A Systems Biology Perspective on Childhood ADHD: Neurochemical Dysregulation, Brain-Behavior Interactions, and Emerging Therapeutics.

Attention deficit hyperactivity disorder (ADHD) is a pervasive neurodevelopmental condition that typically manifests during childhood. Its symptoms manifest much earlier-often before the age of seven. With the disorder's continuous patterns of inattention, hyperactivity, and impulsiveness, it gets in the way of academic, social, and occupational performance.

MDL-800 protects against inflammatory and metabolic dysfunction: role of SIRT6 in the cross-regulation of NFκB, AMPK, and PPAR signaling in rats.

Metabolic syndrome (MetSyn) is a complex, multifactorial disorder characterized by insulin resistance, dyslipidemia, hepatic steatosis, oxidative stress, and chronic inflammation, contributing substantially to the global burden of cardiometabolic diseases. Despite extensive research, effective pharmacological strategies that address the diverse and interconnected pathophysiological mechanisms of MetSyn are lacking. Sirtuin 6 (SIRT6), a NAD-dependent epigenetic regulator, has emerged as a critical modulator of metabolic and inflammatory homeostasis.

Targeting miRNAs in renal cell carcinoma: emerging therapeutic strategies.

About one-third of renal cell carcinoma (RCC) patients present with metastatic disease upon diagnosis because of the retroperitoneal location of the kidneys, which causes many tumors to stay asymptomatic. Besides, shortly after 5 years following successful curative surgery, nearly 30% of individuals develop distant cancer metastases and recurrences. This is mostly attributable to the complex and diverse characteristics of the tumor microenvironment.

Correction: Mohammed et al. Alvespimycin Exhibits Potential Anti-TGF-β Signaling in the Setting of a Proteasome Activator in Rats with Bleomycin-Induced Pulmonary Fibrosis: A Promising Novel Approach. 2023, , 1123.

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The Role of MiRNAs in Moyamoya Disease: Vascular Remodeling and Stroke Risk.

Moyamoya disease (MMD) is a rare degenerative stenosis and occlusive cerebrovascular illness. It is characterized by cerebral ischemia and/or cerebral hemorrhage as the two main clinical signs. It is a common cause of stroke in both children and adults.

Innovative pH-responsive alginate-coated rosuvastatin-loaded chitosan nanoparticles: a targeted approach to inhibiting HMGB1-activated RAGE/TLR4-NFκB signaling in colonic inflammation in rats.

This study developed and optimized an innovative oral pH-dependent drug delivery system utilizing rosuvastatin-loaded chitosan nanoparticles (RSV-CSNPs) coated with sodium alginate (ALG). The goal was to protect RSV-CSNPs from degradation in the acidic gastric environment and facilitate targeted sustained release in the colon to address inflammatory bowel disease. Nanoparticles were initially prepared by ionic gelation.

Unraveling the therapeutic landscape of miRNAs in pancreatic cancer.

Pancreatic cancer, particularly pancreatic ductal adenocarcinoma (PDAC), remains one of the deadliest malignancies with a dismal prognosis due to late diagnosis and limited effective treatments. This review explores the multifaceted role of circulating and exosomal microRNAs (miRNAs) in pancreatic cancer progression, metastasis, diagnosis, prognosis, and therapeutic potential. miRNAs-a class of small non-coding RNAs-regulate gene expression post-transcriptionally, influencing key oncogenic and tumor-suppressor pathways.

Modulation of FOXO3a Nuclear Localization by Linagliptin (BI-1356) reveals a new therapeutic target in chronic ulcerative colitis.

Globally, the incidence and prevalence rates of ulcerative colitis (UC) show a rising pattern. The limited efficacy and significant adverse effects associated with current treatment options underscore the need for novel therapeutic approaches. It has been found that linagliptin, a dipeptidyl peptidase-4 inhibitor, activates AMPK in different disease conditions.

E1231/SR647 protects against unilateral renal ischemia-reperfusion injury by modulating SIRT1/FOXO3 interactions with Nrf2 and NFκB pathways.

Ischemia is a major contributor to acute kidney injury (AKI), for which current treatment options remain limited. One NAD-dependent deacetylase that can preserve renal cells is SIRT1. To date, no research has directly explored the effects of E1231, a SIRT1 activator, in the context of renal ischemia-reperfusion (IR) injury.

E1231/NMN protects against experimental metabolic syndrome: the central role of SIRT1 in modulating AKT/Nrf2/NFκB signaling.

Metabolic syndrome (MetS) is a cluster of several disorders where many challenges hinder effective treatment. The downregulation of SIRT1 or inhibition of its activity is implicated in its pathophysiology. We hypothesized that the combined SIRT1 direct activator E1231 and the SIRT1 stabilizer nicotinamide mononucleotide (NMN) could offer a novel approach to mitigate the pathophysiological features of MetS.

Localized Drug Delivery in Different Gastrointestinal Cancers: Navigating Challenges and Advancing Nanotechnological Solutions.

Different types of cancers affect the gastrointestinal tract (GIT), starting from the oral cavity and extending to the colon. In general, most of the current research focuses on the systemic delivery of the therapeutic agents, which leads to undesired side effects and a limited enhancement in the therapeutic outcomes. As a result, localized delivery within gastrointestinal (GI) cancers is favorable in overcoming these limitations.

Nanoscale Systems for Local Activation of Hypoxia-Inducible Factor-1 Alpha: A New Approach in Diabetic Wound Management.

Chronic wounds in diabetic patients experience significant clinical challenges due to compromised healing processes. Hypoxia-inducible factor-1 alpha (HIF-1α) is a critical regulator in the cellular response to hypoxia, enhancing angiogenesis and tissue restoration. Nevertheless, the cellular response to the developed chronic hypoxia within diabetes is impaired, likely due to the destabilization of HIF-1α via degradation by prolyl hydroxylase domain (PHD) enzymes.

PU-H71 (NSC 750424): a molecular masterpiece that targets HSP90 in cancer and beyond.

Heat shock protein 90 (HSP90) is a pivotal molecular chaperone with multifaceted roles in cellular health and disease. Herein, we explore how HSP90 orchestrates cellular stress responses, particularly through its partnership with heat shock factor 1 (HSF-1). PU-H71, a selective inhibitor of HSP90, demonstrates significant potential in cancer therapy by targeting a wide array of oncogenic pathways.

Unlocking vinpocetine's oncostatic potential in early-stage hepatocellular carcinoma: A new approach to oncogenic modulation by a nootropic drug.

The development of new drugs for the inhibition of hepatocellular carcinoma (HCC) development and progression is a critical and urgent need. The median survival rate for HCC patients remains disappointingly low. Vinpocetine is a safe nootropic agent that is often used to enhance cognitive function.

Nicardipine-chitosan nanoparticles alleviate thioacetamide-induced acute liver injury by targeting NFκB/NLRP3/IL-1β signaling in rats: Unraveling new roles beyond calcium channel blocking.

Liver inflammatory diseases are marked by serious complications. Notably, nicardipine (NCD) has demonstrated anti-inflammatory properties, but its benefits in liver inflammation have not been studied yet. However, the therapeutic efficacy of NCD is limited by its short half-life and low bioavailability.

Modulating the HSP90 control over NFκB/NLRP3/Caspase-1 axis is a new therapeutic target in the management of liver fibrosis: Insights into the role of TAS-116 (Pimitespib).

Aberrant activation of the NLRP3 inflammasome is recognized to induce a chronic inflammatory response in the liver, ultimately leading to hepatic fibrosis. HSP90 is suggested to regulate NLRP3 activation and its downstream signaling. This study is the first to explore the potential therapeutic role of pimitespib in mitigating liver fibrosis in rats.

The multifaceted role of beta-blockers in overcoming cancer progression and drug resistance: Extending beyond cardiovascular disorders.

Beta-blockers are commonly used medications that antagonize β-adrenoceptors, reducing sympathetic nervous system activity. Emerging evidence suggests that beta-blockers may also have anticancer effects and help overcome drug resistance in cancer treatment. This review summarizes the contribution of different isoforms of beta-adrenoceptors in cancer progression, the current preclinical and clinical data on associations between beta-blockers use and cancer outcomes, as well as their ability to enhance responses to chemotherapy and other standard therapies.

Hedgehog signaling mastery: R51211's promise in augmenting the therapeutic efficacy of sorafenib.

Sorafenib is a multikinase inhibitor employed for managing hepatocellular carcinoma (HCC). The emergence of sorafenib resistance presents an obstacle to its therapeutic efficacy. One notable approach to overcoming sorafenib resistance is the exploration of combination therapies.

Cell cycle machinery in oncology: A comprehensive review of therapeutic targets.

The cell cycle is tightly regulated to ensure controlled cell proliferation. Dysregulation of the cell cycle machinery is a hallmark of cancer that leads to unchecked growth. This review comprehensively analyzes key molecular regulators of the cell cycle and how they contribute to carcinogenesis when mutated or overexpressed.

Hedgehog signaling is a promising target for the treatment of hepatic fibrogenesis: a new management strategy using itraconazole-loaded nanoparticles.

Liver fibrosis is a disease with a great global health and economic burden. Existing data highlights itraconazole (ITRCZ) as a potentially effective anti-fibrotic therapy. However, ITRCZ effect is hindered by several limitations, such as poor solubility and bioavailability.