Ex vivo treatment with poly (I:C) alleviates the exhausted phenotype of tumor-infiltrating TCD8+ cells of gastric cancer patients.

Gastric cancer is associated with the phenotypic and functional exhaustion of TCD8+ cells. On the other hand, Toll-like receptor (TLR) agonists are known to reinforce immune responses when used as adjuvants in cancer immunotherapies. Since the compromised signaling of pro-inflammatory pathways is usually associated with T cell exhaustion, the aim of the present study was to evaluate the impact of polyinosinic-polycytidylic acid (poly (I:C))-mediated TLR3 activation in restoring the normal phenotype and function of tumor-infiltrating TCD8+ cells. Peripheral blood and tumor-infiltrating TCD8+ cells of 35 gastric cancer patients were in vitro treated with increasing concentrations of poly (I:C) and the expressions of programmed death-1 (PD-1) and lymphocyte-activation gene 3 (LAG3) on these cells were examined. The peripheral TCD8+ cells of gastric cancer patients showed higher expressions of PD-1 and LAG3 along with lower proliferation compared to TCD8+ cells of the age-matched healthy control individuals. The in vitro treatment of TCD8+ cells with 100 µg/mL concentration of poly (I:C) alleviated the expression of PD-1 and LAG3 inhibitory checkpoint molecules on both peripheral and tumor-infiltrating TCD8+ cells. The mentioned dose of poly (I:C) improved the proliferation of TCD8+ cells in response to a polyclonal activator. Besides, the releases of Interferon gamma (IFN-γ) and Tumor necrosis factor alpha (TNF-α) were increased in the poly (I:C)-treated TCD8+ cells. Poly (I:C) demonstrated a potential to reduce the phenotypic and functional exhaustion of the peripheral and tumor-infiltrating TCD8+ cells and caused them to undergo more proliferation and cytokine release.

Perception and preference of pharmacy students toward e-learning during the COVID-19 pandemic.

This study is designed to evaluate students' knowledge and perceptions about the online learning of pharmacy curricula in Iraq during the COVID-19 quarantine. A descriptive, cross-sectional study involving 278 pharmacy students was done between October 2020 and June 2021. About 42.44% preferred face-face lecturers over other modes of delivery for lectures in the pharmacy curriculum. Most participants preferred both active learning and face-face lectures. The results show that 72.66% of responders chose to stay at home as one of the privileges of e-learning. However, the main barriers that associated with e-learning were lack of patient involvement and some technical issues regarding IT equipment, (74.82%) and (62.23%), respectively. E-learning is seen as a lack of social presence, less social contact, and synchronization of connections. However, e-learning undoubtedly benefits students in several ways. Online learning is an essential podium for students to achieve their studies in periods of crisis.

The relationship between hormonal levels and hematological parameters in cystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) is characterized by the abnormal production of ovarian androgens resulting in elevated levels of male sex hormones in women. This condition is often marked by the development of a group of small cysts, fluid-filled sacs (cysts) in the ovaries. This study aimed to analyze serum levels of prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and specific hematological parameters in women with PCOS. In total, 70 women were enrolled, of which 50 were diagnosed with PCOS at an obstetrics institution in Karbala from February and May 2022, and 20 were excluded. Participant selection was based on the Rotterdam 2003 criteria, and we excluded postmenopausal women, those with hyperprolactinemia, and those with overt thyroid dysfunction. The control group included 20 fertile women with normal hormone levels, regular menstrual cycles, and no signs of hyperandrogenism, as verified by ultrasonography. Ages 15 to 46 were similar with regard to the frequency of illness, with those under 36 having a higher incidence. Data were collected via questionnaires, hormone level assessments, and complete blood count (CBC) tests. There was a significant increase in hormone levels (LH, FSH, prolactin, TSH) and CBC values (WBC, Hb, and Plt) in the PCOS group compared to the control group. We observed that women between 26 and 35 were more susceptible to PCOS. Furthermore, women who were overweight demonstrated a higher susceptibility to the syndrome.

USE OF INFLIXIMAB TO ATTENUATE CEREBRAL APOPTOSIS INDUCED BY CEREBRAL ISCHEMIA/REPERFUSION IN MALE RATS.

OBJECTIVE: The aim: The purpose of the research was to study the role of infiximab global cerebral ischemia-reperfusion injury. PATIENTS AND METHODS: Materials and methods: The rats were split into five groups: Sham group; Control group: occlusion of the common carotid artery for 60 minutes, and sub-sequently reperfusion for an hour without receiving any medication; Vehicle group: as the control group, but 72 hours before to the ischemia, they were given the medication 0.9 NaCl intraperitoneally (i.p); Treated group-1: as the control group, plus 3 mg/kg of IFX intraperitoneally (i.p) 72 hours prior to ischemia; Treated group-2: as the control group, plus 7 mg/kg of IFX intraperitoneally (i.p) 72 hours prior to ischemia. RESULTS: Results: Pre-treatment with IFX significantly reduced the percentage of infarct area, but in the IFX (7 mg/kg) group, the infarct area was smaller than at the low dose. The ischemia group had a significant elevated of TNF- α and caspase-3 while a significant lowered in CAT and SOD levels. The pre-treatment with IFX, the TNF- α and caspase-3 levels lowered significantly, furthermore, significantly increased CAT and SOD levels activity (P≤0.05) as compared with IR group. Among effective groups, I/R+IFX (7mg/kg) group more effective in lowering TNF- α and caspase than I/R+IFX (3mg/kg) group. CONCLUSION: Conclusions: Infiximab has neuroprotective effective due to its powerful TNF- α blocker and limit ROS release and cell death signaling which protects the neurons from injury during cerebral ischemia reperfusion.

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.

Evaluating the neuroprotective activities of vinpocetine, punicalagin, niacin and vitamin E against behavioural and motor disabilities of manganese-induced Parkinson's disease in Sprague Dawley rats.

The current study investigated the neuroprotective activity of some drugs and nutriceuticals with antioxidant and anti-inflammatory potential on the pathogenesis of Parkinson's disease (PD). Rats were categorized into seven groups: Rats received tween80 daily for 5 weeks as a control group, MnCl2 (10 mg/kg, i.p) either alone (group II) or in combination with vinpocetine (VIN) (20 mg/kg) (group III), punicalagin (PUN) (30 mg/kg) (group IV), niacin (85 mg/kg) (group V), vitamin E (Vit E) (100 mg/kg) (group VI) or their combination (group VII). Motor activities was examined using open-field and catalepsy. Striatal monamines, acetylcholinesterase, excitatory/inhibitory neurotransmitters, redox status, pro-oxidant content, brain inflammatory, apoptotic and antioxidant biomarkers levels were assessed. Besides, histopathological investigations of different brain regions were determined. Groups (IV -GVII) showed improved motor functions of PD rats. Applied drugs significantly increased the brain levels of monoamines with the strongest effect to PUN. Meanwhile, they significantly decreased levels of acetylcholinesterase with a strongest effect to PUN. Moreover, they exhibited significant neuronal protection and anti-inflammatory abilities through significant reduction of the brain levels of COX2, TNF-α and Il-1ß with a strongest effect to the PUN. Interestingly; groups (IV - GVII) showed restored glutamate/GABA balance and exhibited a pronounced decrease in caspase-3 content and GSK-3ß protein expression levels. In addition, they significantly increased Bcl2 mRNA expression levels with a strongest effect for PUN. All these findings were further confirmed by the histopathological examinations. As a conclusion, we propose VIN and PUN to mitigate the progression of PD via their antioxidant, anti-inflammatory, anti-apoptotic, neurotrophic and neurogenic activities.

Melatonin and zinc supplements with physical and mental activities subside neurodegeneration and hepatorenal injury induced by aluminum chloride in rats: Inclusion of GSK-3ß-Wnt/ß-catenin signaling pathway.

Alzheimer's disease (AD) is an irreversible, progressive cognitive dysfunction. Inflammaging is the greatest common factor between AD and hepatorenal malfunction. This study aimed to use melatonin (MEL) and zinc sulfate (Zn) in addition to physical and mental activities (PMA) to ameliorate AlCl3-induced AD as well as investigate their impact on the associated hepatorenal impairment. METHODS: Seven groups of rats each received: saline (control group), AlCl3 (70 mg/kg, i.p.), PMA, either alone or with a combination of Mel (10 mg/kg, p.o) and/or Zn (16 mg/kg, p.o). Neurological deterioration was assessed after 5 weeks using behavioral tests, histopathological examination, and measurements of acetylcholinesterase (ACHE), brain monoamines, oxidative stress, and inflammatory markers, Amyloid precursor protein (APP), amyloid-ß (Aß), tau levels, and brain derived neurotrophic factor (BDNF). Moreover, the GSK-3ß-Wnt/ß-catenin signaling pathway was assessed. Additionally, oxidative stress and inflammatory markers were determined in liver and kidney tissues with concurrent evaluation of hepatic and renal functions. RESULTS: The histopathological examination revealed a cerebral cortex and hippocampus deterioration in the AD group with a decline in spatial learning and memory, besides a significant increase in AD markers in the brain and disturbance in GSK-3ß-Wnt/ß-catenin signaling. The AD group showed hepatorenal injuries supported by elevated oxidative stress and inflammatory markers. However, adding Mel and Zn to PMA significantly attenuated the neurodegeneration and enhanced hepatic and renal functions by ameliorating oxidant and inflammatory markers. CONCLUSIONS: Combining Mel and Zn supplements with PMA defends against AlCl3-induced AD by modulating GSK-3ß-Wnt/ß-catenin signaling and palliates the associated hepatorenal dysfunction.