The potential anti-Alzheimer's activity of Oxalis corniculata Linn. Methanolic extract in experimental rats: Role of APOE4/LRP1, TLR4/NF-κß/NLRP3, Wnt 3/ß-catenin/GSK-3ß, autophagy and apoptotic cues.

ETHNOPHARMACOLOGICAL RELEVANCE: Oxalis corniculata (O. corniculata) is a member of Oxalidaceae family, widely distributed in Asia, Europe, America, and Africa, used extensively as food and its traditional folkloric uses include management of epilepsy, gastric disorders, and neurodegenerative diseases, together with its use in enhancing health. Numerous pharmacological benefits of O. corniculata are linked to its anti-inflammatory and antioxidant abilities. One of the most prevalent neurodegenerative disorders is Alzheimer's disease (AD) in which neuroinflammation and oxidative stress are its main pathogenic processes. AIM OF THE STUDY: Our research aimed to study the neuroprotective effect of the methanolic extract of Oxalis corniculata Linn. (O. corniculata ME), compared to selenium (Se) against AlCl3-induced AD. MATERIALS AND METHODS: Forty male albino rats were allocated into four groups (Gps). Gp I a control group, the rest of the animals received AlCl3 (Gp II-Gp IV). Rats in Gp III and IV were treated with Se and O. corniculata ME, respectively. RESULTS: The chemical profile of O. corniculata ME was studied using ultraperformance liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry, allowing the tentative identification of sixty-six compounds, including organic acids, phenolics and others, cinnamic acid and its derivatives, fatty acids, and flavonoids. AlCl3 showed deterioration in short-term memory and brain histological pictures. Our findings showed that O. corniculata ME and selenium helped to combat oxidative stress produced by accumulation of AlCl3 in the brain and in prophylaxis against AD. Thus, Selenium (Se) and O. corniculata ME restored antioxidant defense, via enhancing Nrf2/HO-1 hub, hampered neuroinflammation, via TLR4/NF-κß/NLRP3, along with dampening apoptosis, Aß generation, tau hyperphosphorylation, BACE1, ApoE4 and LRP1 levels. Treatments also promoted autophagy and modulated Wnt 3/ß-catenin/GSK3ß cue. CONCLUSIONS: It was noted that O. corniculata ME showed a notable ameliorative effect compared to Se on Nrf2/HO-1, TLR4/NF-κß/NLRP3, APOE4/LRP1, Wnt 3/ß-catenin/GSK-3ß and PERK axes.

Bromelain ameliorates D-galactosamine-induced acute liver injury: role of SIRT1/LKB1/AMPK, GSK3ß/Nrf2 and NF-κB p65/TNF-α/caspase-8, -9 signalling pathways.

OBJECTIVES: The present research focused on estimating, for the first time, the potential protective effects of bromelain against D-galactosamine-induced acute liver injury in rats as well as identifying the possible underlying mechanisms. METHODS: Silymarin (100 mg/kg/day, p.o.) as a reference drug or bromelain (20 and 40 mg/kg/day, p.o.) were administered for 10 days, and on the 8th day of the experiment, a single dose of galactosamine (400 mg/kg/i.p.) induced acute liver injury. KEY FINDINGS: Pretreatment with bromelain improved liver functions and histopathological alterations induced by galactosamine. Bromelain ameliorated oxidative stress by inducing SIRT1 protein expression and increasing LKB1 content. This resulted in phosphorylating the AMPK/GSK3ß axis, which stimulated Nrf2 activation in hepatic cells and thus increased the activity of its downstream antioxidant enzymes [HO-1 and NQO1]. Besides, bromelain exerted significant anti-apoptotic and anti-inflammatory effects by suppressing hepatic contents of TNF-α, NF-κB p65, as well as caspase-8 and caspase-9. The protective effects of bromelain40 were proved to be better than silymarin and bromelain20 in most of the assessed parameters. CONCLUSIONS: Our results highlight the significant hepatoprotective effects of bromelain against acute liver injury through modulation of SIRT1/LKB1/AMPK, GSK3ß/Nrf2 signalling in addition to NF-κB p65/TNF-α/ caspase-8 and -9 pathway.

The protective effect of thymoquinone or/and thymol against monosodium glutamate-induced attention-deficit/hyperactivity disorder (ADHD)-like behavior in rats: Modulation of Nrf2/HO-1, TLR4/NF-κB/NLRP3/caspase-1 and Wnt/ß-Catenin signaling pathways in rat model.

Both thymoquinone (TQ) and thymol (T) have been proved to possess a positive impact on human health. In this research, we aimed to investigate the effect of these compounds separately and together on the Attention-deficit/hyperactivity disorder (ADHD)-like behavior induced by monosodium glutamate (MSG) in rats. Forty male, Spargue Dawley rat pups (postnatal day 21), were randomly allocated into five groups: Normal saline (NS), MSG, MSG+TQ, MSG+T, and MSG+TQ+T. MSG (0.4 mg/kg/day), TQ (10 mg/kg/day) and T (30 mg/kg/day) were orally administered for 8 weeks. The behavioral tests proved that rats treated with TQ and/or T showed improved locomotor, attention and cognitive functions compared to the MSG group with more pronounced effect displayed with their combination. All treated groups showed improvement in MSG-induced aberrations in brain levels of GSH, IL-1ß, TNF-α, GFAP, glutamate, calcium, dopamine, norepinephrine, Wnt3a, ß-Catenin and BDNF. TQ and/or T treatment also enhanced the mRNA expression of Nrf2, HO-1 and Bcl2 while reducing the protein expression of TLR4, NFκB, NLRP3, caspase 1, Bax, AIF and GSK3ß as compared to the MSG group. However, the combined therapy showed more significant effects in all measured parameters. All of these findings were further confirmed by the histopathological examinations. Current results concluded that the combined therapy of TQ and T had higher protective effects than their individual supplementations against MSG-induced ADHD-like behavior in rats.

Are Prophylactic Measures Necessary to Prevent Recurrence of Penile Keloids?

Keloid scars result from excess collagen deposition in the dermis or subcutaneous tissue in response to surgery or tissue trauma. The penis is a rare site for keloid formation, even in predisposed individuals. Only few cases of penile keloids have been reported so far. In this report, we present penile keloids complicating neonatal circumcision in twin brothers. Risk of recurrence in previous reports and measures to guard against its occurrence are also discussed.

Chemoprophylaxis during transrectal prostate needle biopsy: critical analysis through randomized clinical trial.

PURPOSE: To compare the efficacy of three chemoprophylaxis approaches in prevention of post-transrectal biopsy infectious complications (TBICs). METHODS: Patients were randomly assigned to receive ciprofloxacin 3 days 500 mg B.I.D 3 days starting the night prior to biopsy (standard prophylaxis), augmented prophylaxis using ciprofloxacin and single preprocedure shot of 160 mg gentamicin IM (augmented prophylaxis) and rectal swab culture-based prophylaxis (targeted prophylaxis). Patients were assessed 2 weeks prior to biopsy, at biopsy and 2 weeks after. Primary end point was occurrence of post-TBICs that included simple UTI, febrile UTI or sepsis. Secondary end points were post-biopsy change in the inflammatory markers (TLC, ESR and CRP), unplanned visits, hospitalization and occurrence of fluoroquinolones resistance (FQ-R; bacterial growth on MacConkey agar plate with 10 µg/ml ciprofloxacin) in the fecal carriage of screened men. RESULTS: Between April/2015 and January/2017, standard, augmented and targeted prophylaxes were given to 163, 166 and 167 patients, respectively. Post-TBICs were reported in 43 (26%), 13 (7.8%) and 34 (20.3%) patients following standard, augmented and targeted prophylaxes protocols, respectively (P = 0.000). Post-TBICs included UTI in 23 (4.6%), febrile UTI in 41 (8.2%) and sepsis in 26 (5.2%) patients. Significantly lower number of post-biopsy positive urine culture was depicted in the augmented group (P = 0.000). The number of biopsy cores was statistically different in the three groups (P = 0.004). On multivariate analysis, augmented prophylaxis had independently lower post-TBICs (OR 0.2, 95% CI 0.1-0.4, P = 0.000) when compared with the other two groups regardless of the number of biopsy cores taken (OR 1.07, 95% CI 0.95-1.17, P = 0.229). Post-biopsy hospitalization was needed in four (2%), one (0.6%) and ten (6%) patients following standard, augmented and targeted prophylaxes, respectively (P = 0.014). However, sepsis-related hospitalization was not statistically different. Post-biopsy changes in the inflammatory markers were significantly less in augmented prophylaxis (P < 0.05). FQ-R was depicted in 139 (83.2%) of the screened men. CONCLUSION: Augmented prophylaxis with single-dose gentamicin is an effective and practical approach. Targeted prophylaxis might be reserved for cases with contraindication to gentamicin.