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Neuroscience Letters Jun 2024There are currently no FDA-approved treatments for cocaine use disorder. Recent preclinical and clinical studies showed that deep brain stimulation (DBS) in limbic...
There are currently no FDA-approved treatments for cocaine use disorder. Recent preclinical and clinical studies showed that deep brain stimulation (DBS) in limbic regions reduced drug seeking behavior. Our previous work indicated that DBS of the nucleus accumbens shell attenuated reinstatement of cocaine seeking, a model of relapse, in male rats. The current experiments were designed to evaluate the effect of electrical DBS on cocaine reinstatement in female rats across the estrous cycle. Rats were allowed to self-administer cocaine and lever responding was subsequently extinguished. Cocaine seeking was reinstated by an acute injection of experimenter-delivered cocaine. The effect of nucleus accumbens shell DBS vs. sham stimulation on cocaine-primed reinstatement was evaluated in female and male rats using a within-subjects counterbalanced design. Consistent with previous work, accumbens shell DBS suppressed cocaine seeking in male rats. In sharp contrast, accumbens shell DBS had no effect on cocaine reinstatement in female rats evaluated in either the estrus or non-estrus phases. These results suggest that changes across the estrous cycle are not responsible for the differences in the effect of DBS on cocaine reinstatement between female and male rats.
PubMed: 38945352
DOI: 10.1016/j.neulet.2024.137888 -
Ageing Research Reviews Jun 2024It has been four years since long COVID-the protracted consequences that survivors of COVID-19 face-was first described. Yet, this entity continues to devastate the... (Review)
Review
It has been four years since long COVID-the protracted consequences that survivors of COVID-19 face-was first described. Yet, this entity continues to devastate the quality of life of an increasing number of COVID-19 survivors without any approved therapy. Furthermore, there remains a paucity of clinical trials addressing the biological root causes of this disease. Notably, the symptoms of long COVID-including but not limited to exercise intolerance, cognitive impairment, orthostasis, and functional decline-are typically seen with advancing age. Leveraging this similarity, we posit that Geroscience-which aims to target the biological drivers of aging to prevent age-associated conditions as a group-could offer promising therapeutic avenues for long COVID. Bearing this in mind, this review presents a framework for studying long COVID as a state of effectively accelerated biological aging. Thus, we comprehensively review here the role of biological hallmarks of aging in long COVID, identifying research gaps and proposing directions for future preclinical and clinical studies.
PubMed: 38945306
DOI: 10.1016/j.arr.2024.102400 -
Behavioural Brain Research Jun 2024Major depressive disorder (MDD) affects millions of people worldwide, with women at a higher risk during the childbearing age. Vortioxetine (VOX) and Vilazodone (VLZ)...
Major depressive disorder (MDD) affects millions of people worldwide, with women at a higher risk during the childbearing age. Vortioxetine (VOX) and Vilazodone (VLZ) are newer antidepressants with improved therapeutic profile commonly used, but their safety during pregnancy and long-term effects on offspring are poorly understood due to paucity of literature in preclinical and clinical studies. This study aimed to investigate whether prenatal exposure to VOX and VLZ impacts depressive- and anxiety-like neurobehavioral alterations in offspring, focusing on neurotransmitter-mediated mechanisms. Pregnant Wistar dams received either VOX or VLZ, 1mg/day and 2mg/day of the drug orally from gestation day (GD) 6 to 21. The dams naturally delivered their offspring and reared until they reached postnatal day (PND) 21. Offspring of both sexes were tested for display of depressive-and anxiety-like behaviors from PND 56 to 70. After PND 70, offspring were sacrificed, and their brains were collected to estimate neurotransmitter levels. As per protocol, controls were maintained simultaneously for each experimental design. Prenatal exposure to VOX or VLZ induced an increased state of depressive- and anxiety-like behaviors in both male and female offspring. Additionally, neurotransmitter (serotonin, dopamine, and nor-epinephrine) levels in the prefrontal cortex region of the brain were substantially reduced in exposed offspring. No sex specific neurobehavioral and neurochemical implications were observed in the present study. Our findings suggest that prenatal exposure to VOX and VLZ disrupts neurochemical balance in the fetal brain, leading to long-lasting neurobehavioral impairments in offspring of both sexes.
PubMed: 38945303
DOI: 10.1016/j.bbr.2024.115128 -
International Immunopharmacology Jun 2024Hepatic ischemia-reperfusion (I/R) injury is a clinically fundamental phenomenon that occurs through liver resection surgery, trauma, shock, and transplantation. (Review)
Review
BACKGROUND
Hepatic ischemia-reperfusion (I/R) injury is a clinically fundamental phenomenon that occurs through liver resection surgery, trauma, shock, and transplantation.
AIMS OF THE REVIEW
This review article affords an expanded and comprehensive overview of various natural herbal ingredients that have demonstrated hepatoprotective effects against I/R injury through preclinical studies in animal models.
MATERIALS AND METHODS
For the objective of this investigation, an extensive examination was carried out utilizing diverse scientific databases involving PubMed, Google Scholar, Science Direct, Egyptian Knowledge Bank (EKB), and Research Gate. The investigation was conducted based on specific identifiable terms, such as hepatic ischemia/reperfusion injury, liver resection and transplantation, cytokines, inflammation, NF-kB, interleukins, herbs, plants, natural ingredients, phenolic extract, and aqueous extract.
RESULTS
Bioactive ingredients derived from ginseng, curcumin, resveratrol, epigallocatechin gallate, quercetin, lycopene, punicalagin, crocin, celastrol, andrographolide, silymarin, and others and their effects on hepatic IRI were discussed. The specific mechanisms of action, signaling pathways, and clinical relevance for attenuation of liver enzymes, cytokine production, immune cell infiltration, oxidative damage, and cell death signaling in rodent studies are analyzed in depth. Their complex molecular actions involve modulation of pathways like TLR4, NF-κB, Nrf2, Bcl-2 family proteins, and others.
CONCLUSION
The natural ingredients have promising values in the protection and treatment of various chronic aggressive clinical conditions, and that need to be evaluated on humans by clinical studies.
PubMed: 38944946
DOI: 10.1016/j.intimp.2024.112445 -
Journal of Gastrointestinal and Liver... Jun 2024Chronic liver diseases belong to the most common diseases worldwide and are associated with increased morbidity and mortality. Although more than one in three adults are...
BACKGROUND AND AIMS
Chronic liver diseases belong to the most common diseases worldwide and are associated with increased morbidity and mortality. Although more than one in three adults are estimated to have metabolic dysfunction-associated steatotic liver disease (MASLD), awareness of this condition is low amongst the general public, health care professionals and policy makers. However, meaningful knowledge transfer is essential for raising awareness and improving prevention and treatment. This study set out to investigate the use of the major internet search engine to understand how knowledge transfer has evolved by analyzing liver-related searches trends.
METHODS
We investigated Google search trends by measuring the number of hits relating to liver diseases between 2004 and 2021 in seven languages and European countries but also worldwide. All analyses were performed in R using the R Google trends package gtrendsR.
RESULTS
We found that interest in MASLD [formerly non-alcoholic fatty liver disease (NAFLD)] has generally increased over time, but that interest in metabolic associated steatohepatitis (MASH) - the most severe form of MASLD - has decreased. Interest in viral hepatitis C has decreased, whereas the number of queries regarding viral hepatitis B have been stable but dominated by interest in vaccination for it. Recent medical developments (in viral hepatitis) did not lead to a noticeable change in overall search behavior. Users preferred searching using their native language and less complex medical terms and acronyms (e.g., fatty liver instead of NAFLD).
CONCLUSIONS
In the last two decades, Google search trends have followed the general development in the field of hepatology. Searches were dominated by non-experts and are not being rapidly influenced by novel scientific developments. Also, users preferred search terms in their native languages rather than English and tended to avoid complex medical search terms. Awareness and communication strategies around MASLD should consider these preferences when addressing the general public.
Topics: Humans; Europe; Search Engine; Liver Diseases; Internet; Non-alcoholic Fatty Liver Disease; Information Seeking Behavior; Consumer Health Information
PubMed: 38944876
DOI: 10.15403/jgld-5477 -
Cancer Genomics & Proteomics 2024The efficacy of melatonin and its biological significance in human bladder cancer remain poorly understood. This study aimed to investigate the functional role of...
BACKGROUND/AIM
The efficacy of melatonin and its biological significance in human bladder cancer remain poorly understood. This study aimed to investigate the functional role of melatonin in urothelial carcinogenesis.
MATERIALS AND METHODS
In human normal urothelial SVHUC cells with exposure to the chemical carcinogen 3-methylcholanthrene, we assessed the effects of melatonin on the neoplastic/malignant transformation.
RESULTS
In the in vitro system with carcinogen challenge, melatonin significantly prevented the neoplastic transformation of SV-HUC-1 cells. In addition, melatonin treatment resulted in increased expression of SIRT1, Rb1, and E-cadherin, and decreased expression of N-cadherin and FGFR3 in SV-HUC-1 cells. Furthermore, publicly available datasets from GSE3167 revealed that the expression of melatonin receptor 1 and melatonin receptor 2 was significantly down-regulated in bladder urothelial carcinoma tissues, compared with adjacent normal urothelial tissues.
CONCLUSION
These findings indicate that melatonin serves as a suppressor for urothelial tumorigenesis. To the best of our knowledge, this is the first preclinical study demonstrating the impact of melatonin on the development of urothelial cancer.
Topics: Melatonin; Humans; Cell Transformation, Neoplastic; Carcinogens; Urinary Bladder Neoplasms; Urothelium; Methylcholanthrene
PubMed: 38944424
DOI: 10.21873/cgp.20456 -
International Journal of Pharmaceutics Jun 2024Nanotechnology-based drug delivery systems, including siRNA, present an innovative approach to treating breast cancer, which disproportionately affects women. These... (Review)
Review
Nanotechnology-based drug delivery systems, including siRNA, present an innovative approach to treating breast cancer, which disproportionately affects women. These systems enable personalized and targeted therapies, adept at managing drug resistance and minimizing off-target effects. This review delves into the current landscape of nanotechnology-derived siRNA transport systems for breast cancer treatment, discussing their mechanisms of action, preclinical and clinical research, therapeutic applications, challenges, and future prospects. Emphasis is placed on the importance of targeted delivery and precise gene silencing in improving therapeutic efficacy and patient outcomes. The review addresses specific hurdles such as specificity, biodistribution, immunological reactions, and regulatory approval, offering potential solutions and avenues for future research. SiRNA drug delivery systems hold promise in revolutionizing cancer care and improving patient outcomes, but realizing their full potential necessitates ongoing research, innovation, and collaboration. Understanding the intricacies of siRNA delivery mechanisms is pivotal for designing effective cancer treatments, overcoming challenges, and advancing siRNA-based therapies for various diseases, including cancer. The article provides a comprehensive review of the methods involved in siRNA transport for therapeutic applications, particularly in cancer treatment, elucidating the complex journey of siRNA molecules from extracellular space to intracellular targets. Key mechanisms such as endocytosis, receptor-mediated uptake, and membrane fusion are explored, alongside innovative delivery vehicles and technologies that enhance siRNA delivery efficiency. Moreover, the article discusses challenges and opportunities in the field, including issues related to specificity, biodistribution, immune response, and clinical translation. By comprehending the mechanisms of siRNA delivery, researchers can design and develop more effective siRNA-based therapies for various diseases, including cancer.
PubMed: 38944167
DOI: 10.1016/j.ijpharm.2024.124403 -
Brain, Behavior, and Immunity Jun 2024The gut microbiota and neurological development of neonatal mice are susceptible to environmental factors that may lead to altered behavior into adulthood. However, the...
The gut microbiota and neurological development of neonatal mice are susceptible to environmental factors that may lead to altered behavior into adulthood. However, the role that changed gut microbiota and neurodevelopment early in life play in this needs to be clarified. In this study, by modeling early-life environmental changes by cross-fostering BALB/c mice, we revealed the effects of the environment during the critical period of postnatal development on adult social behavior and their relationship with the gut microbiota and the nervous system. The neural projections exist between the ascending colon and oxytocin neurons in the paraventricular nuclei (PVN), peripheral oxytocin levels and PVN neuron numbers decreased after cross-fostering, and sex-specific alteration in gut microbiota and its metabolites may be involved in social impairments and immune imbalances brought by cross-fostering via the gut-brain axis. Our findings also suggest that social cognitive impairment may result from a combination of PVN oxytocinergic neurons, gut microbiota, and metabolites.
PubMed: 38944162
DOI: 10.1016/j.bbi.2024.06.026 -
American Journal of Infection Control Jun 2024Candida auris is an emerging multidrug-resistant fungus associated with catheter-related bloodstream infections (CRBSI). In-vitro efficacy of chlorhexidine (CHX) and...
The antimicrobial effectiveness of chlorhexidine and chlorhexidine-silver sulfadiazine impregnated central venous catheters against the emerging fungal pathogen Candida auris.
BACKGROUND
Candida auris is an emerging multidrug-resistant fungus associated with catheter-related bloodstream infections (CRBSI). In-vitro efficacy of chlorhexidine (CHX) and CHX/silver sulfadiazine-impregnated (CHX-S) antimicrobial central venous catheters (CVCs) against C. auris was investigated.
MATERIAL AND METHODS
Minimum inhibitory (MIC) and bactericidal (MBC) CHX concentrations were determined against nineteen C. auris isolates. To assess extraluminal efficacy, segments from CVCs impregnated externally (CHX-S1) and both externally and internally (CHX-S2) were plasma-conditioned for 1- and 6-days, and to assess intraluminal efficacy CHX-S2 CVCs were pre-conditioned with saline-lock for 6-days, followed by 24-hour C. auris inoculation and microbial adherence determination on impregnated and non-impregnated CVCs.
RESULTS
CHX inhibited all C. auris isolates with MIC and MBC range of 8-128 μg/mL. C. auris adherence was reduced on CHX-S1 and CHX-S2 extraluminally by 100% on day-1, 86.96%-100% on day-7, and intraluminally on CHX-S2 by 56.86%-90.52% on day-7.
DISCUSSION
CHX and CHX-S CVCs performance against C. auris observed in this study is consistent with antimicrobial benefits observed in prior pre-clinical and randomized controlled clinical studies.
CONCLUSIONS
CHX showed strong inhibitory and cidal effects on C. auris. CHX-S CVCs proved highly efficacious against this pathogen under in vitro conditions. Additional studies, however, are required to confirm clinical benefit.
PubMed: 38944155
DOI: 10.1016/j.ajic.2024.06.015 -
Journal of Psychiatric Research Jun 2024Numerous studies on post-COVID syndrome (PCS) describe persisting symptoms of cognitive impairment. Previous studies, however, often investigated small samples or did...
Numerous studies on post-COVID syndrome (PCS) describe persisting symptoms of cognitive impairment. Previous studies, however, often investigated small samples or did not assess covariates possibly linked to cognitive performance. We aimed to describe 1) global and domain-specific cognitive performance in adults with PCS, controls with previous SARS-CoV-2 infection and healthy controls, 2) associations of sociodemographics, depressive symptoms, anxiety, fatigue, somatic symptoms and stress with cognitive performance and subjective cognitive decline (SCD), using data of the LIFE-Long-COVID-Study from Leipzig, Germany. Group differences in cognitive performance and associations with sociodemographic and neuropsychiatric covariates were assessed using multivariable regression analyses. Our study included n = 561 adults (M: 48.8, SD: 12.7; % female: 70.6). Adults with PCS (n = 410) performed worse in tests on episodic memory (b = -1.07, 95 % CI: -1.66, -0.48) and visuospatial abilities (b = -3.92, 95 % CI: -6.01, -1.83) compared to healthy controls (n = 64). No impairments were detected for executive function, verbal fluency, and global cognitive performance. Odds of SCD were not higher in PCS. A previous SARS-CoV-2 infection without PCS (n = 87) was not linked to cognitive impairment. Higher age and higher levels of stress and fatigue were linked to worse performance in several cognitive domains. Routine administration of tests for episodic memory and visuospatial abilities might aid in the identification of individuals at risk for cognitive impairment when reporting symptoms of PCS. Low numbers of participants with severe COVID-19 infections possibly limit generalizability of our findings.
PubMed: 38944016
DOI: 10.1016/j.jpsychires.2024.06.036