Comparative evaluation of autologous platelet-rich plasma and platelet lysate in patients with knee osteoarthritis.

Autologous platelet-rich plasma (PRP) and platelet lysate (PL) are nowadays promising candidates in the treatment of articular cartilage lesions. We aimed to compare PRP and PL injection effectiveness in patients with knee osteoarthritis (KOA). A total of fifty women with KOA were included in the study. Patients were treated with intra-articular injections of PRP and PL. Clinical outcomes were evaluated using the comparison of VAS, WOMAC, and ROM scores. The concentration levels of growth factors and cytokines were measured by ELISA. All patients showed significant improvements in pain and function following treatment of KOA with PL and PRP compared to baseline. Moreover, PL's concentration of growth factors was significantly higher than PRP. A significant increase was also observed in all of the aforementioned mediators in both PRP and PL products compared to control. These results can introduce PL as a promising and alternative option for KOA therapy in the future.

SARS-CoV2 infection induce miR-155 expression and skewed Th17/Treg balance by changing SOCS1 level: A clinical study.

BACKGROUND: One of the regulators in severe acute respiratory syndrome coronavirus2 (SARS-CoV2) infection is miRNAs. In COVID-19 patients, immunological responses to SARS-CoV2 infection may be impacted by miR-155, a miRNA associated to inflammation. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) of 50 confirmed COVID-19 patients /Healthy Controls (HCs) was isolated by Ficoll. The frequency of T helper 17 and regulatory T cells was analyzed by flowcytometry. The RNA was extracted from each sample and after synthesis of c-DNA, the relative expression of miR-155, suppressor of cytokine signaling (SOCS-1), Signal transducer and activator of transcription 3(STAT3), and Fork Head Box Protein 3 (FoxP3) was evaluated by real-time PCR. The protein level of STAT3, FoxP3 and RORγT in the isolated PBMCs measured by western blotting. The serum level of IL-10, TGF-ß, IL-17 and IL21 was assessed by ELISA method. RESULTS: The population of Th17 cells showed a significant rise, whereas Treg cells reduced in COVID-19 cases. The master transcription factor of Treg (FoxP3) and Th17 (RORγT) relative expression showed the same pattern as flowcytometry. STAT3 level of expression at RNA and protein level increased in COVID-19 cases. FOXP3 and SOCS-1 proteins were down-regulated. The relative expression of miR-155, up-regulated in PBMC of COVID-19 patients and revealed a negative correlation with SOCS-1. The serum cytokine profile showed a reduction in TGF-ß, on the other hand an increase was seen in IL-17, IL-21 and IL-10 in COVID-19 cases toward control group. CONCLUSION: Based on the studies conducted in this field, it can be suggested that Th17/Treg in covid-19 patients can be affected by miR-155 and it can be considered a valuable diagnostic and prognostic factor in this disease.

RNA interference: Promising approach for breast cancer diagnosis and treatment.

Today, cancer is one of the main health-related challenges, and in the meantime, breast cancer (BC) is one of the most common cancers among women, with an alarming number of incidences and deaths every year. For this reason, the discovery of novel and more effective approaches for the diagnosis, treatment, and monitoring of the disease are very important. In this regard, scientists are looking for diagnostic molecules to achieve the above-mentioned goals with higher accuracy and specificity. RNA interference (RNAi) is a posttranslational regulatory process mediated by microRNA intervention and small interfering RNAs. After transcription and edition, these two noncoding RNAs are integrated and activated with the RNA-induced silencing complex (RISC) and AGO2 to connect the target mRNA by their complementary sequence and suppress their translation, thus reducing the expression of their target genes. These two RNAi categories show different patterns in different BC types and stages compared to healthy cells, and hence, these molecules have high diagnostic, monitoring, and therapeutic potentials. This article aims to review the RNAi pathway and diagnostic and therapeutic potentials with a special focus on BC.

Understanding and targeting anoikis in metastasis for cancer therapies.

The development of effective treatments for cancers requires investigations for a more detailed and comprehensive understanding of the basic cellular mechanisms involved in carcinogenesis, cancer progression, and metastasis. One of those driving mechanisms is anoikis, a special type of apoptosis, which is induced by losing anchorage from the extracellular matrix (ECM). In other words, resisting death in detached cells (cells without ECM) forms an anoikis-resistant phenotype. Since the anoikis-resistance state compensates for the initial steps of cancer metastasis, this review aimed to discuss mechanisms of gaining anoikis/anoikis resistance phenotype in tumor cells. Finally, we highlighted the significance of anoikis in malignancies so as to provide clear insight into cancer diagnosis and therapy development.

Paediatric pre-B acute lymphoblastic leukaemia-derived exosomes regulate immune function in human T cells.

Exosomes derived from solid tumour cells are involved in immune suppression, angiogenesis and metastasis; however, the role of leukaemia-derived exosomes has less been investigated. Hence, changes in immune response-related genes and human T cells apoptosis co-incubated with exosomes isolated from patients' pre-B cell acute lymphoblastic leukaemia were evaluated in this in vitro study. Vein blood sample was obtained from each newly diagnosed acute lymphoblastic leukaemia (ALL) patient prior any therapy. ALL serum exosomes were isolated by ultrafiltration and characterized using Western blotting and transmission electron microscopy. Exosomes were then co-incubated with T lymphocytes and the gene expressions, as well as functions of human T cells were quantified by qRT-PCR. Apoptosis and caspase-3 and caspase-9 protein expression were also evaluated by flowcytometry and Western blotting analysis, respectively. Exosomes isolated from ALL patients affected T lymphocytes and elevated the apoptosis. Moreover, these exosomes altered the T cells profile into regulatory type by increasing the expression of FOXP3 and Tregs-related cytokines, including TGF-B and IL-10. The expression level of Th17-related transcription factors (RoRγt) and interleukins (IL-17 and IL-23) decreased after this treatment. According to our findings, exosomes derived from ALL patients' sera carry immunosuppressive molecules, indicating the possible effect of exosomes as liquid biomarkers for cancer staging.

Fatty acids of type 2 diabetic serum decrease the stemness properties of human adipose-derived mesenchymal stem cells.

In type 2 diabetes, dyslipidemia and increased serum free fatty acids (FFAs) exacerbate the development of the disease through a negative effect on insulin secretion. Adipose-derived mesenchymal stem cells (AdMSCs) play a key role in regenerative medicine, and these cells can potentially be applied as novel therapeutic resources in the treatment of diabetes. In this study, AdMSCs were treated with diabetic or nondiabetic serum FFAs isolated from women of menopausal age. Serum FFAs were analyzed using gas-liquid chromatography. The expression level of the stemness markers CD49e and CD90 and the Wnt signaling target genes Axin-2 and c-Myc were evaluated using real-time PCR. The proliferation rate and colony formation were also assessed using a BrdU assay and crystal violet staining, respectively. The level of glutathione was assessed using cell fluorescence staining. Compared to nondiabetic serum, diabetic serum contained a higher percentage of oleate (1.5-fold, p < 0.01). In comparison with nondiabetic FFAs, diabetic FFAs demonstrated decreasing effects on the expression of CD90 (-51%, p < 0.001) and c-Myc (-48%, p < 0.05), and proliferation rate (-35%, p < 0.001), colony formation capacity (-50%, p < 0.01), and GSH levels (-62%, p < 0.05). The negative effect of the FFAs of diabetic serum on the stemness characteristics may impair the regenerative capabilities of AdMSCs.

Platelet lysate and tendon healing: comparative analysis of autologous frozen-thawed PRP and ketorolac tromethamine in the treatment of patients with rotator cuff tendinopathy.

Platelet-rich blood derivatives are being nowadays increasingly used in the treatment of tendon-related pathologies as a rich source of growth factors. We sought to ascertain if local application of platelet lysate (PL) to augment rotator cuff repair ameliorates patient outcomes compared to ketorolac tromethamine treated group. A total of forty patients, with clinical diagnosis of Rotator Cuff Tendinopathy were randomized to receive sub acromial injections of PL every week for a total of 3 injections and two injection of ketorolac tromethamine once every two weeks. Subjective assessments included VAS, SPADI and shoulder range of motion were assessed at baseline and at 1 and 6 months after injection. Taking both control and PL groups, it was vividly seen that the outcomes were identical at the initial state, as well as the short-term one; whereas, when considering the 6-month period, there is a seemingly remarkable superiority in PL group in all parameters.

Anoikis in cancer: The role of lipid signaling.

Malignantly transformed cells must alter their metabolic status to stay viable in a harsh microenvironment and maintain their ability to invade and spread. Anoikis, a specific detachment-related form of apoptotic cell death, is a potential barrier to cancer cell metastasis. Several molecular/pathway alterations have been implicated in preventing anoikis in metastatic cancers. Specific alterations in the lipid metabolism machinery (such as an increase in fatty acid uptake and synthesis) and modifications in the carbohydrate and amino acid metabolism are partially identified mechanisms associated with the anoikis resistance in various types of cancers, among other survival benefits. Following a summary of the molecular basis of the anoikis pathway, its resistance mechanisms, and the fundamentals of lipid metabolism in cancer, this article aims to elucidate the impact of lipid metabolism deviations recruited by cancer cells to escape anoikis.

Porcn as a novel therapeutic target in cancer therapy: A review.

Wingless-related integration site (Wnt) signaling is one of the main oncogenic pathways in different malignancies. Therefore, targeting this pathway has been considered an exciting strategy in cancer treatment. Porcn is among the central enzymes in this pathway that has recently been considered for cancer-targeted therapy. As a membrane-bound O-acyltransferase, Porcn plays a critical role in wnt ligand palmitoylation and its subsequent secretion. In addition to Porcn's role in stem cell signaling and differentiation, recent findings have shown its role in developing and progressing colorectal, pancreatic, liver, head, and neck cancers. Developed small molecule inhibitors have also opened a promising window toward cancer treatment strategies. In this review, the structure and biological role of Porcn in different cancer-related signaling pathways and inhibitors used for inhibiting this enzyme are discussed.

The altered expression of homing factors in CD34+ hematopoietic stem cells following G-CSF injection and its effects on transplantation quality in ALL patients.

Hematopoietic stem cells (HSCs) transplantation is considered a suitable treatment for malignant or nonmalignant hematological diseases. This study aims to investigate the HSCs homing factors in bone marrow (BM) donors of acute lymphoblastic leukemia (ALL) patients following granulocyte colony-stimulating factor (G-CSF) injection, as well as the G-CSF effects on BM transplantation quality in these patients. To mobilize HSCs into peripheral blood, G-CSF was used for ALL patient's BM donors. For HSCs counting, CD34+ cells were evaluated in analogous and autologous donors using flow cytometry. The expression of stem cell homing factors in CD34+ cells and peripheral blood mononuclear cells (PBMCs) were investigated using a real-time polymerase chain reaction. Finally, hematological factors after BM transplantation in ALL patients were assessed. According to our results, after G-CSF injection, the level of CD34+ HSCs was statistically increased. Besides, autologous donors showed a higher level of CD34+ cells compared to analogous donors before and after G-CSF injection. Additionally, a higher number of CD34+ HSCs was achieved in the autologous samples following G-CSF injection. Furthermore, after G-CSF injection, the expression of matrix metalloproteinase (MMP)-2, MMP-9 was increased; while, stromal cell-derived factor 1, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1 expression were decreased. Moreover, the expression of C-X-C chemokine receptor type 4, lymphocyte function-associated antigen 1, and very late antigen-4 in CD34+ cells and PBMCs were decreased. BM transplantation on Day 90 also caused an increased level of white blood cells, red blood cells, and platelets as compared to the first day; however, no statistical differences were observed in hemoglobin level. In conclusion, G-CSF by altering the expression of HSCs homing factors in ALL donors improves BM transplantation quality in ALL patients.

TIGIT and CD155 as Immune-Modulator Receptor and Ligand on CD4+ T cells in Preeclampsia Patients.

One of the main characteristics of preeclampsia (PE) is systemic inflammation. CD4+ FoxP3+ cells play a critical role in both fetomaternal tolerance and successful pregnancy. T-cell immunoglobulin, as well as immunoreceptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT)/CD155 pathway, possesses critical parts in the development of normal pregnancy by promoting regulatory T (Treg) cells. However, in PE, the relationship between TIGIT/CD155 and Treg differentiation has not been entirely clarified. In the current report, we aimed to assess the frequency of TIGIT and CD155 expressing TCD4+ cells in both PE and healthy pregnant women, as well as evaluating the amount of inflammatory and inhibitory cytokines at both mRNA and protein levels before and after blocking TIGIT and CD155. In the present report, 59 healthy, and 52 PE patients were designated to obtain their venous blood. The isolation of peripheral blood mononuclear cells (PBMCs) was performed from the blood samples, and PBMCs were then cultured in the RPMI1640 medium. The percentage of CD155+ and TIGIT+ CD4+ cells was assessed by flow cytometry in PBMCs. Cell culture supernatants were utilized to evaluate the secretory levels of transforming growth factor beta (TGF-ß), interleukin (IL)-10, IL-17, tumor necrosis factor alpha (TNF-α), and IL-1 ß, using enzyme-linked immunosorbent assay technique in pregnant women with or without PE both before and after blocking TIGIT and CD155. The mRNA expression of Foxp3, TIGIT, CD155, SHP-1, TGF-ß, IL-10, IL-17, TNF-α, and IL-1ß was also assessed by qRT-PCR in PBMCs before and after blocking TIGIT and CD155 in both populations. The data showed a significant decrease in the frequency of TIGIT+ CD4+ and CD155+ CD4+ T cells in PE women, compared to the control group. Our results showed decreased protein and mRNA levels of TIGIT, CD155, IL-10, FOXP3, and SHP-1 in PE patients. In addition, significant improvements in the levels of IL-17, TNF-α, and IL-1ß were observed in PE patients, as compared with the controls. However, blocking TIGIT and CD155 could increase these inflammatory cytokines and decrease anti-inflammatory cytokines. The data obtained in this report illustrated that there existed an imbalance between inflammatory and anti-inflammatory profiles, with an inflammatory status polarization, in PE patients. Additionally, TIGIT/CD155 showed a positive effect on immune regulation by activating ITIM, demonstrating the potential therapeutic value of the TIGIT/CD155 pathway in PE treatment. Also, using some proteins or materials that increased TIGIT/CD155 pathways activity and can be a therapeutic approach in PE.

Stearoyl-CoA desaturase 1 as a therapeutic target for cancer: a focus on hepatocellular carcinoma.

One of the main characteristics of cancer cells is the alteration in lipid composition, which is associated with a significant monounsaturated fatty acids (MUFAs) enrichment. In addition to their structural functions in newly synthesized membranes in proliferating cancer cells, these fatty acids are involved in tumorigenic signaling. Increased expression and activity of stearoyl CoA desaturase (SCD1), i.e., an enzyme converting saturated fatty acids to Δ9-monounsaturated fatty acids, has been observed in various cancer cells. This increase in expression and activity has also been associated with cancer aggressiveness and poor patient outcome. Previous studies have also indicated the SCD1 involvement in increased cancer cells proliferation, growth, migration, epithelial to mesenchymal transition, metastasis, chemoresistance, and maintenance of cancer stem cells properties. Hence, SCD1 seems to be a player in malignancy development and may be considered a novel therapeutic target in cancers, including hepatocellular carcinoma (HCC). This review study aims to discuss the impact of SCD1 as a major component in lipid signaling in HCC.

The porcupine inhibitor WNT974 provokes ectodermal lineage differentiation of human embryonic stem cells.

Porcupine (Porcn) enzyme plays an essential role in Wnt signaling activation. Stearoyl-CoA desaturase-1 (SCD1) is required to provide Porcn substrates. The aim of this study was to determine the effect of a novel Porcn inhibitor on the fate of human embryonic stem cells (hESCs) and the reliance of Porcn on SCD1 activity. hESCs were cultured on a feeder layer or Matrigel-coated plates. Small molecules WNT974 (LGK-974) and CAY10566 were used to inhibit Porcn and SCD1 activity, respectively. We assessed the effect of Porcn inhibition on viability, expression of Wnt signaling targets, pluripotency markers, proliferation, differentiation, and protein fatty acylation. hESCs' conditioned medium (CM) containing secreted Wnt proteins were applied in rescue experiments. To examine the catalytic dependency of Porcn on SCD1, the results of combined inhibitor treatment were compared with the SCD1 inhibitor alone. LGK-974 at the selected concentrations showed mild effects on hESCs viability, but significantly reduced messenger RNA and protein expression of Wnt signaling targets (Axin-2 and c-Myc) and pluripotency markers (OCT-4 and SOX-2) (p < .05). Adding 1 µM of Porcn inhibitor reduced proliferation (p = .03) and enhanced differentiation capacity into ectodermal progenitors (p = .02), which were reverted by CM. Click chemistry reaction did not show significant alteration in protein fatty acylation upon LGK-974 treatment. Moreover, combined inhibitor treatment caused no further substantial reduction in Wnt signaling targets, pluripotency markers, and protein fatty acylation relative to CAY10566-treated cultures. The substrate availability for Porcn activity is regulated by SCD1 and targeting Porcn by LGK-974 prompts the transition of hESCs from self-renewal state to ectodermal lineage.

Altered Th17/Treg ratio as a possible mechanism in pathogenesis of idiopathic membranous nephropathy.

Idiopathic membranous nephropathy (IMN) as a single organ autoimmune disease is a main cause of nephrotic syndrome in adults which is determined through autoantibodies to podocytes proteins. Th17/regulatory T (Treg) balance has emerged as a prominent factor in the regulation of autoimmunity. In this study, we evaluated the balance of Th17 and Treg cells, expression level of related master transcription factors, cytokines and microRNAs in mononuclear cells of peripheral blood of 30 patients with IMN and 30 healthy individuals before treatment. No significant variation was observed in Th17 cell frequency, retinoic acid receptor-related orphan nuclear receptor γt (RORÉ£t), signal transducer and Activator of transcription 3(STAT3), IL-17, and IL-23, while IL-21, IL-4, and IL-10 had significant increase in mRNA expression and protein level of peripheral blood mononuclear cells in IMN cases. Reduction in the percentage of Treg cells was also accompanied with significantly decreased expression of Forkhead box P3(FOXP3) and Transforming growth factor beta(TGF-ß) in IMN patients compared to the control group. Our study revealed that Th17 cells themselves might not be engaged in the pathogenesis of newly diagnosed patients with IMN; however, decreased T reg cells and increased ratio of Th17/Treg lymphocytes might display a role in the pathogenesis of IMN before treatment.

Fatty acids of follicular fluid phospholipids and triglycerides display distinct association with IVF outcomes.

RESEARCH QUESTION: Are triglyceride fatty acids in the follicular fluid associated with either follicular fluid phospholipid fatty acids or IVF outcomes and, if so, how are they associated? DESIGN: In a prospective cross-sectional study, 70 women undergoing intracytoplasmic sperm injection were recruited. Follicular fluid phospholipids and triglycerides were separated by thin-layer chromatography. Fatty acids were measured using gas-liquid chromatography and flame ionization detection system. RESULTS: Significant differences in fatty acid composition were observed between follicular fluid phospholipid and triglyceride fractions. Phospholipid stearic acid and n-3 polyunsaturated fatty acids, particularly alpha-linolenic acid, were negatively associated with the number of mature oocytes and cleaved embryos, whereas arachidonic acid was in direct correlation with cleavage rate per IVF cycle (ß = 0.325, P = 0.022). In the case of triglyceride fraction, total monounsaturated fatty acids, oleic acid in particular, displayed significantly positive associations with the number of oocytes (ß = 0.261, P = 0.043) and embryos (ß = 0.310, P = 0.018). Furthermore, cleavage rate correlated inversely with palmitic acid (ß = -0.359, P = 0.007) and directly with pentadecanoic acid (ß = 0.378, P = 0.005). Most of these associations, however, were not independent of predictive fatty acids belonging to phospholipid fraction, according to multivariate analysis. CONCLUSIONS: Fatty acid compositions of phospholipid and triglyceride fractions from human follicular fluid differentially correlate with IVF cycle parameters.

Premature ovarian failure and tissue engineering.

Premature ovarian failure (POF) usually happens former to the age of 40 and affects the female physiological state premenopausal period. In this condition, ovaries stop working long before the expected menopausal time. Of diagnostic symptoms of the disease, one can mention amenorrhea and hypoestrogenism. The cause of POF in most cases is idiopathic; however, cancer therapy may also cause POF. Commonly utilized therapies such as hormone therapy, in-vitro activation, and regenerative medicine are the most well-known treatments for POF. Hence, these therapies may be associated with some complications. The aim of the present study is to discuss the beneficial effects of tissue engineering for fertility rehabilitation in patients with POF as a newly emerging therapy.

Novel therapeutic approaches of tissue engineering in male infertility.

Male reproductive organ plays an important role in sperm production, maintenance and entry to the female reproductive tract, as well as generation and secretion of male sex hormones responsible for the health of male reproductive system. The purpose of this paper is to discuss the experimental and clinical evidence on the utilization of tissue engineering techniques in treating male infertility. Tissue engineering (TE) and regenerative medicine have developed new approaches to treat patients with reproductive disorders such as iatrogenic injuries, congenital abnormalities, and trauma. In some cases, including congenital defects and undescended testis or hypogonadism, the sperm samples are not retrieved. This makes TE a possible future strategy for restoration of male fertility. Here, we have summarized the recent advances in experimental and clinical application of cell-, tissue-, and organ-based regenerative medicine in male reproductive disorders.

Immunological and oxidative stress biomarkers in Ankylosing Spondylitis patients with or without metabolic syndrome.

Ankylosing Spondylitis (AS) is a chronic inflammatory disorder of the spine and sacroiliac joints with unidentified etiology closely associated with metabolic syndrome (MetS). Recent studies have reported that immunological and oxidative stress factors are implicated in AS pathogenesis. The aim of this study was to investigate the oxidative and immunological factors in AS patients with or without MetS compare to control group. Real-Time PCR measured expression level of cytokines, transcription factors and related miRNAs. In addition, Th17 and Treg frequencies and cytokines secretion were evaluated by flowcytometry and ELISA methods, respectively. The oxidative stress biomarkers were also assessed with biochemical methods. In AS patients with MetS, higher Th17 and lower Treg frequency were observed. Increased levels of NF-kB and AP-1 mRNA expression were seen in AS patients with MetS (p = 0.0263 and p = 0.0104, respectively). MiR-146a and miR-223 were significantly decreased (p = 0.0005, p = 0.0161, respectively) and increase in miR-21 (p = 0.0002) was observed in AS patients with MetS compared to AS patients without MetS. Additionally, the secretion of TNF-α (p = 0.0167), IL-1ß (p = 0.303), CCL2 (p = 0.0254), CCL3 (p = 0.0119), CXCL8 (p = 0.0364), adiponectin (p = 0.0183) and the levels of SOD (p = 0.0421), NO (p = 0.0451) and CAT (p = 0.0128) were increased in AS patients with MetS. We were not observed significant differences in TOS and GPX levels between studied groups. The higher levels of oxidative stress and immunological inflammatory markers in AS patients with MetS provide further evidences on the oxidative stress and immunological relationship in these patients.

Arachidonic acid alleviates the detrimental effects of acetylsalicylic acid on human granulosa cells performance in vitro.

Here, we investigated the biological effects of arachidonic acid (AA) in human cumulus granulosa cells (CGCs) after exposure to ASA. Cells were isolated from the follicular fluid and incubated with 0.5 mM acetylsalicylic acid (ASA) and 50 µM AA. Cell viability was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. E2 and P4 levels were measured by chemiluminescence assay. Expression of genes including CYP19A1, FACN, and SCD1 was measured by real-time polymerase chain reaction assay. Oxidative status was analyzed by monitoring glutathione peroxidase activity. The fatty acid profile was analyzed by the gas chromatography technique. Enzyme-linked immunosorbent assay was used to measure prostaglandin E2 (PGE2 ) in CGCs after exposure to ASA and AA. Protein levels of the estrogen receptor were studied by immunofluorescence staining. Ultrastructural changes were evaluated by transmission electron microscopy imaging. ASA treatment reduced E2 production, Cyp19a1 expression, glutathione peroxidase (GPx) activity, and estradiol receptor expression in CGCs. The addition of AA prevented the ASA-induced E2 reduction (p < .05) and expression of Cyp19a1. Moreover, AA increased the antioxidant capacity of CGCs exposed to ASA by promoting GPx activity (p < .05). AA increased monounsaturated fatty acid/saturated fatty acid ratio compared with the ASA group (p < .05). AA supplementation triggered the synthesis and secretion of PGE2 in ASA-treated CGCS (p < .05). Cytoplasmic vacuolation observed in the ASA group and treatment with AA intensified vacuolation rate. The expression of the estrogen receptor was increased after AA supplementation. Data demonstrated that AA decreased the detrimental effects of ASA on human CGCs after 72 hr.

A Review of Data Analytic Applications in Road Traffic Safety. Part 1: Descriptive and Predictive Modeling.

This part of the review aims to reduce the start-up burden of data collection and descriptive analytics for statistical modeling and route optimization of risk associated with motor vehicles. From a data-driven bibliometric analysis, we show that the literature is divided into two disparate research streams: (a) predictive or explanatory models that attempt to understand and quantify crash risk based on different driving conditions, and (b) optimization techniques that focus on minimizing crash risk through route/path-selection and rest-break scheduling. Translation of research outcomes between these two streams is limited. To overcome this issue, we present publicly available high-quality data sources (different study designs, outcome variables, and predictor variables) and descriptive analytic techniques (data summarization, visualization, and dimension reduction) that can be used to achieve safer-routing and provide code to facilitate data collection/exploration by practitioners/researchers. Then, we review the statistical and machine learning models used for crash risk modeling. We show that (near) real-time crash risk is rarely considered, which might explain why the optimization models (reviewed in Part 2) have not capitalized on the research outcomes from the first stream.