Harmine exhibits anti-apoptotic properties and reduces diabetes-induced testicular damage caused by streptozotocin in rats.

Objective: Diabetes mellitus induces fertility problems in men, mainly because of increased free radicals. Natural resources are effective for male infertility treatment. This study investigated the effects of harmine, an alkaloid available in Peganum harmala L., on the male reproductive system of diabetic rats. Methods: We divided 32 rats into four groups, and eight were randomly placed in each group. For diabetes induction, the animals received 50 mg/kg of streptozotocin intraperitoneally. After 1 week, animals received 15 mg/kg of harmine (28 days; intraperitoneal). Histopathological examinations, serum levels of male hormones, levels of nitric oxide (NO) and malondialdehyde (MDA) in the testes, total antioxidant capacity (TAC), insulin serum levels, fasting blood glucose levels, the apoptotic index, and semen analysis were assessed. Results: The diabetes group exhibited morphological changes in testicular tissue, significant decreases in the diameter of the seminiferous tubule, the Johnsen score, testosterone, luteinizing hormone, follicle-stimulating hormone, insulin serum levels, and TAC in testicular tissue (p<0.01). Harmine treatment ameliorated the morphological changes in the testes and improved sperm parameters relative to the diabetes group (p<0.05). The NO and MDA levels in the testes, fasting blood glucose serum levels, and apoptotic index parameters were significantly elevated in the diabetes group, while in the diabetes+harmine group, these parameters were reduced (p<0.01). Conclusion: Harmine protects testicular tissue and sperm against diabetes-induced damage. This effect of harmine is associated with a rebalancing of the antioxidant capacity that subsequently decreases apoptosis in the testes.

The effects of citrus flavonoids supplementation on endothelial function: A systematic review and dose-response meta-analysis of randomized clinical trials.

The present systematic review and dose-response meta-analysis was conducted to synthesize existing data from randomized clinical trials (RCTs) concerning the impact of citrus flavonoids supplementation (CFS) on endothelial function. Relevant RCTs were identified through comprehensive searches of the PubMed, ISI Web of Science, and Scopus databases up to May 30, 2023. Weighted mean differences and their corresponding 95% confidence intervals (CI) were pooled utilizing a random-effects model. A total of eight eligible RCTs, comprising 596 participants, were included in the analysis. The pooled data demonstrated a statistically significant augmentation in flow-mediated vasodilation (FMD) (2.75%; 95% CI: 1.29, 4.20; I2 = 87.3%; p < 0.001) associated with CFS compared to the placebo group. Furthermore, the linear dose-response analysis indicated that each increment of 200 mg/d in CFS led to an increase of 1.09% in FMD (95% CI: 0.70, 1.48; I2 = 94.5%; p < 0.001). The findings from the nonlinear dose-response analysis also revealed a linear relationship between CFS and FMD (Pnon-linearity = 0.903, Pdose-response <0.001). Our findings suggest that CFS enhances endothelial function. However, more extensive RTCs encompassing longer intervention durations and different populations are warranted to establish more precise conclusions.

The relationship between aflatoxin B1 with the induction of extrinsic/intrinsic pathways of apoptosis and the protective role of taraxasterol in TM3 leydig cell line.

Aflatoxins B1 (AFB1) a dangerous type of aflatoxin, poses a serious threat to human health. Meanwhile, Taraxasterol, a bioactive compound in dandelion, exhibits strong anti-inflammatory and antioxidant activity. Therefore, the aim of this study was to investigate the impact of AFB1 on the intrinsic and extrinsic pathways of apoptosis, as well as evaluate the protective role of taraxasterol in the TM3 Leydig cell line. Cell viability was evaluated using an MTT assay, measuring the effects of 3.6 µM AFB1 and varying concentrations of taraxasterol. Expression levels of Caspase 3,8, and 9 were analyzed with RT-qPCR, and flow cytometry was used to assess cell cycle progression and apoptotic alterations. The findings of this study demonstrated that exposure to 3.6 µM of AFB1 resulted in an upregulation of Caspase 3 and Caspase 9 expression, indicating an activation of apoptotic pathways in TM3 cells. Additionally, the analysis of apoptosis revealed a significant increase in cellular apoptosis at this AFB1 concentration. However, when TM3 cells were exposed to 5 µM of taraxasterol, a downregulation of Caspase 3 and Caspase 9 expression was observed, suggesting a protective effect against apoptosis. Moreover, the apoptotic rate in TM3 cells was reduced in the presence of 5 µM of taraxasterol. Consequently, this study highlights the potential of taraxasterol as a protective agent against AFB1-induced apoptosis and suggest its potential application in regulating cell survival and apoptosis-related processes. Further investigations are necessary to elucidate the underlying mechanisms and evaluate the clinical implications of taraxasterol in the context of fertility disorders and other conditions associated with AFB1 exposure.

Synergistic effects of Bacillus coagulans and Newcastle disease virus on human colorectal adenocarcinoma cell proliferation.

Background and Objectives: Colorectal cancer (CRC) is a common type of cancer that has a high death rate and is becoming more common in developed countries. Currently, there are several treatment options available for CRC patients, and clinical trials are being conducted to improve conventional therapies. This study investigates the combined impact of Bacillus coagulans (B.C) and Newcastle disease virus (NDV) on the growth of human colorectal adenocarcinoma cells (HT29 cell line). Materials and Methods: The HT29 cell line was cultured under controlled laboratory conditions. They were treated with Fluorouracil (5-FU), NDV, and B.C., after which various assessments were conducted to determine the effects of these treatments. These assessments included MTT assay for cytotoxicity, evaluation of cell viability, and measurement of caspase 8 and 9 activity levels. The significance of the data was determined at a threshold of P<0.05 following analysis. Results: The usage of NDV and B.C significantly increased cell death and reduced cell growth in the HT29 cell line, when compared to the control group. Moreover, the combined application of NDV and B.C along with 5-FU exhibited a synergistic effect in decreasing the proliferation of HT29 cells. Additionally, the results indicated that intrinsic apoptosis pathway was activated by B.C and NDV. Conclusion: It appears that utilizing oncolytic viruses (OV) and bacteria in conjunction with chemotherapy drugs could potentially aid in reducing the growth of colorectal cancer cells. However, further research is necessary, including animal studies, to confirm the efficacy of this treatment method.

Genotoxic and cytotoxic effects of aflatoxin on the reproductive system: Focus on cell cycle dynamics and apoptosis in testicular tissue.

Aflatoxins (AFs) are inevitable environmental contaminants that are detrimental to human and animal health. AFs interfere with metabolic processes, metabolizing into different hydroxylated derivatives in the liver, as well as mechanistically induce ROS accumulation, S-phase arrest, DNA damage, and cell apoptosis. Chronic consumption of aflatoxin-contaminated foods can adversely affect the male reproductive system, cause testicular damage, prevent testosterone synthesis, decline sperm quality, and cause infertility. Oxidative stress is the fundamental pathogenesis of aflatoxin-induced reproductive toxicity. The overproduction of reactive oxygen substances can cause testicular failure and disturb the process of spermatogenesis. Mitochondria are susceptible to being impaired by oxidative stress, and its damage is associated with infertility. AFs also disturb the process of spermatogenesis by disrupting the regulation of genes related to the progression of the cell cycle such as cyclins and inducing genes related to apoptosis, thereby weakening fertility and negatively affecting the testicular endocrine potential by suppressing androgen synthesis. Additionally, AFs downregulate ERα expression, potentially negatively impacting spermatogenesis by enhancing the apoptotic mechanism. In this review, we provide new insights into the genotoxic and cytotoxic effects of AFB1 on the male reproductive system with a focus on the cell cycle and apoptosis destruction of testicular tissue.

The influence of indole propionic acid on molecular markers of steroidogenesis, ER stress, and apoptosis in rat granulosa cells exposed to high glucose conditions.

Hyperglycemia is known as one of the main causes of infertility in human societies. Indole propionic acid (IPA) is produced by intestinal microbiota and has antioxidant and anti-inflammatory properties. This study aims to investigate the effects of IPA on molecular indices of steroidogenesis, ER stress, and apoptosis induced by high glucose (HG) in granulosa cells. Primary GCs, isolated from ovarian follicles of Rats were cultured in 5 mM (control) and 30 mM (HG) of glucose and in the presence of 10 and 20 µM of IPA for 24 h. The cell viability was assessed by MTT. The gene expression of P450SCC, 3ßHSD, CYP19A, BAX, BCL2, and STAR was evaluated by Real-Time PCR. Protein expression of ATF6, PERK, GRP78, and CHOP determined by western blot. Progesterone, estradiol, IL-1ß, and TNF-α were measured by ELISA. HG decreased the viability, and expression of P450SCC, 3ßHSD, CYP19A, BCL2, STAR, and increased BAX. 10 and 20 µM of IPA increased cell viability, expression of P450SCC, 3ßHSD, CYP19A, BCL2 and STAR and decreased BAX compared to the HG group. The expression of ATF6, PERK, GRP78, and CHOP proteins increased by HG and IPA decreased the expression of these proteins compared to the HG group. Also, HG decreased progesterone and estradiol levels and increased IL-1ß and TNF-α. IPA significantly increased progesterone and estradiol and decreased IL-1ß and TNF-α compared to the HG group. IPA can improve the side effects of HG in GCs of rats, as responsible cells for fertility, by improving steroidogenesis, regulation of ER-stress pathway, suppression of inflammation, and apoptosis.

Toxicity and Hepatoprotective Effects of ZnO Nanoparticles on Normal and High-Fat Diet-Fed Rat Livers: Mechanism of Action.

This experiment aimed to evaluate the beneficial and toxic properties of synthetic zinc oxide nanoparticles (ZnO NPs) on the liver of normal and high-fat diet (HFD) fed-rats. The ZnO NPs were synthesized and, its characterizations were determined by different techniques. Effect of ZnO NP on cell viability, liver enzymes and lipid accumulation were measured in HepG2 cells after 24 h. After that, rats orally received various dosages of ZnO NPs for period of 4 weeks. Toxicity tests were done to determine the appropriate dose. In the subsequent step, the hepatoprotective effects of 5 mg/kg ZnO NPs were determined in HFD-fed rats (experiment 2). The oxidative stress, NLRP3 inflammasome, inflammatory, and apoptosis pathways were measured. Additionally, the activity of caspase 3, nitric oxide levels, antioxidant capacity, and various biochemical factors were measured. Morphological changes in the rat livers were also evaluated by hematoxylin and eosin (H & E) and Masson trichrome. Liver apoptosis rate was also approved by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Treatment of animals with 5 mg/ZnO NPs revealed potential hepatoprotective properties, while ZnO NPs at the doses of above 10 mg/kg showed toxic effects. Antioxidant enzyme gene expression and activity were significantly augmented, while apoptosis, NLRP3 inflammasome, and inflammation pathways were significantly reduced by 5 mg/kg ZnO NPs. Liver histopathological alterations were restored by 5 mg/kg ZnO NPs in HFD. Our study highlights the hepatoprotective effects of ZnO NPs against the HFD-induced liver damage, involving antioxidant, anti-inflammatory, and anti-apoptotic pathways, indicating their promising therapeutic potential.

Selenium mitigates methotrexate-induced testicular injury: Insights from male NMRI mice model.

BACKGROUND AND AIM: Chemotherapy, particularly with methotrexate (MTX), often elicits testicular toxicity, leading to impaired spermatogenesis and hormone imbalances. This study aimed to investigate the potential protective effects of selenium (Se) against MTX-induced testicular injury. MATERIALS AND METHODS: Male mice were divided into control, MTX, Se, and MTX + Se groups. Histopathological examination involved the preparation of testicular tissue sections using the Johnsen's tubular biopsy score (JTBS) for spermatogenesis evaluation. Biochemical tests included the assessment of testosterone, malondialdehyde (MDA), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels. Real-time quantitative polymerase chain reaction (RT-qPCR) was employed to analyze the expression of caspase 3 (casp3), tumor protein 53 (p53), B-cell lymphoma 2 (Bcl2), and Bcl2-associated X protein (Bax) genes. Statistical analysis was performed using ANOVA and Tukey's tests (p < .05). RESULTS: Histopathological analysis revealed significant testicular damage in the MTX group, with decreased spermatogenesis and Leydig cell count, while Se administration mitigated these effects, preserving the structural integrity of the reproductive epithelium. Biochemical analysis demonstrated that MTX led to elevated malondialdehyde (MDA) levels and reduced testosterone, LH, and FSH levels, suggesting oxidative stress and Leydig cell dysfunction. Gene expression analysis indicated that MTX upregulated proapoptotic genes (casp3, p53, and bax) while downregulating the antiapoptotic Bcl2 gene. In contrast, Se treatment reversed these trends, highlighting its potential antiapoptotic properties. CONCLUSION: Our findings underscore the potential of Se as a therapeutic agent to mitigate the reproductive toxicity associated with MTX-induced testicular injury. Se exerts protective effects by regulating oxidative stress, preserving hormone balance, and modulating apoptotic pathways. These results suggest that Se supplementation could be a promising strategy to alleviate chemotherapy-induced testicular damage and preserve male fertility.

Therapeutic effect of sodium alginate on bleomycin, etoposide and cisplatin (BEP)-induced reproductive toxicity by inhibiting nitro-oxidative stress, inflammation and apoptosis.

Impaired spermatogenesis and male infertility are common consequences of chemotherapy drugs used in patients with testicular cancer. The present study investigated the effects of sodium alginate (NaAL) on testicular toxicity caused by bleomycin, etoposide, and cisplatin (BEP). Rats in group 1 received normal saline, while groups 2 and 3 were treated with 25 and 50 mg/kg of NaAL, respectively. Group 4 was treated with a 21-day cycle of BEP (0.5 mg/kg bleomycin, 5 mg/kg etoposide, and 1 mg/kg cisplatin), and groups 5 and 6 received BEP regimen plus 25 and 50 mg/kg of NaAL, respectively. Then, sperm parameters, testosterone levels, testicular histopathology and stereological parameters, testicular levels of malondialdehyde (MDA), nitric oxide (NO), and total antioxidant capacity (TAC), and the expression of apoptosis-associated genes including Bcl2, Bax, Caspase3, p53, and TNF-α were evaluated. Our findings revealed that NaAL improved sperm parameters, testosterone levels, histopathology, and stereology parameters in BEP-administrated rats. NaAL also improved testis antioxidant status by enhancing TAC and ameliorating MDA and NO. Further, modifications to the expression of Bcl2, Bax, Caspase3, p53, and TNF-α suggested that NaAL alleviated BEP-induced apoptosis and inflammation. Collectively, NaAL protects rats' testes against BEP-evoked toxicity damage through the modulation of nitro-oxidative stress, apoptosis, and inflammation.

Utility of vitamin C in ameliorating citalopram-induced testicular toxicity via modulating nitro-oxidative stress and apoptosis in mice.

There is a growing concern that antidepressant drugs impair sexual function and adversely impact spermatogenesis and male fertility. Vitamin C is a natural antioxidant that plays a vital role in the male reproductive system. The present study investigated the ameliorating potential of vitamin C against citalopram (CTL)-evoked testicular toxicity and spermatogenesis impairment in mice. Mice were randomly divided into six groups: control, CTL, vitamin C 100, vitamin C 200, CTL plus vitamin C 100, and CTL plus vitamin C 200. Adult male mice were intraperitoneally (ip) injected with 10 mg/kg of CTL for 35 days with or without vitamin C. At the end of the study, body and testes weight, sperm parameters, histopathology of testes, testosterone level, testicular levels of malondialdehyde (MDA), nitric oxide (NO), total antioxidant capacity (TAC), and apoptosis (TUNEL assay) were evaluated. Our findings revealed that vitamin C restored spermatogenesis by improving sperm count, motility, viability, morphology, and chromatin integrity. Testosterone levels and testes histopathology were significantly improved in the vitamin C-administrated groups. Furthermore, vitamin C administration markedly alleviated CTL-induced nitro-oxidative damage, enhancing TAC levels, and reducing NO and MDA levels. Whilst CTL therapy induced a significant increase in the number of TUNEL-positive cells compared to the control, the administration of vitamin C significantly prevented the apoptotic effects of CTL. Together, vitamin C therapy protects against CTL-induced testicular damage via mitigating nitro-oxidative stress and apoptosis, which provides evidence for vitamin C as a beneficial therapy against antidepressant drug-associated reproductive toxicity and male sub/infertility.

Melatonin Protects Mouse Type A Spermatogonial Stem Cells against Oxidative Stress via The Mitochondrial Thioredoxin System.

OBJECTIVE: Mitochondrial oxidative stress is an important factor in infertility. The mitochondrial thioredoxin system plays an important role in this condition. N-acetyl-5-methoxy tryptamine (melatonin) plays a role in reducing oxidative stress and apoptosis in spermatogonial stem cells (SSCs). In this study, we explore the probable protective effects of melatonin on the mitochondrial thioredoxin system [thioredoxin 2 (Trx2)/Txnip] in SSCs under oxidative stress. MATERIALS AND METHODS: In this experimental study, SSCs were co-cultured two-dimensionally (2D) with Sertoli cells in DMEM culture medium that contained 10% fetal bovine serum (FBS), 1% antibiotics, and 10 ng/ml glial cell-derived neurotrophic factor (GDNF) for 30 days. The cultured cells were subsequently divided into four groups: control; melatonin (250 µM, 24 hours); melatonin (250 µM, 24 hours)+hydrogen peroxide (H2O2, 50 µM, 24 hours); and H2O2 (50 µM, 24 hours). Intracellular reactive oxygen species (ROS) production was determined by flow cytometry. Malondialdehyde (MDA) levels were measured by Fluorometry. The expressions of apoptotic and antioxidant genes and nuclear factor erythroid 2-related factor 2 (Nrf2), Trx2, and nicotinamide nucleotide transhydrogenase (NNT) proteins were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Adenosine triphosphate (ATP) levels were measured by fluorometry. RESULTS: Melatonin reduced H2O2-induced ROS levels and apoptosis in the SSCs. Melatonin also increased mRNA expression of Nrf2, Trx2, NNT, Sirtuin 3 (Sirt3), and decreased mRNA expression of Txnip, and increased protein expressions of Nrf2, Trx2, NNT thereby increasing activity of the mitochondrial thioredoxin system. In addition, melatonin increased ATP levels. CONCLUSION: Melatonin increased Trx2 expression through the Nrf2 pathway. This study suggests that melatonin may protect SSCs from oxidative stress in diseases related to infertility.

Reduction of UreB and CagA expression level by siRNA construct in Helicobacter pylori strain SS1.

BACKGROUND: Two important virulence factors, urease and cagA, play an important role in Helicobacter pylori (H. pylori) gastric cancer. Aim of this study was to investigate the expression level and function of ureB and cagA using small interfering RNAs (siRNA). METHODS: SS1 strain of H. pylori was considered as host for natural transformation. siRNA designed for ureB and cagA genes were inserted in pGPU6/GFP/Neo siRNA plasmid vector to evaluate using phenotypic and genotypic approaches. Then, qPCR was performed for determining inhibition rate of ureB and cagA gene expression. RESULTS: The expression levels of siRNA-ureB and siRNA-cagA in the recombinant strain SS1 were reduced by about 5000 and 1000 fold, respectively, compared to the native H. pylori strain SS1. Also, preliminary evaluation of siRNA-ureB in vitro showed inhibition of urea enzyme activity. These data suggest that siRNA may be a powerful new tool for gene silencing in vitro, and for the development of RNAi-based anti-H. pylori therapies. CONCLUSION: Our results show that targeting ureB and cagA genes with siRNA seems to be a new strategy to inhibit urease enzyme activity, reduce inflammation and colonization rate.

Hydroalcoholic extract of Taraxacum officinale induces apoptosis and autophagy in 4T1 breast cancer cells.

Triple-negative breast cancer (TNBC) is an aggressive and deadly breast cancer sub-type with limited therapeutic options. Dandelion (Taraxacum officinale) exhibiting extensive anti-cancer activity is reported to be effective against TNBC; however, its anti-tumor effect mechanisms have not been fully elucidated. The purpose of this study was to determine the anti-cancer activity of hydroalcoholic extract of dandelion (HADE) on 4T1 cells, and the mechanism of HADE-induced cell death. The effect of HADE on cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays. Apoptotic cell death was monitored by flow cytometry. The DNA fragmentation was evaluated by Acridine orange/Ethidium bromide (AO/EB) staining. Nitric oxide (NO) level was detected using Griess assay. The effects of HADE on Atg-7, Beclin-1, Bcl2, Bax and p53 genes were investigated by real-time reverse transcription-polymerase chain reaction. The results showed that HADE inhibited cell growth and proliferation in a dose- and time-dependent manner. The HADE induced 4T1 breast cancer cell death via apoptosis and autophagy. The DNA fragmentation was improved as the concentration of HADE increased. The NO secretion was declined with increasing concentration of HADE. Gene expression analysis confirmed HADE-induced apoptosis and autophagy in cancer cells. The Bax, Bax/Bcl-2 ratio, p53, Beclin-1 and Atg-7 over-expression as well as Bcl-2 down-regulation were also evident in treated cancer cells.

Falcaria vulgaris L. hydroalcoholic extract protects against harmful effects of mercuric chloride on the rat kidney.

Objective: Mercuric chloride (Merc; HgCl2) is toxic to humans and animals and contributes to environmental pollution, which usually results in nerve and systemic harm to different organs. Falcaria vulgaris (FV) is a medicinal plant rich in antioxidants. This research aimed to assess the FV hydroalcoholic extract effects on kidney toxicity induced by Merc. Materials and Methods: Forty-eight male rats were divided into eight groups: the control group: received saline; the Merc group: received 0.5 ml/day of 0.5 ppm aqueous Merc; FV1, 2, and 3 groups: received 50, 100, 150 mg/kg FV, respectively; and Merc + FV1, 2, and 3 groups: received Merc and FV at three doses. The administration period was 14-days. Subsequently, kidneys and sera were cumulated from each group for the analysis. Samples were analyzed via hematoxylin-eosin staining and biochemical tests. Results: The rats that received Merc displayed significant decrement in the kidney index, the diameter of renal corpuscles, total antioxidant capacity levels, superoxide dismutase activity (all, p<0.01), and 150 mg/kg FV mitigated these outcomes (all, p<0.05). Urea, creatinine, nitric oxide, and the level of apoptosis revealed a significant increment in the kidney of the rats that received Merc (all, p<0.01), and 150 mg/kg FV decreased these results. Furthermore, FV ameliorated histological changes induced by Merc (all, p<0.05). Conclusion: The FV hydroalcoholic extract protects the kidneys against Merc-induced nephrotoxicity. Antioxidant and anti-apoptotic FV hydroalcoholic extract properties were involved in this healing effect.

Effect of melatonin on steroidogenesis-related enzymes expression and testosterone synthesis following CoCl2-induced hypoxia in TM3 Leydig cells.

Objectives: This study examined the effects of melatonin treatment on steroidogenesis dysfunction and testosterone impairment, following CoCl2-induced hypoxia in TM3 Leydig cells. Materials and Methods: The TM3 cells were divided into four groups. The first group received no treatment. The MLT group was treated with a concentration of 1 mM melatonin. In the CoCl2 group, 0.2 mM CoCl2 was added to the medium to induce Hif1α overexpression. The MLT+CoCl2 group received 0.2 mM CoCl2 and 1 mM melatonin. After 24 hr treatment, the cells and supernatants were collected and used for further determination. The MTT assay was performed to estimate the decrease in cell viability throughout the CoCl2 and melatonin treatment. The mRNA and the protein levels were evaluated using Real-time PCR and Western blot analysis. The ELISA assay kit was used to detect the testosterone content. Results: CoCl2 treatment caused Hif1α overexpression in TM3 Leydig cells. Moreover, CoCl2 treatment of these cells led to considerable downregulation of Star, Hsd3b1, and Gata4 well as Mtnr1a and Mtnr1b mRNA/protein expression coupled with testosterone content repression in the cell culture medium. Melatonin administration in cells treated with CoCl2, decreased Hif1α mRNA/protein expression, but had no significant effect on Star, Hsd3b1, Gata4, Mtnr1a mRNA/protein expression, and the testosterone level in the cell culture medium. Melatonin caused recovery of decrease in the Mtnr1b gene and protein expression. Conclusion: There was no significant effect on steroidogenesis-related genes, proteins, and testosterone synthesis in the absence of gonadotropin treatment plus melatonin following CoCl2-induced hypoxia in TM3 Leydig cells.

Synthesis, characterization and hypolipidemic effects of urazine derivatives on rat: Study of molecular modeling and enzyme inhibition.

The prevalence of hyperlipidemia has increased dramatically worldwide. It is a major public health threat, characterized by the presence of an abnormal lipid profile, primarily with elevated serum total cholesterol (TC), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL) levels, and reduced high-density lipoprotein (HDL) level. Genetic factors, dietary and lifestyle habits play important roles in hyperlipidemia. It can increase the risk of chronic metabolic disorders, such as obesity, cardiovascular disease, and type II diabetes. The main objective of the present study was to evaluate the effect of urazine derivatives on serum triglyceride, cholesterol, LDL, HDL, and nitric oxide (NO) levels in high-fat diet (HFD)-induced hyperlipidemic rats. Synthetic compounds were prepared and confirmed by spectroscopic methods. Then, 88 male Sprague-Dawley rats were divided into 11 groups: control, HFD-treated group, HFD plus atorvastatin-treated group, and HFD plus 8 synthetic compounds-treated groups. The body weight, triglyceride, cholesterol, LDL, HDL, and NO levels were measured. The data with p < 0.05 were considered significant. The results indicated that HFD significantly increased cholesterol, triglyceride, and LDL levels and decreased NO concentration and HDL level compared to the control group (p < 0.05). However, HFD plus urazine derivatives significantly decreased NO, cholesterol, and triglyceride levels and increased HDL levels compared to the HFD-treated group (p < 0.05). Urazine derivatives may improve liver dysfunction in HFD-induced hyperlipidemic rats by modulation of detoxification enzymes and their anti-oxidant effects and also blood lipid profile.

Celiac disease and COVID-19 in adults: A systematic review.

BACKGROUND: Celiac disease (CD) is an autoimmune disease affecting around 1.4% of the total human population. Local and systemic manifestations are described in CD. Viral infections seem to trigger CD or even have a worse outcome in CD patients. The evidence on the relationship between CD and coronavirus disease (COVID-19) is limited. To evaluate existing evidence on the association between CD and COVID-19, we conducted the current systematic review. METHODS: We systematically searched Pubmed, Scopus, and Embase databases to find articles that reported risks or outcomes of COVID-19 in CD patients. Papers in any language published up to November 17, 2022, were evaluated for possible inclusion. The results were analyzed qualitatively. This study is registered with PROSPERO(CRD42022327380). RESULTS: We identified 509 studies by searching databases; 14 reported data on the risk or outcome of COVID-19 in CD patients and were eligible for qualitative synthesis. We found that the relative risk of acquiring COVID-19 in CD patients may be lower than in the general population. Approximately 90% of infected patients were treated as an outpatient, and 10% were hospitalized. GFD adherence and Health-related quality of life (HR-QOL) were more or less the same before and during the pandemic. The gluten-free products (GFP) supply seems to be plunged during the pandemic. The data on the psychological effects of the pandemic were conflicting. CONCLUSION: The risk of acquiring COVID-19 in CD patients is lower than in the general population. Females were more likely to be infected by COVID-19, and the most common comorbidity in infected patients was a chronic lower respiratory disease; around 10% of infected patients needed hospitalization, GFD adherence, and HR-QOL was more or less the same before and during the pandemic, depression, anxiety, and stress levels of patients varied among studies. Patients had more difficulties accessing GFPs based on limited data.

Brain targeting based nanocarriers loaded with resveratrol in Alzheimer's disease: A review.

Alzheimer's disease (AD) is one of the chief neurological difficulties in the aged population, identified through dementia, memory disturbance, and reduced cognitive abilities. ß-amyloid (Aß) plaques aggregations, generation of reactive oxygen species, and mitochondrial dysfunction are among the major signs of AD. Regarding the urgent need for the development of novel treatments for neurodegenerative diseases, researchers have recently perused the function of natural phytobioactive combinations, such as resveratrol (RES), in vivo and in vitro (animal models of AD). Investigations have shown the neuroprotective action of RES. This compound can be encapsulated by several methods (e.g. polymeric nanoparticles (NPs), solid lipid nanoparticles, Micelles, and liposomes). This antioxidant compound, however, barely crosses the blood-brain barrier (BBB), thereby limiting its bioavailability and stability at the target sites in the brain. Thanks to nanotechnology, the efficiency of AD therapy can be improved by encapsulating the drugs in a NP with a controlled size (1-100 nm). This article addressed the use of RES, as a Phytobioactive compound, to decrease the oxidative stress. Encapsulation of this compound in the form of nanocarriers to treat neurological diseases to improve BBB crossing is also discussed.

Treadmill aerobic training improve beam-walking test, up-regulate expression of main proteins of myelin and myelination in the hippocampus of cuprizone-fed mice.

Multiple sclerosis (MS) is a potentially disabling disease of the brain and spinal cord (central nervous system). The aim of this study was to investigate the effect of 6 weeks of aerobic training on the main proteins of myelin including myelin basic protein (MBP), myelin oligodendrocyte (MOG), myelin associated glycoprotein (MAG), and myelin proteolipid protein (PLP) at hippocampus of C57BL/6 mouse model of cuprizone-induced MS. Twenty-eight female C57BL/6 mice (23 ± 3 g) were randomly divided into four groups (n = 7 per group): control, exercise (Exe), cuprizone (CPZ), and cuprizone with exercise (CPZ + Exe). Exercise groups performed treadmill aerobic exercise training 5 days a week, 15-22 m/min, and 15-60 min, during 6 weeks. Cuprizone were fed to mice at CPZ and CPZ + Exe groups for 6 weeks. Animals were sacrificed after 6 weeks. Biochemical and molecular biology analyses were performed. Mice at CPZ group had decreased myelination of nerve cells in the hippocampus. In addition, the use of CPZ in the hippocampus caused a decrease in the MBP, MOG gene expression, as well as a decrease in the MAG and PLP gene and protein expression compared to the healthy control group. However, performing aerobic exercise with CPZ consumption increased MBP gene expression and increased MAG and PLP protein expression, as well as increased myelination of nerve cells in the hippocampus compared to the CPZ group (p < 0.05). It seems that regular aerobic exercise in the MS model controls the destruction of myelin in the nerve cells of hippocampus by upregulating MBP, MAG and PLP, which can have positive effects on cognitive and motor performance.

Partners in crime: Autoantibodies complicit in COVID-19 pathogenesis.

Autoantibodies (AABs) play a critical role in the pathogenesis of autoimmune diseases (AIDs) and serve as a diagnostic and prognostic tool in assessing these complex disorders. Viral infections have long been recognized as a principal environmental factor affecting the production of AABs and the development of autoimmunity. COVID-19 has primarily been considered a hyperinflammatory syndrome triggered by a cytokine storm. In the following, the role of maladaptive B cell response and AABs became more apparent in COVID-19 pathogenesis. The current review will primarily focus on the role of extrafollicular B cell response, Toll-like receptor-7 (TLR-7) activation, and neutrophil extracellular traps (NETs) formation in the development of AABs following SARS-CoV-2 infection. In the following, this review will clarify how these AABs dysregulate immune response to SARS-CoV-2 by disrupting cytokine function and triggering neutrophil hyper-reactivity. Finally, the pathologic effects of these AABs will be further described in COVID-19 associate clinical manifestations, including venous and arterial thrombosis, a multisystem inflammatory syndrome in children (MIS-C), acute respiratory distress syndrome (ARDS), and recently described post-acute sequelae of COVID-19 (PASC) or long-COVID.