Analysis of the Home Accidents and Their Risk Factors in Iran: A Systematic Review and Meta-Analysis.

Background: Home accident is among the most common type of trauma, in the second place after traffic accident. We aimed to determine the prevalence and factors affecting the occurrence of home accidents in Iran. Methods: PubMed, Scopus, Web of Science, and national Persian databases including SID, MagIran, and Medical Articles Bank were searched for articles published until September 12, 2021. The pooled prevalence and factors affecting the occurrence of home accidents were calculated. Results: Twenty articles were included in the meta-analysis. The pooled prevalence of home accident was 44% (95%CI: 32% to 56%). The pooled prevalence of foreign object/fall, stab or cut, suffocation, burn, poisoning and were 15% (95%CI: 10% to 20%), 24% (95%CI: 10% to 38%), 1% (95%CI:0.7% to 1.3%), 31% (95%CI:19% to 42.2%), and 6.8% (95%CI:4.2% to 429.4%), respectively. Conclusion: The prevalence of home accidents in Iran is moderate but higher than in other countries. The findings of this review highlight the need for more attention to home accident in children and elderly in the South and Southeast regions of Iran.

Vactosertib potently improves anti-tumor properties of 5-FU for colon cancer.

BACKGROUND: Several studies have shown that the TGF-ß signaling pathway plays a critical role in colorectal cancer (CRC) pathogenesis. The aim of the current study is to investigate the therapeutic potential of Vactosertib (EW-7197), a selective inhibitor of TGF-ß receptor type I, either alone or in combination with the standard first-line chemotherapeutic treatment, 5-Fluorouracil (5-FU), in CRC progression in both cellular and animal models. METHODS: Real-Time PCR, Zymography, enzyme-linked immunosorbent assay (ELISA), Hematoxylin and Eosin (H&E) tissue staining, and Flow cytometry techniques were applied to determine the anti-tumor properties of this novel TGF-ß inhibitor in in vitro (CT-26 cell line) and in vivo (inbred BALB/C mice) samples. RESULTS: Our findings showed that Vactosertib decreased cell proliferation and induced spheroid shrinkage. Moreover, this inhibitor suppressed the cell cycle and its administration either alone or in combination with 5-FU induced apoptosis by regulating the expression of p53 and BAX proteins. It also improved 5-FU anti-cancer effects by decreasing the tumor volume and weight, increasing tumor necrosis, and regulating tumor fibrosis and inflammation in an animal model. Vactosertib also enhanced the inhibitory effect of 5-FU on invasive behavior of CRC cells by upregulating the expression of E-cadherin and inhibiting MMP-9 enzymatic activity. CONCLUSION: This study demonstrating the potent anti-tumor effects of Vactosertib against CRC progression. Our results clearly suggest that this inhibitor could be a promising agent reducing CRC tumor progression when administered either alone or in combination with standard treatment in CRC patients.

Green synthesis of nanohydroxyapatite trough Elaeagnus angustifolia L. extract and evaluating its anti-tumor properties in MCF7 breast cancer cell line.

BACKGROUND: One of the most common types of cancer in women is breast cancer. There are numerous natural plant-based products, which exert anti-tumoral effects including Elaeagnus Angustifolia (EA). It modulates cell-cycle process, heat-shock proteins expression, anti-proliferative properties, apoptosis induction, blocking of angiogenesis, and cell invasion inhibition. The current study aimed to synthesize and evaluate the anticancer effects of hydroalcoholic EA extract (HEAE), Nanohydroxyapatite (nHAp) and nHAp synthesized trough EA (nHA-EA) in MCF-7 breast cancer cell line. METHODS: In the present study, HEAE preparation and green synthesis of nHA-EA was done and phase composition, functional groups, and crystallin phase of nHA-EA and nHAp were determined using Fourier-transform infrared (FTIR) and X-ray diffraction (XRD). The characteristics of synthesized nanoparticles including structural and morphological parameters were investigated using scanning electron microscopy (SEM) and Transmission electron microscopy (TEM) techniques. Then, by using MTT-assay (Dimethylthiazoldiphenyltetrazolium), the in vitro cytotoxic and half maximal inhibitory concentration (IC50) of EA extract, nHAp, and nHA-EA in the MCF-7 breast cancer cell line was evaluated. Next, we assessed the expression of apoptosis-related genes Bax, Bcl2 and p53 using quantitative reverse-transcriptase polymerase-chain-reaction (qRT-PCR) and migration of MCF-7 cells by scratch assay. RESULTS: The FTIR results demonstrated formation of nHAp and its interaction with HEAE during synthesis process. The XRD results of the synthesized nanoparticles showed similar XRD pattern of nHA-EA and nHAp and purity of synthesized nanomaterials. The average IC50 of HEAE, nHAp, and nHA-EA extract after treatment of cancer cells for 24 h was 400 µg/mL, 200 µg/mL, and 100 µg/mL, respectively. Our results revealed that nHA-EA significantly reduced the migration and invasion of the MCF-7 cells, in comparison to the nHAp and EA extract. Moreover, level of Bax/Bcl2 and p53 was significantly higher in the nHA-EA extract group in comparison to the EA extract and nHAp group. CONCLUSION: Taken together, our results demonstrated that bioactive constituents of EA medicinal plant in form of nHA-EA particles, can effectively exerts potential anticancer and chemo preventive effect against breast cancer growth and can be proposed as a promising beneficial candidate for BC therapy. However, further investigations are required to discover what bioactive compounds are responsible for the chemo preventive effect of this extract.

Epigenetic drugs as new emerging therapeutics: What is the scale's orientation of application and challenges?

Epigenetics is the study of heritable changes in gene expression or function without altering the DNA sequence. Important factors are part of epigenetic events, such as methylation, DNA histone rearrangements, nucleosome transposition, and non-coding RNAs. Dysregulated epigenetic mechanics are associated with various cancers' initiation, development, and metastasis. It is known that the occurrence and development of cancer can be controlled by regulating unexpected epigenetic events. Epi-drugs are used singly or in combination with chemotherapy and enhance antitumor activity, reduce drug resistance, and stimulate the host immune response. Despite these benefits, epigenetic therapy as a single therapy or in combination with other drugs leads to adverse effects. This review article introduces and compares the advantages, disadvantages, and side effects of using these drugs for the first time since their introduction. Also, this article describes the mechanism of action of various epigenetic drugs. Recommendations for future use of epigenetic drugs as cancer therapeutics are suggested as an overall conclusion.

Association between adherence to a low carbohydrate dietary (LCD) pattern with breast milk characteristics and oxidative markers in infants' urine: a cross-sectional study.

BACKGROUND: Breast milk (BM) is a dynamic fluid that varies over time and between women. The variations in BM components are most likely associated with maternal diet quality. This study aimed to assess adherence to a low carbohydrate dietary (LCD) pattern with oxidative stress markers of BM characteristics and infants' urine. MATERIALS AND METHODS: In this cross-sectional study 350 breastfeeding mothers and their infants were recruited. BM samples were collected from mothers, and urine specimens were obtained from each infant. To evaluate LCD scores, subjects were divided into 10 deciles according to the percent of energy obtained from carbohydrates, proteins, and fats. Determination of total antioxidant activity was conducted using the ferric reducing antioxidant power (FRAP), 2, 2'-diphenyl-1-picrylhydrazyl (DPPH), thiobarbituric acid reactive substances (TBARs), and Ellman's assay. Biochemical assays of samples including calcium, total protein, and triglyceride level were also performed using commercial kits. RESULTS: Participants with the greatest LCD pattern adherence were placed into the last quartile (Q4), and those with the minimum LCD were in the first quartile (Q1). Individuals in the highest LCD quartile had significantly higher levels of milk FRAP, thiol, and protein, as well as infant urinary FRAP and lower milk MDA levels than those in the lowest quartile. Multivariate linear regression analyses indicated that higher score of the LCD pattern was associated with a higher level of milk thiol, protein, and lower level of milk MDA (p < 0.05). CONCLUSION: Our findings show that adherence to a LCD, as defined by a low level of carbohydrates in daily food intake, is linked with improved BM quality and markers of oxidative stress in infant urine.

Cellular and molecular basis of therapeutic approaches to breast cancer.

In recent decades, there has been a significant amount of research into breast cancer, with some important breakthroughs in the treatment of both primary and metastatic breast cancers. It's a well-known fact that treating breast cancer is still a challenging endeavour even though physicians have a fantastic toolset of the latest treatment options at their disposal. Due to limitations of current clinical treatment options, traditional chemotherapeutic drugs, and surgical options are still required to address this condition. In recent years, there have been several developments resulting in a wide range of treatment options. This review article discusses the cellular and molecular foundation of chemotherapeutic drugs, endocrine system-based treatments, biological therapies, gene therapy, and innovative techniques for treating breast cancer.

Recent advances in glioblastoma multiforme therapy: A focus on autophagy regulation.

Despite conventional treatment options including chemoradiation, patients with the most aggressive primary brain tumor, glioblastoma multiforme (GBM), experience an average survival time of less than 15 months. Regarding the malignant nature of GBM, extensive research and discovery of novel treatments are urgently required to improve the patients' prognosis. Autophagy, a crucial physiological pathway for the degradation and recycling of cell components, is one of the exciting targets of GBM studies. Interventions aimed at autophagy activation or inhibition have been explored as potential GBM therapeutics. This review, which delves into therapeutic techniques to block or activate autophagy in preclinical and clinical research, aims to expand our understanding of available therapies battling GBM.

Kisspeptin levels in relation to sex hormone profile among PCOS patients.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is a common endocrine disease among women in the reproductive age that is associated with consequences such as insulin resistance and hyperandrogenemia. This study was aimed to assess the association of sex hormone profile and kisspeptin levels in PCOS women in Gorgan, Iran. METHODS: In this case-control study, 43 women with diagnosed PCOS between the ages of 15 and 37 years and 40 healthy demographically matched controls were recruited. Sex hormone profile and kisspeptin levels were measured in these subjects using ELISA assay kits. RESULTS: Follicle stimulating hormone (FSH), sex hormone binding globulin (SHBG), and kisspeptin levels were significantly lower in cases than in controls. Luteinizing hormone (LH), free-testosterone (FT), 17-OH-progesterone (17-OH-P), dehydroepiandrosterone sulfate (DHEA-S), estradiol (E2), and free androgen index (FAI) were higher in PCOS significantly. There was a significant positive correlation between kisspeptin levels and LH and E2 in cases (p = 0.037 and p = 0.024, respectively). The results of the regression analysis have shown a significant association between the LH and kisspeptin concentrations in PCOS group (r = 0.275, p = 0.037). CONCLUSION: PCOS patients had lower plasma kisspeptin level that was positively correlated with LH and estradiol levels. Also, higher levels of free androgens were demonstrated in these patients. It is suggested that kisspeptin may be involved in complex interactions of the sex hormone endocrine system of PCOS.

The Prognostic Value of Small Noncoding microRNA-21 Expression in the Survival of Cancer Patients: A Meta-Analysis.

microRNA-21 (miR-21) is a small noncoding RNA that regulates gene expression in different types of human malignancies. The potential prognostic value of miR-21 in cancer progression is controversial. This meta-analysis includes 76 studies of 10,213 cancer patients to test miR-21 prognostic value in various human cancers. We obtain hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for overall survival (OS) to assess association strength. In the pooled analysis, high miR-21 expression is associated with poor OS, with a combined HR of 1.59 (95% CI, 1.49-1.70; p < 0.001; random-effects model). Furthermore, subgroup analysis demonstrates that high miR-21 expression is related to shorter OS in patients with digestive system cancers (HR = 1.02; 95% CI, 1.002 to 1.04; p = 0.026), respiratory system cancers (HR = 1.93; 95% CI, 1.48 to 2.51; p < 0.001), and breast cancer (HR = 2.20; 95% CI, 1.78 to 2.73; p = 0.001). These results indicate that miR-21 may be a clinically useful prognostic biomarker for cancer progression.

The Relationship between Tissue Thioredoxin Reductase Activity and the Psoriasis Area and Severity Index.

INTRODUCTION: Psoriasis is an autoimmune disease. The important role of oxidative stress in the pathogenesis of psoriasis had been investigated in different studies. Thioredoxin reductase (TrxR) is a selenocysteine-containing enzyme which is involved in the protection of cells against oxidative stress. Here, we investigated the TrxR activity in skin lesions of psoriatic patients and the possible correlation between this activity and the severity of the disease that was scored based on the Psoriasis Area and Severity Index (PASI). MATERIALS AND METHODS: TrxR activity was determined using TrxR colorimetric method based on the reduction of 5,5'-dithiobis-(2-nitrobenzoic acid) to 5-thio-2-nitrobenzoic acid by TrxR using nicotinamide adenine dinucleotide phosphate in 20 psoriatic patients (11 men and 9 women) aged 38.9 ± 12.6 years. For evaluating the disease severity, PASI score system (mild [PASI <10], moderate [PASI 10-20], or severe [PASI >20]) was utilized that was based on three factors including thickness, erythema, and scaling of lesions. RESULTS: Our results revealed that the TrxR activity between different groups of psoriatic patients (according to the PASI score) was statistically significant and it was higher in psoriatic patients with mild disease (correlation coefficient = -0.85). CONCLUSION: These results further strengthen the association between psoriasis and oxidative stress. The increased level of TrxR could be due to the protective effect of this enzyme against the inflammatory process and oxidative stress. Moreover, TrxR could be used as a novel marker for evaluating psoriasis severity.

Novel oral transforming growth factor-ß signaling inhibitor potently inhibits postsurgical adhesion band formation.

Here, we have investigated the therapeutic potency of EW-7197, a transforming growth factor-ß type I receptor kinase inhibitor, against postsurgical adhesion band formation. Our results showed that this pharmacological inhibitor prevented the frequency and the stability of adhesion bands in mice model. We have also shown that downregulation of proinflammatory cytokines, reduce submucosal edema, attenuation of proinflammatory cell infiltration, inhibition of oxidative stress, decrease in excessive collagen deposition, and suppression of profibrotic genes at the site of surgery are some of the mechanisms by which EW-7197 elicits its protective responses against adhesion band formation. These results clearly suggest that EW-7197 has novel therapeutic properties against postsurgical adhesion band formation with clinically translational potential of inhibiting key pathological responses of inflammation and fibrosis in postsurgery patients.

Prognostic value of high mobility group protein A2 (HMGA2) over-expression in cancer progression.

The high mobility group A2 (HMGA2; also called HMGI-C) gene is an architectural transcription factor that belonging to the high mobility group AT-hook (HMGA) gene family. HMGA2 is aberrantly regulated in several human tumors. Over-expression of HMGA2 is correlated with a higher risk of metastasis and an unfavorable prognosis in patients with cancer. We performed a meta-analysis to determine the clinic-pathological and prognostic value of HMGA2 overexpression in different human tumors. A comprehensive literature search was performed using PubMed, Embase, Cochrane Library, Scopus, MEDLINE, Google Scholar and ISI Web of Science. Hazard ratios (HRs)/odds ratios (ORs) and their 95% confidence intervals (CIs) were used to assess the strength of the association between HMGA2 expression and overall survival (OS)/progression free survival (PFS)/disease free survival (DFS). A total of 5319 patients with 19 different types of cancer from 35 articles were evaluated. Pooled data analysis indicated that increased HMGA2 expression in cancer patients predicted a poor OS (HR = 1.70; 95% CI = 1.6-1.81; P < 0.001; fixed-effect model). In subgroup analyses, high HMGA2 expression was particularly associated with poor OS in individuals with gastrointestinal (GI) cancer (HR = 1.89, 95% CI: 1.83-1.96; fixed-effect model) and HNSCC cancer (HR-1.78, 95%CI: 1.44-2.21; fixed-effect model). Over-expression of HMGA2 was associated with vascular invasion (OR = 0.16, 95% CI = 0.05-0.49; P = 0.001) and lymphatic invasion (OR = 1.89, 95% CI = 1.06-3.38; P = 0.032). Further studies should be conducted to validate the prognostic value of HMGA2 for patients with GI cancers.

Therapeutic potential of pharmacological TGF-ß signaling pathway inhibitors in the pathogenesis of breast cancer.

The TGF-ß signaling pathway plays an important role in cancer cell proliferation, growth, inflammation, angiogenesis, and metastasis. The role of TGF-ß signaling in the pathogenesis of breast cancer is complex. TGF-ß acts as a tumor suppressor in the early stages of disease, and as a tumor promoter in its later stages. Over-activation of the TGF-ß signaling pathway and over-expression of the TGF-ß receptors are frequently found in breast tumors. Suppression of TGF-ß pathway using biological or pharmacological inhibitors is a potentially novel therapeutic approach for breast cancer treatment. This review summarizes the regulatory role of TGF-ß signaling in the pathogenesis of breast cancer for a better understanding and hence a better management of this disease.

The prognostic value of long noncoding RNA MEG3 expression in the survival of patients with cancer: A meta-analysis.

Long noncoding RNAs (lncRNAs) play an important role in carcinogenesis and cancer progression. lncRNA maternally expressed gene 3 (MEG3) is a tumor suppressor that is downregulated in several cancers. However, its prognostic value in human malignancies remains controversial. We have therefore undertaken a meta-analysis to explore the relationship between cancer survival and the expression of lncRNA MEG3. A systematic literature search identified 13 potentially eligible investigations comprising 1733 patients in nine different cancer types. In the pooled analysis, a low expression of MEG3 was associated with low overall survival (OS) in patients with cancer having a combined hazard ratio (HR) of 0.830 (HR = 0.83; 95% CI: 0.70-0.98; p = 0.03; random effect model). However, subgroup analysis according to cancer type revealed that MEG3 expression was not associated with better OS in gastrointestinal cancer (HR = 0.58, 95% CI = 0.33-1.03; p = 0.06), and patients with breast cancer (HR = 0.85, 95% CI: 0.12-5.88; p = 0.87). In conclusion, our results demonstrate that only in the pooled analysis, there was a significant relationship between MEG3 expression and cancer survival. Further investigation of other molecular biomarkers involved in tumorigenesis-related pathways is necessary.

The prognostic value of MGMT promoter methylation in glioblastoma: A meta-analysis of clinical trials.

The DNA repair protein O6-Methylguanine-DNA methyltransferase (MGMT) is suggested to be associated with resistance to alkylating agents such as Temozolomide which is being used in treatment of patients with glioblastoma (GBM). Therefore, we evaluated the associations between MGMT promoter methylation and prognosis of patients with glioblastoma (GBM). Data were extracted from publications in Embase, PubMed, and the Cochrane Library. Data on overall survival (OS), progression-free survival (PFS), and MGMT methylation status were obtained and 4,097 subjects were enrolled. Data from 34 studies showed that MGMT methylated patients had better OS, compared to GBM unmethylated patients (pooled HRs, 0.494; 95%CI 0.412-0.591; p = 0.001). Meta-analysis of 10 eligible studies reporting on PFS, demonstrated that MGMT promoter methylation was not significantly associated with better PFS (pooled HRs, 0.653; 95%CI 0.414-1.030; p = 0.067). GBM patients with MGMT methylation were associated with longer overall survival, although this effect was not detected for PFS. Moreover, we performed further analysis in patients underwent a comprehensive imaging evaluation. This data showed a significant association with better OS and PFS, although further studies are warranted to assess the value of emerging marker in prospective setting in patients with glioblastoma as a risk stratification biomarker in clinical management of the patients.