Dose-Dependent Impacts of Omega-3 Fatty Acids Supplementation on Anthropometric Variables in Patients With Cancer: Results From a Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Meta-analyses have been conducted with conflicting results on this topic. Due to missing several eligible studies in previous meta-analysis by Lam et al., we conducted an extensive systematic review and dose-response meta-analysis of randomized controlled trials in this regard. A comprehensive search was conducted across various databases, including MEDLINE/PubMed, ISI Web of Knowledge, Scopus, and Google Scholar, until November 2023. Based on the analysis of 33 studies comprising 2,047 individuals, it was found that there was a significant increase in body weight for each 1 g/day increase in omega-3 lipids (standardized MD [SMD], 0.52 kg; 95% confidence interval [CI], 0.31, 0.73; I2 = 95%; Grading of Recommendations Assessment, Development and Evaluation [GRADE] = low). Supplementation of omega-3 fatty acids did not yield a statistically significant impact on body mass index (BMI) (SMD, 0.12 kg/m2; 95% CI, -0.02, 0.27; I2 = 79%; GRADE = very low), lean body mass (LBM) (SMD, -0.02 kg; 95% CI, -0.43, 0.39; I2 = 97%; GRADE = very low), fat mass (SMD, 0.45 kg; 95% CI, -0.25, 1.15; I2 = 96%; GRADE = low), and body fat (SMD, 0.30%; 95% CI, -0.90, 1.51; I2 = 96%; GRADE = very low). After excluding 2 studies, the findings were significant for BMI. Regarding the results of the dose-response analysis, body weight increased proportionally by increasing the dose of omega-3 supplementation up to 4 g/day. Omega-3 fatty acid supplementation can improve body weight, but not BMI, LBM, fat mass, or body fat in cancer patients; large-scale randomized trials needed for more reliable results. Trial Registration: PROSPERO Identifier: CRD42023395341.

Dose-dependent effect of megestrol acetate supplementation in cancer patients with anorexia-cachexia syndrome: A meta-analysis.

There is inconsistent evidence relating to the effects of megestrol acetate (MA) supplementation on cancer patients suffering from anorexia-cachexia syndrome. This review aimed to examine the dose-response effect of MA supplementation in patients with cancer-associated anorexia/cachexia. Relevant keywords were searched in PubMed, Scopus and ISI Web of Science from inception to June 2023 for randomized controlled trials (RCTs) examining the effect of MA on pathologies in patients with cancer-associated cachexia. Our primary outcomes were changes in body weight and appetite. However, fatigue and quality of life were secondary outcomes. The mean difference (MD) and 95% confidence interval (95% CI) were estimated using the random-effects method. Thirteen trials comprising 1229 participants (mean age 60 years) were identified. The results of our highest versus lowest analysis revealed that MA supplementation was not associated with any increase in body weight (MD: 0.64 kg, 95% CI [-0.11, 1.38], P = 0.093, I2 = 69.1%; GRADE = very low certainty). Twelve trials, including 14 effect sizes derived from 1369 patients (intervention = 689, control = 680), provided data on the effect of MA on body weight. Subgroup analyses showed a significant increase in body weight following short-term intervention (≤8 weeks) and a combination of radiation/chemotherapy as concurrent treatment. A linear dose-response meta-analysis indicated that each 200 mg/day increment in MA consumption had a significant increase in weight gain (MD: 0.44; 95% CI [0.13, 0.74], P = 0.005; I2 = 97.1%); however, the magnitude of the effect was small. MA administration significantly affected the quality of life based on pooled effect sizes (MD: 1.15, 95% CI [0.76, 1.54], P < 0.001, I2 = 0%; n = 2 RCTs including 176 patients; GRADE = very low certainty). However, no significant effect of MA supplementation was observed on appetite (MD: 0.29, 95% CI [-0.05, 0.64], P = 0.096, I2 = 18.3%; n = 3 RCTs including 163 patients; GRADE = very low certainty) and fatigue (MD: 0.14, 95% CI [-0.09, 0.36], P = 0.236, I2 = 0%; n = 2 RCTs including 300 patients; GRADE = very low certainty). With very low certainty of the evidence, MA supplementation may not lead to a significantly increased weight gain and other outcomes.

The effect of climatic variables and techno-structural factors on the water pollution caused by nicotine leakage from littered cigarette butts.

Nicotine is one of the main pollutants in cigarette smoke that trapped in the filter. Nicotine leakage from cigarette butts is one of the concerns associated with this hazardous waste. In this study, the concentration of nicotine leaked from cigarette butts into the urban environment was investigated under the influence of three parameters including rainfall, density, and the durability of the littered cigarette butt. The leakage of nicotine into the environment was estimated in six scenarios based on the difference in the durability of cigarette butts in the urban environment and the humidity ratio. The results showed that the density of littered cigarette butts was 0.0019-0.294 number/m2. The density of littered cigarette butts in residential land-use was 52.38% lower than commercial land-use. Nicotine leakage from cigarette butts in commercial, residential, and recreational land-uses was 1.1, 0.484, and .0065 mg/m2, respectively. In the studied scenarios, in the best and worst case, 335,070 and 481,950 gr/year of nicotine will leak from the cigarette butt into the water resources. Considering that cigarette butts are a serious source of toxins including nicotine to the environment, control measures are necessary to reduce its density in the urban environment.

The effect of oral nutrition supplement (ONS) on the nutritional and clinical status of patients undergoing autologous hematopoietic stem cell transplantation: study protocol for a randomized controlled clinical trial.

INTRODUCTION: Several side effects within the patients undergoing hematopoietic stem cell transplantation (HSCT), especially ones that influence nutrition intake, can cause weight loss and malnutrition. Based on studies, oral nutritional supplement (ONS) may reinforce their nutrient intake and progress clinical outcomes. The objective of this research is to investigate the effect of oral nutrition supplements on the nutritional and clinical status of patients undergoing autologous hematopoietic stem cell transplantation. METHODS: After block randomization used the website www.randomization , 38 patients will be enrolled in this study, patients will be allocated to the intervention (ONS) or control groups in a 1: 1 ratio. Patients in the ONS group will receive 250 ml of standard formula (Ensure®, Abbott Nutrition) which has 14-15% protein twice a day, in the morning and bedtime snacks for 21 days. All the procedures done in the control group will be the same as the ONS group except receiving ONS. We will examine the outcomes include; weight, appetite, hand grip strength, calf circumference, mid-arm circumference, total energy intake, protein intake, carbohydrate intake, fat intake, severity of oral mucositis, rate of infection during hospitalization, graft failure, recurrence rate after transplantation, the number of days it takes for neutrophil and platelet engraftment to occur, number of readmissions after transplantation during three months, mortality rate up to three months after transplantation and the three-day food diary record; all the evaluations will be carried out in three steps; 7 days before transplant, on the 14th day after transplantation, and on the 90th day after the transplantation. DISCUSSION: These patients' weight loss and malnourishment are significant concerns. The use of ONS in patients receiving HSCT has not been the subject of any research. TRIAL REGISTRATION: This clinical trial was registered in Iranian Registry of Clinical Trials ( http://www.irct.ir ) on 2022-12-09 with the code number IRCT20220208053971N2.

The Effects of Omega-3 Fatty Acids Supplementation on Inflammatory Factors in Cancer Patients: A Systematic Review and Dose-Response Meta-Analysis of Randomized Clinical Trials.

Until now, no study evaluated the impact of optimum intake of omega-3 fatty acids on inflammatory factors. We aimed to investigate the dose-dependent effects of omega-3 fatty acids supplementation on inflammatory factors in cancer patients. PubMed, Scopus and ISI Web of Science were searched until July 2022 to find randomized controlled trials (RCTs) for examining the efficacy of omega-3 fatty acids on inflammatory factors. Our primary outcomes were interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), and albumin. The results of 33 trials (2068 participants) revealed that each 1 g/day omega-3 fatty acids (oral/enteral) significantly reduced IL-6 (SMD: -1.17 pg/ml; 95% CI: -1.78, -0.55; p < 0.001; GRADE = moderate), and TNF-α (SMD: -2.15 pg/ml; 95% CI: -3.14, -1.16; p < 0.001; GRADE = very low). Moreover, each 0.5 g/kg/day omega-3 fatty acids (parenteral) significantly reduced TNF-α (SMD: -1.11 pg/ml; 95% CI: -2.02, -0.19; p = 0.017; GRADE = low). With moderate and very low evidence certainty, each 1 g/day of omega-3 fatty acids supplementation (oral/enteral) has a beneficial effect on IL-6 and TNF-α. Each 0.5 g/kg/day omega-3 fatty acids (parenteral) could also exert a favorable impact on TNF-α, but the certainty of the evidence was low.

Nutritional interventions for exercise-induced muscle damage: an umbrella review of systematic reviews and meta-analyses of randomized trials.

CONTEXT: Several meta-analyses have been conducted on the effect of nutritional interventions on various factors related to muscle damage. However, the strength of the evidence and its clinical significance are unclear. OBJECTIVES: This umbrella review aimed to provide an evidence-based overview of nutritional interventions for exercise-induced muscle damage (EIMD). DATA SOURCES: PubMed, Scopus, and ISI Web of Science were systematically searched up to May 2022. DATA EXTRACTION: Systematic reviews and meta-analyses of randomized controlled trials investigating nutritional interventions' effects on recovery following EIMD were included. The certainty of the evidence was rated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). RESULTS: Fifty-three randomized controlled trial meta-analyses were included, evaluating 24 nutritional interventions on 10 different outcomes. The results revealed a significant effect of hydroxymethylbutyrate (HMB) supplementation and l-carnitine supplementation for reducing postexercise creatine kinase; HMB supplementation for reducing lactate dehydrogenase; branched-chain amino acids and leaf extract supplementation for reducing the delayed onset of muscle soreness; and l-carnitine, curcumin, ginseng, polyphenols, and anthocyanins for reducing muscle soreness, all with moderate certainty of evidence. CONCLUSIONS: Supplementation with HMB, l-carnitine, branched-chain amino acids, curcumin, ginseng, leaf extract, polyphenols, and anthocyanins showed favorable effects on some EIMD-related outcomes. PROTOCOL REGISTRATION: PROSPERO registration no. CRD42022352565.

The impact of malnutrition on mortality and complications of hematopoietic stem cell transplantation in patients with acute leukemia.

BACKGROUND & AIMS: Malnutrition is common in hematopoietic stem cell transplantation (HSCT) patients. However, there are few studies on the association between malnutrition and post-transplant outcomes, with inconsistent results. No standard screening tool has been established for malnutrition in these patients. Previous research suggests the Global Leadership Initiative on Malnutrition (GLIM) criteria is effective in predicting outcomes in other cancers. This study investigates the link between malnutrition based on the GLIM criteria with mortality and complications following allogeneic HSCT. METHODS: This single-center, observational, longitudinal, and prospective study of 98 adult leukemia patients at the Hematology Center of Shariati Hospital in Tehran, Iran, monitored patients before transplantation until 100 days after the procedure, focusing on overall survival and mortality as a primary outcome, and secondary endpoints including oral mucositis, acute GVHD, infection during hospitalization, and readmission rates. RESULTS: This study involved 98 allogeneic HSCT patients with a median age of 38 years old, 64.3 % with acute myeloid leukemia (AML), and 35.7 % with acute lymphoblastic leukemia (ALL). Among them, 26.5 % were categorized as malnourished based on GLIM criteria. During 100 days of follow-up, 13 patients died, but there was no significant difference in overall survival and mortality between malnourished and well-nourished patients. Malnourished patients demonstrated a noticeable upward trend in the incidence of oral mucositis, hospital readmission, and infection during their hospitalization. It is important to highlight that although this observed trend is discernible, it did not attain statistical significance in statistical analyses (P > 0.05). CONCLUSION: The current study determined that, when assessed using the GLIM criteria, malnutrition did not exert a statistically significant influence on survival, mortality, or complications within the specified age range of 18-55 years, underscoring its limited impact on this cohort of younger patients.

The effects of intermittent fasting diet alone or in combination with probiotic supplementation in comparison with calorie-restricted diet on metabolic and hormonal profile in patients with polycystic ovary syndrome: study protocol for a randomized clinical trial.

INTRODUCTION: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in females characterized by ovulatory dysfunction, hyperandrogenism, and other metabolic disorders. Both intermittent fasting and specific probiotics have been suggested to help improve patients with PCOS through changes in gut microbial composition, circadian clock, and metabolic regulation. Therefore, the present study aims to investigate the effects of intermittent fasting alone or in combination with probiotic supplementation compared to the calorie-restricted (CR) diet on anthropometric measures, metabolic status, inflammation, and oxidative stress in women with PCOS. METHODS: We will carry out a randomized clinical trial for 8 weeks. Participants will be randomly assigned (1:1:1) to one of the three groups: (1) a 14:10 early time-restricted feeding (TRF) diet with probiotic supplementation (n = 30); (2) a 14:10 early TRF diet with placebo supplementation (n = 30); (3) a CR diet (energy-restricted 25% of required calories) with placebo supplementation as a control group (n = 30). The primary outcomes will be changes in body weight and insulin resistance. However, glycemic control, lipid profile, metabolic parameters, sex hormone-binding globulin, dehydroepiandrosterone, anti-Mullerian hormone, free androgen index, hirsutism, acne, antioxidant and oxidant status, inflammation, anthropometric measures, mental health, sleep quality, appetite, eating behavior, food craving, and blood pressure are secondary outcomes. All outcomes of this study will be evaluated in pre- and post-intervention. DISCUSSION: We hypothesized that 10-h TRE administered alone or in combination with probiotic supplementation to overweight and obese PCOS subjects would lead to weight loss and improved metabolic, hormonal, inflammatory, and antioxidant markers compared to control subjects following a standard 3-meal-per-day CR diet. ETHICAL ASPECTS: The current trial received approval from the Medical Ethics Committee of Tehran University of Medical Sciences, Tehran, Iran (IR.TUMS.MEDICNE.REC.1401.425). TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20121110011421N5. Registered on 3 October 2022.

Comparison of three malnutrition screening tools prior to allogeneic hematopoietic stem-cell transplantation.

Background: Previous studies have shown that malnutrition before hematopoietic stem cell transplantation (HSCT) is associated with poor patient prognoses. There is inconsistency among studies on which nutritional status screening tool is appropriate for malnutrition diagnosis before allo-HSCT. The present study aimed to compare nutritional screening tools in patients with leukemia before allo-HSCT. Methods: An observational, cross-sectional, and single-center study was conducted in Tehran, Iran. One hundred four adults allo-HSCT candidates aged 18-55 years with leukemia were selected sequentially. Malnutrition assessment was done using three tools, the Global Leadership Initiative on Malnutrition (GLIM), nutritional risk screening 2002 (NRS-2002) and European Society for Clinical Nutrition and Metabolism (ESPEN) criteria. The agreement between malnutrition assessment tools was evaluated with Cohen's kappa. Results: The agreement between GLIM and NRS-2002 was perfect (κ = 0.817, p < 0.001), while the agreement between GLIM and ESPEN was fair (κ = 0.362, p < 0.001). The agreement between NRS-2002 and ESPEN was fair (κ = 0.262, p < 0.001). We also found a moderate agreement for all tools (κ = 0.489, p < 0.001). Conclusion: NRS-2002 is an accepted tool for screening malnutrition in hospitalized patients. In the current study, the GLIM criterion perfectly agreed with the NRS-2002. Further studies in the HSCT setting are needed to introduce a valid tool.

Targeted Silencing of NRF2 by rituximab-conjugated nanoparticles increases the sensitivity of chronic lymphoblastic leukemia cells to Cyclophosphamide.

BACKGROUND: Targeting influential factors in resistance to chemotherapy is one way to increase the effectiveness of chemotherapeutics. The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway overexpresses in chronic lymphocytic leukemia (CLL) cells and appears to have a significant part in their survival and chemotherapy resistance. Here we produced novel nanoparticles (NPs) specific for CD20-expressing CLL cells with simultaneous anti-Nrf2 and cytotoxic properties. METHODS: Chitosan lactate (CL) was used to produce the primary NPs which were then respectively loaded with rituximab (RTX), anti-Nrf2 Small interfering RNA (siRNAs) and Cyclophosphamide (CP) to prepare the final version of the NPs (NP-Nrf2_siRNA-CP). All interventions were done on both peripheral blood mononuclear cells (PBMCs) and bone marrow mononuclear cells (BMNCs). RESULTS: NP-Nrf2_siRNA-CP had satisfying physicochemical properties, showed controlled anti-Nrf2 siRNA/CP release, and were efficiently transfected into CLL primary cells (both PBMCs and BMNCs). NP-Nrf2_siRNA-CP were significantly capable of cell apoptosis induction and proliferation prevention marked by respectively decreased and increased anti-apoptotic and pro-apoptotic factors. Furthermore, use of anti-Nrf2 siRNA was corresponding to elevated sensitivity of CLL cells to CP. CONCLUSION: Our findings imply that the combination therapy of malignant CLL cells with RTX, CP and anti-Nrf2 siRNA is a novel and efficient therapeutic strategy that was capable of destroying malignant cells. Furthermore, the use of NPs as a multiple drug delivery method showed fulfilling properties; however, the need for further future studies is undeniable. Video Abstract.

The Association between Total Protein, Animal Protein, and Animal Protein Sources with Risk of Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis of Cohort Studies.

We aimed to conduct this dose-dependent meta-analysis to examine the relation between total protein, animal protein, and its sources with inflammatory bowel disease (IBD). We searched databases, comprising PubMed/Medline, Web of Science (ISI), Embase, and Google Scholar, for the published studies up to 28 March 2023. Prospective cohort study designs that investigated associations between dietary intake of various animal protein sources and with risk of IBD in the general population were identified. Eleven prospective cohort studies with 4,302,554 participants and 8067 cases were considered eligible. Findings indicated that higher intake of dairy was significantly associated with a lower risk of IBD (relative risk [RR]: 0.81; 95% confidence interval [CI]: 0.72, 0.90), Crohn disease (RR: 0.69; 95% CI: 0.56, 0.86), and ulcerative colitis (RR: 0.84; 95% CI: 0.75, 0.94). There was no association between different sources of animal protein and the risk of IBD. The dose-response analysis suggested that each 100 g/d increment in dietary total meat consumption was associated with a 38% greater risk of IBD. Moreover, a positive linear association was found between total meat intake and risk of IBD (Pnonlinearity = 0.522, Pdose-response = 0.005). Overall, among the dietary sources of protein, the risk of IBD increased only with increasing total meat intake, and the consumption of protein from dairy products was found to be a protective factor against the IBD risk. This trial was registered at PROSPERO as CRD42023397719.

Effect of probiotic supplementation on chemotherapy- and radiotherapy-related diarrhoea in patients with cancer: an umbrella review of systematic reviews and meta-analyses.

To date, several systematic reviews and meta-analyses (SRMA) have investigated the effects of probiotics, but the certainty of the evidence for an effect on chemotherapy and radiotherapy-related diarrhoea has not been assessed. We conducted an overview of SRMA, searching MEDLINE, Scopus, and ISI Web of Science from inception up to February 2022. We summarised the findings of eligible SRMA. Subsequently, we included randomised clinical trials (RCT) from the SRMA in meta-analyses, using a quality effects model to calculate the OR and 95 % CI for each outcome. We used 'A Measurement Tool to Assess Systematic Reviews' and the Cochrane risk of bias tool to assess the methodological quality of the SRMA and their RCT, respectively. We used the 'Grading of Recommendations Assessment, Development, and Evaluation'.We included thirteen SRMA, which reported pooled effect sizes for chemotherapy and radiotherapy-related diarrhoea based on a total of eighteen RCT. Our meta-analyses demonstrated statistically significant beneficial effects from probiotics on all outcomes, except stool consistency; diarrhoea (any grade) OR 0·35 (95 % CI 0·22, 0·54), grade ≥ 2 diarrhoea 0·43 (0·25, 0·74), grade ≥ 3 diarrhoea 0·30 (0·15, 0·59), use of medication 0·49 (0·27, 0·88), soft stool 1·10 (0·44, 2·76) and watery stool 0·52 (0·29, 1·29). Probiotics use can reduce the incidence of diarrhoea in cancer patients in chemotherapy and radiotherapy, but the certainty of evidence for significant outcomes was very low and low.

The prognostic and therapeutic potential of HO-1 in leukemia and MDS.

BACKGROUND: Heme oxygenase-1 (HO-1), a heme-degrading enzyme, is proven to have anti-apoptotic effects in several malignancies. In addition, HO-1 is reported to cause chemoresistance and increase cell survival. Growing evidence indicates that HO-1 contributes to the course of hematological malignancies as well. Here, the expression pattern, prognostic value, and the effect of HO-1 targeting in HMs are discussed. MAIN BODY: According to the recent literature, it was discovered that HO-1 is overexpressed in myelodysplastic syndromes (MDS), chronic myeloid leukemia (CML), acute myeloblastic leukemia (AML), and acute lymphoblastic leukemia (ALL) cells and is associated with high-risk disease. Furthermore, in addition to HO-1 expression by leukemic and MDS cells, CML, AML, and ALL leukemic stem cells express this protein as well, making it a potential target for eliminating minimal residual disease (MRD). Moreover, it was concluded that HO-1 induces tumor progression and prevents apoptosis through various pathways. CONCLUSION: HO-1 has great potential in determining the prognosis of leukemia and MDS patients. HO-1 induces resistance to several chemotherapeutic agents as well as tyrosine kinase inhibitors and following its inhibition, chemo-sensitivity increases. Moreover, the exact role of HO-1 in Chronic Lymphocytic Leukemia (CLL) is yet unknown. While findings illustrate that MDS and other leukemic patients could benefit from HO-1 targeting. Future studies can help broaden our knowledge regarding the role of HO-1 in MDS and leukemia. Video abstract.

Inhibition of ERAP1 represses HLA-B27 free heavy chains expression on polarized macrophages and interrupts NK cells activation and function from ankylosing spondylitis.

BACKGROUND: We aimed to assess if Endoplasmic reticulum aminopeptidase 1 (ERAP1) polymorphisms might impress Human leukocyte antigen (HLA)-B27-free heavy chains (FHCs) expression on macrophages and eventually NK cell activation in Ankylosing spondylitis (AS). METHODS: Blood samples were obtained from 10 HLAB27+ patients with protective and 10 HLAB27+ patients with non-protective genotype. Monocytes were isolated and polarized toward M1 and M2 macrophages. ERAP1 was inhibited in macrophages, which were then co-cultured with autologous NK cells. RESULTS: Expression of HLA-B27-FHCs on M1 and M2 macrophages was reduced in patients with protective ERAP1 genotype. Co-culturing ERAP1-inhibited M1 macrophages and NK cells from patients with protective genotype resulted in downmodulation of CD69 and CD107a markers on NK cells and reduced number of IFN-γ+ NK cells compared to that of patients with non-protective genotypes. CONCLUSION: Inhibition of ERAP1 activity, by diminishing NK activation, may have therapeutic value in treating AS patients.

Nutritional interventions for the prevention and treatment of cancer therapy-induced oral mucositis: an umbrella review of systematic reviews and meta-analysis.

CONTEXT: To date, the efficacy of nutritional interventions on oral mucositis (OM) in patients with cancer, and the quality of this evidence have not been explored. OBJECTIVE: The goal of this umbrella review was to provide a comprehensive evaluation of nutritional interventions for patients with cancer with OM, as well as to assess the quality of this evidence. DATA SOURCES: Meta-analyses were searched for using PubMed, Scopus, and ISI Web of Science databases until December 2021, with no time restrictions. DATA EXTRACTION: Meta-analyses of randomized control trials that evaluated the effects of nutritional interventions on the incidence of OM in patients with cancer had inclusion criteria for this umbrella review. Data extraction, quality assessment of meta-analyses, and primary studies were done independently by 2 authors. The Grading of Recommendations Assessment, Development, and Evaluation technique was used to grade the certainty of evidence. DATA ANALYSIS: A total of 26 meta-analyses were included in this umbrella review. The results showed that honey, glutamine, and propolis can reduce the incidence of severe OM, based on moderate evidence quality. In addition, zinc supplementation significantly reduced the incidence of OM, regardless of symptom severity; however, low certainty of the evidence was observed. The effects of vitamin E, curcumin, and probiotics on OM were not statistically significant. CONCLUSION: This umbrella review shows that honey, glutamine, and propolis can significantly reduce the incidence of severe OM. These findings need to be confirmed with well-designed, longitudinal randomized controlled trials. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42022301010.

The role of SF3B1 and NOTCH1 in the pathogenesis of leukemia.

The discovery of new genes/pathways improves our knowledge of cancer pathogenesis and presents novel potential therapeutic options. For instance, splicing factor 3b subunit 1 (SF3B1) and NOTCH1 genetic alterations have been identified at a high frequency in hematological malignancies, such as leukemia, and may be related to the prognosis of involved patients because they change the nature of malignancies in different ways like mediating therapeutic resistance; therefore, studying these gene/pathways is essential. This review aims to discuss SF3B1 and NOTCH1 roles in the pathogenesis of various types of leukemia and the therapeutic potential of targeting these genes or their mutations to provide a foundation for leukemia treatment.

Cryotherapy for oral mucositis in cancer: review of systematic reviews and meta-analysis.

BACKGROUND: One of the most common side effects of cancer treatment is oral mucositis. Although studies have shown that oral cryotherapy has a favourable effect on oral mucositis, the reliability of the results is questionable. OBJECTIVE: The goal of this umbrella review was to provide insight into the effects of oral cryotherapy against oral mucositis in patients with cancer, as well as to assess the certainty of this evidence. METHOD: Studies were searched for through PubMed, Scopus and Web of Science, with no restrictions until August 2021. The risk ratio (RR) and 95% CI for each meta-analysis were recalculated using a random-effects model, and the certainty of the evidence was judged using Grading of Recommendations Assessment, Development and Evaluation. RESULTS: Ten meta-analyses including 25 original RCTs that fit our inclusion criteria were included. The use of oral cryotherapy markedly reduced the occurrence of overall (RR 0.72, 95% CI 0.64 to 0.83, n=20 trials), moderate to severe (RR 0.60, 95% CI 0.45 to 0.80, n=16 trials) and severe oral mucositis (RR 0.48, 95% CI 0.34 to 0.67, n=16 trials), as well as average severity score of oral mucositis (standardised mean difference=-0.94, 95% CI -1.28 to -0.59, n=4 trials) in comparison to a control group; however, the certainty of evidence for all outcomes was rated very low. CONCLUSION: In patients with cancer, oral cryotherapy appears to greatly lower the severity and occurrence of oral mucositis, but, with very low certainty of evidence.

Restoration of miR-648 overcomes 5-FU-resistance through targeting ET-1 in gastric cancer cells in-vitro.

BACKGROUND: Endothelin-1 (ET-1) is a peptide overexpressed in gastric cancer (GC) and linked to carcinogenesis and resistance to chemotherapy. Applying microRNAs (miRNAs/miRs) to downregulate ET-1 and reverse resistance to commonly used chemotherapy drugs such as 5-fluorouracil (5-FU) is practical. METHODS: The current study sought to evaluate the miR-648 expression in GC and any plausibility of its replacement, either with or without the combination of chemo agents to downregulate ET-1 expression through interaction with its target gene. To this end, miR-648 and ET-1 expression levels were assessed in GC tissues and adjacent non-tumor tissues driven from 65 patients who had already undergone surgery, fifteen of which had received 5-FU before surgery. The impact of miR-648 and chemo agents on ET-1 expression was measured using qPCR and Western blotting. Further, an MTT assay was conducted to assess its association with cell viability. Ultimately, the association of miR-648 and ET-1 with clinicopathological characteristics was evaluated. RESULTS: The current study revealed that miR-648 was considerably down-regulated, while ET-1 was substantially up-regulated in patients with GC. The 5-FU caused a significant increase in miR-648 and reduced ET-1 expression. It was also determined that overexpression of miR-648 suppressed ET-1 production, notably when combined with 5-FU, leading to survival reduction. These results further showed that miR-648 replacement could sensitize chemoresistant GC cells. Besides, a significant association between ET-1 and miR-648 with clinicopathological features was discovered CONCLUSIONS: miR-648 replacement may serve as a potential oncosuppressive therapeutic approach that warrants further investigation to translate into an effective GC treatment.