into chondrocytes would be impaired. This study aims to explore the effects of diallyl disulfide (DADS) on IL-1ß-mediated inflammation and oxidative stress in human adipose derived mesenchymal stem cells (hADSCs) during chondrogenesis. MTT assay was employed to examine the effects of various concentrations of DADS on the viability of hADSCs at different time scales to obtain non-cytotoxic concentration range of DADS. The effects of DADS on IL-1ß-induced intracellular ROS generation and lipid peroxidation were evaluated in hADSCs. Western blotting was used to analyze the protein expression levels of IκBα (np), IκBα (p), NF-κB (np) and NF-κB (p). Furthermore, the gene expression levels of antioxidant enzymes in hADSCs and chondrogenic markers at days 7, 14 and 21 of differentiation were measured using qRT-PCR. The results showed that addition of DADS significantly enhanced the mRNA expression levels of antioxidant enzymes as well as reduced ROS elevation, lipid peroxidation, IκBα activation and NF-κB nuclear translocation in hADSCs treated with IL-1ß. In addition, DADS could significantly increase the expression levels of IL-1ß-induced impaired chondrogenic marker genes in differentiated hADSCs. Treatment with DADS may provide an effective approach to prevent the pro-inflammatory cytokines and oxidative stress as catabolic causes of chondrocyte cell death and enhance the protective anabolic effects by promoting chondrogenesis associated gene expressions in hADSCs exposed to OA condition.

Long term treatment by mesenchymal stem cells conditioned medium modulates cellular, molecular and behavioral aspects of adjuvant-induced arthritis.

Neuroinflammation plays a crucial role in expression of symptoms of numerous autoimmune and neurodegenerative diseases such as pain during rheumatoid arthritis. Overproduction of pro-inflammatory cytokines and activation of intracellular signaling pathways have been strongly implicated in the generation of pathological pain states, particularly at central nervous system sites and induction of spinal neuroinflammatory symptoms. The wide ranges of research to define new therapeutic approaches, including neuroimmune-modulators like stem cells are in progress. Mesenchymal stem cells conditioned medium (MSC-CM) has anti-inflammatory factors which can regulate the immune responses. The aim of this study was to investigate the effect of administration of MSC-CM on behavioral, cellular and molecular aspects of adjuvant-induced arthritis in male Wistar rats. Complete Freund's adjuvant (CFA)-induced arthritis (AA) was caused by single subcutaneous injection of CFA into the rat's hind paw on day 0. MSC-CM was administered daily (i.p.) and during the 21 days of the study after injection. Hyperalgesia, Edema, Serum TNF-α levels and p38MAPK and NF-κB activities were assessed on days 0,7,14 and 21 of the study. The results of this study indicated the role of MSC-CM in reducing inflammatory symptoms, serum TNF-α levels and activity of intracellular signaling pathway factors during different phases of inflammation caused by CFA. It seems that MSC-CM treatment due to its direct effects on inhibition of intracellular signaling pathways and pro-inflammatory cytokines can alleviate inflammatory symptoms and pain during CFA-induced arthritis.

Evaluating the Protective Effects and Mechanisms of Diallyl Disulfide on Interlukin-1ß-Induced Oxidative Stress and Mitochondrial Apoptotic Signaling Pathways in Cultured Chondrocytes.

The protective effects and mechanisms of DADS on IL-1ß-mediated oxidative stress and mitochondrial apoptosis were investigated in C28I2 human chondrocytes. The effect of various concentrations of DADS (1, 5 10, 25, 50, and 100 µM) on C28I2 cell viability was evaluated in different times (2, 4, 8, 16, and 24 h) to obtain the non-cytotoxic concentrations of drug by MTT-assay. The protective effect of non-toxic concentrations of DADS on experimentally induced oxidative stress and apoptosis by IL-1ß in C28I2 was evaluated. The effects of DADS on IL-1ß-induced intracellular ROS production and lipid peroxidation were detected and the proteins expression of Nrf2, Bax, Bcl-2, caspase-3, total and phosphorylated JNK, and P38 MAPKs were analyzed by Western blotting. The mRNA expression of detoxifying phase II/antioxidant enzymes including heme oxygenase-1, NAD(P)H quinine oxidoreductase, glutathione S-transferase-P1, catalase, superoxide dismutase-1, glutathione peroxidase-1, -3, -4 were evaluated by reverse transcription-polymerase chain reaction. DADS in 1, 5, 10, and 25 µM concentrations had no cytotoxic effect after 24 h. Pretreatment with DADS remarkably increased Nrf2 nuclear translocation as well as the genes expression of detoxifying phase II/antioxidant enzymes and reduced IL-1ß-induced elevation of ROS, lipid peroxidation, Bax/Bcl-2 ratio, caspase-3 activation, and JNK and P38 phosphorylation. DADS could considerably reduce IL-1ß-induced oxidative stress and consequent mitochondrial apoptosis, as the major mechanisms of chondrocyte cell death in an experimental model of osteoarthritis. It may be considered as natural product in protecting OA-induced cartilage damage in clinical setting. J. Cell. Biochem. 118: 1879-1888, 2017. © 2017 Wiley Periodicals, Inc.

Protective Effect of Ginger (Zingiber officinale Roscoe) Extract against Oxidative Stress and Mitochondrial Apoptosis Induced by Interleukin-1ß in Cultured Chondrocytes.

AIMS: The protective effects of ginger (Zingiber officinale Roscoe) extract on IL-1ß-mediated oxidative stress and mitochondrial apoptosis were investigated in C28I2 human chondrocytes. METHODS: The effects of various concentrations of ginger extract on C28I2 human chondrocyte viability were evaluated in order to obtain noncytotoxic concentrations of the drug by methylthiotetrazole assay. The cells were pretreated with 5 and 25 µg/mL ginger extract for 24 h, followed by incubation with IL-1ß (10 ng/mL) for 24 h. The effects of ginger extract on IL-1ß-induced intracellular reactive oxygen species (ROS) production and lipid peroxidation were examined. The mRNA expressions of antioxidant enzymes including catalase, superoxide dismutase-1, glutathione peroxidase-1, glutathione peroxidase-3, and glutathione peroxidase-4 were evaluated by reverse transcription polymerase chain reaction. The protein expressions of Bax, Bcl-2, and caspase-3 were analyzed by Western blotting. RESULTS: No cytotoxicity was observed at any concentration of ginger extract in C28I2 cells. Ginger extract pretreatment remarkably increased the gene expression of antioxidant enzymes and reduced the IL-1ß-induced elevation of ROS, lipid peroxidation, the Bax/Bcl-2 ratio, and caspase-3 activity. CONCLUSIONS: Ginger extract could considerably reduce IL-1ß-induced oxidative stress and consequent mitochondrial apoptosis as the major mechanisms of chondrocyte cell death. These beneficial effects of ginger extract may be due to its antioxidant properties. It may be considered as a natural herbal product to prevent OA-induced cartilage destruction in the clinical setting.

PRIMA-1 induces caspase-mediated apoptosis in acute promyelocytic leukemia NB4 cells by inhibition of nuclear factor-κB and downregulation of Bcl-2, XIAP, and c-Myc.

Restoration of p53 function triggers cell death and eliminates tumors in vivo. Identification of p53-reactivating small molecules such as PRIMA-1 holds promise for effective new anticancer therapies. Here, we investigated the effects of small molecule PRIMA-1 on cell viability and expression of p53-regulated genes and proteins in the acute promyelocytic leukemia-derived NB4 cell line. Our results showed that PRIMA-1 had antileukemic properties in acute promyelocytic leukemia-derived NB4 cells. PRIMA-1-triggered apoptosis in a dose-dependent and time-dependent manner as indicated by the MTT assay and annexin-V staining. Apoptosis induction by PRIMA-1 was associated with caspase-9, caspase-7 activation and PARP cleavage. p21 protein expression was increased after PRIMA-1 treatment and real-time PCR analysis of proapoptotic p53 target genes indicated upregulation of Bax and Noxa. Western blot analysis showed that IκBα phosphorylation and its degradation were inhibited by PRIMA-1. Moreover, protein expression of nuclear factor-κB-regulated antiapoptotic (Bcl-2 and XIAP) and proliferative (c-Myc) gene products was decreased. Importantly, PRIMA-1 did not show any significant apoptotic effect in normal human peripheral blood mononuclear cells. These in-vitro studies imply that p53 reactivation by small compounds may become a novel anticancer therapy in acute promyelocytic leukemia.