Malaria: biochemical, physiological, diagnostic, and therapeutic updates.

Background: Malaria has been appraised as a significant vector-borne parasitic disease with grave morbidity and high-rate mortality. Several challenges have been confronting the efficient diagnosis and treatment of malaria. Method: Google Scholar, PubMed, Web of Science, and the Egyptian Knowledge Bank (EKB) were all used to gather articles. Results: Diverse biochemical and physiological indices can mirror complicated malaria e.g., hypoglycemia, dyslipidemia, elevated renal and hepatic functions in addition to the lower antioxidant capacity that does not only destroy the parasite but also induces endothelial damage. Multiple trials have been conducted to improve recent points of care in malaria involving biosensors, lap on-chip, and microdevices technology. Regarding recent therapeutic trials, chemical falcipain inhibitors and plant extracts with anti-plasmodial activities are presented. Moreover, antimalaria nano-medicine and the emergence of nanocarrier (either active or passive) in drug transportation are promising. The combination therapeutic trials e.g., amodiaquine + artemether + lumefantrine are presented to safely counterbalance the emerging drug resistance in addition to the Tafenoquine as a new anti-relapse therapy. Conclusion: Recognizing the pathophysiology indices potentiate diagnosis of malaria. The new points of care can smartly manipulate the biochemical and hematological alterations for a more sensitive and specific diagnosis of malaria. Nano-medicine appeared promising. Chemical and plant extracts remain points of research.

Evaluating the hepatotoxic versus the nephrotoxic role of iron oxide nanoparticles: One step forward into the dose-dependent oxidative effects.

The present study has been designed to detect the dose-dependent effect of iron oxide nanoparticles (IONPs) on the liver and kidney of rats by evaluating three different doses 30, 300, 1000 mg/kg/day IONPs for 28 days. Forty rats were divided into four groups; I (control), II (low dose), III (medium dose) and IV (high dose). There also was a statistically-significant elevation in the serum levels of hepatic enzymes; AST and ALT in medium & high dose. The elevation of serum ALP, on the other hand, was significant in all IONPs doses. There was significant elevation in the levels of urea creatinine, and MDA in the medium and high doses of IONPs. The activity of superoxide dismutase (SOD) and glutathione peroxidase (GPx) showed significant decrease in the high dose only compared to the control group. The serum iron levels increased in a dose-dependent manner in the IONPs-treated groups with highly significant increase in the moderate and high dose groups. On comparing the effect of different doses of IONPs between the liver and kidney, the high dose revealed statistically significant difference (p < 0.05) in the area percent of collagen deposition (54.4 ± 3.9 versus 6.1 ± 2.6) and alpha smooth muscle actin (α-SMA) reaction (7.7 ± 1.5 versus 17.8 ± 4.3) in the liver relative to the kidney. The medium and high doses revealed statistically significant difference in optical density of Periodic acid Schiff (PAS) reaction (45 ± 3.4 versus 50.3 ± 1.8 in the medium dose, and 38.9 ± 6 versus 63 ± 3 in the high dose) and area percent of inducible nitric oxide synthase (iNOS) reaction (12.98 ± 2.7 versus 3.5 ± 0.5 in the medium dose, and 27.91 ± 1.5 versus 7.7 ± 0.6 in the high dose) in the liver relative to the kidney.

Prenatal intake of omega-3 promotes Wnt/ß-catenin signaling pathway, and preserves integrity of the blood-brain barrier in preeclamptic rats.

BACKGROUND: Preeclampsia is a systemic, multi-organ endotheliopathy, associated with oxidative injury to the blood-brain barrier (BBB). Preeclampsia initiates a cascade of events that include neuroinflammation. Recently, it was documented that Wnt/ß-catenin signaling pathway exerts neuroprotective effects and maintain BBB integrity. We investigate the protective effect of omega-3 against neurovascular complication of preeclampsia and its relation to Wnt/ß-catenin signaling pathway. METHODOLOGY: After confirmation of day 0 pregnancy (G0), 24 adult pregnant female Wistar rats were divided into four groups control pregnant, pregnant supplemented with omega-3, preeclampsia (PE); female rats received N (ω)-nitro-L-arginine methyl ester (L-NAME) (50 mg/kg/day SC from day 7 to day 16 of pregnancy for induction of preeclampsia) and PE rats supplemented with omega-3. The intake of omega-3 started on day zero (0) of pregnancy until the end of the study (144 mg/kg\day orally). RESULTS: We found that omega-3 supplementation significantly improved cognitive functions and EEG amplitude, decreased blood pressure, water contents of brain tissues, sFlt-1, oxidative stress, proteinuria, and enhanced Wnt\ß-catenin proteins. Histological examination showed improved cerebral microangiopathy, increased expression of claudin-1 and -3, CD31, and VEGF in the cerebral cortical microvasculature and choroid plexus in PE rats treated with omega-3. A positive correlation between protein expression level of Wnt \ß-catenin and cognitive functions, and a negative correlation between claudin-5 relative expression, claudin-1 and -3 area % from one side and water content of the brain tissues from the other side were observed. CONCLUSION: Wnt/ß-catenin signaling pathway suspected to have an important role to improve BBB integrity. Neuroprotective, antioxidant, and anti-inflammatory effects of omega-3 were observed and can be suggested as protective supplementation for preeclampsia.

Possible role of rice bran extract in microglial modulation through PPAR-gamma receptors in alzheimer's disease mice model.

Alzheimer's Disease (AD), the most prevalent neurodegenerative disorder among elderly people, is ordinarily associated with progressive cognitive decline. Peroxisome proliferator-activated receptors-gamma (PPAR-γ) agonists can be targeted as a beneficial therapeutic strategy against AD. In the present study, we aimed to investigate the preventive and therapeutic effects of rice bran extract (RBE) as a possible PPAR-γ agonist on the microglial phenotype modulation in AD in mice compared to the effects of pioglitazone. This study included 64 adult male Swiss Albino mice divided into 8 groups, each group comprised 8 mice; control group, RBE group, lipopolysaccharide-induced neurodegeneration (a) (LPSa) group, (LPSb) group, RBE-preventive group (RBE + LPSa), pioglitazone-preventive group (PG + LPSa), RBE-treated group (RBE + LPSb), and pioglitazone-treated group (PG + LPSb). Cognitive functions were assessed by Y-maze and Morris water maze tests. The expression of PPAR-γ, CD45, arginase1, CD36, and CD163 genes was assessed by real time qPCR and the estimation of NF-kß protein level was done by Western blot technique. Moreover, the assessment of Aß42 and P-tau levels was performed by ELISA. Histopathological examination of brain tissues was performed for all the studied groups. Our results showed that RBE and pioglitazone could modulate microglial phenotype from M1 to M2 where they significantly decreased the expression of NF-κß and the pro-inflammatory microglial marker (CD45) in parallel with increasing the expression of the anti-inflammatory microglial and phagocytic markers (arginase1, CD163, and CD36). In addition, RBE and pioglitazone significantly increased PPAR-γ expression and reduced Aß42 deposition as well as p-tau protein levels. In conclusion, our study identified the possible role of PPAR-γ agonistic activity of RBE as a preventive and therapeutic agent in the treatment of the neuro-inflammation associated with AD.

Histological, immunohistochemical, and molecular investigation on the hepatotoxic effect of potassium dichromate and the ameliorating role of Persea americana mill pulp extract.

The current study has been designed to assess the role of Persea americana (P. americana) pulp extract on potassium dichromate-induced hepatotoxicity in rats. P. americana pulp extract administration improved the hepatic vascular congestion, blood extravasation, inflammatory cellular infiltration, Kupffer cell hyperplasia, and nuclear changes. It also significantly ameliorated hepatic interstitial and peri-portal fibrosis and caused retrieval of the PAS-positive reaction in the liver parenchyma and around the central vein with restoration of the glycogen granules. P. americana also significantly attenuated the immunohistochemical expression of NF-kß p65 and its downstream inflammatory cytokines IL6 and TNFα in the liver parenchyma. The antioxidant effect of P. americana was evidenced by significant modulation of the three major components of the thioredoxin (Trx) antioxidant system, the Trx, the thioredoxin reductase (TrxR), and the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase along with significant increase in the level of superoxide dismutase and glutathione, and decrease in the lipid peroxidation product malondialdehyde. P. americana pulp extract also caused significant elevation of hepatic protein phosphatase 5 with subsequent down-regulation of Apoptosis signal-regulating kinase1 (ASK1) and its downstream signaling targets MAPK kinase 4 (MKK4), p38 mitogen-activated protein kinases (p38-MAPKs), the c-JUN N-terminal kinase (JNK), and the extracellular signal-regulated kinase 1/2 (ERK 1/2). Also, In conclusion, P. americana pulp extract has anti-oxidative and anti-inflammatory effects against potassium dichromate-induced hepatotoxicity.

The impact of l-arginine supplementation on the enteral phase of experimental Trichinella spiralis infection in treated and untreated mice.

The role of nitric oxide (NO) in the immunopathological response during Trichinella spiralis (T. spiralis) infection remains controversial. The amino acid, l-arginine is a NO precursor commonly used by athletes and bodybuilders as a protein supplement. As to our knowledge, there are no published studies which have tested the effect of l-arginine on the intestinal phase of experimental trichinellosis. The present work aims to investigate the effect of l-arginine on the enteral phase of experimental T. spiralis infection in albendazole-treated and untreated mice. Forty BALB/C mice infected orally with T. spiralis larvae were divided into 4 groups as follows: Group A were infected and untreated (control) mice, Group B received albendazole alone, Group C received l-arginine alone, and Group D received both l-arginine and albendazole. Compared to the control group, l-arginine supplementation showed; a significant increase in the intestinal adult worm burden, a significantly high inducible NO synthase (iNOS) expression, elevated immune markers; tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), and enhanced apoptosis. Albendazole treated-group had a significant reduction in the adult worm number (90.9%), while combined albendazole-arginine regimen showed a lower percentage of worm reduction (72.7%). During the enteral phase of T. spiralis infection, l-arginine supplementation should be taken cautiously, as it may modulate the proinflammatory immune response and subsequently affect the outcome of the infection and/or treatment.

Hepatotoxic Effect of Oral Zinc Oxide Nanoparticles and the Ameliorating Role of Selenium in Rats: A histological, immunohistochemical and molecular study.

Despite the emerging concerns about the hepatotoxic risks associated with Zinc oxide nanoparticles (ZnO NPs), yet, the morphological and molecular alterations associated with these extensively-used nanoparticles remain to be elucidated. Thus, the current study has been designed to analyze the effect of ZnO NPs on the hepatic histopathological and immunohistochemical changes, along with the modulation of the oxidative-stress induced JNK/p38MAPK and the STAT-3 signalling. The study also explored the potential protective role of selenium against those alterations. ZnO NPs disrupted the hepatic architecture, elevated the serum liver enzyme alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) levels and caused dose-dependent decrease in the activity of the antioxidant enzymes glutathione-peroxidase, superoxide dismutase and catalase along with an increase in the lipid peroxidation product malondialdehyde. ZnO NPs also increased the area of immune-reactivity of the apoptotic protein bax and decreased the area of immune-reactivity of the anti-apoptotic protein bcl2 together with augmentation of the hepatic caspase 3 gene expression. The role of selenium in ameliorating the hepatotoxicity, oxidative stress injury, and apoptosis induced by ZnO-NPs, along with its role in modulating the JNK/p38MAPK and the STAT-3 signalling and improving the histopathological hepatic changes, offers selenium as a promising adjunctive therapy in individuals subjected to high concentrations of ZnO NPs especially in cases of extensive occupational, medicinal and industrial exposure.

The neurotoxic effect of long-term use of high-dose Pregabalin and the role of alpha tocopherol in amelioration: implication of MAPK signaling with oxidative stress and apoptosis.

Pregabalin abuse has become an emerging concern; thus, the current study has been designed to study the neurotoxic hazards of prolonged high-dose of pregabalin (akin to that abused by addicts) and to evaluate the effect of alpha tocopherol as a possible ameliorating agent. The current study evaluated the brain neurotransmitters; dopamine, glutamate, and norepinephrine. The study also assessed the expression of the apoptosis-related markers Bax, Bcl2, and caspase 3. Western-blotted analysis of the three major mitogen-activated protein kinases (MAPKs), the c-JUN N-terminal kinase (JNK), the p38 MAPK, and the extracellular signal-regulated kinase (ERK), has also been performed. The study also evaluated oxidative stress via assessment of the cortical tissue levels of reduced glutathione and malondialdehyde and the activity of superoxide dismutase. Histopathological examination and histomorphometric evaluation of the darkly degenerated cortical neurons have also been performed. Pregabalin in high doses (150 mg/kg/day and 300 mg/kg/day) disrupted the ERK/JNK/p38-MAPK signaling, reversed the bax/bcl2 ratio, and induced oxidative stress. It also diminished the release of dopamine, glutamate, and norepinephrine and increased the count of degenerated neurons. Alpha tocopherol treatment significantly attenuated the deleterious effects induced by pregabalin. The role of alpha tocopherol in ameliorating the oxidative stress injury, and apoptosis induced by pregabalin, along with its role in normalizing neurotransmitters, modulating the ERK/JNK/p38-MAPK signaling pathways and improving the histopathological cortical changes, offers alpha tocopherol as a promising adjunctive therapy in patients undergoing prolonged pregabalin therapy as those suffering from prolonged seizures and neuropathies.

Selenium protection against mercury neurotoxicity: Modulation of apoptosis and autophagy in the anterior pituitary.

AIMS: The aim of the present study is to shed light on the modulating action of selenium on two of the most crucial cellular pathways; apoptosis and autophagy and the possible interplay between them in determining the pituitary fate in the context of mercury intoxication through demonstration of the molecular, histopathological, immunohistochemical, and ultrastructural features of selenium mercury-treated adenohypophysis. METHODS: Thirty adult Sprague Dawley male albino rats were assigned into control group, mercury-treated group and mercury­selenium concomitantly-treated group. The adenohypophysis was subjected to structural, molecular and protein expression assessment of autophagy and apoptotic markers and western blotted analysis of Beclin 1 as a key cross-regulator of autophagy and apoptosis. KEY FINDINGS: Selenium treatment ameliorated the mercury-induced apoptosis detected by improvement in PCR and immunohistochemical expression of the apoptotic markers Bax, Bcl-2 and Caspase-3. Selenium also improved mercury-induced autophagic dysfunction with statistically significant improvement in western blotted levels of the autophagy markers LC3I, LC3II and Beclin1. The histopathological and ultrastructural studies strongly confirmed those findings. SIGNIFICANCE: The crosstalk between the apoptotic Bcl-2 family of proteins and the autophagic Beclin-1LC3 pathway in the context of mercury intoxication paves the way for developing novel effective treatment strategies for several mercury-induced pituitary diseases.