CSF and blood levels of Neurofilaments, T-Tau, P-Tau, and Abeta-42 in amyotrophic lateral sclerosis: a systematic review and meta-analysis.

Recent literature suggests that markers of neuroaxonal damage, such as neurofilaments and tau protein, might serve as potential biomarkers for ALS. We conducted this systematic review and meta-analysis study to compare cerebrospinal fluid (CSF) and blood levels of total tau (t-tau), phosphorylated tau (p-tau), amyloid beta peptide 42 (Abeta-42), and neurofilaments in ALS patients and controls. A systematic search of Cochrane Library, PubMed, Embase, and ISI Web of Science was conducted on March 18, 2022, and updated on January 26, 2023. Observational studies that compared the concentrations of neurofilament light chain (NfL), neurofilament heavy chain (NFH), t-tau, p-tau, or Abeta-42 in CSF or peripheral blood of ALS patients and controls were included. Data from relevant studies were independently extracted and screened for quality using a standard tool, by at least two authors. Meta-analysis was conducted when a minimum of 3 studies reported the same biomarker within the same biofluid. A total of 100 studies were eligible for at least one meta-analysis. CSF and blood levels of NfL (standardized mean difference (SMD) [95% CI]; CSF: 1.46 [1.25-1.68]; blood: 1.35 [1.09-1.60]) and NFH (CSF: 1.32 [1.13-1.50], blood: 0.90 [0.58-1.22]) were significantly higher in ALS patients compared with controls. The pooled differences between ALS patients and controls were not significant for CSF t-tau, blood t-tau, and CSF Abeta-42, but CSF p-tau was lower in ALS patients (-0.27 [-0.47- -0.07]). Significantly decreased p-tau/t-tau ratios were found in ALS patients compared with controls (-0.84 [-1.16- -0.53]). Heterogeneity was considerable in most of our meta-analyses. CSF and blood neurofilament levels, as well as the CSF p-tau/t-tau ratio, might be potential candidates for improving ALS diagnosis. Further research is warranted to better understand the underlying mechanisms and the clinical implications of these biomarker alterations.

Nanomedicine marvels: crafting the future of cancer therapy with innovative statin nano-formulation strategies.

Statins, traditionally used for managing hyperlipidemia and cardiovascular diseases, have garnered significant interest for their potential anti-cancer properties. Research indicates that statins can inhibit critical processes in cancer development, such as apoptosis, angiogenesis, and metastasis. Despite their promising anti-cancer effects, the clinical application of statins in oncology has been hampered by their inherent low solubility and bioavailability. These pharmacokinetic challenges can be effectively addressed through the use of nano-based drug delivery systems. Nano-formulations enhance the delivery and therapeutic efficacy of statins by improving their solubility, stability, and targeting ability, thus maximizing their concentration within the tumor microenvironment and minimizing systemic side effects. This review delves into the potential of nanoparticles as carriers for statins in cancer therapy. It explores the mechanisms by which statins exert their anti-cancer effects, such as through the inhibition of the mevalonate pathway, modulation of immune responses, and induction of apoptosis. Furthermore, the review examines the development of various statin-loaded nano-formulations, highlighting their advantages over conventional formulations. The novelty of this review lies in its focus on recent advancements in nanoformulations that enhance statin delivery to the tumor microenvironment. By discussing the current advancements and prospects of statin nano-formulations, this review aims to provide a comprehensive understanding of how these innovative strategies can improve cancer treatment outcomes and enhance the quality of life for patients. The integration of nanotechnology with statin therapy offers a novel approach to overcoming existing therapeutic limitations and paving the way for more effective and safer cancer treatments.

Reprogramming tumor-associated macrophages using exosomes from M1 macrophages.

Macrophages, abundant in tumors, are classified as M1 or M2 types with M2 dominating the tumor microenvironment. Shifting macrophages from M2 to M1 using exosomes is a promising intervention. The properties of exosomes depend on their source cells. M1-exosomes are expected to polarize macrophages towards M1 phenotype. We compared M1-exosomes and M0-exosomes' effects on M2 macrophage polarization. The RAW264.7 cells were cultured and one group of them was exposed to LPS. The serum-free medium was collected and exosomes were extracted. Exosomes were analyzed by scanning and transmission electron microscopy, dynamic light scattering and Western blot. Subsequently, M1 or M0 exosomes were applied to M2 macrophages induced by IL4. The macrophages polarization, including M1 and M2 genes and surface markers expression, cytokines secretion, and phagocytosis ability were evaluated. It was demonstrated that M1-exosomes induced macrophage polarization toward the M1 phenotype, characterized by an upregulation of M1-specific markers and a downregulation of M2 markers. Furthermore, the secretion of TNF-α was increased, while the secretion of IL-10 was decreased. The phagocytosis ability of M1-exosome-treated macrophages was also augmented. This research suggested that M1-exosomes might be promising candidates for modulating immune response in situations marked by an overabundance of M2 polarization, like in cancer.

The molecular landscape of T cell exhaustion in the tumor microenvironment and reinvigoration strategies.

Immunotherapy has emerged as a promising therapeutic approach for cancer treatment by harnessing the immune system to target cancer cells. However, the efficacy of immunotherapy is hindered by the tumor microenvironment (TME), comprising regulatory T cells (Tregs), macrophages, myeloid-derived suppressor cells (MDSCs), neutrophils, soluble factors (TGF-ß, IL-35, IL-10), and hypoxia. These components interact with inhibitory receptors (IRs) on T cells, leading to alterations in T cell transcriptomes, epigenomes, and metabolism, ultimately resulting in T cell exhaustion and compromising the effectiveness of immunotherapy. T cell exhaustion occurs in two phases: pre-exhaustion and exhaustion. Pre-exhausted T cells exhibit reversibility and distinct molecular properties compared to terminally exhausted T cells. Understanding these differences is crucial for designing effective interventions. This comprehensive review summarizes the characteristics of pre-exhausted and exhausted T cells and elucidates the influence of TME components on T cell activity, transcriptomes, epigenomes, and metabolism, ultimately driving T cell exhaustion in cancer. Additionally, potential intervention strategies for reversing exhaustion are discussed. By gaining insights into the mechanisms underlying T cell exhaustion and the impact of the TME, this review aims to inform the development of innovative approaches for combating T cell exhaustion and enhancing the efficacy of immunotherapy in cancer treatment.

The immune system normally attacks any external factor or abnormal cell in the body, however, sometimes abnormal cells such as cancerous cells can escape the immune system and form a tumor. A class of therapy known as immunotherapy relies on reinforcing the immune system in fighting cancerous cells. However, it cannot have a sustained effect because due to chronic exposure to cancerous cells, T cells, which are the pivotal cells in anti-cancer immunity, gradually lose their activity, a phenomenon known as T cell exhaustion. Exhausted T cells differ from normal T cells in metabolism, transcriptomes, and epigenomes and express different molecules, consequently leading to their dysfunction. By having a comprehensive knowledge of exhausted T cells properties and the factors that give rise to exhaustion, scientists can think of new strategies to make immunotherapy more robust.

Polymeric nanoparticles as a promising platform for treating triple-negative breast cancer: Current status and future perspectives.

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that lacks expression of estrogen, progesterone, and HER2 receptor targets for therapy. Polymeric nanoparticles help address the challenges in treating TNBC by enabling tailored and targeted drug delivery. Biocompatible polymeric nanoparticles leverage enhanced tumor permeability for site-specific accumulation and ligand-mediated active targeting to boost specificity. Controlled, sustained intratumorally release of encapsulated chemotherapies, such as paclitaxel and curcumin, improves antitumor efficacy as demonstrated through preclinical TNBC models. However, the practical application of these nanomedicines still has room for improvement. Advancing personalized nanoparticle platforms that align treatments to TNBC's expanding molecular subtypes shows promise. Expanding the polymer range through novel copolymers or drug conjugates may improve tumor penetration, stability, and drug encapsulation. Incorporating gene therapies, imaging agents, or triggering stimuli responsiveness into polymeric nanoparticles can also overcome innate and acquired drug resistance in TNBC while monitoring outcomes. This article reviews the different types of nanoparticles used to treat TNBC and the different mechanisms of nanoparticles that can deliver drugs to tumor cells. Collaboration across different disciplines aimed at developing combination therapies, immuno-oncology, tumor-targeting ligands, and translating preclinical safety/efficacy via scalable manufacturing practices is essential. Well-designed polymeric nanoparticles offer immense potential for patient-centric TNBC treatment, but continued optimization across bench to bedside efforts is critical for clinical realization and transforming patient outcomes.

The role of interleukin-2 in graft-versus-host disease pathogenesis, prevention and therapy.

Graft-versus-host disease (GVHD) is a significant complication following allogeneic hematopoietic cell transplantation (allo-HCT), posing substantial risks to patient survival. In the late follow-up phase of transplanted patients, GVHD is also a major cause of morbidity and disability, mostly due to low response to first-line steroids and the lack of effective standard therapies in the second line. This review provides a description of GVHD pathogenesis, with a focus on the central role of Interleukin-2 (IL-2). IL-2 is one of the critical mediators in the complex pathogenesis of GVHD, contributing to the intricate balance between regulatory T cells (Tregs) and effector T cells (Teffs). Due to this pivotal role, several studies investigate the potential of IL-2 as a therapeutic option for GVHD management. We discuss the outcomes of low-dose IL-2 therapies and their impact on Treg proliferation and steroid dependency reduction. Additionally, the effects of combining IL-2 with other treatments, such as extracorporeal photopheresis (ECP) and Treg-enriched lymphocyte infusions, are highlighted. Novel approaches, including modified IL-2 complexes and IL-2 receptor blockade, are explored for their potential in selectively enhancing Treg function and limiting Teff activation. The evolving understanding of IL-2's pivotal role in immune regulation presents promising prospects for applying treatment and prevention strategies for GVHD.

Targeting Bruton's tyrosine kinase (BTK) as a signaling pathway in immune-mediated diseases: from molecular mechanisms to leading treatments.

Bruton's tyrosine kinase (BTK), a nonreceptor tyrosine kinase, plays a remarkable role in the transmission and amplification of extracellular signals to intracellular signaling pathways. Various types of cells use the BTK pathway to communicate, including hematopoietic cells particularly B cells and T cells. The BTK pathway plays a role in controlling the proliferation, survival, and functions of B cells as well as other myeloid cells. First, second, and third-generation BTK inhibitors are currently being evaluated for the treatment of immune-mediated diseases in addition to B cell malignancies. In this article, the available evidence on the action mechanisms of BTK inhibitors is reviewed. Then, the most recent data obtained from preclinical studies and ongoing clinical trials for the treatment of autoimmune diseases, such as pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, systemic lupus erythematosus, Sjögren's disease, rheumatoid arthritis, systemic sclerosis, multiple sclerosis, myasthenia gravis, and inflammatory diseases such as psoriasis, chronic spontaneous urticaria, atopic dermatitis, and asthma are discussed. In addition, adverse effects and complications associated with BTK inhibitors as well as factors predisposing patients to BTK inhibitors complications are discussed.

An overview of early genetic predictors of IgA deficiency.

INTRODUCTION: Inborn errors of immunity (IEIs) refer to a heterogeneous category of diseases with defects in the number and/or function of components of the immune system. Immunoglobulin A (IgA) deficiency is the most prevalent IEI characterized by low serum level of IgA and normal serum levels of IgG and/or IgM. Most of the individuals with IgA deficiency are asymptomatic and are only identified through routine laboratory tests. Others may experience a wide range of clinical features including mucosal infections, allergies, and malignancies as the most important features. IgA deficiency is a multi-complex disease, and the exact pathogenesis of it is still unknown. AREAS COVERED: This review compiles recent research on genetic and epigenetic factors that may contribute to the development of IgA deficiency. These factors include defects in B-cell development, IgA class switch recombination, synthesis, secretion, and the long-term survival of IgA switched memory B cells and plasma cells. EXPERT OPINION: A better and more comprehensive understanding of the cellular pathways involved in IgA deficiency could lead to personalized surveillance and potentially curative strategies for affected patients, especially those with severe symptoms.

Endosomal Toll-Like Receptors intermediate negative impacts of viral diseases, autoimmune diseases, and inflammatory immune responses on the cardiovascular system.

INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of morbidity globally, with chronic inflammation as a key modifiable risk factor. Toll-like receptors (TLRs), pivotal components of the innate immune system, including TLR-3, -7, -8, and -9 within endosomes, trigger intracellular cascades, leading to inflammatory cytokine production by various cell types, contributing to systemic inflammation and atherosclerosis. Recent research highlights the role of endosomal TLRs in recognizing self-derived nucleic acids during sterile inflammation, implicated in autoimmune conditions like myocarditis. AREAS COVERED: This review explores the impact of endosomal TLRs on viral infections, autoimmunity, and inflammatory responses, shedding light on their intricate involvement in cardiovascular health and disease by examining literature on TLR-mediated mechanisms and their roles in CVD pathophysiology. EXPERT OPINION: Removal of endosomal TLRs mitigates myocardial damage and immune reactions, applicable in myocardial injury. Targeting TLRs with agonists enhances innate immunity against fatal viruses, lowering viral loads and mortality. Prophylactic TLR agonist administration upregulates TLRs, protecting against fatal viruses and improving survival. TLRs play a complex role in CVDs like atherosclerosis and myocarditis, with therapeutic potential in modulating TLR reactions for cardiovascular health.

Mental Healthcare in Pediatrics During the COVID-19 Pandemic: A Call for International Public Health Action.

Public health measures associated with coronavirus disease 2019 (COVID-19), such as lockdowns and quarantine of suspected cases, can negatively affect children's mental health status. Although the current crisis provides personal growth and family cohesion opportunities, pitfalls appear to outweigh the benefits. The magnitude and quality of its impact on children depend on several factors, including anxiety, lack of social contact, and a reduced opportunity for stress regulation, along with an increased risk for parental mental health issues, child maltreatment, and domestic violence. Children with special needs and social disadvantages like trauma experiences, disabilities, pre-existing mental illness, e.g., autism spectrum disorders and hyperactivity, and low socioeconomic status, may be at higher risk in this context. Here, the potentials social support can provide for pediatrics, both healthy children and children with special needs, are reviewed after an overview of quarantine's adverse effects on this special population during a pandemic. The most common psychological issues associated with the COVID-19 pandemic are sleep disorders, mood swings, depression, anxiety, decreased attention, stress, irritability, anger, and fear. Moreover, the impact of COVID-19 on children's physical health includes weight gain, reduced physical activity, immune dysregulation, and cardiometabolic disorders. All support systems, involving parents, teachers/school counselors, pediatricians, mental healthcare workers, and Health and Art (HEART) groups, need to enter the scene and make their share of children's mental health care.

The Role of Alpha-Synuclein in Neurodevelopmental Diseases.

Neurodevelopmental disorders are a group of diseases with cognitive, motor, and emotional development deficits. Alpha-synuclein (α-syn) is a synaptic protein involved in transmission and neurodevelopment. This protein was previously shown to be associated with several disorders, including Parkinson's disease. Furthermore, a close link between neurodevelopmental disorders and Parkinson's has also been found. Changes in synaptic function have been noticed in neurodevelopmental disorders, including autism spectrum disorder. Impaired neurogenesis and related cognitive problems have been associated with altered expression of α-syn. Various studies reported α-syn in different body fluids and tissues such as blood and serum. Alpha-synuclein can help in better understanding the pathogenesis of neurodevelopmental diseases and facilitating their early diagnosis. This review aims to go over the recent advances in the role of α-syn in the pathophysiology of neurodevelopmental disorders, including autism spectrum disorder, attention deficit hyperactivity disorder, and motor and social impairment, and its value as a diagnostic biomarker.

Immune landscape of hepatocellular carcinoma: From dysregulation of the immune responses to the potential immunotherapies.

Hepatocellular carcinoma (HCC) presents a considerable global health burden due to its late diagnosis and high morbidity. The liver's specific anatomical and physiological features expose it to various antigens, requiring precise immune regulation. To the best of our knowledge, this is the first time that a comprehensive overview of the interactions between the immune system and gut microbiota in the development of HCC, as well as the relevant therapeutic approaches are discussed. Dysregulation of immune compartments within the liver microenvironment drives HCC pathogenesis, characterized by elevated regulatory cells such as regulatory T cells (Tregs), myeloid-derived suppressor cells, and M2 macrophages as well as suppressive molecules, alongside reduced number of effector cells like T cells, natural killer cells, and M1 macrophages. Dysbiosis of gut microbiota also contributes to HCC by disrupting intestinal barrier integrity and triggering overactivated immune responses. Immunotherapy approaches, particularly immune checkpoint inhibitors, have exhibited promise in HCC management, yet adoptive cell therapy and cancer vaccination research are in the early steps with relatively less favorable outcomes. Further understanding of immune dysregulation, gut microbiota involvement, and therapeutic combination strategies are essential for advancing precision immunotherapy in HCC.

Clinical, Immunological, and Genetic Features in Patients with NFKB1 and NFKB2 Mutations: a Systematic Review.

BACKGROUND: Inborn errors of immunity (IEIs) encompass various diseases with diverse clinical and immunological symptoms. Determining the genotype-phenotype of different variants in IEI entity precisely is challenging, as manifestations can be heterogeneous even in patients with the same mutated gene. OBJECTIVE: In the present study, we conducted a systematic review of patients recorded with NFKB1 and NFKB2 mutations, two of the most frequent monogenic IEIs. METHODS: The search for relevant literature was conducted in databases including Web of Science, PubMed, and Scopus. Information encompassing demographic, clinical, immunological, and genetic data was extracted from cases reported with mutations in NFKB1 and NFKB2. The comprehensive features of manifestations in patients were described, and a comparative analysis of primary characteristics was conducted between individuals with NFKB1 loss of function (LOF) and NFKB2 (p52-LOF/IκBδ-gain of function (GOF)) variants. RESULTS: A total of 397 patients were included in this study, 257 had NFKB1 mutations and 140 had NFKB2 mutations. There were 175 LOF cases in NFKB1 and 122 p52LOF/IκBδGOF cases in NFKB2 pivotal groups with confirmed functional implications. NFKB1LOF and p52LOF/IκBδGOF predominant cases (81.8% and 62.5% respectively) initially presented with a CVID-like phenotype. Patients with NFKB1LOF variants often experienced hematologic autoimmune disorders, whereas p52LOF/IκBδGOF patients were more susceptible to other autoimmune diseases. Viral infections were markedly higher in p52LOF/IκBδGOF cases compared to NFKB1LOF (P-value < 0.001). NFKB2 (p52LOF/IκBδGOF) patients exhibited a greater prevalence of ectodermal dysplasia and pituitary gland involvement than NFKB1LOF patients. Most NFKB1LOF and p52LOF/IκBδGOF cases showed low CD19 + B cells, with p52LOF/IκBδGOF having more cases of this type. Low memory B cells were more common in p52LOF/IκBδGOF patients. CONCLUSIONS: Patients with NFKB2 mutations, particularly p52LOF/IκBδGOF, are at higher risk of viral infections, pituitary gland involvement, and ectodermal dysplasia compared to patients with NFKB1LOF mutations. Genetic testing is essential to resolve the initial complexity and confusion surrounding clinical and immunological features. Emphasizing the significance of functional assays in determining the probability of correlations between mutations and immunological and clinical characteristics of patients is crucial.

Allergies and risk of head and neck cancer: a case-control study.

Although the relationship between allergies and cancer has been investigated extensively, the role of allergies in head and neck cancer (HNC) appears less consistent. It is unclear whether allergies can independently influence the risk of HNC in the presence of substantial environmental risk factors, including consumption of alcohol, betel quid, and cigarettes. This study aims to find this association. We examined the relationship between allergies and HNC risk in a hospital-based case-control study with 300 cases and 375 matched controls. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals, controlling for age, sex, tobacco smoking and opium usage history, alcohol consumption, and socioeconomic status. Our study showed a significant reduction in the risk of HNC associated with allergy symptoms after adjusting for confounders. The risk of HNC was greatly reduced among those with any type of allergy (OR 0.42, 95% CI 0.28, 0.65). The ORs were considerably reduced by 58-88% for different kinds of allergies. The risk of HNC reduction was higher in allergic women than in allergic men (71% vs. 49%). Allergies play an influential role in the risk of HNC development. Future studies investigating immune biomarkers, including cytokine profiles and genetic polymorphisms, are necessary to further delineate the relationship between allergies and HNC. Understanding the relationship between allergies and HNC may help to devise effective strategies to reduce and treat HNC.

Stem cell therapies for neurological disorders: current progress, challenges, and future perspectives.

Stem cell-based therapies have emerged as a promising approach for treating various neurological disorders by harnessing the regenerative potential of stem cells to restore damaged neural tissue and circuitry. This comprehensive review provides an in-depth analysis of the current state of stem cell applications in primary neurological conditions, including Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), stroke, spinal cord injury (SCI), and other related disorders. The review begins with a detailed introduction to stem cell biology, discussing the types, sources, and mechanisms of action of stem cells in neurological therapies. It then critically examines the preclinical evidence from animal models and early human trials investigating the safety, feasibility, and efficacy of different stem cell types, such as embryonic stem cells (ESCs), mesenchymal stem cells (MSCs), neural stem cells (NSCs), and induced pluripotent stem cells (iPSCs). While ESCs have been studied extensively in preclinical models, clinical trials have primarily focused on adult stem cells such as MSCs and NSCs, as well as iPSCs and their derivatives. We critically assess the current state of research for each cell type, highlighting their potential applications and limitations in different neurological conditions. The review synthesizes key findings from recent, high-quality studies for each neurological condition, discussing cell manufacturing, delivery methods, and therapeutic outcomes. While the potential of stem cells to replace lost neurons and directly reconstruct neural circuits is highlighted, the review emphasizes the critical role of paracrine and immunomodulatory mechanisms in mediating the therapeutic effects of stem cells in most neurological disorders. The article also explores the challenges and limitations associated with translating stem cell therapies into clinical practice, including issues related to cell sourcing, scalability, safety, and regulatory considerations. Furthermore, it discusses future directions and opportunities for advancing stem cell-based treatments, such as gene editing, biomaterials, personalized iPSC-derived therapies, and novel delivery strategies. The review concludes by emphasizing the transformative potential of stem cell therapies in revolutionizing the treatment of neurological disorders while acknowledging the need for rigorous clinical trials, standardized protocols, and multidisciplinary collaboration to realize their full therapeutic promise.

The multidisciplinary approach to diagnosing inborn errors of immunity: a comprehensive review of discipline-based manifestations.

INTRODUCTION: Congenital immunodeficiency is named primary immunodeficiency (PID), and more recently inborn errors of immunity (IEI). There are more than 485 conditions classified as IEI, with a wide spectrum of clinical and laboratory manifestations. AREAS COVERED: Regardless of the developing knowledge of IEI, many physicians do not think of IEI when approaching the patient's complaint, which leads to delayed diagnosis, misdiagnosis, serious infectious and noninfectious complications, permanent end-organ damage, and even death. Due to the various manifestations of IEI and the wide spectrum of associated conditions, patients refer to specialists in different disciplines of medicine and undergo - mainly symptomatic - treatments, and because IEI are not included in physicians' differential diagnosis, the main disease remains undiagnosed. EXPERT OPINION: A multidisciplinary approach may be a proper solution. Manifestations and the importance of a multidisciplinary approach in the diagnosis of main groups of IEI are discussed in this article.

Ferroptosis as a promising targeted therapy for triple negative breast cancer.

PURPOSE: Triple negative breast cancer (TNBC) is a challenging subtype characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. Standard treatment options are limited, and approximately 45% of patients develop distant metastasis. Ferroptosis, a regulated form of cell death triggered by iron-dependent lipid peroxidation and oxidative stress, has emerged as a potential targeted therapy for TNBC. METHODS: This study utilizes a multifaceted approach to investigate the induction of ferroptosis as a therapeutic strategy for TNBC. It explores metabolic alterations, redox imbalance, and oncogenic signaling pathways to understand their roles in inducing ferroptosis, characterized by lipid peroxidation, reactive oxygen species (ROS) generation, and altered cellular morphology. Critical pathways such as Xc-/GSH/GPX4, ACSL4/LPCAT3, and nuclear factor erythroid 2-related factor 2 (NRF2) are examined for their regulatory roles in ferroptosis and their potential dysregulation contributing to cancer cell survival and resistance. RESULTS: Inducing ferroptosis has been shown to inhibit tumor growth, enhance the efficacy of conventional therapies, and overcome drug resistance in TNBC. Lipophilic antioxidants, GPX4 inhibitors, and inhibitors of the Xc- system have been demonstrated to be potential ferroptosis inducers. Additionally, targeting the NRF2 pathway and exploring other ferroptosis regulators, such as ferroptosis suppressor protein 1 (FSP1), and the PERK-eIF2α-ATF4-CHOP pathway, may offer novel therapeutic avenues. CONCLUSION: Further research is needed to understand the mechanisms, optimize therapeutic strategies, and evaluate the safety and efficacy of ferroptosis-targeted therapies in TNBC treatment. Overall, targeting ferroptosis represents a promising approach to improving treatment outcomes and overcoming the challenges posed by TNBC.

The role of AMPK in pancreatic cancer: from carcinogenesis to treatment.

Pancreatic cancer has doubled over the previous two decades. Routine therapies are becoming incredibly resistant and failing to compensate for the burden caused by this aggressive neoplasm. As genetic susceptibility has always been a highlighted concern for this disease, identifying the molecular pathways involved in the survival and function of pancreatic cancer cells provides insight into its variant etiologies, one of which is the role of AMPK. This regulating factor of cell metabolism is crucial in the homeostasis and growth of the cell. Herein, we review the possible role of AMPK in pancreatic cancer while considering its leading effects on glycolysis and autophagy. Then, we assess the probable therapeutic agents that have resulted from the suggested pathways. Studying the underlying genetic changes in pancreatic cancer provides a chance to detect and treat patients suffering from advanced stages of the disease, and those who have given up their hope on conventional therapies can gain an opportunity to combat this cancer.

New insight into impact of humidity on direct air capture performance by SIFSIX-3-Cu MOF.

Removal of CO2 from air is one of the key human challenges in battling global warming. SIFSIX-3-Cu is a promising metal-organic framework (MOF) suggested for carbon capture even at low CO2 concentrations. However, the impact of humidity on its performance in direct air capture (DAC) is poorly understood. To evaluate the MOF performance for DAC application under humid conditions, we investigate the adsorption of H2O, CO2, and N2 using density functional theory (DFT), grand canonical Monte Carlo (GCMC), and molecular dynamics (MD) simulations. The simulation results show a higher tendency of SIFSIX-3-Cu towards H2O adsorption rather than CO2 (and N2). The results agree with the adsorption isotherms for the pure compounds from the Sips model. The extended Sips model shows 1.34 mmol g-1 CO2 adsorption at the atmospheric pressure and 298 K for the CO2/N2 mixture containing 400 ppm CO2, and low CO2 adsorption (less than 0.75 mmol g-1) at a low relative humidity (RH) of 20%. This finding highlights the efficiency of SIFSIX-3-Cu for DAC in dry air and the negative impact of humidity on the CO2 selective adsorption. Therefore, we suggest to consider the impairing of humidity effects when designing a SIFSIX-3-Cu-based CO2 separation process and removal of any water vapor before introduction of the air to SIFSIX-3-Cu.