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Consumption of palatable food (PF) can alleviate anxiety, and pain in humans. Contrary, spontaneous withdrawal of long-term PF intake produces anxiogenic-like behavior and abnormal pain sensation, causing challenges to weight-loss diet and anti-obesity agents. Thus, we examined α7-nicotinic acetylcholine receptors (α7nAChR) involvement since it plays essential role in nociception and psychological behaviors., Methods: Adult male C57BL/6 mice were placed on a Standard Chow (SC) alone or with PF on intermittent or continuous regimen for 6 weeks. Then, mice were replaced with normal SC (spontaneous withdrawal). Body weight, food intake, and calories intake with and without the obesogenic diet were measured throughout the study. During PF withdrawal, anxiety-like behaviors and pain sensitivity were measured with PNU-282987 (α7nAChR agonist) administration., Results: Six weeks of SC + PF-intermittent and continuous paradigms produced a significant weight gain. PF withdrawal displayed hyperalgesia and anxiety-like behaviors. During withdrawal, PNU-282987 significantly attenuated hyperalgesia and anxiety-like behaviors., Conclusion: The present study shows that a PF can increase food intake and body weight. Also, enhanced pain sensitivity and anxiety-like behavior were observed during PF withdrawal. α7nAChR activation attenuated anxiolytic-like behavior and hyperalgesia in PF abstinent mice. These data suggest potential therapeutic effects of targeting α7 nAChRs for obesity-withdrawal symptoms in obese subjects., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Cancer is a complex heterogeneous disease that poses a significant public health challenge. In recent years, lipid-based nanoparticles (LBNPs) have expanded drug delivery and vaccine development options owing to their adaptable, non-toxic, tuneable physicochemical properties, versatile surface functionalisation, and biocompatibility. LBNPs are tiny artificial structures composed of lipid-like materials that can be engineered to encapsulate and deliver therapeutic agents with pinpoint accuracy. They have been widely explored in oncology; however, our understanding of their pharmacological mechanisms, effects of their composition, charge, and size on cellular uptake, tumour penetration, and how they can be utilised to develop cancer vaccines is still limited. Hence, we reviewed LBNPs' unique characteristics, biochemical features, and tumour-targeting mechanisms. Furthermore, we examined their ability to enhance cancer therapies and their potential contribution in developing anticancer vaccines. We critically analysed their advantages and challenges impeding swift advancements in oncology and highlighted promising avenues for future research.

Scientific evidences reported the deleterious effect of cigarette smoking or passive smoking on brain health particularly cognitive functions, blood-brain barrier (BBB) permeability, up-regulation of inflammatory cascades, and depletion of the antioxidant system. These combined effects become more progressive in the events of stroke, traumatic brain injury (TBI), and many other neurodegenerative diseases. In the current study, we investigated the long-term administered therapeutic potential of quercetin in ameliorating the deleterious neurobiological consequences of chronic tobacco smoke exposure in TBI mice. After exposure to 21 days of cigarette smoke and treatment with 50 mg/kg of quercetin, C57BL/6 mice were challenged for the induction of TBI by the weight drop method. Subsequently, a battery of behavioral tests and immunohistochemical analyses revealed the beneficial effect of quercetin on the locomotive and cognitive function of TBI + smoked group mice (p < 0.05 vs control sham). Immunohistochemistry analysis (Nrf2, HO-1, NFkB, caspase 3) demonstrated a marked protection after 21 days of quercetin treatment in the chronic tobacco smoking group possibly by up-regulation of antioxidant pathways, and decreased apoptosis. In conclusion, our findings support the therapeutic effectiveness of quercetin in partly protecting the central neurological functions that become aberrantly impaired in combined habitual cigarette-smoking individuals impacted with TBI., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Purpose of Review: The management of dyslipidemia in patients with diabetes is a key component of cardiovascular risk reduction. In particular, the atherogenic dyslipidemia of diabetes often requires combination therapy to target aspects of the lipid profile beyond low-density lipoprotein cholesterol. This article will review the characteristics of dyslipidemia in diabetes, and discuss guidelines and strategies for treatment to reduce cardiovascular disease risk., Recent Findings: A number of clinical outcomes trials supports the use of statins to reduce cardiovascular events in patients with type 2 diabetes mellitus. The disappointing results of clinical trials involving torcetrapib to increase high-density lipoprotein levels may lead to renewed interest and utilization of niacin for the management of atherogenic dyslipidemia. Long-term use of fibrate therapy in patients with atherogenic dyslipidemia has recently been associated with reduction in all-cause, cancer, and cardiovascular mortality rates. Ongoing trials are investigating whether addition of niacin or fibrate to statin therapy is superior to statin therapy alone in preventing cardiovascular events., Summary: Aggressive low-density lipoprotein control continues to be the primary goal of therapy in dyslipidemia management. Given the growing body of evidence showing the cardiovascular benefits of treating other lipid components, however, it is easy to anticipate that full normalization of the lipid profile may become the standard of care for diabetic dyslipidemia.

Background: Increases in carotid intimal medial thickness (IMT), as measured by noninvasive ultrasonography, have been associated with increased risk of myocardial infarction and stroke, particularly in adults 65 years of age or older. We investigated the value of age-normalized carotid IMT measurements in predicting major adverse cardiovascular events in a population of patients referred for carotid IMT measurement., Methods: Since 1995, 727 patients had carotid IMT measured at the University of Virginia's Preventive Cardiology practice. We successfully contacted 706 of these patients to determine clinical outcomes; 21 patients were lost to follow-up. The 706 patients were entered into a database, age-specific quartiles of carotid thickness developed, and odds ratios were calculated with logistic regression., Results: Over a mean follow-up period of 4.78 years (range, 2.0-9.3 years), 20 patients had major adverse cardiovascular events: seven patients had myocardial infarctions; seven required revascularization; and six had a stroke or transient ischemic attack. The incidence of events directly correlated with age-normalized measurements of carotid bulb and internal carotid IMT. The highest quartile of carotid bulb IMT demonstrated an odds ratio for all events of 5.8 (95% confidence interval, 1.3-26.6; P = 0.023) when compared to the quartile with the lowest thickness (P = 0.007 for trend). A similar trend for quartiles of internal carotid IMT was also observed (P = 0.03). Common carotid IMT did not significantly predict events., Conclusions: Age-normalized measurement of carotid bulb and internal carotid IMT may be helpful in determining which individuals would most benefit from aggressive risk-factor modification.

Although the pathogenetic significance of hepatitis B virus x protein (HBxAg) in chronic hepatitis, liver cirrhosis, and primary hepatocellular carcinoma has already been studied, the comparative analyses of both the actual serum HBxAg levels and antibody production against various HBx epitopes have been examined to lesser extent. We have simultaneously investigated the relationship between antibody production (IgG and IgM) against the HBxAg fragments and HBxAg level in the sera of patients with acute (14) or chronic hepatitis (80) and symptomless carriers (12). A recently developed sandwich-type ELISA was used for the quantitative measurements of HBxAg. Overlapping recombinant and synthetic antigens were used to map the fine epitope specificities of circulating anti-HBx antibodies. In acute hepatitis, we have found high and homogenous correlation in the IgM type immune responses against all the examined HBxAg regions. Moreover, strong correlation has been observed between IgG type immune responses to a characteristic C-terminal region (C1: 79-117) and the longest fragment (X: 10-143). Moderate correlation has been found between HBxAg concentration and the IgG type anti-HBx antibody levels against C-terminus of HBxAg in patients with chronic hepatitis. In the case of symptomless carriers, there were also demonstrable associations in the immune responses against the C-terminal sequences; however, significant correlations were found for antibody production against the N-terminal region as well. The examinations show that the C-terminal sequence, responsible for transactivation, promotes an efficient IgG antibody response in all three groups of patients, whereas the negative regulator N-terminal part of the HBxAg molecule for the most part does not trigger antibody production. This suggests that the immune responses against various - biologically active - epitopes of the HBxAg may have a different role in the pathogenesis of hepatitis and may be used as prognostic markers in human HBV infections.

Orthostatic intolerance (OI) is a cause of significant disability in otherwise healthy women seen by gynecologists. Orthostatic tachycardia is often the most obvious hemodynamic abnormality found in OI patients, but symptoms may include dizziness, visual changes, discomfort in the head or neck, poor concentration, fatigue, palpitations, tremulousness, anxiety, and, in some cases, fainting (syncope). It is the most common disorder of blood pressure regulation after essential hypertension, and patients with OI are traditionally women of childbearing age. Estimates suggest that at least 500,000 Americans suffer from some form of OI, and such patients comprise the largest group referred to centers specialized in autonomic disorders. This article reviews recent advances made in the understanding of this condition, potential pathophysiological mechanisms contributing to orthostatic intolerance, and therapeutic alternatives currently available for the management of these patients.