Cedrol supplementation ameliorates memory deficits by regulating neuro-inflammation and cholinergic function in lipopolysaccharide-induced cognitive impairment in rats.

Background: Cedrol, a sesquiterpene alcohol, is found in a high amount in several conifers. It possess several beneficial health effects, including antioxidant and anti-inflammatory properties. Objective: This study evaluates the neuroprotective role of cedrol against lipopolysaccharide (LPS)-induced neuroinflammation and memory loss in rats. Methods: Wistar rats were treated with cedrol (7.5, 15, and 30 mg/kg, oral, two weeks). During the last week, the rats (except for the control group) were treated with LPS (intraperitoneal injection, 1 mg/kg) to induce memory impairment. After that, the animals were subjected to behavioral studies (Morris water maze and passive avoidance) and biochemical assessments. Results: Our results showed a significant decrease in learning and memory function-in LPS-induced rats which were reversed by cedrol. Also, there was a significant increase in the cerebral levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and malondialdehyde (MDA) as well as acetylcholinesterase (AChE) activity in LPS-treated rats. Besides, a significant reduction in total thiol and superoxide dismutase levels was observed in LPS-treated rats. However, cedrol significantly decreased the brain level of AChE, TNF-α, and IL-1ß. Administration of cedrol also restored the oxidative stress markers. Conclusion: the beneficial effects of cedrol against LPS-induced memory impairment could be due to antioxidant activities and modulation of neuro-inflammatory mediators.

The Effects of Curcumin Plus Piperine Co-administration on Inflammation and Oxidative Stress: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: The beneficial effects of curcumin against various chronic disorders have been shown in the last few decades. However, due to its low bioavailability, therapeutic effects are less than expected. Piperine has been used in scientific evaluations as an effective compound to increase the bioavailability of curcumin. The present review investigated the impact of curcumin plus piperine intake on oxidative stress and inflammatory markers of Randomized Clinical Trials (RCTs). METHODS: Using relevant keywords, we searched Cochrane Library, Scopus, PubMed, and Web of Science between January 1st, 1970, and September 30th, 2022. A comprehensive search for RCTs was performed. Continuous data were pooled by Standard Mean Difference (SMD) and 95% confidence interval. All related statistical analyses were performed using Comprehensive Meta-Analysis (CMA) software. RESULTS: A total of 13 articles were incorporated into the final meta-analysis. According to the current meta-analysis, curcumin plus piperine administration showed a significantly increased SOD activity and GSH levels while significantly decreased MDA concentrations. In addition, our study revealed that curcumin plus piperine significantly decreased TNF-α and IL-6 concentrations. CONCLUSION: These results indicated that curcumin plus piperine administration could effectively reduce oxidative stress and inflammation.

Corrigendum: Cardioprotective effect of Sanguisorba minor against isoprenaline-induced myocardial infarction in rats.

[This corrects the article DOI: 10.3389/fphar.2023.1305816.].

Neuro-protective Effect of Acetyl-11-keto-ß-boswellic Acid in a Rat Model of Scopolamine-induced Cholinergic Dysfunction.

BACKGROUND: Acetyl-11-keto-ß-boswellic acid (AKBA) is a major component of the oleo-gum resin of B. serrata with multiple pharmacological activities. The objective of this study was to explore the underlying mechanisms of neuroprotective potential of AKBA against scopolamine-mediated cholinergic dysfunction and memory deficits in rats. METHODS: The rats received AKBA (2.5, 5, and 10 mg/kg, oral) for 21 days. In the third week, scopolamine was administered 30 min before the Morris water maze and passive avoidance tests. In order to perform biochemical assessments, the hippocampus and prefrontal cortex were extracted from the rats euthanized under deep anesthesia. RESULTS: In the MWM test, treatment with AKBA (5 and 10 mg/kg) decreased the latency and distance to find the platform. Moreover, in the PA test, AKBA remarkably increased latency to darkness and stayed time in lightness while decreasing the frequency of entry and time in the darkness. According to the biochemical assessments, AKBA decreased acetylcholinesterase activity and malondialdehyde levels while increasing antioxidant enzymes and total thiol content. Furthermore, AKBA administration restored the hippocampal mRNA and protein levels of brain-derived neurotrophic factor (BDNF) and mRNA expression of B-cell lymphoma (Bcl)- 2 and Bcl-2- associated X genes in brain tissue of scopolamine-injured rats. CONCLUSION: The results suggested the effectiveness of AKBA in preventing learning and memory dysfunction induced by scopolamine. Accordingly, these protective effects might be produced by modulating BDNF, cholinergic system function, oxidative stress, and apoptotic markers.

Effect of Nigella sativa Consumption on Lipid Profile and Glycemic Index in Patients with Metabolic Syndrome: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Metabolic syndrome is a multifactorial disorder and genetics, lifestyle, and aging play important roles in its prevalence. Nigella sativa has several pharmacological benefits, including anti-inflammatory, antitumor, anti-diabetic, antioxidant, and hypolipidemic effects. This meta-analysis of randomized controlled trials assesses the effect of N. sativa consumption on lipid profile and glycemic indices in patients with metabolic syndrome. METHODS: We systematically researched Cochrane Library, PubMed, Scopus, and Web of Science databases. The literature research identified 171 studies with duplication. Of those, 73 articles were screened for titles and abstracts, and 7 studies were finally selected for the meta-analysis. Because of the high degree of heterogeneity, we performed subgroup analyses based on the dose of N. sativa (<=500 mg/day or >500 mg/day). RESULTS: The results revealed that N. sativa intake significantly decreased total cholesterol (SMD: -0.71; 95% CI, -1.44 to -0.38; P = 0.00), LDL-C (SMD: -1.06; 95% CI, -1.45 to -0.66; P = 0.00) and HDL-C (SMD: -0.31; 95% CI, 0.09 to 0.53; P = 0.01) concentrations. In addition, N. sativa significantly decreased FBS (SMD: -0.8; 95% CI, -1.21 to -0.39; P = 0.00) and HbA1c (SMD: -0.37; 95% CI, -0.66 to -0.09; P = 0.01) concentrations. No publication bias was observed, and sensitivity analysis showed stable results. CONCLUSION: The current systematic review and meta-analysis indicates that N. sativa could improve lipid profile and glycemic index in patients with metabolic syndrome.

Immunoregulatory effects of nanocurcumin in inflammatory milieu: Focus on COVID-19.

The use of natural compounds, such as curcumin, to treat infections caused by bacteria, viruses, fungi, parasites, inflammatory diseases, and various types of cancer is an active and dynamic area of research. Curcumin has a long history of use in the food industry, and there is currently a growing interest in its therapeutic applications. Numerous clinical trials have consistently shown that curcumin, a polyphenolic compound, is safe and well-tolerated even at high doses. There is no toxicity limit. However, the clinical efficacy of curcumin has been limited by its constraints. However, scientific evidence indicates that the use of adjuvants and carriers, such as nanoparticles, exosomes, micelles, and liposomes, can help overcome this limitation. The properties, functions, and human benefits of using nanocurcumin are well-supported by scientific research. Recent evidence suggests that nanocurcumin may be a beneficial therapeutic modality due to its potential to decrease gene expression and secretion of specific inflammatory biomarkers involved in the cytokinestorm seen in severe COVID-19, as well as increase lymphocyte counts. Nanocurcumin has demonstrated the ability to improve clinical manifestations and modulate immune response and inflammation in various autoinflammatory diseases. Additionally, its efficacy, affordability, and safety make it a promising replacement for residual cancer cells after tumor removal. However, further studies are necessary to evaluate the safety and efficacy of nanocurcumin as a new therapeutic in clinical trials, including appropriate dosage, frequency, and duration.

Minocycline mitigated enduring neurological consequences in the mice model of sepsis.

AIM: Sepsis-associated encephalopathy is a frequently observed consequence of sepsis, often resulting in chronic brain inflammation and injury, ultimately leading to a range of behavioral abnormalities. This study explores the potential preventive effects of minocycline on the long-lasting outcome of sepsis in a mice model of sepsis. METHODS: Adult male C57 mice were subjected to experimental sepsis through a single intraperitoneal injection of 5 mg/kg lipopolysaccharide (LPS). Minocycline administration via oral gavage (12.5, 25, and 50 mg/kg) commenced three days before sepsis induction and continued on the day of induction. Mice underwent behavioral assessments one month post-sepsis, with subsequent brain tissue analysis to investigate oxidative stress markers and cholinergic function. KEY FINDINGS: One month following sepsis induction, mice exhibited significant anxiety- and depressive-like behaviors as determined by assessments in the elevated plus maze (EPM), open field, and tail suspension test (TST). Additionally, they displayed impaired recognition memory in the novel object recognition (NOR) test. Brain tissue analysis revealed a notable increase in oxidative stress markers and acetylcholinesterase (AChE) activity in septic mice. Notably, minocycline treatment effectively mitigated the long-term behavioral abnormalities resulting from sepsis, attenuated oxidative stress markers, and reduced AChE activity. SIGNIFICANCE: These findings underscore the potential of minocycline as a therapeutic intervention during sepsis induction to prevent the enduring behavioral and neurological consequences of experimental sepsis.

Folic acid improved memory and learning function in a rat model of neuroinflammation induced by lipopolysaccharide.

Folic acid (FA) plays an important role in the maintenance of normal neurological functions such as memory and learning function. Neuroinflammation contributes to the progression of cognitive disorders and Alzheimer's disease. Thus, this study aimed to investigate the effect of FA supplementation on cognitive impairment, oxidative stress, and neuro-inflammation in lipopolysaccharide (LPS)-injured rats. For this purpose, the rats were given FA (5-20 mg/kg/day, oral) for 3 weeks. In the third week, LPS (1 mg/kg/day; intraperitoneal injection) was given before the Morris water maze (MWM) and passive avoidance (PA) tests. Finally, the brains were removed for biochemical assessments. In the MWM test, LPS increased the escape latency and traveled distance to find the platform compared to the control group, whereas all doses of FA decreased them compared to the LPS group. The findings of the probe trial showed that FA increased the traveling time and distance in the target area. LPS impaired the performance of the rats in the PA test. FA increased delay and light time while decreasing the frequency of entry and time in the dark region of PA. LPS increased hippocampal levels of interleukin (IL)-6 and IL-1ß. The hippocampal level of malondialdehyde was also increased but thiol content and superoxide dismutase activity were decreased in the LPS group. However, treatment with FA restored the oxidative stress markers along with a reduction in the levels of pro-inflammatory cytokines. In conclusion, FA could ameliorate the memory and learning deficits induced by LPS via normalizing the inflammatory response and oxidative stress markers in the brain.

Protective potential of naringenin and its nanoformulations in redox mechanisms of injury and disease.

Increasing evidence suggests that elevated intracellular levels of reactive oxygen species (ROS) play a significant role in the pathogenesis of many diseases. Increased intracellular levels of ROS can lead to the oxidation of lipids, DNA, and proteins, contributing to cellular damage. Hence, the maintenance of redox hemostasis is essential. Naringenin (NAR) is a flavonoid included in the flavanones subcategory. Various pharmacological actions have been ascribable to this phytochemical composition, including antioxidant, anti-inflammatory, antibacterial, antiviral, antitumor, antiadipogenic, neuro-, and cardio-protective activities. This review focused on the underlying mechanism responsible for the antioxidative stress properties of NAR and its' nanoformulations. Several lines of in vitro and in vivo investigations suggest the effects of NAR and its nanoformulation on their target cells via modulating signaling pathways. These nanoformulations include nanoemulsion, nanocarriers, solid lipid nanoparticles (SLN), and nanomicelle. This review also highlights several beneficial health effects of NAR nanoformulations on human diseases including brain disorders, cancer, rheumatoid arthritis, and small intestine injuries. Employing nanoformulation can improve the pharmacokinetic properties of NAR and consequently efficiency by reducing its limitations, such as low bioavailability. The protective effects of NAR and its' nanoformulations against oxidative stress may be linked to the modulation of Nrf2-heme oxygenase-1, NO/cGMP/potassium channel, COX-2, NF-κB, AMPK/SIRT3, PI3K/Akt/mTOR, BDNF, NOX, and LOX-1 pathways. Understanding the mechanism behind the protective effects of NAR can facilitate drug development for the treatment of oxidative stress-related disorders.

Ameliorative effects of thiamin on learning behavior and memory dysfunction in a rat model of hypothyroidism: implication of oxidative stress and acetylcholinesterase.

Hypothyroidism causes learning and memory impairment. Considering the neuroprotective properties of thiamine (Vitamin B1), this study was conducted to investigate the effects of thiamine on acetylcholinesterase (AChE) activity, oxidative damage, and memory deficits in hypothyroid rats.In this study, 50 rats (21 days old) were randomly divided into 5 groups and treated with propylthiouracil (0.05% in drinking water) and thiamine (50, 100, and 200 mg/kg, oral) for 7 weeks. Following that, Morris water maze (MWM) and passive avoidance (PA) tests were performed. Finally, oxidative stress indicators and AChE activity were measured in brain tissue.Treatment of hypothyroid rats with thiamine, especially at 100 and 200 mg/kg, alleviated the ability to remember the location of the platform as reflected by less time spent and distance to reach the platform, during the MWM test (P < 0.05 to P < 0.001). In the PA test, the latency to enter the dark chamber and light stay time were increased in rats who received thiamine compared to the hypothyroid group (P < 0.05 to P < 0.001). In addition, thiamine increased the levels of total thiol groups and superoxide dismutase while decreasing the levels of malondialdehyde and AChE.Our results suggest that thiamine supplementation could effectively improve memory loss in a rat model of hypothyroidism. The positive effects of thiamin on the learning and memory of hypothyroid rats may be due to amelioration of redox hemostasis and cholinergic disturbance.

The Effects of Resveratrol Supplementation on the Metabolism of Lipids in Metabolic Disorders.

Lipids are stored energy sources in animals, and disturbance of lipid metabolism is associated with metabolic disorders, including cardiovascular diseases, obesity, nonalcoholic fatty liver disease, and diabetes. Modifying dysregulated lipid metabolism homeostasis can lead to enhanced therapeutic benefits, such as the use of statin therapy in cardiovascular disease. However, many natural compounds may have therapeutic utility to improve lipid metabolism. Resveratrol is a polyphenol extracted from dietary botanicals, including grapes and berries, which has been reported to affect many biological processes, including lipid metabolism. This review evaluates the effects of resveratrol on lipid metabolism dysregulation affecting atherosclerosis, diabetes, and nonalcoholic fatty liver disease (NAFLD). In addition, it details the mechanisms by which resveratrol may improve lipid metabolism homeostasis.

Vitamin D alleviates hypothyroidism associated liver dysfunction: Histological and biochemical evidence.

There is a complex correlation between thyroid hormones (THs) and liver function. Hypothyroidism as a failure of the thyroid gland to produce adequate thyroid hormones to fulfill the metabolic requirements of the body, may perturb liver structure and function. Emerging evidence suggests the protective effects of vitamin D against liver damage. Herein, this study aimed to investigate the role of vitamin D in hypothyroidism-associated liver injury. Forty male Wistar rats were classified into 4 groups: control, hypothyroid (Hypo) group received 0.05% PTU, Hypo- Vitamin D groups were given 100 and 500 IU/kg vitamin D orally via gavage for 6 weeks. Serum level of liver function including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were measured. Malondialdehyde (MDA) level, superoxide dismutase (SOD) enzyme activity, and total thiol content were measured as oxidative stress indicators in the liver tissue. Furthermore, to estimate liver tissue fibrosis, Masson's trichrome staining was done. Our findings showed that hypothyroidism-induced liver fibrosis was associated with increased levels of ALT, AST and ALP. Though, vitamin D administration could significantly reduce the ALT, AST and ALP in the serum and suppress the accumulation of collagen fibers. Moreover, the activity of SOD and total thiol content was notably reduced, while the MDA content was significantly increased in the PTU- induced hypothyroid rats compared to the control group. Nonetheless, treatment with vitamin D improved mentioned oxidative stress markers in the Hypo-vitamin D groups. In conclusion, vitamin D due to its potential antioxidant and anti-fibrotic properties could be effective in the decrease of hypothyroidism-associated liver injury.

Capparis spinosa Promoted BDNF and Antioxidant Enzyme Levels to Protect Against Learning and Memory Deficits Induced by Scopolamine.

BACKGROUND: Alzheimer's disease (AD) is a major neurodegenerative disorder with multiple manifestations, including oxidative stress, brain-derived neurotrophic factor (BDNF) depletion, and cholinergic dysfunction. Capparis spinosa (C. spinosa) is identified as a potential source of nutrition for alleviating various ailments. The current study assessed the ameliorating properties of C. spinosa hydroethanolic extract on memory dysfunction and the possible roles of oxidative stress and BDNF in the scopolamine (Scop)-treated rats. METHODS: Forty male Wistar rats were divided into the following four groups: Control, Scop (2 mg/kg, intraperitoneal injection (i.p.)), Scop + C. spinosa 150, and Scop + C. spinosa 300 groups. The rats were given C. spinosa extract (150 or 300 mg/kg, oral) for 3 weeks. During the third week, Passive Avoidance (PA) and Morris Water Maze (MWM) tests were done to assess memory and learning performance. Finally, oxidative stress markers and BDNF in the brain tissue were evaluated. RESULTS: Scop injection was associated with a significant increase in the time latency and travelled distance to reach the platform during the learning phase of MWM In the probe test, the Scoptreated rats showed a lower time and distance in the target area. Furthermore, Scop injection significantly decreased the latency to enter the dark while increasing the dark time and the frequency of entries to the dark zone of the PA task. C. spinosa extract effectively reversed the behavioural changes induced by Scop. Treatment with the extract also significantly increased the levels of superoxide dismutase, catalase, thiols, and BDNF, while decreasing malondialdehyde production in the brains of the Scop-injured rats. CONCLUSION: C. spinosa hydroethanolic extract successfully ameliorated Scop-induced memory impairment by modifying BDNF and oxidative stress markers in the brain of amnesic rats.

Zataria multiflora and its constituent, carvacrol, counteract sepsis-induced aortic and cardiac toxicity in rat: Involvement of nitric oxide and oxidative stress.

BACKGROUND: Zataria multiflora and carvacrol showed various pharmacological properties including anti-inflammatory and anti-oxidant effects. However, up to now no studies have explored its potential benefits in ameliorating sepsis-induced aortic and cardiac injury. Thus, this study aimed to investigate the effects of Z. multiflora and carvacrol on nitric oxide (NO) and oxidative stress indicators in lipopolysaccharide (LPS)-induced aortic and cardiac injury. METHODS: Adult male Wistar rats were assigned to: Control, lipopolysaccharide (LPS) (1 mg/kg, intraperitoneal (i.p.)), and Z. multiflora hydro-ethanolic extract (ZME, 50-200 mg/kg, oral)- and carvacrol (25-100 mg/kg, oral)-treated groups. LPS was injected daily for 14 days. Treatment with ZME and carvacrol started 3 days before LPS administration and treatment continued during LPS administration. At the end of the study, the levels of malondialdehyde (MDA), NO, thiols, and antioxidant enzymes were evaluated. RESULTS: Our findings showed a significant reduction in the levels of superoxide dismutase (SOD), catalase (CAT), and thiols in the LPS group, which were restored by ZME and carvacrol. Furthermore, ZME and carvacrol decreased MDA and NO in cardiac and aortic tissues of LPS-injected rats. CONCLUSIONS: The results suggest protective effects of ZME and carvacrol on LPS-induced cardiovascular injury via improved redox hemostasis and attenuated NO production. However, additional studies are needed to elucidate the effects of ZME and its constituents on inflammatory responses mediated by LPS.

miR-27a/b Level is Associated with ABCA1 Expression and is a Potential PBMC-Based Biomarker for Coronary Artery Disease

Abstract Background: Coronary artery disease (CAD) is the most common form of cardiac disease with high morbidity and mortality rates. Objectives: In this study, we evaluated the expression of miR-27a and miR-27b as biomarkers in peripheral blood mononuclear cells (PBMCs) of patients with CAD and investigated its correlation with cholesterol-efflux transporter, ATP-binding cassette transporter A1 (ABCA1). Method: This study was performed on 54 men with CAD and 51 healthy, sex- and age-matched control participants. The expression of miR-27a/b and ABCA1 genes in PBMCs were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression of ABCA1 was assessed by Western blotting. Concurrently, the specificity and sensitivity of miR-27a/b was evaluated through receiver operating characteristic (ROC) curve. The significance level adopted in the statistical analysis was 5%. Results: We found that miR-27a and miR-27b expression were significantly increased, while both mRNA and protein expression of ABCA1 were markedly reduced in the PBMCs of CAD patients in comparison to non-CAD controls. miR-27a/27b expression was also shown to be inversely correlated with ABCA1. ROC analysis showed that the miR-27a had an area under the ROC curve (AUC) of about 92.6 (sensitivity 83.3٪ and specificity 86.6٪) and miR-27b had an AUC of about 93.0 (sensitivity 86.6٪ and specificity 80.0 (%, suggesting the diagnostic potential of miR-27a/b in CAD patients. Conclusions: Our data suggested a possible role of miR-27a/b in CAD pathogenesis. Additionally, we proposed that miR-27a/b expression in PBMCs may have potential clinical implications in the diagnosis of CAD patients, but further validations in large cohorts are required.

A review on the efficacy and safety of lipid-lowering drugs in neurodegenerative disease.

There is a train of thought that lipid therapies may delay or limit the impact of neuronal loss and poor patient outcomes of neurodegenerative diseases (NDDs). A variety of medicines including lipid lowering modifiers (LLMs) are prescribed in NDDs. This paper summarizes the findings of clinical and observational trials including systematic reviews and meta-analyses relating to LLM use in NDDs published in the last 15 years thus providing an up-to-date evidence pool. Three databases were searched PubMed, CINAHL, and Web of Science using key terms relating to the review question. The findings confirm the benefit of LLMs in hyperlipidemic patients with or without cardiovascular risk factors due to their pleotropic effects. In NDDs LLMs are proposed to delay disease onset and slow the rate of progression. Clinical observations show that LLMs protect neurons from α-synuclein, tau, and Aß toxicity, activation of inflammatory processes, and ultimately oxidative injury. Moreover, current meta-analyses and clinical trials indicated low rates of adverse events with LLMs when used as monotherapy. LLMs appear to have favorable safety and tolerability profiles with few patients stopping treatment due to severe adverse effects. Our collated evidence thus concludes that LLMs have a role in NDDs but further work is needed to understand the exact mechanism of action and reach more robust conclusions on where and when it is appropriate to use LLMs in NDDs in the clinic.

Memantine, an NMDA receptor antagonist, protected the brain against the long-term consequences of sepsis in mice.

AIMS: Long-term neuroinflammation and brain dysfunction have frequently been reported in sepsis survivors. In this study, the protective effect of memantine (an NMDA receptor antagonist) on the long-term consequences of sepsis on the brain was investigated in mice. MATERIALS AND METHODS: Eighty-five male C57 mice were included. Memantine was administrated through gavage at 5, 10, and 20 mg/kg three days before sepsis and continued for three days after sepsis induction. Sepsis was induced by intraperitoneal injection of 5 mg/kg LPS. A cohort of mice was sacrificed on the 4th day post sepsis to measure NF-κB, TNF-α, and IL-1ß mRNA expression and oxidative stress markers in the brain. The second cohort was used for behavioral tests one month after sepsis induction and then sacrificed for oxidative stress markers and acetylcholinesterase (AChE) activity measurement. KEY FINDINGS: MDA levels and mRNA expression of NF-κB, TNF-α, and IL-1ß ameliorated by memantine at the early days of sepsis induction, and total thiol content and SOD activity were increased. Post-septic mice showed significant disruption of recognition memory in novel object recognition (NOR) and depressive and anxiety-like behaviors in tail suspension test, elevated plus maze (EPM), and open field tests one month after sepsis. Memantine at 10 and 20 mg/kg dose-dependently ameliorated behavioral abnormalities, reduced AChE activity and MDA levels, and enhanced SOD activity and thiol content one month after sepsis. SIGNIFICANCE: These findings suggest that early treatment of septic mice with memantine could ameliorate brain inflammation and oxidative damage and prevent long-term behavioral consequences of sepsis.

The Antioxidant Activity of Betanin protects MRC-5 cells Against Cadmium Induced Toxicity.

Cadmium (Cd) can induce both acute and chronic effects in the lungs depending on the time and the exposure route. Betanin is a component derived from the roots of red beets and it is well-known for its antioxidant and anti-apoptosis effects. The current study aimed to survey the protective effects of betanin on cell toxicity induced by Cd. Different concentration of Cd alone and in combination with betanin was assessed in MRC-5 cells. The viability and oxidative stress were measured using resazurin and DCF-DA methods respectively. Apoptotic cells were assessed by PI staining of the fragmented DNA and western blot analysis detected the activation of caspase 3 and PARP proteins. Cd exposure for 24 h declined viability and increased ROS production in MRC-5 cells compared to the control group (p < 0.001). Also, Cd (35 µM) elevated DNA fragmentation (p < 0.05), and the level of caspase 3-cleaved and cleaved PARP proteins in MRC-5 cells (p < 0.001). Co-treatment of cells with betanin for 24 h significantly enhanced viability in concentrations of 1.25 and 2.5 µM (p < 0.001) and 5 µM (p < 0.05) and declined ROS generation (1.25 and 5 µM p < 0.001, and 2.5 µM p < 0.01). As well as, betanin reduced DNA fragmentation (p < 0.01), and the markers of apoptosis (p < 0.001) compared to the Cd-treated group. In conclusion, betanin protects lung cells against Cd-induced toxicity through antioxidant activity and inhibition of apoptosis.

B lymphocytes in COVID-19: a tale of harmony and discordance.

B lymphocytes play a vital role in the human defense against viral infections by producing specific antibodies. They are also critical for the prevention of infectious diseases by vaccination, and their activation influences the efficacy of the vaccination. Since the beginning of coronavirus disease 2019 (COVID-19), which became the main concern of the world health system, many efforts have been made to treat and prevent the disease. However, for the development of successful therapeutics and vaccines, it is necessary to understand the interplay between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, and the immune system. The innate immune system provides primary and nonspecific defense against the virus, but within several days after infection, a virus-specific immune response is provided first by antibody-producing B cells, which are converted after the resolution of disease to memory B cells, which provide long-term immunity. Although a failure in B cell activation or B cell dysfunction can cause a severe form of the disease and also lead to vaccination inefficiency, some individuals with B cell immunodeficiency have shown less production of the cytokine IL-6, resulting in a better disease outcome. In this review, we present the latest findings on the interaction between SARS-CoV-2 and B lymphocytes during COVID-19 infection.

Psidium guajava induces cytotoxicity in human malignant glioblastoma cell line: Role of reactive oxygen species.

One of the deadliest types of CNS primary brain cancers is glioblastoma multiforme (GBM), and the survival rate of patients is about 7.2%. The standard treatment for GBM is surgical interventions followed by temozolomide. We investigated for the first time, the cytotoxic impacts of Psidium guajava (P. guajava) on the U87 GBM cell line. We measured cell toxicity through the MTT test following 24 h, 48 h, and 72 h treatment with different concentrations of fruit and seed hydroalcoholic extracts of P. guajava (25-400 µg/ml). Lipid peroxidation assay, reactive oxygen species (ROS) production, and apoptosis rate were evaluated 24 h after treatment by extracts of P. guajava. Moreover, to determine the Bax/Bcl-2 and NF-κB genes expression, we performed a real-time polymerase chain reaction (RT-PCR). Our finding demonstrated that 50-400 µg/ml of P. guajava extracts dose-dependently decreased the viability of U87 cells. Also, treatment by extracts increased lipid peroxidation, ROS production, and apoptosis in a dose-dependent manner. Moreover, the RT-PCR demonstrated an up-regulation in Bax\Bcl-2 and NF-κB. Thus, P. guajava inhibited the proliferation of U87 GBM cells and increased apoptosis probably through Bax/Bcl-2 and NF-κB regulation.