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Sci Rep ; 12(1): 20765, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36456799


Hypertension-induced ventricular and vascular remodeling causes myocardial infarction, heart failure, and sudden death. Most available pharmaceutical products used to treat hypertension lead to adverse effects on human health. Limited data is available on apitherapy (bee products) combinations for treatment of hypertension. This study aims to evaluate the antihypertensive effects of combinations of natural apitherapy compounds used in the medical sector to treat a variety of diseases. Rats were assigned into six groups consisting of one control group and five hypertensive groups where hypertension (blood pressure > 140/90) was induced with dexamethasone. One of these groups was used as a hypertension model, while the remaining four hypertensive groups were treated with a propolis, royal jelly, and bee venom combination (PRV) at daily oral doses of 0.5, 1.0, and 2.0 mg/kg, and with losartan 10 mg/kg. The PRV combination at all doses decreased arterial blood pressure below the suboptimal value (p < 0.001), and PRV combination treatment improved dexamethasone-induced-ECG changes. The same treatment decreased angiotensin-II, endothelin-1, and tumor growth factor ß serum levels in hypertensive rats. Additionally, PRV combination improved histopathological structure, and decreased serum levels of NF-kB and oxidative stress biomarkers. We concluded that PRV combination therapy may be used as a potential treatment for a variety of cardiovascular diseases.

Hipertensão , Infarto do Miocárdio , Humanos , Ratos , Animais , Pressão Sanguínea , Antioxidantes/farmacologia , Apiterapia , Hipertensão/tratamento farmacológico , Ventrículos do Coração , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Dexametasona/farmacologia
Int J Gen Med ; 15: 5073-5087, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35615469


Background: Dysregulated immunity is a hallmark of SARS-CoV-2 infection. Immune suppression is indicated by low monocyte expression of human leukocyte antigen D-related (mHLA-DR). T cells are important antiviral cells. We aimed to assess the role of mHLA-DR and T lymphocyte frequency in predicting COVID-19 severity. Patients and Methods: This cross-sectional study enrolled 97 SARS-CoV-2 positive patients, including mild to moderate (n = 49) and severe cases admitted to intensive care unit (ICU) (n = 48). These ICU cases were further subdivided into survivors (n = 35) and non-survivors (n = 13). Results: Severe cases had a significant decrease in the mHLA-DR mean fluorescence intensity (MFI) and T lymphocyte percentage compared to mild to moderate cases (P<0.001). Non-survivors had a lower T lymphocyte percentage (P=0.004) than survivors. The mHLA-DR MFI and T lymphocyte percentage correlated with oxygen saturation (r=0.632, P<0.001) and (r=0.669, P<0.001), respectively. According to the ROC curves, mHLA-DR MFI, at a cutoff of 143 and an AUC of 0.9, is a reliable biomarker for distinguishing severe COVID-19 cases, with 89.6% sensitivity and 81.6% specificity, while T lymphocyte frequency had 81.3% sensitivity and 81.6% specificity at a cutoff of 54.4% and an AUC of 0.9. The T lymphocyte percentage as a predictor of ICU survival at a cutoff of 38.995% exhibited 100% sensitivity and 57.1% specificity. According to multivariate regression analysis, reduced mHLA-DR MFI and T lymphocyte percentage are independent predictors of COVID-19 severity (OR = 0.976, 95% CI: 0.955-0.997, P = 0.025) and (OR = 0.849, 95% CI: 0.741-0.972, P = 0.018), respectively. Conclusion: Reduced mHLA-DR expression and T-lymphocyte percentage are independent predictors of COVID-19 severity. Oxygen saturation percentage is correlated with mHLA-DR MFI and T lymphocyte frequency. The T lymphocyte frequency is a proposed predictor of COVID-19 survival in ICU admitted patients.

Int J Pharm ; 610: 121256, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34732362


Hepatocellular carcinoma (HCC) is one of most common causes of cancer death worldwide. MicroRNA (miRNA) replacement gene therapy is a novel approach for HCC management. MiR-218 is a promising tumor suppressor miRNA that is down-regulated in HCC. Here, our aim was the targeted delivery of miR-218 expressing DNA plasmid (pmiR-218) to suppress HCC in vitro and in vivo. Hyperbranched polyamidoamine was synthesized via simple and economically one-pot reaction followed by decoration with lactobionic acid (LA-PAMAM) to selectively deliver and restore miR-218 expression in HCC. In vitro cytotoxicity investigations revealed the high biocompatibility of LA-PAMAM. Furthermore, decoration of hyperbranched polymer with LA moieties enabled LA-PAMAM to deliver pmiR-218 more efficiently to HepG2 cells compared to both PMAMA and naked pmiR-218. Such efficient delivery of miR-218 resulted in suppression of HepG2 proliferation and down-regulation of its oncogenic HOXA1 target. In vivo, LA-PAMAM/pmiR-218 treatment of HCC induced by DEN and CCl4 in mice leads to an obvious decrease in the number and size of HCC nodules. In addition, LA-PAMAM/pmiR-218 significantly improved the liver histological features, as well as down-regulated the HOXA1 in liver tissue. In conclusion, this study showed the potential of LA-PAMAM carrier for the targeted delivery of tumor suppressor miR-218 as a therapeutic candidate for HCC.

Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Camundongos , MicroRNAs/genética , Poliaminas