Bosnian Journal of Basic Medical Sciences (BJBMS)
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Tenofovir-silver nanoparticles conjugate ameliorates neurocognitive disorders and protects ultrastructural and cytoarchitectonic properties of the prefrontal cortex in diabetic rats
Get PDFTenofovir disoproxil fumarate (TDF) is the highly recommended antiretroviral drug in human immunodeficiency virus management. Although research has shown the neurological and metabolic disorders associated with TDF administration, the effect of TDF-silver nanoparticles conjugate (TDF-AgNPs) on the disorders has not been fully elucidated. Thus, this study evaluated the neuroprotective effects of TDF-AgNPs on ultrastructural and cytoarchitectonic properties of the prefrontal cortex (PFC) in diabetic rats. Forty-two adult male Sprague-Dawley rats (250 ± 13 g) were randomly divided into non-diabetic groups (1-3) and diabetic groups (4-6), each administered distilled water (0.5 ml/100g, p.o), TDF (26.8 mg/kg/bw, p.o) or TDF-AgNPs (6.7 mg/kg, i.p). After eight weeks of administration, cognitive function, oxidative injury and tissue inflammation were evaluated. Also, PFC ultrastructure was observed using transmission electron microscopy, Nissl staining and immunohistochemistry. Diabetic rats administered TDF exhibited cognitive deficits; and increases in blood glucose, malondialdehyde and interleukin-1 beta (IL-1β) levels, which correlate with decreases in glutathione level, and superoxide dismutase (SOD) and catalase activities. Furthermore, loss of PFC astrocytes and neuronal organelles was observed. Conversely, TDF-AgNPs administration to diabetic rats improved cognitive deficits; and increased glutathione, SOD, and catalase, but reduced PFC malondialdehyde and IL-1β concentrations. Notably, TDF-AgNPs prevented loss of PFC neurons and astrocytic cells, and morphology aberration of neuronal organelles. This study suggests that TDF-AgNPs attenuated cognitive deficits via silver nanoparticles\u27 antioxidant and anti-inflammatory properties, preventing the loss of PFC astrocytes and neurons. The TDF-AgNPs may be utilized to ameliorate the neurological dysfunction caused by prolonged TDF administration
Dynamic microglial activation is associated with LPS-induced depressive-like behavior in mice: An [18F] DPA-714 PET imaging study
Get PDFMajor depressive disorder (MDD) is a highly pervasive, severe psychological condition for which the precise underlying pathophysiology is incompletely understood, although microglial activation is known to play a role in this context. In this study we analyzed the association between neuroinflammation and depressive-like behaviors in a lipopolysaccharide (LPS)-induced mouse model system using 10-12-week-old male C57BL/6 mice. Microglial activation and associated neuroinflammatory activity were monitored via positron emission tomography (PET) imaging. Animals were assessed at three time points, including 24 h prior to LPS injection, 24 h post-LPS injection, and 72 h post-LPS injection. Analyses of microglial activation and hippocampal neuroinflammation were conducted through [18]F DPA-714 PET imaging and immunohistochemical staining for ionized calcium-binding adapter molecule 1 (Iba-1) and translocator protein (TSPO). Moreover, NOD-like receptor protein 3 (NLRP3) inflammasome activity and interleukin-1β (IL-1β) levels were assessed at 24 h post-LPS injection. We found that LPS treatment was associated with a marked increase in depressive-like behavior at 24 h post-injection time point, and that it was less pronounced at the 72 h post-injection time point. These changes coincided with enhanced [18F] DPA-714 PET uptake in the whole brain, hippocampus, cortex and amygdala together with increased hippocampal microglial activation as evidenced by immunofluorescent staining. By 72 h post-injection, however, these PET and immunofluorescence phenotypes had returned to baseline levels. Furthermore, increased NLRP3 inflammasome activation and IL-1β expression were evident at 24 h post-LPS injection. These data demonstrate that dynamic microglial activation is associated with LPS-induced depressive-like behaviors and hippocampal neuroinflammation in a mouse model system
Exploring autophagy-related prognostic genes of Alzheimer\u27s disease based on pathway crosstalk analysis
No full textRecent studies have shown that different signaling pathways are involved in the pathogenesis of Alzheimer\u27s disease (AD), with complex molecular connections existing between these pathways. Autophagy is crucial for the degradation and production of pathogenic proteins in AD, and it shows link with other AD-related pathways. However, current methods for identifying potential therapeutic targets for AD are primarily based on single-gene analysis or a single signal pathway, both of which are somewhat limited. Finding other methods is necessary for providing novel underlying AD therapeutic targets. Therefore, given the central role of autophagy in AD and its interplay with its pathways, we aimed to identify prognostic genes related to autophagy within and between these pathways based on pathway crosstalk analysis. The method of pathway analysis based on global influence (PAGI) was applied to find the feature mRNAs involved in the crosstalk between autophagy and other AD-related pathways. Subsequently, the weighted gene co-expression network analysis (WGCNA) was used to construct a co-expression module of feature mRNAs and differential lncRNAs. Finally, based on 2 autophagy-related crosstalk genes (CD40 and SMAD7), we constructed a prognosis model by multivariate Cox regression, which could predict the overall survival of AD patients with medium-to-high accuracy. In conclusion, we provided an effective method for extracting autophagy-related significant genes based on pathway crosstalk in AD. We found the biomarkers valuable to the AD prognosis, which may also play an essential role in the development and treatment of AD
The first detection of Pneumocystis jirovecii in asthmatic patients post-COVID-19 in Jordan
Get PDFPneumocystis jirovecii pneumonia (PCP), caused by fungal species named Pneumocystis jirovecii, is a frequent opportunistic infection in those with human immunodeficiency virus (HIV) infection. However, PCP has been documented in immunocompetent patients. This study aims to determine if P. jirovecii detection occurs in asthma patients following coronavirus disease 2019 (COVID-19) in a Jordanian cohort. Also, to evaluate a method of TaqMan quantitative polymerase chain reaction (qPCR) assay to detect P. jirovecii, from sputum samples. The nasopharyngeal swabs were used to detect SARS-CoV-2 and sputum samples were tested for P. jirovecii using real time qPCR assay. Beta-tubulin (BT) and Dihydrofolate reductase (DHFR) genes were the directed targets of P. jirovecii. The results showed that the mean qPCR efficiencies of BT and DHFR were 96.37% and 100.13%, respectively. Three out of 31 included patients (9.7%) had a positive P. jirovecii. All of the three patients had used oral corticosteroids (OCS) in the last two months due asthma exacerbation and were treated with OCS for COVID-19. This is the first study based in Jordan to demonstrate that P. jirovecii and COVID-19 can co-exist and that it is important to maintain a broad differential diagnosis, especially in immunocompromised patients. Chronic lung disease can be a risk factor for the P. jirovecii colonization possibly due to corticosteroid\u27s immunosuppression
Urine amylase level after Whipple resection might be a predictive factor of postoperative complications
Get PDFThe association between urine amylase levels and the development of postoperative complications after Whipple resection is still unknown. Aim of this study was to determine the prognostic value of urine amylase levels for postoperative complications in patients who underwent Whipple resection. In this retrospective cohort study, we analyzed amylase levels in urine, serum and drains in 52 patients who underwent Whipple resection preoperatively and on Postoperative Day 1 (POD1) after the intervention. Patients were followed up for 3 months to assess their predictive value for postoperative complications. In patients with complications, urine amylase levels were significantly higher on POD1 than before resection (198.89 ± 28.41 vs. 53.70 ± 7.44, p=0.000). Considering the sensitivity and specificity of the urine amylase level on POD1, an area under the ROC curve of 0.918 was obtained (p<0.001, 95% CI: 0.894-0.942). Patients with urine amylase levels ³140.00 U/L had significantly higher risks of postoperative pancreatic fistula (POPF) grade C (definition of POPF done according to the ISGP) (RR:20.26; 95% CI: 1.18-347.07; p=0.038), readmission to hospital (RR: 6.61; 95% CI: 1.53-28.58; p=0.011), reoperation (RR: 5.67; 95% CI: 1.27-25.27; p=0.023), and mortality (RR:17.00; 95% CI: 2.33-123.80; p=0.005) than patients with urine amylase levels <140.00 U/L. Urine amylase levels on POD1 displayed strong and significant positive correlations with serum amylase levels (r=0.92, p=0.001) and amylase levels in drains (r=0.86, p=0.002). We can conclude that urine amylase levels on POD1 have good prognostic value for postoperative complications after Whipple resection and might be used as an additional predictive risk factor
Genetic risk factors in melanoma etiopathogenesis and the role of genetic counseling: A concise review
Get PDFMelanoma is a highly aggressive cancer originating from melanocytes. Its etiopathogenesis is strongly related to genetic, epigenetic, and environmental factors. Melanomas encountered in clinical practice are predominantly sporadic, whereas hereditary melanomas account for approximately 10% of the cases. Hereditary melanomas mainly develop due to mutations in the CDKN2A gene, which encodes two tumor suppressor proteins involved in the cell cycle regulation. CDKN2A, along with CDK4, TERT, and POT1 genes, is a high-risk gene for melanoma. Among the genes that carry a moderate risk are MC1R and MITF, whose protein products are involved in melanin synthesis. The environment also contributes to the development of melanoma. Patients at risk of melanoma should be offered genetic counseling to discuss genetic testing options and the importance of skin UV protection, avoidance of sun exposure, and regular preventive dermatological examinations. Although cancer screening cannot prevent the development of the disease, it allows for early diagnosis when the survival rate is the highest
Effect of bisoprolol on central aortic systolic pressure in Chinese hypertensive patients after the initial dose and long-term treatment
Get PDFWe conducted a prospective open-label cohort study with the aim of examining the effects of the highly β1-selective agent bisoprolol on central aortic systolic pressure (CASP) after the first dose and after 6 weeks’ treatment and whether the CASP response could be predicted from the early response. Chinese patients with primary hypertension (BP ≥ 140/90 mmHg) on no therapy or background amlodipine were treated with bisoprolol 2.5 mg daily for 6 weeks. Brachial systolic BP (Br-SBP), resting heart rate (HR) and CASP were determined at baseline, 24h after the first dose, and pre-dose after treatment for 6 weeks using the BPro® device. In 42 patients (age 54 ± 9 years) the mean reductions in CASP and Br-SBP after 6 weeks of treatment were not significantly different from each other at -14.5 ± 12.7 and -15.4 ± 12.9 mmHg (both p<0.01), respectively. Changes in CASP and Br-SBP were highly correlated after the first dose (r = 0.964, p<0.01) and after 6 weeks (r = 0.963, p<0.01) and the reductions in CASP after 6 weeks were also associated with the reduction in CASP after the first dose (r = 0.577, p<0.01). Bisoprolol was shown to effectively reduce CASP and this effect was directly proportional to the reduction in Br-SBP and of a similar magnitude. More favourable CASP responses to long term therapy may be predicted by greater reductions in CASP after the first dose
Astrocytes and human artificial blood-brain barrier models
Get PDFThe blood-brain barrier (BBB) functions as a highly selective border of endothelial cells, protecting the central nervous system from potentially harmful substances by selectively controlling the entry of cells and molecules, including components of the immune system. To study the BBB properties, find suitable therapies, and identify new drug targets, there is a need to develop representative in vitro BBB models. In this article, we describe the astrocyte roles in the BBB functioning and human in vitro BBB models
The impact of vitamin and mineral supplements usage prior to COVID-19 infection on disease severity and hospitalization
Get PDFThe COVID-19 pandemic has caused a global public health emergency. Nutritional status is suggested to be related to the severity of COVID-19 infection. Herein, we aimed to explore the impact of using vitamin and mineral supplements prior to COVID-19 infection on disease severity and hospitalization. In addition, the prior use of aspirin as an anticoagulant on the disease severity was investigated. A cross-sectional, self-administered survey was conducted between March and July 2021. Recovered COVID-19 individuals (age ≥ 18 years, n = 2148) were recruited in the study. A multivariate logistic regression was used to evaluate the associations of supplements and aspirin use with COVID-19 disease severity and hospitalization status. Among the participants, 12.1% reported symptoms consistent with severe COVID-19, and 10.2% were hospitalized due to COVID-19. After adjustment for confounding variables (age, gender, BMI, cigarette smoking status, and the number of comorbidities), the multivariate logistic regression model showed that the consumption of vitamin D supplements prior to COVID-19 infection was associated with a significant decrease in disease severity (OR = 0.68, 95% CI 0.50 - 0.92; P = 0.01), and a lower risk of hospitalization (OR = 0.64, 95% CI 0.45 - 0.89; P = 0.01). On the other hand, there were no significant differences in the frequencies of severe illness and hospitalizations with the consumption of vitamin A, folic acid, vitamin B12, vitamin B complex, vitamin C, zinc, iron, selenium, calcium, magnesium, omega 3, and aspirin before COVID-19 infection. Among the investigated nutrients, the use of vitamin D prior to COVID-19 infection was associated with reduced disease severity and hospitalization. However, more studies are required to confirm this finding
Strategies and safety considerations of booster vaccination in COVID-19
Get PDFThe first-generation SARS-CoV-2 vaccines have played a significant role in controlling the COVID-19 pandemic, preventing severe diseases, and reducing mortality. However, the continuous emergence of SARS-CoV-2 variants, the persistence of breakthrough infections, and the seemingly rapid decline in the protective efficacy of SARS-CoV-2 vaccines have presented additional challenges for the next phase. There is an urgent need to confirm the necessity of further booster vaccination and combination vaccine approaches. This paper summarizes the latest literature on SARS-CoV-2 variants and vaccine effectiveness and concludes that it is essential to implement booster immunization strategies. Priority should be given to high-risk groups, the elderly, and immunocompromised people. In addition, heterologous vaccination has a longer duration of effect and a broader spectrum than homologous vaccination, making it more conducive to managing the immune escape of SARS-CoV-2 variants