Comprehensive analysis of the role of ubiquitin-specific peptidases in colorectal cancer: A systematic review.

BACKGROUND: Colorectal cancer (CRC) is the third most frequent and the second most fatal cancer. The search for more effective drugs to treat this disease is ongoing. A better understanding of the mechanisms of CRC development and progression may reveal new therapeutic strategies. Ubiquitin-specific peptidases (USPs), the largest group of the deubiquitinase protein family, have long been implicated in various cancers. There have been numerous studies on the role of USPs in CRC; however, a comprehensive view of this role is lacking. AIM: To provide a systematic review of the studies investigating the roles and functions of USPs in CRC. METHODS: We systematically queried the MEDLINE (via PubMed), Scopus, and Web of Science databases. RESULTS: Our study highlights the pivotal role of various USPs in several processes implicated in CRC: Regulation of the cell cycle, apoptosis, cancer stemness, epithelial-mesenchymal transition, metastasis, DNA repair, and drug resistance. The findings of this study suggest that USPs have great potential as drug targets and noninvasive biomarkers in CRC. The dysregulation of USPs in CRC contributes to drug resistance through multiple mechanisms. CONCLUSION: Targeting specific USPs involved in drug resistance pathways could provide a novel therapeutic strategy for overcoming resistance to current treatment regimens in CRC.

Association of nonalcoholic fatty liver disease with the different types of dietary carbohydrates: a cross-sectional study.

Background: Many factors like sedentary lifestyle, metabolic syndrome, and obesity are involved in the increased prevalence of nonalcoholic fatty liver disease (NAFLD). Dietary consumption of carbohydrates may has a role in the risk of NAFLD. This study aimed to investigate the association of NAFLD with the different types of dietary carbohydrates. Methods: This cross-sectional study was carried out on 4200 participants including 660 patients with NAFLD and 3540 helathy individuals without NAFLD ages 35 to 70 in sabzevar, Iran. Data on socio-deomgraphic status, anthropomrtric measurments, blood tests, and dietary intake of different types of dietary carbohydrates was collected. Results: The patients with NAFLD had a significantly higher dietary intake of glucose (29.38 ± 18.29 vs. 27.42 ± 15.96 g/d, P = 0.01) and fructose (33.99 ± 20.19 vs. 31.95 ± 18.34 g/d, P = 0.01) compared to the healthy people. A positive association was observed between NAFLD with the total intake of carbohydrates after adjustment for age, sex, and BMI (OR: 1.001, CI 95%: 1-1.002, P = 0.04) The association remained significant after further adjustments for for education level, marital status, physical activity, smoking, and drinking alcohol (Model 2) and after additional adjustments for calorie intake (Model 3). Conclusions: This study showed a positive association between total dietary carbohydrate and NAFLD. In particular, the amount of dietary of carbohydrates (regardless of the type of carbohydrate) may worsen NAFLD. Further longitudinal studies are warranted.

Associations between the dietary inflammatory index with obesity and body fat in male adolescents.

BACKGROUND: Obesity and body composition may be affected by the pro-inflammatory and anti-inflammatory components of diets. The aim of this study was to investigate associations between the dietary inflammatory index (DII) and body fat percentage (BF%) in male adolescents. METHODS: This cross-sectional study was carried out on 535 adolescent boys in Tehran, Iran. Bio-impedance analyzer (BIA) scale was used to measure body mass index (BMI) and body composition. A validated semi-quantitative food frequency questionnaire (FFQ) was used to measure DII. RESULTS: Participants with higher BF% (≥ 19.2%) had higher BMI (P < 0.001), DII, and intake of saturated fatty acids (SFAs), compared with the participants with lower BF%. Participants with a lower DII had significantly higher intakes of fibers (P < 0.001) and lower intakes of fats, SFAs, monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), oleic acid and linoleic acid (P < 0.05) compared with the participants with higher DII (P < 0.01). High BF% was positively associated to DII (OR = 1.6, CI 95%: 1.1-2.3, P = 0.019). Adjustments for age, BMI, physical activity, mothers' marital status and educational level and the number of siblings did not change the results. CONCLUSIONS: Following a diet with a low inflammatory index score was associated to lower BF% in male adolescents. Thus, a diet rich in anti-inflammatory factors may effectively improve body composition and prevent obesity in adolescents. Further comprehensive studies are necessary to verify these findings and to identify the underlying mechanisms.

Effect of glutamine supplementation on inflammatory markers in critically ill patients supported with enteral or parenteral feeding.

BACKGROUND: Glutamine plays an important role in acute catabolic conditions in critically ill patients. This meta-analysis aimed to investigate the effect of glutamine supplementation on inflammatory markers in critically ill patients supported with enteral feeding (EN) or parenteral feeding (PN). METHODS: PubMed, Web of Science, Scopus, and Embase were explored to identify the studies investigating the effect of glutamine on serum inflammatory markers in intensive care unit patients. All randomized clinical trials that assessed the effect of glutamine supplementation on "inflammatory markers" in EN or PN were included in the study. Because a small number of studies were included, SE was adjusted for overall effect size by using the Knapp-Hartung method. RESULTS: In this study, 2728 eligible studies were initially included, and 10 eligible case-control studies were finally enrolled for further investigations. There was a statistical reduction between preintervention and postintervention CRP levels (standardized mean difference [SMD] = -0.38 mg/L; 95% CI, -0.72 to -0.03). No significant association was found between L-glutamine supplementation in the EN/PN and interleukin 6 (IL-6) (SMD = -0.58 pg/ml; 95% CI, -2.15 to 0.99) and tumor necrosis factor alpha (TNF-α) (SMD = 2.69 pg/ml; 95% CI, -9.66 to 15.03) compared with the control group. CONCLUSIONS: This study identified that glutamine supplementation might have an important effect on CRP in acute conditions and no significant effect on IL-6 and TNF-α in acute conditions.

The Potential Role of Extracellular Vesicles in COVID-19 Treatment: Opportunity and Challenge.

SARS-CoV-2 infection has become an urgent public health concern worldwide, severely affecting our society and economy due to the long incubation time and high prevalence. People spare no effort on the rapid development of vaccine and treatment all over the world. Amongst the numerous ways of tackling this pandemic, some approaches using extracellular vesicles (EVs) are emerging. In this review, we summarize current prevalence and pathogenesis of COVID-19, involving the combination of SARS-CoV-2 and virus receptor ACE2, endothelial dysfunction and micro thrombosis, together with cytokine storm. We also discuss the ongoing EVs-based strategies for the treatment of COVID-19, including mesenchymal stem cell (MSC)-EVs, drug-EVs, vaccine-EVs, platelet-EVs, and others. This manuscript provides the foundation for the development of targeted drugs and vaccines for SARS-CoV-2 infections.

The Impact of COVID-19 on Cancer Care in the Post Pandemic World: Five Major Lessons Learnt from Challenges and Countermeasures of Major Asian Cancer Centres.

OBJECTIVE: The COVID-19 pandemic has dramatically affected healthcare services around Asia. The Asian National Cancer Centres Alliance and the Asia-Pacific Organisation for Cancer Prevention collaborated to assess the mid- and long- term impact of COVID-19 to cancer care in Asia. METHODS: The two entities organised a combined symposium and post-meeting interactions among representatives of major cancer centres from seventeen Asian countries to outlining major challenges and countermeasures. RESULTS: Participating stakeholders distilled five big questions. 1) "Will there be an explosion of late-stage cancers after the pandemic?" To address and recover from perceived delayed prevention, screening, treatment and care challenges, collaboration of key stakeholders in the region and alignment in cancer care management, policy intervention and cancer registry initiatives would be of essential value. 2) "Operations and Finance" The pandemic has resulted in significant material and financial casualties. Flagged acute challenges (shortages of supplies, imposition of lockdown) as well as longer-standing reduction of financial revenue, manpower, international collaboration, and training should also be addressed. 3) "Will telemedicine and technological innovations revolutionize cancer care?" Deploying and implementing telemedicine such as teleconsultation and virtual tumour boards were considered invaluable. These innovations could become a new regular practice, leading to expansion of tele-collaboration through collaboration of institutions in the region. 4) "Will virtual conferences continue after the pandemic?" Virtual conferences during the pandemic have opened new doors for knowledge sharing, especially for representatives of low- and middle-income countries in the region, while saving time and costs of travel. 5) "How do we prepare for the next pandemic or international emergency?" Roadmaps for action to improve access to appropriate patient care and research were identified and scrutinised. CONCLUSION: Through addressing these five big questions, focused collaboration among members and with international organisations such as City Cancer Challenge will allow enhanced preparedness for future international emergencies.
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Review on the Oncology Practice in the Midst of COVID-19 Crisis: The Challenges and Solutions.

As of late 2019, the outbreak of novel coronavirus disease (COVID-19) -that started in China- has rapidly afflicted all over the world. The COVID-19 pandemic has challenged health-care facilities to provide optimal care. In this context, cancer care requires special attention because of its peculiar status by including patients who are commonly immunocompromised and treatments that are often highly toxic. In this review article, we have classified the main impacts of the COVID-19 pandemic on oncology practices -followed by their solutions- into ten categories, including impacts on (1) health care providers, (2) medical equipment, (3) access to medications, (4) treatment approaches, (5) patients' referral, (6) patients' accommodation, (7) patients' psychological health, (8) cancer research, (9) tumor board meetings, and (10) economic income of cancer centers. The effective identification and management of all these challenges will improve the standards of cancer care over the viral pandemic and can be a practical paradigm for possible future crises.
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Index of Nutritional Quality (INQ) and the Risk of Obesity in Male Adolescents: a Case-Control Study.

Dietary factors may play a key role in the etiology of obesity. The Index of Nutritional Quality (INQ) provides a comprehensive overview of the nutrients content of the diet. This study aimed to investigate the association between INQ and obesity in male adolescents. We hypothesize that receiving a high-quality diet reduces the risk of overweight or obese. This study was carried out on 214 obese/overweight as the case group and 321 normal-weight male adolescents as the control group. Dietary intakes of the participants were collected using a food frequency questionnaire (FFQ). The FFQ-derived dietary data were used to calculate the INQ scores. After adjustments for age and height, an inverse association was found between obesity and INQ of iron, vitamin B6, and magnesium, and a positive association was found between obesity and INQ of zinc (all P < 0.05). After further adjustments for nutritional knowledge and calorie intake, an inverse association was observed between obesity and INQ of vitamin C, iron, vitamin B6, pantothenic acid, selenium, and magnesium (all P < 0.05). The positive association of obesity and INQ of zinc remained significant after adjustments. A higher intake of vitamin C, iron, vitamin B6, pantothenic acid, selenium, and magnesium and a lower intake of zinc may be protective against adolescent obesity. More longitudinal studies are required to investigate the relationship between these nutrients and obesity.

Association between FTO gene polymorphisms and breast cancer: the role of estrogen.

Introduction: The fat mass and obesity-associated (FTO) gene may be associated with breast cancer risk. This study aimed to systematically investigate the association between FTO gene polymorphisms and breast cancer and the possible role of estrogen in this association.Areas covered: We performed an extensive search of electronic databases such as PubMed, Science Direct, Scopus, and Cochran for published original studies on the association of FTO gene polymorphisms with breast cancer risk. Keywords such as breast cancer and/or FTO gene and/or polymorphism were used in order to identify the related articles. We excluded studies unrelated to the FTO genotype and the outcome of breast cancer.Expert opinion: FTO gene may have a significant association with the risk of breast cancer. The association between FTO gene polymorphisms and breast cancer was influenced by the status of estrogen receptors. Estrogen may promote breast cancer cell proliferation through up-regulation of FTO gene expression and activation of the PI3 K/Akt signaling pathway in estrogen receptor positive patients. Further studies are warranted to identify the underlying mechanisms and signaling pathways involved in the interactions between FTO gene, estrogen, and the risk of breast cancer.

Interactions between macro-nutrients' intake, FTO and IRX3 gene expression, and FTO genotype in obese and overweight male adolescents.

This study is the first to identify the effects of FTO genotype on the interactions between the level of macro-nutrients intake and the expression level of fat mass and obesity associated (FTO) and homeobox transcription factor iriquois-3 (IRX3) genes This longitudinal study was carried out on 84 overweight and obese adolescent boys in Tehran, Iran. The rs9930506 SNP in FTO was genotyped at baseline and the level of FTO and IRX3 expression in PBMCs and macro-nutrients' intake were assessed at baseline and after 18 weeks of the intervention. The results identified that the higher carbohydrates intake significantly up-regulated the FTO gene (P = 0.001) and down-regulated the IRX3 gene (P = 0.01). Protein intake up-regulated the FTO gene (P = 0.001). In carriers of GG genotype of FTO gene, the amount of dietary carbohydrate had a positive association with FTO gene expression (p = 0.001, and p = 0.04, respectively). In AA/AG carriers, dietary protein was positively associated with FTO gene expression (p = 0.001) and dietary carbohydrate was negatively associated with IRX3 gene expression (P = 0.04). Therefore, dietary carbohydrateseems to be associated with FTO and IRX3 genes expression. These associations are influenced by FTO genotype.

Up-regulation of FTO gene expression was associated with increase in skeletal muscle mass in overweight male adolescents.

INTRODUCTION: The modifying effect of FTO gene expression level on change in body mass index and body composition has not been studied before. This study aimed to investigate the association between change in the expression level of the FTO gene and changes in anthropometric measurements in obese and overweight adolescent boys. MATERIAL AND METHODS: Eighty-four boys aged 12 to 16 years participated in this longitudinal study. A Bio Impedance Analyzer (BIA) was used to estimate percentage of body fat (%BF) and percentage of skeletal muscle (%SM). The FTO gene expression level in peripheral blood mononuclear cells was assessed using quantitative real-time PCR (qPCR). All measurements were performed at baseline and after 18 weeks. RESULTS: After 18 weeks, mean weight was reduced by 2.39 kg, body mass index by 0.09 kg/m2, %BF by 0.82% and %SM increased by 0.44%. Moreover, the level of FTO gene expression increased 0.42-fold higher than baseline. The change in expression level of the FTO gene was positively associated with change in %SM (ß = 0.31, p = 0.02). CONCLUSIONS: FTO gene expression change was associated with change in %SM in male adolescents. Future studies are required to assess the interactions between FTO gene expression in different tissues and body composition.

Burden Assessment of Thyroid cancer in Iran from 1990 to 2010: Lessons Obtained from Global Burden of Disease Report 2010.

BACKGROUND: Thyroid tumors are generally regarded as rare malignancies. Nowadays, however, their global incidence is growing continuously partially due to western life style and utilization of more sensitive methods of early detection. It is approximately three times more prevalent in females than in males. Most cases of thyroid cancer are asymptomatic nodules or just have local cervical symptoms or adenopathy in early stages. MATERIALS AND METHODS: The Global Burden of Diseases report 2010 study (released 3/2013) profited from 100 collaborators worldwide and used a vast network of data on health outcomes, vital registries, and population surveys. It shared many of the Global Burden of Diseases 1990 principal databases such as all available data on injuries, diseases, risk factors, as well as comparable metrics, and used different scientific approved methods to estimate important health status data like: death rate, life expectancy, healthy adjusted life expectancy, disability-adjusted life years (DALY), years of living lost due to premature death and years of life with disabilities. RESULTS: DALY as thyroid cancer burden per 100,000 Iranian populations had increased by about 14% during 1990 to 2010 in all ages; from 6.1 (95% UI 4.2-9.74) years in 1990 to 6.95 (95% UI 5.06-9.18) years in 2010 in both sex. The 2010 peak age-group was estimated at 45-49 years in males and 40-45 years in females.

Time trends in the occurrence of major GI cancers in Iran.

OBJECTIVE: The aim of this study was to study the changes in occurrence of esophageal, stomach and colon cancers (cancers of interest) over the last 30 years in Iran. MATERIAL AND METHODS: Cancer cases referred to two main cancer centers in the country (the Shiraz cancer center and the Tehran cancer center) during last 30 years and published by the two centers were utilized. Morbidity odds ratios (MOR) were used to study trend in the occurrence of each cancer site in each center. For this purpose the cancers of interest were considered as cases; childhood cancers as controls; and calendar year as exposure. A regression line was fitted to morbidity odds ratios over years and the slope of the regression line was considered to indicate the overall trend. MORs and 95% CIs comparing the last five and first five years were computed to measure the magnitude of the change over time. RESULT: The overall trend for esophageal cancer was decrease (slopes = -0.02 for Shiraz and -0.03 for Tehran); for stomach was increase (slopes = 0.04 for Shiraz and 0.08 for Tehran), and for colon cancer was sharp increase (slopes = 0.02 for Shiraz and 0.10 for Tehran). The magnitude of changes showed stomach cancer to increase by 35% in Shiraz (MOR = 1.35 with 95% CI 1.1, 1.65) and 13% in Tehran (MOR = 1.13 with 95% CI 0.96, 1.38), esophageal cancer to decrease by 20% in Shiraz (MOR = 0.82 with 95% CI 0.62, 1.11) and 50% in Tehran (MOR = 0.52 with 95% CI 0.45, 0.60), and colon cancer to increase by 65% in Shiraz (MOR = 1.65 with 95% CI 1.26, 2.16) and 82% in Tehran (MOR = 1.82 with 95% CI 1.52, 2.25). CONCLUSION: During the last thirty years the occurrence of major GI cancers has changed in Iran with sharp increase in colon cancer, slight to moderate increase in stomach cancer and sharp decrease in esophageal cancer.

Grand challenges in global health and the practical prevention program? Asian focus on cancer prevention in females of the developing world.

In response to the request for 'Breakthrough Questions' for 'Grand Challenges in Global Health' recently published in Nature, the Asian Pacific Organization for Cancer Prevention should focus its attention on what projects are of the highest priority for integration with its Practical Prevention Program (PPP). The most common female cancers in most of the countries of Asia are carcinoma of the breast, followed by the uterine cervix. While the incidences of breast adenocarcinomas are still generally lower than in the Western world they are rapidly increasing, and squamous cell carcinomas of the cervix are a major problem. Clearly there are many areas which would reward research. One factor which appears of major relevance in the mammary gland case is the diet, and particularly the phytoestrogens included in 'tofu', along with physical exercise. The age at which these could be operating needs to be elucidated, with reference to timing of menarche and menopause, and also breast mammographic density, another predictor of likelihood of neoplasia. In the cervix, the predominant influence is well established to be persistent infection with a high risk 'oncogenic' type of human papilloma virus (HPV). Vaccines therefore hold much promise, but a better understanding of the mechanisms underlying spontaneous clearance of both infection and cervical intraepithelial neoplasia (CIN) of different grades is also essential for optimal intervention. The roles of smoking and antioxidant intake in particular deserve emphasis. In Asia, with the considerable variation evident in both breast and cervical cancer incidence rates, as well as in cultural and other environmental factors, we are in a very favourable position to meet two specific challenges: 1). elucidation of how diet in adolescence determines susceptibility to neoplasia of the mammary glands; and 2). determination of what governs persistence of HPV infection. Realisation of these pivotal research aims, with especial emphasis on the context of the PPP, is our shared goal.