Bilirubin, an endogenous antioxidant that affects p53 protein and its downstream apoptosis/autophagy-related genes in LS180 and SW480 cell culture models of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the commonest neoplasms worldwide, which its pathogenesis is strongly correlated with p53 mutations. Antioxidants are believed to decelerate the CRC progression, possibly through interfering with p53 and its downstream target genes and mechanisms. Regarding the potential antioxidant effects of bilirubin, as an incredible endogenous antioxidant, we sought to investigate how bilirubin affected the expression levels of p53 protein and its downstream target genes, including Mdm2, Bcl-2, BECN1 and LC3, in LS180 and SW480 cell culture models of CRC. METHODS AND RESULTS: Using the MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazolium bromide) assay, 50 and 100 µM concentrations of bilirubin were determined to be non-toxic for both LS180 and SW480 cell lines. Western blot analysis was employed to evaluate the protein expression levels of p53. The results revealed that p53 protein levels were higher in LS180 cells treated with bilirubin compared to the control group. Notwithstanding, in SW480 cells, no considerable changes were observed in p53 protein levels of treated cells compared to the control ones. The quantitative reverse transcriptase-polymerase chain reaction (q RT-PCR) method was used to measure the mRNA expression levels of the apoptosis/autophagy-related genes, Mdm2, Bcl-2, BECN1, and LC3 , as the p53's downstream target genes. Consequently, the expression of Bcl-2 and Mdm2 genes were affected by p53, while BECN1 and LC3 expression levels were decreased in both cell lines. CONCLUSION: Bilirubin is an endogenous antioxidant with significant anti-tumor effects in the studied CRC cell lines, probably through the regulation of p53 protein expression levels and subsequent control of apoptosis and autophagy, as two key processes involved in cell survival and progression of tumor cells.

Surgical debridement and maggot debridement therapy can survive patient with diabetic foot ulcer after foot trauma: A case report.

INTRODUCTION AND IMPORTANCE: Diabetic foot ulcers, a common issue associated with diabetes, can pose challenges in treatment, especially when they do not respond to traditional therapies. Maggot therapy, known as larval therapy, has surfaced as a substitute approach for managing stubborn wounds. CASE PRESENTATION: A 42-year-old male with a history of type 2 diabetes and peripheral neuropathy presents at the clinic with a long-lasting sore on the bottom of his right foot. The individual reveals that the ulcer has persisted for multiple months and has shown no improvement despite trying different remedies like creams and dressings. CLINICAL DISCUSSION: Diabetic foot ulcers are significant complications associated with diabetes, commonly triggered by neuropathy, peripheral artery disease, and impaired wound healing mechanisms. These ulcers can result in severe infections, amputations, and reduced quality of life for those affected. CONCLUSION: Maggot therapy arises as a valuable additional option for chronic ulcers in diabetic patients, providing a secure and efficient method for cleaning wounds and promoting healing.

Hemorrhagic stroke as a rare complication of opening the permanent dialysis catheter by Reteplase: A case report study.

INTRODUCTION AND IMPORTANCE: Thrombosis of permanent hemodialysis catheters is one of the most important problems in hemodialysis centers. Drug methods such as heparin, aspirin and warfarin along with urokinase are used to keep these catheters open. CASE PRESENTATION: The present case report is of a 52-year-old Kurdish patient with a 7-year history of type 2 diabetes and hypertension leading to end-stage renal disease (ESRD). The patient has been undergoing hemodialysis for two months with two 3-h sessions per week. After several dialysis sessions, the patient is referred to Imam Khomeini Hospital in Urmia to open the catheter due to dysfunction. Because of catheter dysfunction, Reteplase (Retavase; Centocor, Malvern, PA) was administered at a dose of 3 U/lm (total dose 6 U). After administration of reteplase, the patient experienced sudden onset of headache and arterial hypertension. A computed tomography scan (CT) was immediately performed and revealed hemorrhagic stroke. Unfortunately, due to the extensive hemorrhagic stroke, the patient died one day later. CLINICAL DISCUSSION: Retavase (reteplase) is a thrombolytic drug used to dissolve blood clots. Reteplase increases your risk for bleeding, which can be severe or life-threatening. CONCLUSION: Thrombolysis with tissue plasminogen activator has been shown to be useful in some conditions. However, reteplase has a narrow therapeutic window and serious side effects, such as an increased risk of bleeding.

The crosstalk between ubiquitin-conjugating enzyme E2Q1 and p53 in colorectal cancer: An in vitro analysis.

Colorectal cancer (CRC) is a prevalent gastrointestinal neoplasm that ranks fourth in terms of cancer-related deaths worldwide. In the process of CRC progression, multiple ubiquitin-conjugating enzymes (E2s) are involved; UBE2Q1 is one of those newly identified E2s that is markedly expressed in human colorectal tumors. Since p53 is a well-known tumor suppressor and defined as a key factor to be targeted by the ubiquitin-proteasome system, we hypothesized that UBE2Q1 might contribute to CRC progression through the modulation of p53. Using the lipofection method, the cultured SW480 and LS180 cells were transfected with the UBE2Q1 ORF-containing pCMV6-AN-GFP vector. Then, quantitative RT-PCR was used to assay the mRNA expression levels of p53's target genes, i.e., Mdm2, Bcl2, and Cyclin E. Moreover, Western blot analysis was performed to confirm the cellular overexpression of UBE2Q1 and assess the protein levels of p53, pre- and post-transfection. The expression of p53's target genes were cell line-dependent except for Mdm2 that was consistent with the findings of p53. The results of Western blotting demonstrated that the protein levels of p53 were greatly lower in UBE2Q1-transfected SW480 cells compared to the control SW480 cells. However, the reduced levels of p53 protein were not remarkable in the transfected LS180 cells compared to the control cells. The suppression of p53 is believed to be the result of UBE2Q1-dependent ubiquitination and its subsequent proteasomal degradation. Furthermore, the ubiquitination of p53 can act as a signal for degradation-independent functions, such as nuclear export and suppressing the p53's transcriptional activities. In this context, the decreased Mdm2 levels can moderate the proteasome-independent mono-ubiquitination of p53. The ubiquitinated p53 modulates the transcriptional levels of target genes. Therefore, the up-modulation of UBE2Q1 may influence the transcriptional activities depending on p53, and thereby contributes to CRC progression through regulating the p53.

Autophagy and Ubiquitination as Two Major Players in Colorectal Cancer: A Review on Recent Patents.

BACKGROUND: As one of the most commonly diagnosed cancers among men and women, Colorectal Cancer (CRC) leads to high rates of morbidity and mortality across the globe. Recent anti- CRC therapies are now targeting specific signaling pathways involved in colorectal carcinogenesis. Ubiquitin Proteasome System (UPS) and autophagy are two main protein quality control systems, which play major roles in the carcinogenesis of colorectal cancer. A balanced function of these two pathways is necessary for the regulation of cell proliferation and cell death. OBJECTIVE: In this systematic review, we discuss the available evidence regarding the roles of autophagy and ubiquitination in progression and inhibition of CRC. METHODS: The search terms "colorectal cancer" or "colon cancer" or "colorectal carcinoma" or "colon carcinoma" in combination with "ubiquitin proteasome" and "autophagy" were searched in PubMed, Web of Science, and Scopus databases, and also Google Patents (https://patents.google .com) from January 2000 to Feb 2020. RESULTS: The most important factors involved in UPS and autophagy have been investigated. There are many important factors involved in UPS and autophagy but this systematic review shows the studies that have mostly focused on the role of ATG, 20s proteasome and mTOR in CRC, and the more important factors such as ATG8, FIP200, and TIGAR factors that are effective in the regulation of autophagy in CRC cells have not been yet investigated. CONCLUSION: The most important factors involved in UPS and autophagy such as ATG, 20s proteasome and mTOR, ATG8, FIP200, and TIGAR can be considered in drug therapy for controlling or activating autophagy.

Persuasive discourse impairments in traumatic brain injury.

BACKGROUND: Considering the cognitive and linguistic complexity of discourse production, it is expected that individuals with traumatic brain injury (TBI) should face difficulties in this task. Therefore, clinical examination of discourse has become a useful tool for studying and assessment of communication skills of people suffering from TBI. Among different genres of discourse, persuasive discourse is considered as a more cognitively demanding task. However, little is known about persuasive discourse in individuals suffering from TBI. OBJECTIVES: The purpose of this study was to evaluate the performance of adults with TBI on a task of spoken persuasive discourse to determine the impaired linguistic measures. PATIENTS AND METHODS: Thirteen TBI nonaphasic Persian speaking individuals, ranged between 19 to 40 years (Mean = 25.64 years; SD = 6.10) and 59 healthy adults matched by age, were asked to perform the persuasive discourse task. The task included asking the participants to express their opinion on a topic, and after the analysis of the produced discourse, the two groups were compared on the basis of their language productivity, sentential complexity, maze ratio and cohesion ratio. RESULTS: The TBI group produced discourses with less productivity, sentential complexity, cohesion ratio and more maze ratio compared the control group. CONCLUSIONS: As it is important to consider acquired communication disorders particularly discourse impairment of brain injured patients along with their other clinical impairments and regarding the fact that persuasive discourse is crucial in academic and social situations, the persuasive discourse task presented in this study could be a useful tool for speech therapists, intending to evaluate communication disorders in patients with TBI.

An Analytical Comparison of the Opinions of Physicians Working in Emergency and Trauma Surgery Departments at Tabriz and Vienna Medical Universities Regarding Family Presence during Resuscitation.

The present study evaluated the opinions of physicians working in the emergency and trauma surgery departments of Vienna Medical University, in Austria, and Tabriz Medical University, in Iran, regarding the presence of patients' relatives during resuscitation. In a descriptive-analytical study, the data obtained from questionnaires that had been distributed randomly to 40 specialists and residents at each of the participating universities were analyzed. The questionnaire consisted of two sections aimed at capturing the participants' demographic data, the participants' opinions regarding their support for the family's presence during resuscitation, and the multiple potential factors affecting the participants' attitudes, including health beliefs, triggers that could facilitate the procedure, self-efficacy, intellectual norms, and perceived behavioral control. The questionnaire also included a direct question (Question 16) on whether the participants approved of family presence. Each question could be answered using a Likert-type scale. The results showed that the mean scores for Question 16 were 4.31 ± 0.64 and 3.57 ± 1.31 for participants at Vienna and Tabriz universities, respectively. Moreover, physicians at Vienna University disapproved of the presence of patients' families during resuscitation to a higher extent than did those at Tabriz University (P = 0.018). Of the studied prognostic factors affecting the perspectives of Vienna Medical University's physicians, health beliefs (P = 0.000; B = 1.146), triggers (P = 0.000; B = 1.050), and norms (P = 0.000; B = 0.714) were found to be significant. Moreover, of the studied prognostic factors affecting the perspectives of Tabriz Medical University's physicians, health beliefs (P = 0.000; B = 0.875), triggers (P = 0.000; B = 1.11), self-efficacy (P = 0.001; B = 0.5), and perceived behavioral control (P = 0.03; B = 0.713) were significant. Most physicians at Vienna and Tabriz Medical universities were not open towards family members' presence during resuscitation.

Opposite Clear Corneal Incisions versus Steep Meridian Incision Phacoemulsification for Correction of Pre-existing Astigmatism.

PURPOSE: To compare the efficacy of adding an opposite clear corneal incision (OCCI) on the steep meridian versus performing surgery on the steep meridian alone during phacoemulsification in reducing pre-existing corneal astigmatism. METHODS: This randomized clinical trial was performed on 120 eyes with corneal astigmatism of >1D undergoing phacoemulsification. Incisions were made based on the type of astigmatism as follows: superior or superior+OCCI for with-the-rule and temporal or temporal+OCCI for against-the-rule astigmatism. Patients were followed with refraction, keratometry and topography. Statistical analysis was performed using one- and two-way ANOVA and Tukey-a test. RESULTS: Mean corneal astigmatism was 1.82±0.86 D in the superior+OCCI group and 1.74±0.86 D in the temporal+OCCI group preoperatively which decreased to 1.31±0.59(P=0.013) and 1.19±0.64 (P=0.009) postoperatively respectively. No significant change occurred in the amount of astigmatism in any of the two single incision groups. CONCLUSION: Paired OCCI on the steep axis is a useful technique to correct mild to moderate pre-existing astigmatism with no need for particular skill or additional instruments.