Potential Mechanism and Perspectives of Mesenchymal Stem Cell Therapy for Ischemic Stroke: A Review.

Mesenchymal stem cells (MSCs), as a stem cell type with multiple differentiation potentials and immune regulatory abilities, have shown broad prospects in the treatment of ischemic stroke in recent years. The main characteristics of MSCs include their self-renewal ability, differentiation potential for different types of cells, and the ability to secrete various bioactive factors such as cytokines, chemokines, and growth factors, which play a key role in tissue repair and regeneration. In the treatment of ischemic stroke, MSCs exert therapeutic effects through various mechanisms, including promoting vascular regeneration of damaged brain tissue, reducing inflammatory responses, and protecting neurons from damage caused by apoptosis. Research have shown that MSCs can promote the repair of ischemic areas by releasing neurotrophic factors and angiogenic factors, while inhibiting immune responses triggered by ischemia, thereby improving neurological function. With the in-depth study of its biological mechanism, MSCs have gradually shown good safety and effectiveness in clinical applications. Therefore, fully exploring and utilizing the potential of MSCs in the treatment of ischemic stroke may provide new ideas and solutions for future neural repair and regenerative medicine.

Assessment of the feed additive consisting of Levilactobacillus brevis DSM 16680 for all animal species for the renewal of its authorisation (Microferm Ltd.).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the assessment of the application of renewal of Levilactobacillus brevis DSM 16680 as a technological feed additive (functional group: silage additives) for all animal species. The applicant has provided evidence that the additive currently on the market complies with the existing terms of the authorisation. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the additive remains safe for all animal species, consumers and the environment. Regarding user safety, the additive should be considered as an eye irritant and a skin and respiratory sensitiser. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Decoding Clonal Hematopoiesis: Emerging Themes and Novel Mechanistic Insights.

Clonal hematopoiesis (CH), the relative expansion of mutant clones, is derived from hematopoietic stem cells (HSCs) with acquired somatic or cytogenetic alterations that improve cellular fitness. Individuals with CH have a higher risk for hematological and non-hematological diseases, such as cardiovascular disease, and have an overall higher mortality rate. Originally thought to be restricted to a small fraction of elderly people, recent advances in single-cell sequencing and bioinformatics have revealed that CH with multiple expanded mutant clones is universal in the elderly population. Just a few years ago, phylogenetic reconstruction across the human lifespan and novel sensitive sequencing techniques showed that CH can start earlier in life, decades before it was thought possible. These studies also suggest that environmental factors acting through aberrant inflammation might be a common theme promoting clonal expansion and disease progression. However, numerous aspects of this phenomenon remain to be elucidated and the precise mechanisms, context-specific drivers, and pathways of clonal expansion remain to be established. Here, we review our current understanding of the cellular mechanisms driving CH and specifically focus on how pro-inflammatory factors affect normal and mutant HSC fates to promote clonal selection.

Cxcl10 and Cxcr3 regulate self-renewal and differentiation of hematopoietic stem cells.

BACKGROUND: The function of hematopoietic stem cells (HSC) is regulated by HSC internal signaling pathways and their microenvironment. Chemokines and chemokine ligands play important roles in the regulation of HSC function. Yet, their functions in HSC are not fully understood. METHODS: We established Cxcr3 and Cxcl10 knockout mouse models (Cxcr3-/- and Cxcl10-/-) to analyze the roles of Cxcr3 or Cxcl10 in regulating HSC function. The cell cycle distribution of LT-HSC was assessed via flow cytometry. Cxcr3-/- and Cxcl10-/- stem/progenitor cells showed reduced self-renewal capacity as measured in serial transplantation assays. To study the effects of Cxcr3 or Cxcl10 deficient bone marrow microenvironment, we transplanted CD45.1 donor cells into Cxcr3-/-or Cxcl10-/- recipient mice (CD45.2) and examined donor-contributed hematopoiesis. RESULTS: Deficiency of Cxcl10 and its receptor Cxcr3 led to decreased BM cellularity in mice, with a significantly increased proportion of LT-HSC. Cxcl10-/- stem/progenitor cells showed reduced self-renewal capacity in the secondary transplantation assay. Notably, Cxcl10-/- donor-derived cells preferentially differentiated into B lymphocytes, with skewed myeloid differentiation ability. Meanwhile, Cxcr3-deficient HSCs demonstrated a reconstitution disadvantage in secondary transplantation, but the lineage bias was not significant. Interestingly, the absence of Cxcl10 or Cxcr3 in bone marrow microenvironment did not affect HSC function. CONCLUSIONS: The Cxcl10 and Cxcr3 regulate the function of HSC, including self-renewal and differentiation, adding to the understanding of the roles of chemokines in the regulation of HSC function.

Establishment of porcine embryonic stem cells in simplified serum free media and feeder free expansion.

BACKGROUND: The establishment of stable porcine embryonic stem cells (pESCs) can contribute to basic and biomedical research, including comparative developmental biology, as well as assessing the safety of stem cell-based therapies. Despite these advantages, most pESCs obtained from in vitro blastocysts require complex media and feeder layers, making routine use, genetic modification, and differentiation into specific cell types difficult. We aimed to establish pESCs with a single cell-passage ability, high proliferative potency, and stable in long-term culture from in vitro-derived blastocysts using a simplified serum-free medium. METHODS: We evaluated the establishment efficiency of pESCs from in vitro blastocysts using various basal media (DMEM/F10 (1:1), DMEM/F12, and a-MEM) and factors (FGF2, IWR-1, CHIR99021, and WH-4-023). The pluripotency and self-renewal capacity of the established pESCs were analyzed under feeder or feeder-free conditions. Ultimately, we developed a simplified culture medium (FIW) composed of FGF2, IWR-1, and WH-4-023 under serum-free conditions. RESULTS: The pESC-FIW lines were capable of single-cell passaging with short cell doubling times and expressed the pluripotency markers POU5F1, SOX2, and NANOG, as well as cell surface markers SSEA1, SSEA4, and TRA-1-60. pESC-FIW showed a stable proliferation rate and normal karyotype, even after 50 passages. Transcriptome analysis revealed that pESC-FIW were similar to reported pESC maintained in complex media and showed gastrulating epiblast cell characteristics. pESC-FIW were maintained for multiple passages under feeder-free conditions on fibronectin-coated plates using mTeSR™, a commercial medium used for feeder-free culture, exhibiting characteristics similar to those observed under feeder conditions. CONCLUSIONS: These results indicated that inhibition of WNT and SRC was sufficient to establish pESCs capable of single-cell passaging and feeder-free expansion under serum-free conditions. The easy maintenance of pESCs facilitates their application in gene editing technology for agriculture and biomedicine, as well as lineage commitment studies.

Assessment of the feed additive consisting of sodium propionate for all terrestrial animal species for the renewal of its authorisation (BASF SE).

Sodium propionate is authorised containing at least 98.5% of sodium propionate. The applicants requested for the renewal of the authorisation of sodium propionate when used as a feed additive for all terrestrial animal species. The applicant has provided evidence that the additive in the market complies with the conditions of the authorisation. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP Panel) confirms that the use of sodium propionate under the current authorised conditions of use is safe for the target species, the consumers and the environment. Considering the user safety, the additive is corrosive to skin, eyes and respiratory tract, but is not a skin sensitiser. There is no need for assessing the efficacy of the additive in the context of the renewal of the authorisation.

Autophagy accompanying the developmental process of male germline stem cells.

Germline stem cells are a crucial type of stem cell that can stably pass on genetic information to the next generation, providing the necessary foundation for the reproduction and survival of organisms. Male mammalian germline stem cells are unique cell types that include primordial germ cells and spermatogonial stem cells. They can differentiate into germ cells, such as sperm and eggs, thereby facilitating offspring reproduction. In addition, they continuously generate stem cells through self-renewal mechanisms to support the normal function of the reproductive system. Autophagy involves the use of lysosomes to degrade proteins and organelles that are regulated by relevant genes. This process plays an important role in maintaining the homeostasis of germline stem cells and the synthesis, degradation, and recycling of germline stem cell products. Recently, the developmental regulatory mechanism of germline stem cells has been further elucidated, and autophagy has been shown to be involved in the regulation of self-renewal and differentiation of germline stem cells. In this review, we introduce autophagy accompanying the development of germline stem cells, focusing on the autophagy process accompanying the development of male spermatogonial stem cells and the roles of related genes and proteins. We also briefly outline the effects of autophagy dysfunction on germline stem cells and reproduction.

Therapeutic potential of tLyp-1-EV-shCTCF in inhibiting liver cancer stem cell self-renewal and immune escape via SALL3 modulation in hepatocellular carcinoma.

The progression of hepatocellular carcinoma (HCC) is influenced by disrupted metabolic processes, presenting challenges in prognostic outcomes. Hepatocellular carcinoma (HCC), a leading cause of cancer-related mortality, is closely associated with metabolic reprogramming and stem cell-like properties in liver cancer stem cells (LCSCs). This study explored the potential molecular mechanisms by which tLyP-1-modified extracellular vesicles (EVs) delivering CTCF shRNA (tLyp-1-EV-shCTCF) regulate mitochondrial DNA methylation-induced glycolytic metabolic reprogramming and LCSC self-renewal. Through a series of methods, including Western blot, nanoparticle tracking analysis, and immunofluorescence, we demonstrated the successful delivery and internalization of tLyp-1-EV in HCC cells. Our results identified SALL3 as a critical factor underexpressed in HCC and LCSCs, while CTCF was overexpressed. Overexpression of SALL3 inhibited LCSC self-renewal and immune evasion by blocking the CTCF-DNMT3A interaction, thus repressing DNMT3A methyltransferase activity and subsequent mitochondrial DNA methylation-mediated glycolytic metabolic reprogramming. In vivo experiments further supported these findings, showing that tLyp-1-EV-shCTCF treatment significantly reduced tumor growth by upregulating SALL3 expression, thereby inhibiting glycolytic metabolic reprogramming and enhancing the immune response against HCC cells. This study provides novel insights into the role of SALL3 and mitochondrial DNA methylation in HCC progression, offering potential therapeutic targets for combating HCC and its stem cell-like properties.

Propagating pluripotency - The conundrum of self-renewal.

The discovery of mouse embryonic stem cells in 1981 transformed research in mammalian developmental biology and functional genomics. The subsequent generation of human pluripotent stem cells (PSCs) and the development of molecular reprogramming have opened unheralded avenues for drug discovery and cell replacement therapy. Here, I review the history of PSCs from the perspective that long-term self-renewal is a product of the in vitro signaling environment, rather than an intrinsic feature of embryos. I discuss the relationship between pluripotent states captured in vitro to stages of epiblast in the embryo and suggest key considerations for evaluation of PSCs. A remaining fundamental challenge is to determine whether naïve pluripotency can be propagated from the broad range of mammals by exploiting common principles in gene regulatory architecture.

Psilocybin Facilitates Fear Extinction: Importance of Dose, Context, and Serotonin Receptors.

A variety of classic psychedelics and MDMA have been shown to enhance fear extinction in rodent models. This has translational significance because a standard treatment for post-traumatic stress disorder (PTSD) is prolonged exposure therapy. However, few studies have investigated psilocybin's potential effect on fear learning paradigms. More specifically, the extents to which dose, timing of administration, and serotonin receptors may influence psilocybin's effect on fear extinction are not understood. In this study, we used a delay fear conditioning paradigm to determine the effects of psilocybin on fear extinction, extinction retention, and fear renewal in male and female mice. Psilocybin robustly enhances fear extinction when given acutely prior to testing for all doses tested. Psilocybin also exerts long-term effects to elevate extinction retention and suppress fear renewal in a novel context, although these changes were sensitive to dose. Analysis of sex differences showed that females may respond to a narrower range of doses than males. Administration of psilocybin prior to fear learning or immediately after extinction yielded no change in behavior, indicating that concurrent extinction experience is necessary for the drug's effects. Cotreatment with a 5-HT2A receptor antagonist blocked psilocybin's effects for extinction, extinction retention, and fear renewal, whereas 5-HT1A receptor antagonism attenuated only the effect on fear renewal. Collectively, these results highlight dose, context, and serotonin receptors as crucial factors in psilocybin's ability to facilitate fear extinction. The study provides preclinical evidence to support investigating psilocybin as a pharmacological adjunct for extinction-based therapy for PTSD.

Signalling unpaired unconditional stimuli during extinction does not impair their effect to reduce renewal of conditional fear.

Presenting unpaired unconditional stimuli (US) during extinction training reduces the renewal of conditional fear due to context change and slows re-acquisition. The present study investigated whether this reduced return of fear is mediated by Pavlovian inhibitory conditioning to the conditional stimulus paired with the US during acquisition (CS+) that is acquired when this stimulus is presented without the US in an excitatory extinction context. Using an ABA renewal paradigm that trained extinction in a context different from acquisition and renewal test, participants either received no USs (Standard), five unsignalled US presentations (Unsignalled) or five presentations of the US preceded by a novel, third CS (Signalled) during extinction training. Extinction was followed by tests for renewal and re-acquisition. Replicating previous results, renewal of electrodermal conditional responses was observed in group Standard, but not in group Unsignalled. Signalling the additional USs, and thus reducing context conditioning and the potential for inhibitory conditioning, did not reduce their effect in that renewal was absent in group Signalled. These results are inconsistent with an inhibitory conditioning account of the effects of unpaired US presentations during extinction. A trial sequence learning account or an arousal account may explain the effects of unpaired presentations of the US during extinction.

The Formation and Renewal of Photoreceptor Outer Segments.

The visual system is essential for humans to perceive the environment. In the retina, rod and cone photoreceptor neurons are the initial sites where vision forms. The apical region of both cone and rod photoreceptors contains a light-sensing organelle known as the outer segment (OS), which houses tens of thousands of light-sensitive opsins. The OSs of photoreceptors are not static; they require rhythmic renewal to maintain normal physiological functions. Disruptions in OS renewal can lead to various genetic disorders, such as retinitis pigmentosa (RP). Understanding the patterns and molecular mechanisms of photoreceptor OS renewal remains one of the most intriguing topics in visual biology. This review aims to elucidate the structure of photoreceptor OSs, the molecular mechanisms underlying photoreceptor OS renewal, and the retinal diseases resulting from defects in this renewal process. Additionally, we will explore retinal diseases related to photoreceptor OS renewal and potential therapeutic strategies, concluding with a discussion on future research directions for OS renewal.

A novel study on CXXC5: unraveling its regulatory mechanisms in hematopoietic stem cell biology through proteomics and gene editing.

BACKGROUND: This study investigates the role of CXXC5 in the self-renewal and differentiation of hematopoietic stem cells (HSCs) within the bone marrow microenvironment, utilizing advanced methodologies such as single-cell RNA sequencing (scRNA-seq), CRISPR-Cas9, and proteomic analysis. METHODS: We employed flow cytometry to isolate HSCs from bone marrow samples, followed by scRNA-seq analysis using the 10x Genomics platform to examine cell clustering and CXXC5 expression patterns. CRISPR-Cas9 and lentiviral vectors facilitated the knockout and overexpression of CXXC5 in HSCs. The impact on HSCs was assessed through qRT-PCR, Western blot, CCK-8, CFU, and LTC-IC assays, alongside flow cytometry to measure apoptosis and cell proportions. A mouse model was also used to evaluate the effects of CXXC5 manipulation on HSC engraftment and survival rates. RESULTS: Our findings highlight the diversity of cell clustering and the significant role of CXXC5 in HSC regulation. Knockout experiments showed reduced proliferation and accelerated differentiation, whereas overexpression led to enhanced proliferation and delayed differentiation. Proteomic analysis identified key biological processes influenced by CXXC5, including cell proliferation, differentiation, and apoptosis. In vivo results demonstrated that CXXC5 silencing impaired HSC engraftment in a bone marrow transplantation model. CONCLUSION: CXXC5 is crucial for the regulation of HSC self-renewal and differentiation in the bone marrow microenvironment. Its manipulation presents a novel approach for enhancing HSC function and provides a potential therapeutic target for hematological diseases.

Unraveling the role of long non-coding RNAs in therapeutic resistance in acute myeloid leukemia: New prospects & challenges.

Acute Myeloid Leukemia (AML) is a fatal hematological disease characterized by the unchecked proliferation of immature myeloid blasts in different tissues developed by various mutations in hematopoiesis. Despite intense chemotherapeutic regimens, patients often experience poor outcomes, leading to substandard remission rates. In recent years, long non-coding RNAs (lncRNAs) have increasingly become important prognostic and therapeutic hotspots, due to their contributions to dysregulating many functional epigenetic, transcriptional, and post-translational mechanisms leading to alterations in cell expressions, resulting in increased chemoresistance and reduced apoptosis in leukemic cells. Through this review, I highlight and discuss the latest advances in understanding the major mechanisms through which lncRNAs confer therapy resistance in AML. In addition, I also provide perspective on the current strategies to target lncRNA expressions. A better knowledge of the critical role that lncRNAs play in controlling treatment outcomes in AML will help improve existing medications and devise new ones.

A second chance for first impressions: evidence for altered impression updating in borderline personality disorder.

BACKGROUND: Individuals with borderline personality disorder (BPD) frequently alter between idealizing and devaluing other persons, which has been linked to an increased tendency to update self-relevant beliefs and impressions. We hypothesized that increased impression updating could stem from reduced attitude contextualization, i.e., a process in which impression-disconfirming information is linked to contextual cues. METHODS: Individuals diagnosed with BPD and controls (recruited online, with unknown diagnostic status) completed an impression formation paradigm. They first learned about the positive or negative behaviors of others in one Context A (e.g., Person 1 is helpful), followed by learning about behaviors of the opposite valence in a second Context B (Person 1 is rude). We also manipulated between participants whether the observed behaviors were directed toward the study participants (self-relevant) or, more generally, at other people (other-relevant). The contexts were marked by differently-colored backgrounds (e.g., yellow vs. blue), to avoid influences of prior knowledge or experiences. After exposure to information in both contexts, participants rated their impressions of the persons in Context A, Context B, and, crucially, a previously unknown Context C (white background). We examined whether the initial or an updated impression (re-)emerged in Context C. RESULTS: Initial impressions remained stable and dominated the ratings of controls across contexts A, B, and C for both self-relevant and other-relevant behaviors, consistent with contextualizing impression-disconfirming information. As expected, however, individuals with BPD only showed updated impression ratings in Context C for self-relevant behaviors, consistent with the assumed reduced tendency to contextualize impression-disconfirming self-relevant information. Further exploratory analyses suggest that more severe BPD symptoms predicted more pronounced impression updating in the self-relevant condition. CONCLUSIONS: The findings help to illuminate the mechanisms underlying interpersonal problems in individuals with BPD. People with BPD are not just more inclined to discard positive first impressions but to re-evaluate disliked others when they behave positively, contributing to the volatility of interactions with others. Contextualization has known and modifiable antecedents, and the study may thus provide potential targets for therapeutic intervention. Future studies will need to replicate the findings with specified controls.

Changes in the tissue elements of the gastric mucosa interacting with different strains of Helicobacter pylori, taking into consideration the patient's genotype.

The present study aimed to investigate the peculiarities of adaptation of tissue elements of the gastric mucosa during interaction with Helicobacter pylori, as determined by genetic characteristics of the bacterium and the host. Venous blood and biopsy samples of the mucosa of the antrum and body of the stomach from young patients (18 to 25 years old) were examined. The condition of the gastric mucosa was assessed using stained histological preparations. Venous blood was collected from the patients to ascertain the polymorphisms of the IL-lß and IL-IRN genes. The most pronounced changes were observed in the parameters of reparative regeneration of epithelial differentiation during colonization of the gastric mucosa by H. pylori strains carrying the CagA(+) and BabA2(+) genes. These included an increase in proliferation and apoptosis rates and alterations in epithelial differentiation markers characterized by elevated production of Shh and MUC5AC, as well as a reduction in the production of the protective mucin MUC6 by isthmus gland cells. The presence of the vacAs1 and vacAs2 genes of H. pylori results in a high level of apoptosis in epithelial cells without accelerating proliferation. It was found that after eradication, patients with preserved cellular infiltrates in their gastric mucosa plates were carriers of mainly the IL-1ß*T/IL-1RN*2R haplotypes after 12 months.

Emergence of the reproduction matrix in epidemic forecasting.

During the recent COVID-19 pandemic, the instantaneous reproduction number, R(t), has surged as a widely used measure to target public health interventions aiming at curbing the infection rate. In analogy with the basic reproduction number that arises from the linear stability analysis, R(t) is typically interpreted as a threshold parameter that separates exponential growth (R(t) > 1) from exponential decay (R(t) < 1). In real epidemics, however, the finite number of susceptibles, the stratification of the population (e.g. by age or vaccination state), and heterogeneous mixing lead to more complex epidemic courses. In the context of the multidimensional renewal equation, we generalize the scalar R(t) to a reproduction matrix, [Formula: see text], which details the epidemic state of the stratified population, and offers a concise epidemic forecasting scheme. First, the reproduction matrix is computed from the available incidence data (subject to some a priori assumptions), then it is projected into the future by a transfer functional to predict the epidemic course. We demonstrate that this simple scheme allows realistic and accurate epidemic trajectories both in synthetic test cases and with reported incidence data from the COVID-19 pandemic. Accounting for the full heterogeneity and nonlinearity of the infection process, the reproduction matrix improves the prediction of the infection peak. In contrast, the scalar reproduction number overestimates the possibility of sustaining the initial infection rate and leads to an overshoot in the incidence peak. Besides its simplicity, the devised forecasting scheme offers rich flexibility to be generalized to time-dependent mitigation measures, contact rate, infectivity and vaccine protection.

The impact of the left inferior frontal gyrus on fear extinction: A transcranial direct current stimulation study.

INTRODUCTION: Fear extinction is a fundamental component of exposure-based therapies for anxiety-related disorders. The renewal of fear in a different context after extinction highlights the importance of contextual factors. In this study, we aimed to investigate the causal role of the left inferior frontal gyrus (LiFG) in the context-dependency of fear extinction learning via administration of transcranial direct current stimulation (tDCS) over this area. METHODS: 180 healthy subjects were assigned to 9 groups: 3 tDCS conditions (anodal, cathodal, and sham) × 3 context combinations (AAA, ABA, and ABB). The fear conditioning/extinction task was conducted over three consecutive days: acquisition, extinction learning, and extinction recall. tDCS (2 mA, 10min) was administered during the extinction learning phase over the LiFG via a 4-electrode montage. Skin conductance response (SCR) data and self-report assessments were collected. RESULTS: During the extinction learning phase, groups with excitability-enhancing anodal tDCS showed a significantly higher fear response to the threat cues compared to cathodal and sham stimulation conditions, irrespective of contextual factors. This effect was stable until the extinction recall phase. Additionally, excitability-reducing cathodal tDCS caused a significant decrease of the response difference between the threat and safety cues during the extinction recall phase. The self-report assessments showed no significant differences between the conditions throughout the experiment. CONCLUSION: Independent of the context, excitability enhancement of the LiFG did impair fear extinction, and led to preservation of fear memory. In contrast, excitability reduction of this area enhanced fear extinction retention. These findings imply that the LiFG plays a role in the fear extinction network, which seems to be however context-independent.

Register-based study on prescription renewal without the prescriber meeting the patient.

Renewing prescriptions is important for the continuity of pharmacotherapy. However, renewing without the prescriber meeting the patient might lead to insufficient pharmacotherapy monitoring. This study investigated the prevalence of renewed prescriptions, prescriptions renewed without the prescriber meeting the patient and the factors associated with renewals made without meeting the patient. This register-based study employed data on electronic prescriptions and health care contacts from Finnish registers. Prescriptions were classified as renewed if there was a renewal request or a previous prescription for the same ATC code. Prescriptions were considered as being renewed without meeting the patient if there was no patient contact on the renewal date. Descriptive and logistic generalized estimating equation analyses were conducted. The random sample of prescriptions (10%) from the year 2019 amounted to 2 804 048. Of these, 41.9% were original, 35.4% were renewals without meeting the patient and 22.7% were renewed with meeting the patient. Characteristics such as male sex, age 35-54 years, prescription for cardiovascular system preparations and the prescription being renewed during the summer (June-August) were associated with renewals made without meeting the patient. Further research is needed on the implementation of pharmacotherapy monitoring in the case of renewals without the prescriber meeting the patient.

Balancing the maintenance strategies to making decisions using Monte Carlo method.

This study aims to develop comprehensive maintenance strategies tailored to enhance the dependability, performance, and lifespan of critical assets within industrial and organizational settings. By integrating proactive, preventive, predictive, and corrective maintenance tactics, our strategy seeks to minimize downtime, reduce costs, and optimize asset performance. Drawing from extensive case studies across various industrial sectors, our research utilizes robust data analysis to inform strategy development. We employ mathematical cost models and simulations using the Monte Carlo Method in MATLAB to evaluate the performance and robustness of different maintenance strategies, including time-based and condition-based approaches. Our findings demonstrate that a holistic maintenance approach significantly improves operational efficiency and asset longevity. Specifically, our analysis reveals that integrated maintenance strategies lead to reduced downtime, lower maintenance costs, and enhanced asset reliability. Policy implications of our research suggest that organizations should adopt integrated maintenance strategies to enhance asset reliability and performance, ultimately achieving sustained operational excellence. By emphasizing the importance of proactive maintenance measures alongside traditional reactive approaches, organizations can effectively manage their critical assets, leading to improved operational outcomes and long-term success.-Integration of proactive, preventive, predictive, and corrective maintenance tactics-Evaluation of performance and robustness through mathematical cost models-Application of the Monte Carlo Method in MATLAB for comparative analysis.