Aboul Ella Hassanien (Abo)

BACKGROUND: Hepatic and renal damage is a cisplatin (Cis)-induced deleterious effect that is a major limiting factor in clinical chemotherapy.

OBJECTIVES: The current study was designed to investigate the influence of pretreatment with olive leaf extract (OLE), bone-marrow-derived mesenchymal stem cells (BM-MSC), and their conditioned media (CM-MSC) against genotoxicity, nephrotoxicity, hepatotoxicity, and immunotoxicity induced by cisplatin in rats.

METHODS: The rats were randomly divided into six groups (six rats each) as follows: Control; OLE group, treated with OLE; Cis group, treated with a single intraperitoneal dose of Cis (7 mg/kg bw); Cis + OLE group, treated with OLE and cisplatin; Cis + CM-MSC group, treated with BM-MSC conditioned media and Cis; and Cis + MSC group, treated with BM-MSC in addition to Cis.

RESULTS: Cis resulted in a significant deterioration in hepatic and renal functions and histological structures. Furthermore, it increased inflammatory markers (TNF-α, IL-6, and IL-1β) and malondialdehyde (MDA) levels and decreased glutathione (GSH) content, total antioxidant capacity (TAC), catalase (CAT), and superoxide dismutase (SOD) activity in hepatic and renal tissues. Furthermore, apoptosis was evident in rat tissues. A significant increase in serum 8-hydroxy-2-deoxyguanosine (8-OH-dG), nitric oxide (NO) and lactate dehydrogenase (LDH), and a decrease in lysozyme activity were detected in Cis-treated rats. OLE, CM-MSC, and BM-MSC have significantly ameliorated Cis-induced deterioration in hepatic and renal structure and function and improved oxidative stress and inflammatory markers, with preference to BM-MSC. Moreover, apoptosis was significantly inhibited, evident from the decreased expression of Bax and caspase-3 genes and upregulation of Bcl-2 proteins in protective groups as compared to Cis group.

CONCLUSIONS: These findings indicate that BM-MSC, CM-MSC, and OLE have beneficial effects in ameliorating cisplatin-induced oxidative stress, inflammation, and apoptosis in the hepatotoxicity, nephrotoxicity, immunotoxicity, and genotoxicity in a rat model.

Anxiety is a neuropsychiatric disturbance that is commonly manifested in various dementia forms involving Alzheimer's disease (AD). The mechanisms underlying AD-associated anxiety haven't clearly recognized the role of energy metabolism in anxiety represented by the amygdala's autophagic sensors; liver kinase B1 (LKB1)/adenosine monophosphate kinase (AMPK). Dapagliflozin (DAPA), a SGLT2 inhibitor, acts as an autophagic activator through LKB1 activation in several diseases including AD. Herein, the propitious yet undetected anxiolytic potential of DAPA as an autophagic enhancer was investigated in AD animal model with emphasis on amygdala's GABAergic neurotransmission and brain-derived neurotrophic factor (BDNF). Alzheimer's disease was induced by ovariectomy (OVX) along with seventy-days-D-galactose (D-Gal) administration (150 mg/kg/day, i.p). On the 43rd day of D-Gal injection, OVX/D-Gal-subjected rats received DAPA (1 mg/kg/day, p.o) alone or with dorsomorphin the AMPK inhibitor (DORSO, 25 μg/rat, i.v.). In the amygdala, LKB1/AMPK were activated by DAPA inducing GABA receptor stimulation; an effect that was abrogated by DORSO. Dapagliflozin also replenished the amygdala GABA, NE, and 5-HT levels along with glutamate suppression. Moreover, DAPA triggered BDNF production with consequent activation of its receptor, TrkB through activating GABA-related downstream phospholipase C/diacylglycerol/protein kinase C (PLC/DAG/PKC) signaling. This may promote GABA expression, verifying the crosstalk between GABA and GABA. The DAPA's anxiolytic effect was visualized by improved behavioral traits in elevated plus maze together with amendment of amygdala' histopathological abnormalities. Thus, the present study highlighted DAPA's anxiolytic effect which was attributed to GABA activation and its function to induce BDNF/TrkB and GABA expression through PLC/DAG/PKC pathway in AMPK-dependent manner.

Anxiety is a neuropsychiatric disturbance that is commonly manifested in various dementia forms involving Alzheimer's disease (AD). The mechanisms underlying AD-associated anxiety haven't clearly recognized the role of energy metabolism in anxiety represented by the amygdala's autophagic sensors; liver kinase B1 (LKB1)/adenosine monophosphate kinase (AMPK). Dapagliflozin (DAPA), a SGLT2 inhibitor, acts as an autophagic activator through LKB1 activation in several diseases including AD. Herein, the propitious yet undetected anxiolytic potential of DAPA as an autophagic enhancer was investigated in AD animal model with emphasis on amygdala's GABAergic neurotransmission and brain-derived neurotrophic factor (BDNF). Alzheimer's disease was induced by ovariectomy (OVX) along with seventy-days-D-galactose (D-Gal) administration (150 mg/kg/day, i.p). On the 43rd day of D-Gal injection, OVX/D-Gal-subjected rats received DAPA (1 mg/kg/day, p.o) alone or with dorsomorphin the AMPK inhibitor (DORSO, 25 μg/rat, i.v.). In the amygdala, LKB1/AMPK were activated by DAPA inducing GABA receptor stimulation; an effect that was abrogated by DORSO. Dapagliflozin also replenished the amygdala GABA, NE, and 5-HT levels along with glutamate suppression. Moreover, DAPA triggered BDNF production with consequent activation of its receptor, TrkB through activating GABA-related downstream phospholipase C/diacylglycerol/protein kinase C (PLC/DAG/PKC) signaling. This may promote GABA expression, verifying the crosstalk between GABA and GABA. The DAPA's anxiolytic effect was visualized by improved behavioral traits in elevated plus maze together with amendment of amygdala' histopathological abnormalities. Thus, the present study highlighted DAPA's anxiolytic effect which was attributed to GABA activation and its function to induce BDNF/TrkB and GABA expression through PLC/DAG/PKC pathway in AMPK-dependent manner.

Advancements in shoot regeneration systems support biotechnology-based tools used in the genetic improvement of plant crops. This study aims to enhance shoot regeneration in potatoes by boosting polyamine content by adding AgNO3 to the shoot regeneration medium (MS medium supplemented with 30 g L−1 sucrose, 100 mg L−1 myoinositol, and 2.25 BA mg L−1). Five concentrations of AgNO3 (2, 4, 6, 8, and 10 mg L−1) were used in addition to a control. The effect of AgNO3 on regeneration assumed a more or less concentration-dependent bell-shaped curve peaking at 4 mg L−1. Enhancements in shoot regeneration were attributed to the known role of AgNO3 as an ethylene action blocker in addition to improvements in polyamine accumulation without an increase in H2O2 content, lipid peroxidation, or DNA damage. The uncoupling of shoot regeneration and polyamine content recorded at high AgNO3 concentrations can be attributed to the consumption of polyamines to counteract the synchronized oxidative stress manifested by increases in H2O2 content, lipid peroxidation, and DNA damage.

OBJECTIVES: The study aimed to assess the effect of Electroconvulsive Therapy (ECT) on plasma BDNF levels in patients with resistant schizophrenia.

METHODS: It was a cohort study that included 60 patients with resistant schizophrenia fulfilling the DSM-5 criteria of schizophrenia and APA criteria of resistant schizophrenia. They were divided into two groups, followed over 4 weeks, and compared to their baseline assessment. Group (A) included 45 patients who received 4-10 sessions of ECT while Group (B) included 15 patients who received the usual treatment with antipsychotics without ECT. The assessment included the severity of psychotic symptoms assessed by the Positive and Negative Symptom Scale (PANSS) in addition to plasma BDNF level.

RESULTS: Patients in Group (A) had an increased level of BDNF after treatment with a statistically significant difference in comparison to their baseline BDNF level ( = 0.027). Meanwhile, patients in group (B) showed a non-significant increase in BDNF. Patients in both groups improved significantly in all PANSS subscales after treatment.

CONCLUSIONS: It was concluded that plasma BDNF levels in patients with resistant schizophrenia increase after electroconvulsive therapy in association with clinical improvement.Key pointsBDNF increases after ECT treatment of resistant schizophrenia.BDNF is not correlated with the severity of psychotic symptomsPatients treated with ECT showed a better response.

Motors are the higher energy-conversion devices that consume around 40% of the global electrical generated energy. Induction motors are the most popular motor type due to their reliability, robustness, and low cost. Therefore, both condition monitoring and fault diagnosis of induction motor faults have motivated considerable research efforts. In this paper, a comprehensive review of the recent techniques proposed in the literature for broken bar faults detection and diagnosis is presented. This paper mainly investigates the fault detection methods in line-fed and inverter-fed motors proposed after 2015 and published in most relevant journals and conferences. The introduced review has deeply discussed the main features of the reported methods and compared them in many different aspects. Finally, the study has highlighted the main issues and the gaps that require more attention from researchers in this field.

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/GSK3β 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, GSK3β/Nrf2 signalling in addition to NF-κB p65/TNF-α/ caspase-8 and -9 pathway.

Host defense mechanisms are categorized into different strategies, namely, avoidance, resistance and tolerance. Resistance encompasses mechanisms that directly kill the pathogen while tolerance is mainly concerned with alleviating the harsh consequences of the infection regardless of the pathogen burden. Resistance is well-known strategy in immunology while tolerance is relatively new. Studies addressed tolerance mainly using mouse models revealing a wide range of interesting tolerance mechanisms. Herein, we aim to emphasize on the interspecies comparative approaches to explore potential new mechanisms of disease tolerance. We will discuss mechanisms of tolerance with focus on those that were revealed using comparative study designs of mammals followed by summarizing the reasons for adopting comparative approaches on disease tolerance studies. Disease tolerance is a relatively new concept in immunology, we believe combining comparative studies with model organism study designs will enhance our understanding to tolerance and unveil new mechanisms of tolerance.

The aim of this study was to compare the efficacy of calcium infusion versus cabergoline in the prevention of ovarian hyperstimulation syndrome (OHSS) in IVF patients at high risk for OHSS. One hundred and seventy patients who were stimulated using the long luteal GnRH agonist protocol and at high risk for developing OHSS were randomised in a 1:1 ratio to cabergoline group and calcium gluconate group. In cabergoline group, 0.5 mg of cabergoline was administered once daily p.o. for eight days starting on the day of HCG administration. In calcium gluconate group, intravenous calcium gluconate (10%, 10 ml in 200 ml of physiologic saline) was administered daily for four days starting on the day of ovum pickup. Six patients in cabergoline group and eight patients in calcium gluconate group developed moderate OHSS. One patient in each group developed severe OHSS. The incidence of moderate/severe OHSS was comparable between both groups (8.24% vs. 10.59%, value  =  .599, OR = 0.76, 95% CI [0.269-2.138]). The implantation, clinical and ongoing pregnancy rates were similar in the two groups (16.91% vs. 15.84%,  = .771, 35.29% vs. 32.94%,  = .746, and 30.59% vs. 28.24%,  = .736, respectively). In conclusion, calcium infusion and cabergoline have comparable effectiveness in the prevention of OHSS. Both drugs are well tolerated, cheap and have no adverse effects on the reproductive outcomes of IVF cycle. The trial was registered on clinical trials.gov database [NCT02875587].Impact Statement The effectiveness of cabergoline in the prevention of OHSS in IVF patients at high risk for OHSS is confirmed by overwhelming scientific evidence. Calcium infusion is a novel strategy for prevention of OHSS. Few studies reported the use of calcium infusion in the prevention of OHSS. A retrospective study and a randomised controlled study revealed that calcium infusion reduces the incidence of OHSS. Moreover, a quasi-randomised study revealed that calcium infusion is as effective as cabergoline in the prevention of OHSS. Calcium infusion and cabergoline have comparable effectiveness in the prevention of OHSS. Both drugs are well tolerated, cheap and have no adverse effects on the reproductive outcomes of IVF cycle. Calcium infusion should be used to minimise the incidence of OHSS in IVF patients at high risk for OHSS.