Therapeutic potency of heat-shock protein-70 in the pathogenesis of colorectal cancer: current status and perspectives.

Heat-shock protein-70 (HSP70) is critical to the folding, stability, and activity of several client proteins including many responsible for cancer cell proliferation, apoptosis, drug toxicity, and metastasis. Up-regulation of HSP70 is positively associated with increased tumorigenicity as well as poor survival in colon cancer patients, supporting the diagnostic, prognostic, and therapeutic potencies of HSP70 in colorectal cancer. The administration of specific pharmacological inhibitors or gene knock-down for HSP70 suppresses tumor progression and enhances tumor cell chemosensitivity. This review summarizes the different tumorigenic properties of HSP70 and the potential therapeutic potency of HSP70 inhibitors in terms of a novel strategy for colorectal cancer therapy, for a better understanding, and hence better management of this disease.

The effects of NLRP3 rs10754558 and rs4612666 polymorphisms on preeclampsia susceptibility, onset, and severity: a case-control study and in silico analysis.

Preeclampsia (PE) is one of the serious complications of pregnancy and its exact etiology is unknown. Inflammasomes are multiportion complexes whose relation with PE has been described. Evidence showed the effect of NLRP3 inflammasome in PE pathogenesis. In the current study, we investigated the possible impacts of NLRP3 polymorphisms on PE. A total of 252 PE and 258 control pregnant women were selected for the study. The PCR-RFLP method was employed to genotype rs10754558 and rs4612666 polymorphisms. The RNAsnp and SpliceAid 2 software were used for in silico analysis. There was no relationship between NLRP3 polymorphisms and PE. In comparison to control women, the NLRP3 rs10754558 could increase the risk of severe PE in codominant and dominant models (OR=1.89, 95% CI=1.19-3.01, P=0.012, OR=1.95, 95% CI=1.24-3.06, P=0.0037, respectively). The findings of the in silico analysis revealed the effects of rs10754558 C to G and rs4612666 C to T substitutions on protein binding sites and rs10754558 C to G substitution on secondary RNA structure. These findings could confirm the finding those studies reported the impacts of these variants on various diseases. In conclusion, the NLRP3 rs10754558 variant was associated with an increased risk of EOPE and severe PE.

Paraneoplastic acute eosinophilic pneumonia due to carotid angiosarcoma: A rare case.

Key Clinical Message: This case report emphasizes that we should analyze a patient's signs and symptoms as a whole rather than relying exclusively on a common pattern to diagnose the condition and indicates that thorough histological investigation and sample collection are needed to accurately diagnose this malignancy. Abstract: Angiosarcoma is a rare, fatal, and poorly understood malignant tumor of vascular endothelial cells which is a challenging disease to diagnose in the clinical settings and requires early diagnosis to achieve a favorable prognosis. Paraneoplastic syndromes associated with angiosarcoma can include hypercoagulability, thrombocytopenia, anemia, fever, weight loss, and night sweats. In some cases, the paraneoplastic syndrome can be the first sign of the underlying malignancy. Here, we present a 47-year-old individual with angiosarcoma over the right scapula accompanied by hemoptysis and other pulmonary complaints whom at first was thought to be metastatic polmunary involvement. However, the patient's dramatic response to corticosteroids, in addition to further imaging and paraclinical studies, led us to an acute eosinophilic pneumonia (AEP) diagnosis which is an eosinophilic infiltrations of alveolar spaces. The patient received chemotherapy for angiosarcoma and radiation, since the brachial nerve network was disrupted, leaving the tumor unresectable. After 3 years of continuous follow-up, the patient is now completely cured.

Association Between HOTAIR rs920778 and H19 rs3741219 Polymorphisms with Hashimoto's Thyroiditis (HT) and Graves' Disease (GD).

Background: Graves' disease (GD) and Hashimoto's thyroiditis (HT) are two autoimmune thyroid diseases (AITDs). The current study aimed to assess possible association between HOTAIR rs920778 and H19 rs3741219 polymorphisms with GD and HT. Methods: We recruited 248 patients with autoimmune thyroid disease (133 HT patients and 115 GD patients) and 135 age- and sex-matched controls. The PCR-RFLP method was applied for genotyping of HOTAIR rs920778, and H19 rs3741219 polymorphisms. Results: The HOTAIR rs920778 GA frequency was significantly higher in control compared to HT group. The Overdominant model showed a significant association with the risk of HT. However, no significant association was observed between this polymorphism and HT susceptibility in dominant and recessive models. The H19 rs3741219 GA was more repeated in HT patients compared to control group, but the difference was not significant. There was no association between HOTAIR rs920778 and H19 rs3741219 polymorphisms with GD in all genetic models. Discussion: Our findings indicated that HOTAIR rs920778 polymorphism decreased the risk of HT. Since, this the first study, further studies with different races are required to confirm our results.

Effects of some anti-diabetic herbal extracts on the insulin-degrading enzyme in human colon cancer Caco-2 cell line.

Objective: Type 2 diabetes mellitus (T2DM) is a condition characterized by insufficient insulin production or insulin resistance. The insulin-degrading enzyme (IDE) is responsible for degrading insulin and is a potential drug target for T2DM treatment. Numerous activities have been proposed for plant extracts, but research on the effects of plant extracts on IDE expression and activity is riddled with drawbacks. Materials and Methods: We investigated the effect of Phaseolus vulgaris, Allium cepa, Portulaca oleracea, Cinnamomum verum, and Citrullus colocynthis extracts on the expression and activity of IDE in the Caco-2 cell line. Results: Findings of RT-PCR showed that IDE gene expression was reduced following treatment with P. vulgaris, C. colocynthis, and C. verum extracts. The results of IDE activity with fluorogenic peptide substrate V also indicated that P. vulgaris, C. colocynthis, and P. oleracea extracts reduced IDE activity in a significant and dose-dependent manner. Conclusion: The hydroalcoholic extracts studied, except for A. cepa, can prevent insulin degradation by reducing the expression and activity of the IDE enzyme. This new insight into the effects of herbal medicines on IDE activity can help future studies.