The impact of chronic fentanyl administration on the cerebral cortex in mice: Molecular and histological effects.

PURPOSE: Fentanyl, a fully synthetic opioid, is widely used for severe pain management and has a huge abuse potential for its psychostimulant effects. Unlike other opioids, the neurotoxic effects of chronic fentanyl administration are still unclear. In particular, little is known about its effect on the cerebral cortex. The current study aims to test the chronic toxicity of fentanyl in the mice model. METHODS: Adult male Balb/c mice were chronically treated with low (0.05 mg/kg, i.p) and high (0.1 mg/kg, i.p) doses of fentanyl for 5 consecutive weeks, and various neurotoxic parameters, including apoptosis, oxidative stress, and neuroinflammatory response were assessed in the cortex. Potential histological as well as neurochemical changes were also evaluated. RESULTS: The results of this study show that chronic fentanyl administration induced intense levels of apoptosis, oxidative stress, and neuroinflammation in the cerebral cortex. These findings were found to be correlated with histopathological characteristics of neural degeneration and white matter injury. Moreover, fentanyl administration was found to reduce the expression of both NMDA receptor subunits and dopamine receptors and elevate the level of epidermal growth factor (EGF). CONCLUSION: Fentanyl administration induced neurotoxic effects in the mouse cerebral cortex that could be primarily mediated by the evoked oxidative-inflammatory response. The altered expression of NMDA receptors, dopamine receptors, and EGF suggests the pernicious effects of fentanyl addiction that may end in the development of toxic psychosis.

Human monkeypox virus in the shadow of the COVID-19 pandemic.

BACKGROUND: The end of smallpox in 1980 and the subsequent stopping of vaccination against smallpox was followed by the emergence of monkeypox (mpox), a viral disease of animal origin, meaning that it is transmitted from animal to human. The symptoms of mpox are similar to smallpox, except that they are less severe in terms of clinical features. In the case of public health, the mpox virus is one of the most important orthopoxviruses (such as variola, cowpox, and vaccinia) that come from the family Poxviridae. Mpox occurs mostly in central Africa and sometimes in tropical rainforests or some urban areas. Also, there are threats other than COVID-19, that must be addressed and prevented from spreading, as there has been an outbreak of mpox cases since May 7, 2022, throughout the USA, Europe, Australia, and part of Africa. OBJECTIVES: In this review, we will discuss mpox between the past, the present and during the COVID-19 pandemic. Also, it offers an updated summary of the taxonomy, etiology, transmission, and epidemiology of mpox illness. In addition, the current review aims to highlight the importance of emerging pandemics in the same era such as mpox and COVID-19. METHODS: A literature search was done for the study using online sources like PubMed and Google Scholar. Publications in English were included. Data for study variables were extracted. After the duplicate articles were eliminated, full-text screening was performed on the papers' titles and abstracts. RESULTS: The evaluation included a series documenting mpox virus outbreaks, and both prospective and retrospectiveinvestigations. CONCLUSIONS: monkeypox is a viral disease caused by the monkeypox virus (MPXV), which is primarily found in central and western Africa. The disease is transmitted from animals to humans and presents symptoms similar to those of smallpox, including fever, headache, muscle aches, and a rash. Monkeypox can lead to complications such as secondary integument infection, bronchopneumonia, sepsis, and encephalitis, as well as corneal infection that can result in blindness. There is no specific clinically proven treatment for monkeypox, and treatment is primarily supportive. However, antiviral drugs and vaccines are available for cross-protection against the virus, and strict infection control measures and vaccination of close contacts of affected individuals can help prevent and control outbreaks.

Acute Hepatic Injury Associated with Acute Administration of Synthetic Cannabinoid XLR-11 in Mouse Animal Model.

The widespread recreational use of synthetic cannabinoids (SCs) has become a serious health issue. Reports of life-threatening intoxications related to SC consumption have markedly increased in recent years, including neurotoxicity, cardiotoxicity, nephrotoxicity, and hepatotoxicity. We investigated the impact of acute administration of the synthetic cannabinoid XLR-11 (3 mg/kg, i.p. for 5 consecutive days) on the liver in BALB/c mouse animal model. Using real-time quantitative RT-PCR, MDA assay, and TUNEL assay, we found consistent up-regulation of a variety of genes involved in oxidative stress (NOX2, NOX4, and iNOS), inflammation (TNF-α, IL-1ß, IL-6), and apoptosis (Bax) in the liver of XLR-11 treated mice compared to control mice. These finding were supported with an elevation of MDA levels and TUNEL positive cells in the liver of XLR-11 treated mice which further confirm increased oxidative stress and apoptosis, respectively. Histopathological analysis of the liver of XLR-11 treated mice confirmed pronounced hepatic necrosis associated with inflammatory cell infiltration. Furthermore, elevated ALT and AST serum levels were also identified in XLR-11 treated mice indicating possible liver damage. Overall, SC-induced hepatotoxicity seems to be mainly mediated by activated oxidative stress and inflammatory processes in the liver, but the specific mechanisms involved require further investigations. However, the present study shed light on the potential deleterious role of acute administration of SCs in the progression to acute hepatic injury which enhances our understanding of the adverse effect of SC consumption.

SARS-CoV-2 and Coronavirus Disease Mitigation: Treatment Options, Vaccinations and Variants.

COVID-19 is caused by a novel coronavirus (2019-nCoV), which was declared as a pandemic after it emerged in China 2019. A vast international effort has been conducted to prevent and treat COVID-19 due to its high transmissibility and severe morbidity and mortality rates, particularly in individuals with chronic co-morbidities. In addition, polymorphic variants increased the need for proper vaccination to overcome the infectivity of new variants that are emerging across the globe. Many treatment options have been proposed and more than 25 vaccines are in various stages of development; however, the infection peaks are oscillating periodically, which raises a significant question about the effectiveness of the prevention measures and the persistence of this pandemic disease. In this review, we are exploring the most recent knowledge and advances in the treatment and vaccination options as well as the new emerging variants of 2019-nCoV and the possible mitigation of one of the most aggressive pandemics in the last centuries.

Correlation of Sperm Mitochondrial DNA 7345 bp and 7599 bp Deletions with Asthenozoospermia in Jordanian Population.

BACKGROUND: Alterations in sperm mitochondrial DNA (mtDNA) affect the functions of some OXPHOS proteins which will affect sperm motility and may be associated with asthenozoospermia. The purpose of this study was to investigate the correlation between 7599-bp and 7345-bp sperm mtDNA deletions and asthenozoospermia in Jordan. METHODS: Semen specimens from 200 men including 121 infertile and 79 healthy individuals were collected at the Royal Jordanian Medical Services In-vitro fertilization (IVF) units. The mtDNA was extracted followed by mtDNA amplification. Polymerase chain reaction (PCR) was conducted for the target sequences, then DNA sequencing was performed for the PCR products. Chi-square, Fisher's and Spearman's tests were used to calculate the correlation. RESULTS: The results showed a significant correlation between the presence of 7599-bp mtDNA deletion and infertility where the frequency of the 7599-bp deletion was 63.6% in the infertile group compared to the fertile 34.2% (p<0.001, (OR=3.37, 95% CI=1.860 to 6.108)). Additionally, the sperm motility showed a significant association with the frequency of the 7599-bp deletion (p=0.001, r=-0.887). The 7345-bp mtDNA deletion showed no assoctiation with the infertility (p=0.65, (OR=0.837, 95% CI= 0.464-1.51)) or asthenozoospermia (p=0.98, r=0.008). CONCLUSION: We demonstrated a significant correlation between asthenozoospermia and the 7599-bp mtDNA deletion but not the 7345-bp mtDNA deletion in the infertile men in Jordan. Screening for deletions in sperm mtDNA can be used as a pre-diagnostic molecular marker for male infertility.

Association between MTHFR 677C>T Polymorphism and Vitamin B12 Deficiency: A Case-control Study.

BACKGROUND: Vitamin B12 (cobalamin) deficiency is a prevalent worldwide health concern. Several factors are associated with vitamin B12 deficiency including lifestyle, genetic predisposition, and malfunctions in the absorption and transport of vitamin B12. In the current case-control study, we aimed at investigating the association between MTHFR polymorphisms and vitamin B12 deficiency in a Jordanian population. METHODS: Two polymorphic sites of the MTHFR gene (c.677C>T, rs1801133 and c.1286A>C, rs1801131) were analyzed using RFLP and DNA sequencing in a group of vitamin B12 deficient individuals (45 males and 55 females). As a control, 100 matching individuals (age and sex) with vitamin B12 levels > 200 ng/mL were also recruited for this study. RESULTS: The MTHFR c.677C>T variant was significantly associated with vitamin B12 deficiency in individuals from northern Jordan. The frequency of the homozygous MTHFR c.677C>T genotype was significantly higher in B12 deficient individuals in comparison with the control group (X2 = 8.397, p = 0.0150). The T allele frequency showed significant association with vitamin B12 deficiency in the study population (OR= 1.684, 95% CI: 1.116 to 2.542, p = 0.017). On the other hand, the MTHFR c.1286A>C variant did not show significant association with vitamin B12 deficiency in the selected population. CONCLUSIONS: Our results showed a significant association between homozygous MTHFR c.677C>T variant and T allele frequencies and vitamin B12 deficiency in the Jordanian population.