Thirst and hunger are fundamental survival drives that modulate various aspects of animal behavior through specific neural circuits. Previous studies have demonstrated that dopaminergic neurons (DANs) innervating the mushroom body (MB) in the Drosophila brain play essential roles in innate and learned thirst- and hunger-dependent behaviors, with most experiments focusing on acute water or food deprivation. However, it is unclear whether acute water or food deprivation alters dopamine production and neural activity in MB-innervating DANs. We genetically expressed green fluorescent protein (GFP) in MB-innervating DANs using broadly and specifically labeled GAL4 lines under satiety, thirst, and hunger states. The brains were immunostained with anti-tyrosine hydroxylase (TH) to assess dopamine biosynthesis. Additionally, the transcriptional reporter of intracellular Ca2+ (TRIC) was expressed in these DANs using the same GAL4 lines to monitor neural activity under different internal states. Normalized anti-TH and TRIC signals in specific MB compartments were compared between the satiety and thirst groups and between the satiety and hunger groups using unpaired two-tailed t-tests. Neither TH levels nor neural activity in the 13 subtypes of MB-innervating DANs exhibited significant differences during the satiety, thirst, and hunger conditions. This study suggests that 16-hour water deprivation or 24-hour food deprivation does not significantly alter dopamine production and neural activity in MB-innervating DANs. These findings offer insights into the independence of baseline dopaminergic activity from internal states in thirst- or hunger-related behaviors.

BackgroundCancer metastasis is the leading cause of cancer-related deaths, underscoring the importance of understanding its underlying mechanisms. Hepatocellular carcinoma (HCC), a highly malignant type of cancer, was selected as our research model. Material and methodsWe aimed to develop high-metastatic cell lines using in vitro and in vivo selection strategies and identify critical metastasis-related genes through microarray analyses by comparing them with parental cells. ResultsOur results showed that the high-metastatic cell lines exhibited significantly stronger invasion abilities than parental cells. Microarray analyses identified cytidine deaminase (CDA), a gene associated with systemic chemotherapy resistance, as one of the overexpressed genes in the high-metastatic cells. Data analysis from The Cancer Genome Atlas Program revealed that while CDA is downregulated in HCC, patients with high CDA expression tend to have poorer prognoses. Cell models confirmed that CDA overexpression enhances cell migration and invasion, whereas CDA knockdown inhibits these abilities. Investigating the key molecules involved in the epithelial-mesenchymal transition (EMT), we found that CDA overexpression increases the expression of fascin, N-cadherin, β-catenin, and snail while decreasing E-cadherin expression. Conversely, CDA knockdown produced opposite results. Additionally, we discovered that CDA regulates NF-κB signaling, which controls the expression of N-cadherin, thereby promoting the invasion capability of HCC cells. ConclusionsWe isolated highly metastatic cells and identified potential HCC metastasis-related genes. CDA promotes cell invasion by regulating EMT through the NF-κB pathway. Future studies are warranted to explore the potential of CDA as a biomarker for prognosis and therapeutic decision-making.

Plasminogen activator inhibitor-1 (PAI-1) is a key driver of aging and contributes to diverse pathologies. This review examines PAI-1's multifaceted contributions to aging. At the cellular level, PAI-1 amplifies senescence, exhausts stem cell niches, and disrupts metabolism. These cellular alterations translate into physiological decline: PAI-1 drives cardiovascular aging by promoting vascular senescence and arterial stiffening, contributes to cognitive decline by impairing amyloid-beta clearance, fuels cancer progression through angiogenesis and immune suppression, and exacerbates muscle atrophy by hindering regeneration. A rare loss-of-function SERPINE1 mutation extends lifespan, illustrating how lifelong PAI-1 reduction can positively impact the human healthspan. Looking forward, targeting PAI-1 with inhibitors could mitigate senescence, restore stem cell function, improve metabolic profile, enhance physiological health, and promise a longer healthspan.

Cell-to-cell communication is a major process for accommodating cell functioning to changes in the environments and to preserve tissue and organism homeostasis. It is achieved by different mechanisms characterized by the origin of the message, the molecular nature of the messenger, its speed of action and its reach. Purinergic signalling is a powerful mechanism initiated by extracellular nucleotides, such as ATP, acting on plasma membrane purinoreceptors. Purinergic signalling is tightly controlled in time and space by the action of ectonucleotidases. Recent studies have highlighted the critical role of purinergic signalling in controlling the generation, release and fate of extracellular vesicles and, in this way, mediating long-distance responses. Most of these discoveries have been made in immune and cancer cells. This review is aimed at establishing the current knowledge on the way which purinoreceptors control extracellular vesicle-mediated communications and consequences for recipient cells.

BackgroundThe functions of activating transcription factor 3 (ATF3) within the human bladder remain unexplored. This study delves into the expressions, functions, and regulatory mechanisms of ATF3 in human bladder cancer. Material and methodsGene expressions were determined by immunoblot, RT-qPCR, and reporter assays. Assays of Ki67, colony formation, Matrigel invasion, and the xenograft animal study were used to assess the cell proliferation, invasion, and tumorigenesis in vitro and in vivo. Silico analysis from TCGA database examined the correlations between GDF15 and ATF3 expressions, clinicopathologic features, and progression-free survival rates. ResultsSilico analysis confirmed that ATF3 is an antitumor gene, and the expression positively correlates with GDF15 in bladder cancer tissues. Multivariate analysis revealed that low ATF3/GDF15 but not a single low expression of ATF3 is an independent prognostic factor for progression-free survival of bladder cancer patients. Ectopic overexpression of ATF3 downregulated cell proliferation and invasion in bladder cancer cells in vitro, while ATF3-knockdown reversed these results. Knockdown of ATF3 upregulated EMT markers to enhance cell invasion in vitro and downregulated GDF15, NDRG1, and KAI-1 to elevate tumor growth in vivo. The activation of metformin on ATF3 and GDF15 in bladder cancer cells was blocked by SB431542, a TGFβ receptor inhibitor. ATF3 positively regulated GDF15 expression in bladder cancer cells through a feedback loop. ConclusionsOur results identify that ATF3 is a metformin-upregulated antitumor gene. Results of Silico analysis align with cell-based studies suggesting that low ATF3/GDF15 could be a negative prognostic marker for bladder cancer.

Asymmetric cell division (ACD) plays a pivotal role in development, tissue homeostasis, and stem cell maintenance. Emerging evidence suggests that long non-coding RNAs (lncRNAs) are key regulators of ACD, orchestrating the intricate molecular machinery that governs cell fate determination. This review summarizes current literature to elucidate the diverse roles of lncRNAs in modulating ACD across various biological contexts. The regulatory mechanisms of asymmetric cell division mediated by lncRNAs, including their interactions with protein effectors, epigenetic regulation, and subcellular localization are explored. Additionally, we discuss the implications of dysregulated lncRNAs in mediating ACD that lead to tumorigenesis. By integrating findings from diverse experimental models and cell types, this review provides insights into the multifaceted roles of lncRNAs in governing asymmetric cell division, shedding light on fundamental biological processes. Further research in this area may lead to the development of novel therapies targeting dysregulated lncRNAs to restore proper cell division and function. The knowledge of lncRNAs regulating ACD could potentially revolutionize the field of regenerative medicine and cancer therapy by targeting specific lncRNAs involved in ACD. By unraveling the complex interactions between lncRNAs and cellular processes, the potential novel opportunities for precision medicine approaches may be uncovered.

Rationale & objectiveThe data on tenofovir alafenamide (TAF) in kidney transplant recipients (KTRs) with chronic hepatitis B virus (HBV) infection is limited.Study designRetrospective cohort study.Setting & study populationsHBsAg-positive KTRs who received TAF between 2019 and 2022 were included in the analysis, categorized into treatment-naïve and treatment-experienced groups. Additionally, a subgroup of patients receiving ETV was analyzed for comparison.ResultsFour treatment-naïve (Group I) and 35 treatment-experienced (Group II) patients received TAF for 26.4 ± 11.3 and 43.7 ± 19.0 months, respectively. Both groups showed significant HBV DNA reduction, but Group I achieved higher rates of undetectable HBV DNA (50%, 75%, 75%, 100% at 6, 12, 24, 30 months, compared with 16.7%, 25.3%, 31.4%, 34.7% in Group II, p = 0.018). Renal allograft function remained stable during follow-up, and bone toxicity was minimal. For ETV, 10 patients demonstrated excellent viral suppression (HBV DNA undetectable in 70% at 48 weeks and 100% at 96 weeks) with stable renal function over a median of 5.2 years.LimitationsRetrospective study with a lack of prospective comparison of TAF and ETV.ConclusionsOur results suggest that TAF provides favorable efficacy, renal safety, and tolerability in KTRs. ETV also provided effective and sustainable viral suppression. TAF may offer additional advantages such as no concern of viral resistance and dose adjustment by eGFR levels for long-term management of HBsAg-positive KTRs.

BackgroundCerebral Palsy (CP) poses a substantial challenge to pediatric motor function, necessitating effective rehabilitative interventions. This review focuses on the potential of Repetitive Transcranial Magnetic Stimulation (rTMS) as a therapeutic approach for pediatric CP. The context and purpose are framed within the need for novel strategies to enhance motor function in affected children.Material and methodsThe study scrutinizes existing literature to assess the efficacy of rTMS in pediatric CP. Methodological details, including stimulation protocols, are explored. Statistical tests employed in the reviewed studies are outlined, providing insight into the scientific rigor applied in evaluating rTMS outcomes.ResultsThe main findings from the literature review highlight the positive impact of rTMS on motor function and spasticity reduction in children with CP. The synergistic effects observed when combining rTMS with conventional therapies such as physical or occupational therapy and constraint-induced movement therapy are emphasized.ConclusionsEvidences from literature review affirm that rTMS yields constructive outcomes, encompassing enhanced motor function and diminished spasticity, especially when combined with therapies like physical or occupational therapy, and constraint-induced movement therapy. Nevertheless, optimizing rTMS necessitates further fine-tuning of stimulation parameters. Ethical considerations and adherence to safety guidelines are crucial in pediatric settings, despite rare and typically benign side effects. Future research should focus on larger samples, stringent research designs, and long-term follow-ups to rTMS as an effective therapy for managing motor impediments in children with CP.

Hepatocellular carcinoma (HCC) ranks the sixth most common malignancy but the third leading cause of cancer-related mortality in the world. Significant breakthroughs have been made in systemic treatment for HCC over the past two decades, which have improved treatment outcomes. In addition to multiple tyrosine kinase inhibitors (mTKIs), immune checkpoint inhibitors (ICIs) and antiangiogenic drugs are increasingly being applied. The combination of ICI and antiangiogenic or dual ICIs has become the new standard of care due to remarkable response rates. However, currently available systemic regimens are primarily reserved for certain patients in the intermediate and advanced stages who will not benefit from locoregional treatments. Evidence supporting the use of systemic treatment as neoadjuvant or adjuvant therapies in patients with early-stage HCC, especially the high risk of recurrence after curative treatments, remains limited. This review identified recent developments in systemic therapy, including mTKIs and ICIs, considering results on first- and second-line treatment, role of neoadjuvant and adjuvant settings, and combination with loco-regional therapy. Various ongoing clinical trials regarding the role of systemic therapies and potential novel targets in patients with early-, intermediate-, and advanced-stage HCC were also summarized and revealed that systemic therapy is no longer limited to advanced-stage HCC. Moreover, the introduction of T-cell redirecting strategies, including bispecific antibodies and chimeric antigen receptor T cells, has revolutionized the treatment landscape for HCC. Future research should focus on an in-depth exploration of the mechanisms governing the establishment of tumor barriers.