Phytic acid attenuates acetaminophen-induced hepatotoxicity via modulating iron-mediated oxidative stress and SIRT-1 expression in mice.

Introduction: Administration of high doses of acetaminophen (APAP) results in liver injury. Oxidative stress and iron overload play roles in the pathogenesis of APAP-induced hepatotoxicity. The present study assessed the potential hepatoprotective effects of phytic acid (PA), a natural antioxidant and iron chelator, on APAP-induced hepatotoxicity and the possible underlying mechanism through its effects on CYP2E1 gene expression, iron homeostasis, oxidative stress, and SIRT-1 expression levels. Methods: Twenty-four adult male albino mice were used in this study. Mice were divided into four groups (six mice in each group): control, APAP-treated, PA-treated and APAP + PA-treated groups. Liver function tests, serum and liver tissue iron load were evaluated in all the study groups. Hepatic tissue homogenates were used to detect oxidative stress markers, including malondialdehyde (MDA) and reduced glutathione (GSH). Histological hepatic evaluation and immunohistochemistry of SIRT-1 were performed. Quantitative real-time PCR was used for the assessment of CYP2E1 and SIRT-1 gene expressions. APAP-induced biochemical and structural hepatic changes were reported. Results: PA administration showed beneficial effects on APAP-induced hepatotoxicity through improvements in liver functions, decreased CYP2E1 gene expression, decreased serum and liver iron load, decreased MDA, increased GSH, increased SIRT-1 expression level and improvement in hepatic architecture. Conclusion: Conclusively, PA can be considered a potential compound that can attenuate acetaminophen-induced hepatotoxicity through its role as an iron chelator and antioxidant, as well as the up-regulation of SIRT-1 and down-regulation of CYP2E1.

Probiotics Attenuate Myopathic Changes in Aging Rats via Activation of the Myogenic Stellate Cells.

Aging represents a complex biological process associated with decline in skeletal muscle functions. Aging impairs satellite cells that serve as muscle progenitor cells. Probiotic supplementation may have many beneficial effects via various mechanisms. We examined the possible effects of probiotics in stimulating the proliferation of myogenic stellate cells in aging rats. Twenty-four male albino Sprague-Dawley rats were classified equally into four groups: adult control, old control, adult + probiotics, and old + probiotics. Probiotics (Lactobacillus LB) were administered gavage at a dose of 1 ml (1 × 109 CFU/ml/day) for 4 weeks. A significant increase in the relative gastrocnemius weight ratio and improvement of contractile parameters was detected in the old + probiotics group (0.6 ± 0.01) compared to the old control group (0.47 ± 0.01; P < 0.001). Probiotics significantly upregulated the activities of GSH, while NO and MDA were markedly decreased compared to control groups (P ≤ 0.001). Also, probiotics increased the mRNA and protein expressions of myogenin and CD34 (P < 0.05) as determined by real-time PCR and immunohistochemistry. Moreover, the old + probiotics group showed apparent restoration of the connective tissue spaces, reflecting the all-beneficial effects of probiotics. Our findings indicated that probiotics attenuated myopathic changes in aging rats probably through activation of the myogenic stellate cells. Probiotics improved the muscle weight, function, antioxidant activity, and myogenic transcription factors of the skeletal muscle.

Memory T Cells Discrepancies in COVID-19 Patients.

The immune response implicated in Coronavirus disease 2019 (COVID-19) pathogenesis remains to be fully understood. The present study aimed to clarify the alterations in CD4+ and CD8+ memory T cells' compartments in SARS-CoV-2-infected patients, with an emphasis on various comorbidities affecting COVID-19 patients. Peripheral blood samples were collected from 35 COVID-19 patients, 16 recovered individuals, and 25 healthy controls, and analyzed using flow cytometry. Significant alterations were detected in the percentage of CD8+ T cells and effector memory-expressing CD45RA CD8+ T cells (TEMRA) in COVID-19 patients compared to healthy controls. Interestingly, altered percentages of CD4+ T cells, CD8+ T cells, T effector (TEff), T naïve cells (TNs), T central memory (TCM), T effector memory (TEM), T stem cell memory (TSCM), and TEMRA T cells were significantly associated with the disease severity. Male patients had more CD8+ TSCMs and CD4+ TNs cells, while female patients had a significantly higher percentage of effector CD8+CD45RA+ T cells. Moreover, altered percentages of CD8+ TNs and memory CD8+CD45RO+ T cells were detected in diabetic and non-diabetic COVID-19 patients, respectively. In summary, this study identified alterations in memory T cells among COVID-19 patients, revealing a sex bias in the percentage of memory T cells. Moreover, COVID-19 severity and comorbidities have been linked to specific subsets of T memory cells which could be used as therapeutic, diagnostic, and protective targets for severe COVID-19.

Artemisinin attenuates type 2 diabetic cardiomyopathy in rats through modulation of AGE-RAGE/HMGB-1 signaling pathway.

Diabetes mellitus is a common metabolic disorder. About two-thirds of diabetic patients develop diabetic cardiomyopathy (DCM), which becomes a challenging issue as it severely threatens the patient's life. Hyperglycemia and the resulting advanced glycated end products (AGE) and their receptor (RAGE)/High Mobility Group Box-1 (HMGB-1) molecular pathway are thought to be key players. Recently, artemisinin (ART) has gained more attention owing to its potent biological activities beyond its antimalarial effect. Herein, we aim to evaluate the effect of ART on DCM and the possible underlying mechanisms. Twenty-four male Sprague-Dawley rats were divided into: control, ART, type 2 diabetic and type 2 diabetic treated with ART groups. At the end of the research, the ECG was recorded, then the heart weight to body weight (HW/BW) ratio, fasting blood glucose, serum insulin and HOMA-IR were evaluated. Cardiac biomarkers (CK-MB and LDH), oxidative stress markers, IL-1ß, AGE, RAGE and HMGB-1 expression were also measured. The heart specimens were stained for H&E as well as Masson's trichrome. DCM induced disturbances in all studied parameters; contrary to this, ART improved these insults. Our study concluded that ART could improve DCM through modulation of the AGE-RAGE/HMGB-1 signaling pathway, with subsequent impacts on oxidative stress, inflammation and fibrosis. ART could therefore be a promising therapy for the management of DCM.

Synthesis of Green Copper Nanoparticles Using Medicinal Plant Krameria sp. Root Extract and Its Applications.

Nanotechnology is one of the most dynamic research areas and the fastest-growing market. Developing eco-friendly products using available resources to acquire maximum production, better yield, and stability is a great challenge for nanotechnology. In this study, copper nanoparticles (CuNP) were synthesized via the green method using root extract of the medical plant Rhatany (Krameria sp.) as a reducing and capping agent and used to investigate the influence of microorganisms. The maximum production of CuNP was noted at 70 °C after 3 h of reaction time. The formation of nanoparticles was confirmed through UV-spectrophotometer, and the product showed an absorbance peak in the 422-430 nm range. The functional groups were observed using the FTIR technique, such as isocyanic acid attached to stabilize the nanoparticles. The spherical nature and average crystal sizes of the particle (6.16 nm) were determined using Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), and X-ray diffractometer (XRD) analysis. In tests with a few drug-resistant pathogenic bacteria and fungus species, CuNP showed encouraging antimicrobial efficacy. CuNP had a significant antioxidant capacity of 83.81% at 200 g/m-1. Green synthesized CuNP are cost-effective and nontoxic and can be applied in agriculture, biomedical, and other fields.

Renoprotective effect of N-acetylcystein and vitamin E in bisphenol A-induced rat nephrotoxicity; Modulators of Nrf2/ NF-κB and ROS signaling pathway.

BACKGROUND AND AIM OF THE WORK: Bisphenol A (BPA) is a chemical product that is widely used as a plastic precursor. It acts directly on the kidney mitochondria, causing renal dysfunction. N-acetylcysteine is effective in protecting the kidneys from chemical-induced damage. Vitamin E is an antioxidant that protects cells from the damaging effects of free radicals. The aim of this study is to further evaluate and compare NAC and vitamin E to oppose the nephrotoxicity caused by BPA. RESEARCH DESIGN AND METHODS: Forty-two adult male rats were divided into 7 groups:  control, BPA, NAC, vitamin E, BPA plus NAC, BPA plus vitamin E, and combined BPA, NAC and vitamin E. BPA, NAC, vitamin E were given orally at doses of 50 mg/kg, 200 mg/kg, and 1000 mg/kg respectively, for 5 weeks. RESULTS: NAC and vitamin E groups showed improved kidney function tests and alleviated BPA-induced oxidative stress; increased GSH and decreased MDA, NO and iNOS levels. NAC and vitamin E significantly attenuated inflammation; decreased NF-κB and increased IL-4, and Nrf2, in addition there was alleviation of renal histopathology. To some extent, vitamin E administration showed significant improvement. Moreover, combined NAC and vitamin E treatment showed more significance than either NAC or vitamin E separate groups. CONCLUSIONS: This study determined the substantial protective effects of NAC and/or vitamin E in BPA-induced nephrotoxicity through modulation of Nrf2 with subsequent improvement of oxidative stress and inflammation. The alleviation was more significant in combined NAC and vitamin E treatment mainly through their synergistic effect on Nrf2.

Neuroprotective and therapeutic effects of calcitriol in rotenone-induced Parkinson's disease rat model.

Parkinson's disease (PD) is the second most common neurodegenerative disease. Treatment of PD is challenging, as current treatment strategies are only symptomatic and do not stop disease development. Recent studies reported neuroprotective effects of calcitriol in PD through its antioxidant and anti-inflammatory properties. The exact pathomechanisms of PD are not yet fully understood. So, investigation of different molecular pathways is challenging. Sirtuin-1 (Sirt1) modulates multiple physiological processes, including programmed cell death, DNA repair, and inflammation. Furthermore, defective autophagy is considered a key pathomechanism in PD as it eliminates protein aggregation and dysfunctional cell organelles. The present study investigated the involvement of autophagy and Sirt1/NF-κB molecular pathway in rotenone-induced PD and explored the protective and restorative effects of calcitriol through these mechanisms. Therefore, behavioral tests were used to test the effect of calcitriol on motor disability and equilibrium. Furthermore, the histological and neuronal architecture was assessed. The expression of genes encoding neuroinflammation and autophagy markers was determined by qPCR while their protein levels were determined by Western blot analysis and immune-histochemical staining. Our results indicate that behavioral impairments and dopaminergic neuron depletion in the rotenone-induced PD model were improved by calcitriol administration. Furthermore, calcitriol attenuated rotenone-induced neuroinflammation and autophagy dysfunction in PD rats through up-regulation of Sirt1 and LC3 and down-regulation of P62 and NF-κB expression levels. Thus, calcitriol could induce a neuro-protective and restorative effect in the rotenone-induced PD model by modulating autophagy and Sirt1/NF-κB pathway.

Chitosan and Nano-Chitosan for Management of Harpophora maydis: Approaches for Investigating Antifungal Activity, Pathogenicity, Maize-Resistant Lines, and Molecular Diagnosis of Plant Infection.

The rapid spread of late wilt disease among maize cultivations has resulted in serious economic losses in many countries. Harpophora maydis is the main cause of this destructive vascular disease. Here we evaluate the fungicidal activity of chitosan and nano-chitosan against six aggressive isolates of H. maydis collected from different Egyptian governorates. Pathogenicity tests for these isolates show that the highest disease severity was found for the Giza isolate. The isolates were tested for their response to the fungicide Permis, chitosan, and nano-chitosan treatments in vitro and in vivo. Nano-chitosan treatments fully inhibited the radial growth of H. maydis isolates at concentrations of 5 and 10 mM, compared to the full control growth (9 cm in diameter). On the other hand, in vitro, in vivo, and molecular diagnosis results showed high antifungal activity of chitosan and nano-chitosan compared to the Permis fungicide. Chitosan at the nano and normal scales proved a potent ability to enhance plant resistance in response to H. maydis. Disease severity (DS%) was extremely decreased among the tested cultivars by using nano-chitosan; the highest percentage was obtained on Giza 178 cv, where the DS% was 21.7% compared to 42.3% for the control. Meanwhile, the lowest percentage was obtained on Giza 180 cv with DS% 31.2 and the control with 41.3%. The plants treated with nano-chitosan showed the highest growth parameters for all cultivars. Such natural treatments could reduce the impact on the environment as they are non-pollutant natural compounds, protect the plants by reducing fungal activity, and induce plant resistance.

Cardiac glycosides use and the risk and mortality of cancer; systematic review and meta-analysis of observational studies.

BACKGROUND: Cardiac glycosides (CGs) including digitalis, digoxin and digitoxin are used in the treatment of congestive heart failure and atrial fibrillation. Pre-clinical studies have investigated the anti-neoplastic properties of CGs since 1960s. Epidemiological studies concerning the association between CGs use and cancer risk yielded inconsistent results. We have performed a systematic review and meta-analysis to summarize the effects of CGs on cancer risk and mortality. METHODS: PubMed, Scopus, Cochrane library, Medline and Web of Knowledge were searched for identifying relevant studies. Summary relative risks (RR) and 95% confidence intervals (CI) were calculated using random-effects model. RESULTS: We included 14 case-control studies and 15 cohort studies published between 1976 and 2016 including 13 cancer types. Twenty-four studies reported the association between CGs and cancer risk and six reported the association between CGs and mortality of cancer patients. Using CGs was associated with a higher risk of breast cancer (RR = 1.330, 95% CI: 1.247-1.419). Subgroup analysis showed that using CGs increased the risk of ER+ve breast cancer but not ER-ve. Using CGs wasn't associated with prostate cancer risk (RR = 1.015, 95% CI: 0.868-1.87). However, CGs decreased the risk in long term users and showed a protective role in decreasing the risk of advanced stages. CGs use was associated with increased all-cause mortality (HR = 1.35, 95% CI: 1.248-1.46) but not cancer-specific mortality (HR = 1.075, 95% CI: 0.968-1.194). CONCLUSION: The anti-tumor activity of CGs observed in pre-clinical studies requires high concentrations which can't be normally tolerated in humans. However, the estrogen-like activity of CGs could be responsible for increasing the risk of certain types of tumors.

Clinical and Laboratory Profile of Urinary Tract Infections Associated with Extended Spectrum ß-Lactamase Producing Escherichia coli and Klebsiella pneumoniae.

BACKGROUND: Urinary tract infection (UTI) is mainly due to invasion of the urethra, bladder or kidneys by pathogens. The emergence of extended spectrum ß-lactamases (ESBL) is responsible for frequently observed empirical therapy failures. OBJECTIVES: To study the clinical and laboratory characteristics of UTIs caused by ESBL producing Escherichia coli (E. coli) and Klebsiella pneumonia (K. pneumonia). METHODS: A cross-sectional clinical and laboratory study was performed at King Khalid Hospital, Hafr Al Batin, Saudi Arabia between March 2014 to October 2015. A total of 908 urine samples from suspected UTI patients was collected. Samples were isolated on Cysteine Electrolyte-Deficient (CLED) agar. Positive cultures were identified and tested for antimicrobial susceptibility by MicroScan(®) WalkAway-96 SI System, and then ESBL was confirmed by double disc synergy test (DDST) and phenotypic confirmatory disc diffusion test (PCDDT). RESULTS: A total of 680 samples (288 males and 392 females) were culture positive. 520 samples (76.5%) of E. Coli were found and 160 samples of K. pneumonia were identified (23.5%). ESBL testing showed 296 (218 E. coli and 78 K. pneumonia) samples of positive isolates. Non-ESBL isolates showed highest resistance to ampicillin followed by Mezocillin and Trimethoprim-Sulphamethoxazole-which are usually recommended as the initial treatment of UTI-while ESBL isolates showed resistance to third generation cephalosporin along with Ampicillin and Trimethoprim-Sulphamethoxazole. In this study, four significant risk factors for ESBL infection such as diabetes, recurrent UTI, previous use of antibiotics and previous hospitalization were found. CONCLUSION: Identifying the risk factors and antibiotic susceptibility patterns associated with ESBL producing E. coli and K. pneumonia is a useful guide for treatment strategy and control of ESBL UTI.

Antifungal activity of peppermint and sweet basil essential oils and their major aroma constituents on some plant pathogenic fungi from the vapor phase.

The vapors of peppermint oil and two of its major constituents (menthol and menthone), and sweet basil oil and two of its major constituents (linalool and eugenol), were tested against Sclerotinia sclerotiorum (Lib.), Rhizopus stolonifer (Ehrenb. exFr.) Vuill and Mucor sp. (Fisher) in a closed system. These fungi cause deterioration and heavy decay of peach fruit during marketing, shipping and storage. The essential oils, their major individual aroma constituents and blends of the major individual constituents at different ratios inhibited the growth of the fungi in a dose-dependent manner. Menthol was found to be the individual aroma constituent responsible for the antifungal properties of peppermint essential oil, while menthone alone did not show any effect at all doses. In the case of basil oil, linalool alone showed a moderate antifungal activity while eugenol showed no activity at all. Mixing the two components in a ratio similar to their concentrations in the original oil was found to enhance the antifungal properties of basil oil indicating a synergistic effect.