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Parkinson's disease (PD) is a chronic and ongoing neurological condition. Unfortunately, as the dopaminergic terminals continue to deteriorate, the effectiveness of anti-Parkinson therapy decreases. This study aimed to examine the effects of BM-MSCs-derived exosomes in rats induced with Parkinson's disease. The goal was to determine their potential for neurogenic repair and functional restoration. Forty male albino rats were divided into four groups: control (group I), PD (group II), PD-L-Dopa (group III), and PD-exosome (group IV). Motor tests, histopathological examinations, and immunohistochemistry for tyrosine hydroxylase were performed on brain tissue. The levels of α-synuclein, DJ-1, PARKIN, circRNA.2837, and microRNA-34b were measured in brain homogenates. Rotenone induced motor deficits and neuronal alterations. Groups (III) and (IV) showed improvement in motor function, histopathology, α-synuclein, PARKIN, and DJ-1 compared to group (II). Group (IV) showed improvement in microRNA-34b and circRNA.2837 compared to groups (III) and (II). MSC-derived exosomes showed a greater suppression of neurodegenerative disease (ND) compared to L-Dopa in Parkinson's patients.
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Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Ratos , Animais , Masculino , Doença de Parkinson/tratamento farmacológico , Levodopa/farmacologia , alfa-Sinucleína , RNA Circular/genética , Ubiquitina-Proteína Ligases/genética , MicroRNAs/genética , Modelos Animais de DoençasRESUMO
Vitamin D effects are mediated by vitamin D receptors (VDRs), which are influenced by various genetic polymorphisms, including ApaI and BsmI. These polymorphisms have been linked to several diseases, including rheumatoid arthritis (RA). This study aimed to compare the frequency and association of VDR ApaI and BsmI gene polymorphisms, serum 25-hydroxy vitamin D (25-(OH)-D) levels, and calcium (Ca) levels between a RA group and a matched healthy control group. In one hundred RA patients and fifty healthy controls, the genotypes of the VDR ApaI and BsmI gene polymorphisms were analyzed using polymerase chain reaction restriction fragment length polymorphisms (PCR-RFLP). Both Serum 25-(OH)-D level and calcium level were measured in the two groups. There was no significant difference between the cases and controls regarding the VDR ApaI gene polymorphism (p = 0.89). A significant difference was observed between the cases and controls in terms of the VDR BsmI gene polymorphism (p = < 0.001). The serum levels of 25-(OH)-D and calcium were significantly lower in the RA group compared to the control group (p = 0.04 and < 0.001 respectively). Significantly higher serum vitamin D levels were associated with the aa genotype (p = 0.007). Significantly increased calcium levels were associated with the AA genotype (p = 0.02). No significant difference was found among BsmI polymorphisms regarding vitamin D and Ca levels (p = 0.25 and 0.87 respectively). Vitamin D receptor gene BsmI polymorphism but not ApaI polymorphism could be a marker of RA susceptibility. Vitamin D and Ca levels are negatively affected by RA. Vitamin D receptor gene ApaI polymorphism contributes to vitamin D and Ca levels.
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PURPOSE: Male fertility is multifaceted and its integrity is as well multifactorial. Normal spermatogenesis is dependent on competent testicular function; namely normal anatomy, histology, physiology and hormonal regulation. Lifestyle stressors, including sleep interruption and even deprivation, have been shown to seriously impact male fertility. We studied here both the effects and the possible underlying mechanisms of vitamin C on male fertility in sleep deprived rats. METHODS: Thirty male Wistar albino rats were used in the present study. Rats were divided (10/group) into: control (remained in their cages with free access to food and water), sleep deprivation (SD) group (subjected to paradoxical sleep deprivation for 5 consequent days, rats received intra-peritoneal injections of vehicle daily throughout the sleep deprivation), and sleep deprivation vitamin C-treated (SDC) group (subjected to sleep deprivation for 5 consequent days with concomitant intra-peritoneal injections of 100 mg/kg/day vitamin C). Sperm analysis, hormonal assay, and measurement of serum oxidative stress and inflammatory markers were performed. Testicular gene expression of Nrf2 and NF-κß was assessed. Structural changes were evaluated by testicular histopathology, while PCNA immunostaining was conducted to assess spermatogenesis. RESULTS: Sleep deprivation had significantly altered sperm motility, viability, morphology and count. Serum levels of cortisol, corticosterone, IL-6, IL-17, MDA were increased, while testosterone and TAC levels were decreased. Testicular gene expression of Nrf2 was decreased, while NF-κß was increased. Sleep deprivation caused structural changes in the testes, and PCNA immunostaining showed defective spermatogenesis. Administration of vitamin C significantly countered sleep deprivation induced deterioration in male fertility parameters. CONCLUSION: Treatment with vitamin C enhanced booth testicular structure and function in sleep deprived rats. Vitamin C could be a potential fertility enhancer against lifestyle stressors.
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Antioxidantes/uso terapêutico , Ácido Ascórbico/uso terapêutico , Infertilidade Masculina/tratamento farmacológico , Privação do Sono/tratamento farmacológico , Motilidade dos Espermatozoides/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Infertilidade Masculina/metabolismo , Infertilidade Masculina/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Ratos , Ratos Wistar , Privação do Sono/metabolismo , Privação do Sono/patologia , Motilidade dos Espermatozoides/fisiologiaRESUMO
BACKGROUND: Previous studies have reported the role of genes in different metabolic processes in the human body, and any variation in gene polymorphisms could lead to disturbances in these processes and different diseases. OBJECTIVE: This study aimed to compare vitamin D receptor (VDR) FokI and TaqI genotypes in terms of parathyroid hormone (PTH) and some biomarkers of inflammation and susceptibility to rheumatoid arthritis (RA) disease. METHODS: This study included 100 patients with rheumatoid arthritis (RA). Genotyping was performed by polymerase chain reaction (PCR) and examined by specific restriction enzymes using restriction fragment length polymorphism (RFLP). Serum intact PTH, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), and anti-cyclic citrullinated peptide antibodies (ACCPs) levels were measured. RESULTS: An increased PTH level (> 65 pg/ml) was found in 8% of patients. No significant differences among FokI and TaqI vitamin D receptor genes polymorphism regarding positive and negative RF or ACCPs were found. A significant difference was found among FokI (p = 0.009) and none in TaqI genotypes regarding intact parathyroid hormone level categories. No significant correlation was found between the serum intact PTH level and ESR or CRP levels (P = 0.13 and 0.28, respectively). The parathyroid hormone level was not a good predictor for RF or ACCPs (P = 0.5 and 0.06, respectively). CONCLUSION: The FokI gene may play a role in controlling PTH levels in patients with RA. There was no significant correlation found between the serum intact PTH level and RA severity according to ESR and CRP inflammatory biomarkers. There are no differences between VDR genes FokI and TaqI polymorphism in terms of RA susceptibility (for RF and ACCPs).
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Artrite Reumatoide , Receptores de Calcitriol , Humanos , Artrite Reumatoide/sangue , Artrite Reumatoide/genética , Biomarcadores , Proteína C-Reativa , Estudos de Casos e Controles , Predisposição Genética para Doença , Genótipo , Hormônio Paratireóideo/sangue , Hormônio Paratireóideo/genética , Polimorfismo Genético , Receptores de Calcitriol/genética , Vitamina DRESUMO
OBJECTIVE: Vitamin D is important for bone and cartilage metabolism. Changes in vitamin D blood level may be related to pathological disorders such as rheumatoid arthritis (RA). The main aim of this study is to investigate the association between RA and the vitamin D receptor (VDR) genes FokI and TaqI polymorphisms. One hundred RA patients and fifty healthy matched controls were assessed for VDR FokI and TaqI genotyping. Intact parathyroid hormone (PTH) and calcium (Ca) levels were measured, categorized, and compared between the cases and control groups. RESULTS: We found that the FokI genotype frequencies for the RA cases and control groups were FF:Ff:ff = 46%:52%:2% and 50%:50%:0%, respectively (P = 0.76). The TaqI genotype frequencies for the RA cases and control groups were TT:Tt:tt = 45%:44%:11% and 42%:42%:16%, respectively (P = 0.69). A statistically significant high serum PTH level was associated with the ff genotype (p = 0.03), and a significantly low serum Ca level was associated with the TT genotype (p = 0.003). In comparison with controls, no influence of VDR FokI and TaqI genotypes on RA susceptibility or risk was demonstrated.
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Artrite Reumatoide , Receptores de Calcitriol , Humanos , Receptores de Calcitriol/genética , Genótipo , Artrite Reumatoide/genética , Vitamina D , Alelos , Predisposição Genética para Doença , Estudos de Casos e ControlesRESUMO
Introduction: In this research, we investigated any possible effect of receiving hyperbaric oxygen therapy (HBOT) or risperidone on the core symptoms of autism in children diagnosed with autism spectrum disorder (ASD). Methods: This study was a randomized, controlled clinical trial in Minia and Assiut University hospitals in Egypt with three parallel groups. One hundred and eighty children with autism, aged 5-8 years were divided into three equal groups (n=60). Group 1 (G1) received 40 sessions of HBOT within two months, group 2 (G2) received risperidone (dose: 0.25 mg per day in children weighing less than 20 kg and 0.5 mg per day in cases weighing more) for six months, and group 3 (G3) as the control group, received a placebo for six months. The assessment was done using childhood autism rating scale (CARS) and autism treatment evaluation checklist (ATEC) at the beginning of the study (baseline) and after one year. Results: The mean total CARS and ATEC scores significantly decreased (improved) by varying degrees in the three groups after a year of follow-up compared to the baseline scores, but the best results were found in G1, G2, and G3, respectively. Conclusion: Using HBOT or risperidone is effective in treating the core symptoms of autism in children diagnosed with autism spectrum disorder, but using HBOT gives better results than risperidone therapy. Highlights: Non-pharmacologic therapy can be used for the treatment of the core symptoms of autism.Both hyperbaric oxygen therapy and risperidone reduce the core symptoms of autism.Hyperbaric oxygen therapy gives better effects than risperidone in reducing the core symptoms of autism. Plain Language Summary: Since the long-term use of drug therapy in children with autism leads to the occurrence of side effects in addition to the difficulty in complying with the drugs for long-term use, efforts have begun to use non-traditional alternative treatments, such as hyperbaric oxygen therapy. The current study assessed the therapeutic effect of hyperbaric oxygen therapy and risperidone on the core symptoms of autism. The results revealed that both hyperbaric oxygen therapy and risperidone reduced the core symptoms of autism, but hyperbaric oxygen therapy gave better therapeutic results than risperidone.
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Introduction: This study was designed to differentiate between the impact of the topical nasal spray of corticosteroids, antihistamines, a combination of them, and normal 0.2% saline in treating patients with post-coronavirus disease 2019 (COVID-19) smell dysfunction. Materials and Methods: Patients with hyposmia or anosmia (n = 240), who recently recovered from COVID-19, were enrolled in this trial and were randomly assigned to four parallel groups. Group I (G1) received a combination of topical corticosteroid and antihistamine nasal spray (n = 60). Group II (G2) received topical corticosteroid nasal spray (n = 60). Group III (G3) received antihistamine nasal spray (n = 60). Group IV (G4) received 0.2% normal nasal saline nasal spray (n = 60). The treatments were used in all groups for 3 weeks. The sense of smell was assessed using the butanol threshold and discrimination tests. The smell tests were evaluated weekly for 3 weeks. Results: The mean age of the patients was 51.9 ± 7.1 years; moreover, 83.8% and 16.2% were male and female, respectively. The results of the smell tests in the first week significantly improved with those in the third week (P< 0.001). The greatest degree of improvement was found in the first group, followed by the second, third, and fourth groups. Conclusions: The results suggest the ability of combination therapy of corticosteroid and antihistamine nasal spray to manage post-COVID-19 hyposmia or anosmia; however, this combination therapy was not superior to corticosteroid nasal spray. Trial registration ID: UMIN000043537.
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BACKGROUND: Psychological morbidity has been documented in medical and pharmaceutical undergraduate students in different countries around the world. In this study, we examined the impact of coronavirus disease 2019 (COVID-19) home quarantine on the depressive psychological aspects of last-grade pharmacy students. METHODS: A cross-sectional study was conducted by the Department of Clinical Pharmacy, Faculty of Pharmacy, Deraya University, Egypt. Two hundred and sixty-eight last-grade pharmacy students were included in this study, and they completed a self-administered, pre-designed, anonymous questionnaire. The main outcome measures were the Hamilton Depression Rating Scale (HRS) and Patient Health Questionnaire-9 (PHQ-9), which were measured to screen for the symptoms of psychological depression and determine the degree of depression severity between the beginning and the end of the COVID-19 home quarantine period. Data entry and analysis were done using the Statistical Package for Social Science (SPSS) software version 26. Descriptive statistics were employed for analyses of the data, and categorical variables were described by frequencies and percentages. Bivariate and multivariable analyses were performed to examine relations between demographic data and psychological scales. The study protocol was approved by the Faculty of Pharmacy, Minia University Ethical Committee. RESULTS: A total of 268 students participated in this study (102 males and 166 females). The mean ± SD score of baseline HRS and HRS at the end of the study was 6.3 ± 4.45, 7.95 ± 5.36, respectively, with the presence of a statistically significant difference between the two scores (p < 0.001). The mean ± SD score of baseline PHQ-9 and PHQ-9 at the end of the study was 4.35 ± 3.45, 5.37 ± 4.14, respectively, with the presence of a statistically significant difference between the two scores (p < 0.001). The results showed that the COVID-19 home quarantine period led to a depressive psychological effect on the students in this study. CONCLUSIONS: Students' psychological depression causes morbidity and, in some cases, mortality. Psychological depressive problems were significantly associated with the COVID-19 home quarantine period, which calls for early intervention to solve it. Student counselling services must be more accessible and affordable to overcome this problem.
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BACKGROUND: Many thrombotic complications are linked to coronavirus disease 2019 (COVID-19). Antithrombotic treatments are important for prophylaxis against these thrombotic events. OBJECTIVES: This study was designed to compare enoxaparin and rivaroxaban as prophylactic anticoagulants in moderate cases of COVID-19 in terms of efficacy, safety, and clinical outcomes. METHODS: The study involved 124 patients with moderate COVID-19 (pneumonia without hypoxia) divided into two groups. The first group (G1) comprised 66 patients who received enoxaparin subcutaneously at a dose of 0.5 mg/kg every 12 h until discharge from the hospital. The second group (G2) comprised 58 patients who received oral rivaroxaban at a dose of 10 mg once daily until discharge from the hospital. The outcomes evaluated in this study were as follows: intermediate care unit (IMCU) duration, the number of patients transferred from the IMCU to the intensive care unit (ICU), ICU duration, the total length of hospital stay, in-hospital mortality, and thrombotic and bleeding complications. RESULTS: No significant differences in IMCU duration (p = 0.39), ICU duration (p = 0.96), and total length of hospital stay (p = 0.73) were observed between the two groups. The percentage of patients requiring ICU admission after hospitalization was 21.2% in G1 and 22.4% in G2 (p = 0.87). The mortality rate was 12.1% in G1 and 10.3% in G2 (p = 0.76). The proportion of patients who had thrombotic complications was 9.1% in G1 and 12.1% in G2 (p = 0.59). The incidence of mild bleeding was 3% in G1 and 1.7% in G2 (p = 0.64). CONCLUSION: Either enoxaparin or rivaroxaban may be used as thromboprophylaxis agents in managing patients with moderate COVID-19. Either medication has no clear advantage over the other.
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COVID-19 , Tromboembolia Venosa , Humanos , Enoxaparina/uso terapêutico , Enoxaparina/efeitos adversos , Anticoagulantes/uso terapêutico , Rivaroxabana/uso terapêutico , Tromboembolia Venosa/prevenção & controleRESUMO
BACKGROUND: Psoriasis is a chronic, immune-related disorder; inflammation, higher rate of epidermal proliferation, and angiogenesis are the main pathognomonic features. Cluster of differentiation 93 (CD93), an angiogenic element, plays a role in cell adhesion regulation and has a putative function in inflammation. OBJECTIVE: To assess CD93 immunohistochemical expression in psoriatic skin and the association of CD93 single nucleotide polymorphisms (SNPs) rs2749817 to disease pathogenesis and severity. METHODS: This case-control study was done on 50 patients with psoriasis vulgaris beside 50 age- and sex-matched healthy controls. Assessment of psoriasis severity was done by Psoriasis Area and Severity Index (PASI) score. 3 mm punch skin biopsies were taken from every participant, and hematoxylin and eosin staining and immunohistochemical staining for CD93 antibody were done. Assessment of CD93 rs2749817 gene polymorphism by the TaqMan allelic discrimination assay technique (real-time PCR) was done. RESULTS: Immunohistochemical expression of CD93 showed membrano-cytoplasmic localization in both endothelial and inflammatory cells of cases and controls with significant more positivity in dermal endothelial and inflammatory cells of cases than controls (p = 0.001 and 0.014 respectively). Strong intensity was present in 18 of cases endothelial cells and 24 inflammatory cells with absence in controls (p = 0.001 for both) with significantly higher H-score and higher percent of positive cells (p = 0.001 for both). The TC genotype was lower in patients compared to control (p-value = 0.006) and CC genotype which was present only in cases (p-value = 0.021). CONCLUSION: Cluster of differentiation 93 has an essential role in psoriasis and an encouraging future therapy for psoriasis.
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Células Endoteliais , Psoríase , Estudos de Casos e Controles , Células Endoteliais/patologia , Humanos , Glicoproteínas de Membrana , Polimorfismo de Nucleotídeo Único , Psoríase/genética , Receptores de Complemento , Pele/metabolismoRESUMO
The immunomodulatory effects of antibiotics could influence the degree of systemic and local responses to infection, so investigation of their intrinsic influence on the host's inflammatory response appears to be essential. Fluoroquinolones are known to exert modulatory activity on immune responses to microbial infection. However the mechanism of this immunmodulation has not been well elucidated. The aim of the work, is to assess the immunomodulatory effects of a levofloxacin, through examining its effect on the concentrations of tumor necrosis factor α (TNF-α) and Interleukin - 10 (IL-10) in serum of pneumonic patients. After following local research ethics committee approval and informed consent. This study included 40 patients with different types of pneumonia, admitted to department of Chest Diseases, Faculty of Medicine, Assiut University Hospitals, Egypt. Also, 10 healthy volunteers served as randomized controls. Both patients and controls received levofloxacin (750 mg once daily for 10 days). Serum levels of TNF-α and IL-10 were measured in patients and control before and after levofloxacin administration (750 mg once daily for 10 days) using human TNF-α and IL-10 ELISA kits respectively. Levofloxacin caused a statistically significant decrease in the mean level of TNF-α in both patients (20.82 ± 1.31 pg/ml) (P < 0.009) and control group (17.12 ± 0.84 pg/ml) (P < 0.004). In contrast, there was statistically significant increase (P < 0.000) in the mean level of IL-1 0 in patients (61.75 ± 2.85 pg/ml) while statistically significant decrease (P < 0.005) in control group (28.57 ± 1.37 pg/ml). In conclusion, our study demonstrates that treatment with levofloxacin affects production of TNF-α as a pro-inflammatory cytokine and IL-10 as an anti-inflammatory cytokines which may provide additional benefits in treatment of respiratory tract infections that are independent of its antibacterial properties.
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Antibacterianos/uso terapêutico , Levofloxacino/uso terapêutico , Pneumonia/tratamento farmacológico , Egito , Feminino , Hospitais Universitários , Humanos , MasculinoRESUMO
In this study, five Egyptian species were tested for their In vitro antimicrobial activities. The antimicrobial screening was carried out via disc diffusion method toward four strains of the clinical antibiotic resistant pathogens including Escherichia coli, Staphylococcus aureus, Candida albicans and Aspergillus niger. Among the methanolic extracts screened, Azadirachta indica, Tectona grandis and Ficus sycomorus showed a broad antimicrobial spectrum against three strains with inhibition zones between 13-27 mm followed by Gmelina arborea and Ficus microcarpa with inhibition zones between 11-17 mm, all plants showed no activity against Aspergillus niger except Gmelina arborea with inhibition zones 12 mm. Penicillin G was used as positive control at concentration of 100 μg/disc with inhibition zones (Staphylococcus aureus 28mm, Escherichia coli 22mm, Candida albicans 25mm and Aspergillus niger 0mm). Owing to the high activity of the methanolic extracts, these extracts were defatted via petroleum ether then were fractionated via; chloroform, ethyl acetate and n-butanol. The n-butanol of Azadirachta indica was the most active against Candida albicans (25 mm), ethyl acetate of Ficus sycomorus against Staphylococcus aureus (18 mm), n-butanol of Gmelina arborea against Staphylococcus aureus (17 mm) and n-butanol of Ficus microcarpa against Staphylococcus aureus (15 mm). These results suggest that the tested plants may be effective potential sources of natural antimicrobials, and are potent inhibitors of antibiotic resistant pathogens.