New emerging targets in osteosarcoma therapy: PTEN and PI3K/Akt crosstalk in carcinogenesis.

Osteosarcoma (OS) is a malignant bone carcinoma that affects people in childhood and adulthood. The heterogeneous nature and chromosomal instability represent certain characteristics of OS cells. These cancer cells grow and migrate abnormally, making the prognosis undesirable for patients. Conventional and current treatments fail to completely eradicate tumor cells, so new therapeutics targeting genes may be considered. PI3K/Akt is a regulator of events such as growth, cell death, migration, and differentiation, and its expression changes during cancer progression. PTEN reduces PI3K/Akt expression, and its mutations and depletions have been reported in various tumors. Experimental evidence shows that there is upregulation of PI3K/Akt and downregulation of PTEN in OS. Increasing PTEN expression may suppress PI3K/Akt to minimize tumorigenesis. In addition, PI3K/Akt shows a positive association with growth, metastasis, EMT and metabolism of OS cells and inhibits apoptosis. Importantly, overexpression of PI3K/Akt causes drug resistance and radio-resistance and its level can be modulated by miRNAs, lncRNAs and circRNAs. Silencing PI3K/Akt by compounds and drugs can suppress OS. Here, we review in detail the function of the PTEN/PI3K/Akt in OS, revealing its biological function, function in tumor progression, resistance to therapy, and pharmacological significance.

Diagnostic Performance of Magnetic Resonance Imaging for Detection of Acute Appendicitis in Pregnant Women; a Systematic Review and Meta-Analysis.

Introduction: The diagnosis of acute appendicitis (AA) in pregnant women is commonly challenging owing to the normal results of laboratory tests, organ displacement, and normal physiological inflammatory alterations. This meta-analysis aimed to investigate the accuracy of magnetic resonance imaging (MRI) in diagnosis of AA in pregnant women. Methods: Two investigators independently performed a comprehensive systematic literature search of electronic databases including MEDLINE, Cochrane Central, EMBASE, Web of Science, Scopus, and Google Scholar to identify studies that reported accuracy of MRI for diagnosis of AA in pregnant women from inception to April 1, 2022. Results: Our systematic search identified a total of 525 published papers. Finally, a total of 26 papers were included in the meta-analysis. The pooled sensitivity and specificity of MRI in diagnosis of AA in pregnant women were 0.92 (95% CI: 0.88-0.95) and 0.98 (95% CI 0.97-0.98), respectively. The pooled positive likelihood ratio and negative likelihood ratio were 29.52 (95% CI: 21.90-39.81) and 0.10 (95% CI: 0.04-0.25), respectively. The area under hierarchical summary receiver operating characteristic (HSROC) curve indicated that the accuracy of MRI for diagnosis of AA in pregnant women is 99%. Conclusion: This meta-analysis showed that MRI has high sensitivity, specificity, and accuracy for diagnosis of AA in pregnant women and can be used as a first-line imaging modality for suspected cases of AA during pregnancy. Furthermore, it should be noted that when the result of ultrasonography is inconclusive, the use of MRI can reduce unnecessary appendectomy in pregnant patients.

Combination therapy of flaxseed and hesperidin enhances the effectiveness of lifestyle modification in cardiovascular risk control in prediabetes: a randomized controlled trial.

BACKGROUND: Regarding the increasing prevalence of cardiometabolic abnormalities, and its association with non-communicable chronic diseases, providing preventive and therapeutic strategies is a priority. A randomized placebo-controlled study was conducted to assess the effects of combination therapy of milled brown flaxseed and hesperidin during lifestyle intervention on controlling cardiovascular risk in prediabetes. METHODS: A total of forty-eight subjects were randomly assigned to receive lifestyle intervention plus combination therapy of brown flaxseed (30 g milled) and hesperidin (two 500 mg capsules) or lifestyle modification alone for 12 weeks. Changes from baseline in anthropometric measures, lipid profile and atherogenic indices, glucose homeostasis parameters, and inflammatory biomarkers was assessed as a primary end point. RESULTS: Anthropometric data comparison between the two groups showed a significant reduction in weight (p = 0.048). Waist circumference reduction was about twice that of the control group (- 6.75 cm vs - 3.57 cm), but this difference was not statistically significant. Comparison of blood pressure changes throughout the study indicated a greater reduction in blood pressure in the intervention group rather than control group (- 5.66 vs. - 1.56 mmHg, P = 0.049). Improvements of lipid profile and atherogenic indices, glucose homeostasis parameters, and inflammatory biomarkers in flaxseed-hesperidin group was significantly more than the control group after 12 weeks of intervention (p < 0.05). CONCLUSION: Our results indicate that co-administration of flaxseed and hesperidin as an adjunct to lifestyle modification program is more effective than lifestyle modification alone in the metabolic abnormalities remission of prediabetic patients. TRIAL REGISTRATION:  The trial was registered with ClinicalTrials.gov, number NCT03737422. Registered 11 November 2018. Retrospectively registered, https://clinicaltrials.gov/ct2/results?cond=&term=NCT03737422&cntry=&state=&city=&dist= .