In silico exploration of anti-prostate cancer compounds from differential expressed genes.

Prostate cancer (PCa) is a complex and biologically diverse disease with no curative treatment options at present. This study aims to utilize computational methods to explore potential anti-PCa compounds based on differentially expressed genes (DEGs), with the goal of identifying novel therapeutic indications or repurposing existing drugs. The methods employed in this study include DEGs-to-drug prediction, pharmacokinetics prediction, target prediction, network analysis, and molecular docking. The findings revealed a total of 79 upregulated DEGs and 110 downregulated DEGs in PCa, which were used to identify drug compounds capable of reversing the dysregulated conditions (dexverapamil, emetine, parthenolide, dobutamine, terfenadine, pimozide, mefloquine, ellipticine, and trifluoperazine) at a threshold probability of 20% on several molecular targets, such as serotonin receptors 2a/2b/2c, HERG protein, adrenergic receptors alpha-1a/2a, dopamine D3 receptor, inducible nitric oxide synthase (iNOS), epidermal growth factor receptor erbB1 (EGFR), tyrosine-protein kinases, and C-C chemokine receptor type 5 (CCR5). Molecular docking analysis revealed that terfenadine binding to inducible nitric oxide synthase (-7.833 kcal.mol-1) and pimozide binding to HERG (-7.636 kcal.mol-1). Overall, binding energy ΔGbind (Total) at 0 ns was lower than that of 100 ns for both the Terfenadine-iNOS complex (-101.707 to -103.302 kcal.mol-1) and Ellipticine-TOPIIα complex (-42.229 to -58.780 kcal.mol-1). In conclusion, this study provides insight on molecular targets that could possibly contribute to the molecular mechanisms underlying PCa. Further preclinical and clinical studies are required to validate the therapeutic effectiveness of these identified drugs in PCa disease.

Effect of coconut water and milk on heat stress-induced gastrointestinal tract dysmotility in rats: Role of oxidative stress and inflammatory response.

The potential effects of coconut water (CCW) and milk (CCM) on gastrointestinal motility {intestinal transit (IT), intestinal fluid accumulation (IFA) and colonic motility}, tissue oxidative, and inflammatory responses in heat-stressed rats were investigated. There were four (4) temperature exposure groups; (i) Control at 30°C, (CON), (ii) heat-stressed (HS) group exposed to the ambiance of 40°C, (iii) heat-stressed pre-treated with coconut water (HS+ CCW), and (iv) coconut milk (HS + CCM). Skin temperatures (ST) and rectal temperatures (RT) were taken daily, before and after 2 hr heat exposure. GE, IT, and IFA were assessed using standard methods while colonic motility was assessed by colonic bead expulsion (CBE) time after the 14-day exposure. Serum cortisol and lipid peroxidation, antioxidant enzyme activities, inflammatory cytokines in intestinal samples were assessed. Stomach and intestinal morphology were equally examined on histomorphometry. Increased GE, IT, IFA, and colonic motility were observed in HS. CCW and CCM reversed the increases in GE, IT, IFA, and colonic motility in the heat-stressed rats (p < .05). Elevated serum cortisol level and intestinal MDA were significantly reduced in the CCW and CCM treated. Tissue GPx, T-AOC, and T-SOD were all enhanced in HS + CCW and HS + CCM. While tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were suppressed in the HS group, interleukin-4 (IL-4) and interleukin-10 (IL-10) were enhanced with CCW and CCM. Altered intestinal morphology in the HS was also significantly mitigated by CCW and CCM. We showed that coconut water and milk could ameliorate intestinal dysmotility associated with heat stress via oxidative stress reduction and suppression of inflammatory responses. PRACTICAL APPLICATIONS: Heat stress impacts negatively on intestinal health and integrity in both humans and animals via oxidative stress and inflammation. Conversely, coconut has demonstrated anti-oxidative and anti-inflammatory properties in health and medicinal applications. From the findings of this study, coconut water and milk display beneficial potentials against the untoward heat stress effect on gastrointestinal health.

Acute effects of aqueous leaf extract of Aspilia africana C.D. Adams on some haematological parameters in rats.

Several medicinal plants have been documented for their haematological effects either at low or high concentration but very little is known about Aspilia africana. The aim of the study was to investigate the acute effects of aqueous leaf extract of Aspilia africana at different concentrations on some haematological parameters in rats. Following 14 days of oral administration of aqueous extract of A. africana, Haematocrit (HCT), Haemoglobin concentration (HB), Mean Cell Haemoglobin Concentration (MCHC), Red Blood Cell Count (RBC Count), Total White Blood Cell Count (Total WBC Count), Absolute Neutrophils count (NEUT#), Absolute Lymphocytes count (LYM#), Absolute Eosinophils Count (EOSIN#) and Absolute Monocytes (MONO#) were evaluated in twenty (20) male Wistar albino rats. The rats weighed 174 ± 20 g, and were randomly assigned into 4 groups viz: Group 1, Control; Group 2, 250 mg/Kg/d aqueous extract; Group 3, 500 mg/Kg/d aqueous extract; and Group 4, 750 mg/Kg/d aqueous extract. HCT, HB, MCHC, RBC Count, Total WBC Count, NEUT#, LYM#, EOSIN# and MONO# were significantly increased (P<0.001) in 500 mg/Kg/d of A. africana extract (61.13 ± 1.65%, 13.5 ± 1.29 g/dl, 23.33 ± 0.0.02 g/dl, 3.68 ± 0.02 X 10(12)Cells/l, 2.33 ± 0.02 X 10(9)Cells/l, 1.32 ± 0.04 X 10(9)Cells/l, 1.43 ± 0.05 X 10(9)Cells/l, 0.47 ± 0.02 X 10(9)Cells/l and 0.47 ± 0.04 X 10(9)Cells/l, respectively) when compared to the Control (51.13 ± 0.85%, 9.56 ± 0.43 g/dl, 19.22 ± 0.19 g/dl, 2.69 ± 0.01 X 10(12)Cells/l, 1.79 ± 0.01 X 10(9)Cells/l, 0.80 ± 0.00 X 10(9)Cells/l, 0.83 ± 0.00 X 10(9)Cells/l, 0.18 ± 0.00 X 10(9)Cells/l and 0.24 ± 0.00 X 10(9)Cells/l, respectively) which received no extract at all. The 500 mg/Kg of A. africana extract proved to be the most effective, while the 750 mg/Kg proved to be the least effective in comparison with the control. The results of this study further strengthened the earlier works on the medicinal benefits of Aspilia africana and its virtue as a good pharmacological source of haematopoiesis.