Potential JAK2 Inhibitors from Selected Natural Compounds: A Promising Approach for Complementary Therapy in Cancer Patients.

Background: Janus-activated kinase 2 (JAK2) plays a pivotal role in numerous essential biological processes, including proliferation, apoptosis, and metastasis in human cells. Prior studies have indicated that inhibiting JAK2 could be a promising strategy to mitigate cell proliferation and induce apoptosis in tumor cells. Objectives: This study aimed to estimate the binding affinity of 79 herbal compounds, comprising 46 flavonoids, 21 anthraquinones, and 12 cinnamic acids, to the ATP-binding cleft of JAK2 to identify potential herbal inhibitors of JAK2. Methods: The binding affinities between ligands and JAK2 were calculated utilizing AutoDock 4.0 software in conjunction with the Cygwin environment. Cross-validation was conducted using the Schrödinger tool. Molecular dynamics simulations were employed to evaluate the stability of docked poses for the most significant JAK2 inhibitors. Furthermore, the Discovery Studio Visualizer tool was utilized to elucidate interactions between the top-ranked JAK2 inhibitors and residues within the JAK2 ATP-binding site. Results: Twelve flavonoids, two anthraquinones, and three cinnamic acids demonstrated substantial binding affinities to the protein kinase domain of the receptor, with a criterion of ΔGbinding < -10 kcal/mol. Among the studied flavonoids, anthraquinones, and cinnamic acid derivatives, orientin, chlorogenic acid, and pulmatin emerged as the most potent JAK2 inhibitors, exhibiting ΔGbinding scores of -14.49, -11.87, and -10.76 kcal/mol, respectively. Furthermore, the docked poses of orientin, pulmatin, and chlorogenic acid remained stable throughout 60 ns computer simulations. The average root mean square deviation values calculated for JAK2 when complexed with orientin, chlorogenic acid, and pulmatin were 2.04 Å, 2.06 Å, and 1.95 Å, respectively. Conclusion: This study underscores the robust inhibitory potential of orientin, pulmatin, and chlorogenic acid against JAK2. The findings hold promise for the development of novel and effective drugs for cancer treatment.

Evaluation of Salivary Alkaline Phosphatase and Albumin in HIV Infected Patients: A Historical Cohort Study.

BACKGROUND: Saliva is a very important complex biological oral fluid .Antioxidants are present in all body fluids. Uric acid, albumin and vitamins are some of the non- enzymatic molecular antioxidants. Alkaline phosphatase is related to cell injury and death. OBJECTIVES: The aim of this study was the evaluation of salivary alkaline phosphatase and albumin level in HIV positive patients in comparison to healthy control group. METHODS: Case groups were 49 HIV positive subjects, compared with 49 healthy control group. Oral clinical examination was carried out. Five ml unstimulated whole saliva was collected during 5 min with the Navazesh method. Alkaline phosphatase was determined by spectrophotometric assay. Albumin was assessed by the nephelometric method. RESULTS: The results of this study showed significantly lower salivary albumin in the case group in comparison to healthy control group (p= 0.001). HIV positive group had greater alkaline phosphatase than the healthy control group. However, this difference was not statistically significant (p=0.458). CONCLUSION: Salivary albumin level was significantly decreased and salivary alkaline phosphatase level slightly increased in HIV positive patients in comparison to healthy control group. All of the HIV infected patients were in early phase of HIV infection with normal immune status. More research is needed to estimate these enzymes changes in late phase of HIV infection and AIDS step.

Evaluation of Salivary Melatonin Levels in HIV-positive Patients: A Historical Cohort Study.

BACKGROUND: Human immunodeficiency virus (HIV) affects lymphocytes, resulting in acquired immunodeficiency syndrome. Oxidative stress may play an important role in HIV pathogenesis. Melatonin has antioxidant, antiinflammatory and immunomodulatory effects. OBJECTIVE: The aim of this study was to evaluate salivary melatonin levels in HIV-positive patients and a healthy control group. METHODS: Forty-nine HIV-positive and 49 healthy subjects were included in this study. Patients' drug consumption and clinical examination results were registered in questionnaires. Unstimulated whole saliva was collected in the morning. The melatonin levels were measured by melatonin ELISA kits. Statistical analyses were performed with STATA 12, using t-test and chi-squared test. RESULTS: Salivary melatonin levels were significantly lower in the case group in comparison with the healthy control group (P=0.001). Age was significantly higher in the case group. Chi-squared test showed no statistically significant difference between the case and control groups in smoking (P=0.591) and addiction (P=0.204) but gender differences were observed (P=0.001). CONCLUSION: Salivary melatonin level as an antioxidant was lower in HIV-positive patients. Further studies are necessary to understand the exact role of melatonin in HIV-positive patients and its therapeutic effects.

Evaluation of Salivary Vitamin C and Catalase in HIV Positive and Healthy HIV Negative Control Group.

BACKGROUND: Saliva is a complex oral biologic fluid secreted by major and minor salivary glands. Saliva has immunological, enzymatic and antioxidant defense mechanisms. Infection with human immunodeficiency virus (HIV) is a life-threatening disease. OBJECTIVE: The aim of this study was to evaluate salivary vitamin C and catalase levels in HIV-positive patients in comparison to a healthy control group. METHOD: Forty-nine HIV-infected individuals and 49 healthy subjects were selected. Five mL of unstimulated saliva was collected in 5 minutes using a sterilized Falcon tube with Navazesh method. Catalase and vitamin C levels were assessed by spectrophotometric assay. Data were analyzed with STATA 12. RESULTS: Salivary catalase levels were 7.99±2.40 and 8.37±1.81 in the case and control groups, respectively. Catalase level was lower in the case group but the difference was not statistically significant (P=0.380). Salivary vitamin C levels in the case and control groups were 3.76±1.92 and 4.87±2.20, respectively (P=0.009). CONCLUSION: HIV can alter salivary antioxidant capacity as well as vitamin C and catalase levels. Saliva may reflect serum antioxidative changes in these patients. Therefore, further research is necessary on salivary and serum oxidants and the antioxidant changes.