Unveiling the potential of FOXO3 in lung cancer: From molecular insights to therapeutic prospects.

Lung cancer poses a significant challenge regarding molecular heterogeneity, as it encompasses a wide range of molecular alterations and cancer-related pathways. Recent discoveries made it feasible to thoroughly investigate the molecular mechanisms underlying lung cancer, giving rise to the possibility of novel therapeutic strategies relying on molecularly targeted drugs. In this context, forkhead box O3 (FOXO3), a member of forkhead transcription factors, has emerged as a crucial protein commonly dysregulated in cancer cells. The regulation of the FOXO3 in reacting to external stimuli plays a key role in maintaining cellular homeostasis as a component of the molecular machinery that determines whether cells will survive or dies. Indeed, various extrinsic cues regulate FOXO3, affecting its subcellular location and transcriptional activity. These regulations are mediated by diverse signaling pathways, non-coding RNAs (ncRNAs), and protein interactions that eventually drive post-transcriptional modification of FOXO3. Nevertheless, while it is no doubt that FOXO3 is implicated in numerous aspects of lung cancer, it is unclear whether they act as tumor suppressors, promotors, or both based on the situation. However, FOXO3 serves as an intriguing possible target in lung cancer therapeutics while widely used anti-cancer chemo drugs can regulate it. In this review, we describe a summary of recent findings on molecular mechanisms of FOXO3 to clarify that targeting its activity might hold promise in lung cancer treatment.

Automated diagnosis of autism with artificial intelligence: State of the art.

Autism spectrum disorder (ASD) represents a panel of conditions that begin during the developmental period and result in impairments of personal, social, academic, or occupational functioning. Early diagnosis is directly related to a better prognosis. Unfortunately, the diagnosis of ASD requires a long and exhausting subjective process. We aimed to review the state of the art for automated autism diagnosis and recognition in this research. In February 2022, we searched multiple databases and sources of gray literature for eligible studies. We used an adapted version of the QUADAS-2 tool to assess the risk of bias in the studies. A brief report of the methods and results of each study is presented. Data were synthesized for each modality separately using the Split Component Synthesis (SCS) method. We assessed heterogeneity using the I 2 statistics and evaluated publication bias using trim and fill tests combined with ln DOR. Confidence in cumulative evidence was assessed using the GRADE approach for diagnostic studies. We included 344 studies from 186,020 participants (51,129 are estimated to be unique) for nine different modalities in this review, from which 232 reported sufficient data for meta-analysis. The area under the curve was in the range of 0.71-0.90 for all the modalities. The studies on EEG data provided the best accuracy, with the area under the curve ranging between 0.85 and 0.93. We found that the literature is rife with bias and methodological/reporting flaws. Recommendations are provided for future research to provide better studies and fill in the current knowledge gaps.

White-brown adipose tissue interplay in polycystic ovary syndrome: Therapeutic avenues.

This study highlights the therapeutic potential of activating brown adipose tissue (BAT) for managing polycystic ovary syndrome (PCOS), a prevalent endocrine disorder associated with metabolic and reproductive abnormalities. BAT plays a crucial role in regulating energy expenditure and systemic insulin sensitivity, making it an attractive target for the treatment of obesity and metabolic diseases. Recent research suggests that impaired BAT function and mass may contribute to the link between metabolic disturbances and reproductive issues in PCOS. Additionally, abnormal white adipose tissue (WAT) can exacerbate these conditions by releasing adipokines and nonesterified fatty acids. In this review, we explored the impact of WAT changes on BAT function in PCOS and discussed the potential of BAT activation as a therapeutic strategy to improve PCOS symptoms. We propose that BAT activation holds promise for managing PCOS; however, further research is needed to confirm its efficacy and to develop clinically feasible methods for BAT activation.

Strategies for modifying the chimeric antigen receptor (CAR) to improve safety and reduce toxicity in CAR T cell therapy for cancer.

Immune cell therapy with chimeric antigen receptor (CAR) T cells, which has shown promising efficacy in patients with some hematologic malignancies, has introduced several successfully approved CAR T cell therapy products. Nevertheless, despite significant advances, treatment with these products has major challenges regarding potential toxicity and sometimes fatal adverse effects for patients. These toxicities can result from cytokine release or on-target off-tumor toxicity that targets healthy host tissue following CAR T cell therapy. The present study focuses on the unexpected side effects of targeting normal host tissues with off-target toxicity. Also, recent safety strategies such as replacing or adding different components to CARs and redesigning CAR structures to eliminate the toxic impact of CAR T cells, including T cell antigen coupler (TAC), switch molecules, suicide genes, and humanized monoclonal antibodies in the design of CARs, are discussed in this review.

Curcumin and targeting of molecular and metabolic pathways in multiple sclerosis.

Multiple sclerosis (MS) is a life-threading disease that poses a great threat to the human being lifestyle. Having said extensive research in the realm of underlying mechanisms and treatment procedures, no definite remedy has been found. Over the past decades, many medicines have been disclosed to alleviate the symptoms and marking of MS. Meanwhile, the substantial efficacy of herbal medicines including curcumin must be underscored. Accumulated documents demonstrated the fundamental role of curcumin in the induction of the various signaling pathways. According to evidence, curcumin can play a role in mitochondrial dysfunction and apoptosis, autophagy, and mitophagy. Also, by targeting the signaling pathways AMPK, PGC-1α/PPARγ, and PI3K/Akt/mTOR, curcumin interferes with the metabolism of MS. The anti-inflammatory, antioxidant, and immune regulatory effects of this herbal compound are involved in its effectiveness against MS. Thus, the present review indicates the molecular and metabolic pathways associated with curcumin's various pharmacological actions on MS, as well as setting into context the many investigations that have noted curcumin-mediated regulatory effects in MS.

Implantable smart hyperthermia nanofibers for cancer therapy: Challenges and opportunities.

Nanofibers (NFs) with practical drug-loading capacities, high stability, and controllable release have caught the attention of investigators due to their potential applications in on-demand drug delivery devices. Developing novel and efficient multidisciplinary management of locoregional cancer treatment through the design of smart NF-based systems integrated with combined chemotherapy and hyperthermia could provide stronger therapeutic advantages. On the other hand, implanting directly at the tumor area is a remarkable benefit of hyperthermia NF-based drug delivery approaches. Hence, implantable smart hyperthermia NFs might be very hopeful for tumor treatment in the future and provide new avenues for developing highly efficient localized drug delivery systems. Indeed, features of the smart NFs lead to the construction of a reversibly flexible nanostructure that enables hyperthermia and facile switchable release of antitumor agents to eradicate cancer cells. Accordingly, this study covers recent updates on applications of implantable smart hyperthermia NFs regarding their current scope and future outlook. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants.

A placebo-controlled randomized clinical trial of amantadine hydrochloride for evaluating the functional improvement of patients following severe acute traumatic brain injury.

BACKGROUND: Considering the known derangements in the dopaminergic neurotransmitter systems following traumatic brain injury (TBI), dopamine agonists are used as a pharmacologic option. In this study, we evaluate the effects of amantadine hydrochloride on the functional improvement of severe TBI patients. METHODS: Within a triple-blinded (patients, intervention administrators, and outcome assessors) placebo-controlled randomized clinical trial, we evaluated the effects of amantadine (100 mg BD (twice a day) for 14 days, then 150 mg BD for another 7 days, and 200 mg BD for another 21 days) on outcome measurements of weekly mean Glasgow Outcome Scale (GOS) and Disability Rating Scale (DRS), through six weeks of trial for 57 patients (29 amantadine, 28 placeboes) with severe TBI admitted in our hospital. RESULTS: Although both groups had improvement in their DRS, the change from baseline was significantly better in the amantadine group (10.88±5.24 for amantadine vs. 8.04±4.07 for placebo, P=0.015). No significant difference was observed between groups for GOS (1.04±0.55 for amantadine vs. 1.12±1.05 for placebo, P=0.966). CONCLUSIONS: Based on our findings, amantadine hydrochloride might improve the speed of functional ability improvement in severe TBI patients, evaluated by DRS, and is also well tolerated by patients. Although, there were some limitations in this study, including small sample size, short time interval, not providing a wash-off period and invalidity of GOS for measuring recovery rates in short-term periods.

The expression of miR-181b, CYLD, CBX-7, BCL2, and p53 in osteosarcoma patients and correlation with clinicopathological factors.

Osteosarcoma is a common human malignancy with a high mortality rate worldwide. Recent studies have been focused on understanding the involvement of microRNA (miRNAs) in the pathogenesis of osteosarcoma. Therefore, the present study aimed to measure the expression levels of miR-181a, cylindromatosis (CYLD), chromo box homolog 7 (CBX7), B-cell lymphoma 2 (BCL2), and tumor protein p53 in tumor tissue and adjacent normal tissues in patients with osteosarcoma and its relationship with clinicopathological factors. The expression levels of miR-181a, CYLD, CBX7, BCL2, and p53 were measured in 60 patients with osteosarcoma using quantitative real-time polymerase chain reaction. Finally, we compared the relationship between these gene levels and clinicopathological factors in tumor and healthy tissues. Our results showed that the expression levels of miR-181a, BCL2, and p53 were significantly higher in osteosarcoma tissue in comparison with normal tissues (p < .05). On the contrary, CYLD and CBX7 were downregulated in osteosarcoma tumor tissues compared to adjacent healthy tissues (p < .05). In addition, the expression levels of miR-181a in tumor tissues were strongly correlated with patients' age, tumor size, clinical stage, cancer grade, and lymph node metastasis (p < .05). Our findings highlight new insights into understanding the role of miR-181a in the pathogenesis of osteosarcoma. However, further studies are needed to elucidate miRNA as therapeutic targets for osteosarcoma.

The mirror mechanism in schizophrenia: A systematic review and qualitative meta-analysis.

Background: Mirror neuron system (MNS) consists of visuomotor neurons that are responsible for the mirror neuron activity (MNA), meaning that each time an individual observes another individual performing an action, these neurons encode that action, and are activated in the observer's cortical motor system. Previous studies report its malfunction in autism, opening doors to investigate the underlying pathophysiology of the disorder in a more elaborate way and coming up with new rehabilitation methods. The study of MNA function in schizophrenia patients has not been as frequent and conclusive as in autism. In this research, we aimed to evaluate the functional integrity of MNA and the microstructural integrity of MNS in schizophrenia patients. Methods: We included case-control studies that have evaluated MNA in schizophrenia patients compared to healthy controls using a variety of objective assessment tools. In August 2022, we searched Embase, PubMed, and Web of Science for eligible studies. We used an adapted version of the NIH Quality Assessment of Case-Control Studies tool to assess the quality of the included studies. Evidence was analyzed using vote counting methods of the direction of the effect and was tested statistically using the Sign test. Certainty of evidence was assessed using CERQual. Results: We included 32 studies for the analysis. Statistical tests revealed decreased MNA (p = 0.002) in schizophrenia patients. The certainty of the evidence was judged to be moderate. Investigations of heterogeneity revealed a possible relationship between the age and the positive symptoms of participants in the included studies and the direction of the observed effect. Discussion: This finding contributes to gaining a better understanding of the underlying pathophysiology of the disorder by revealing its possible relation to some of the symptoms in schizophrenia patients, while also highlighting a new commonality with autism. Systematic review registration: PROSPERO identifier: CRD42021236453.

Investigating the Role of Quercetin in Increasing the Rate of Cisplatin-Induced Apoptosis Via the NF-κB Pathway in MG-63 Cancer Cells.

INTRODUCTION: Numerous studies suggest that the co-treatment of chemotherapeutic agents with flavonoids such as Quercetin (Que) may enhance tumor cells' susceptibility to these agents. Hence, in the current study, we investigated Que's role in combination with Cisplatin to promote cell apoptosis by focusing on the NF-κB signaling pathway in the osteosarcoma cell lines. METHODS: The Que, Cisplatin, and their combination's general cytotoxicity effects were evaluated using an MTT assay for 72 hrs. The protein expression levels of NF-κB were detected by an enzyme-linked immunosorbent assay (ELISA) Kit. Flow cytometry was used to evaluate cell apoptosis. RESULTS: Que considerably elevated the cytotoxicity of Cisplatin (P<0.05). Que also dramatically down-regulated the expression levels of NF-κB in MG-63 cells compared to mono-treatment (P<0.05). Besides, Que promotes cisplatin-induced apoptosis in MG-63 cells. CONCLUSION: Our study's findings provide an exact point in the field of adjuvant therapy in osteosarcoma. In other words, this study could provide new insights into a better understanding of the role of Que in elevating cisplatin-induced apoptosis with NF-κB down-regulation.

Abstract screening using the automated tool Rayyan: results of effectiveness in three diagnostic test accuracy systematic reviews.

OBJECTIVE: To evaluate the performance of the automated abstract screening tool Rayyan. METHODS: The records obtained from the search for three systematic reviews were manually screened in four stages. At the end of each stage, Rayyan was used to predict the eligibility score for the remaining records. At two different thresholds (≤2.5 and < 2.5 for exclusion of a record) Rayyan-generated ratings were compared with the decisions made by human reviewers in the manual screening process and the tool's accuracy metrics were calculated. RESULTS: Two thousand fifty-four records were screened manually, of which 379 were judged to be eligible for full-text assessment, and 112 were eventually included in the final review. For finding records eligible for full-text assessment, at the threshold of < 2.5 for exclusion, Rayyan managed to achieve sensitivity values of 97-99% with specificity values of 19-58%, while at the threshold of ≤2.5 for exclusion it had a specificity of 100% with sensitivity values of 1-29%. For the task of finding eligible reports for inclusion in the final review, almost similar results were obtained. DISCUSSION: At the threshold of < 2.5 for exclusion, Rayyan managed to be a reliable tool for excluding ineligible records, but it was not much reliable for finding eligible records. We emphasize that this study was conducted on diagnostic test accuracy reviews, which are more difficult to screen due to inconsistent terminology.

Thymoquinone Potentiates Methotrexate Mediated-Apoptosis in Saos-2 Osteosarcoma Cell Line.

INTRODUCTION: Recently, various studies have concentrated on the therapeutic potential of thymoquinone (TQ), a natural polyphenol, in various human malignancies, including osteosarcoma. However, the underlying mechanisms in TQ-mediated anti-cancer effects are not yet fully understood. Therefore, the present study investigated the effect of TQ on methotrexate (MTX)-induced apoptosis in Saos-2 cells. METHODS: Saos-2 cells were treated with MTX, TQ, and a combination of both, and cell viability was assessed by MTT assay. mRNA expression of apoptotic markers, including Bax, Bcl-2, and caspase-3, was assessed using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: MTX resulted in significant inhibition of cell proliferation in a dose-dependent manner. The combination of TQ and MTX inhibited proliferation compared to single treatments (P<0.05). TQ also induced apoptosis by regulating pro-apoptotic markers including Bax and caspase-3 and reducing anti-apoptotic mediators including Bcl-2. In addition, TQ increased MTX-induced apoptosis in Saos-2 cells. CONCLUSION: The findings of the present study highlight new insights into understanding the role of TQ as a potential therapeutic agent in osteosarcoma by increasing MTX-induced apoptosis.

A comprehensive review on methods for promotion of mechanical features and biodegradation rate in amniotic membrane scaffolds.

Amniotic membrane (AM) is a biological tissue that surrounds the fetus in the mother's womb. It has pluripotent cells, immune modulators, collagen, cytokines with anti-fibrotic and anti-inflammatory effect, matrix proteins, and growth factors. In spite of the biological characteristics, some results have been released in preventing the adhesion on traumatized surfaces. Application of the AM as a scaffold is limited due to its low biomechanical resistance and rapid biodegradation. Therefore, for using the AM during surgery, its modification by different methods such as cross-linking of the membrane collagen is necessary, because the cross-linking is an effective way to reduce the rate of biodegradation of the biological materials. In addition, their cross-linking is likely an efficient way to increase the tensile properties of the material, so that they can be easily handled or sutured. In this regard, various methods related to cross-linking of the AM subsuming the composite materials, physical cross-linking, and chemical cross-linking with the glutraldehyde, carbodiimide, genipin, aluminum sulfate, etc. are reviewed along with its advantages and disadvantages in the current work.

The safety and efficacy of umbilical cord blood mononuclear cells in individuals with spastic cerebral palsy: a randomized double-blind sham-controlled clinical trial.

INTRODUCTION: The current multi-center, randomized, double-blind study was conducted among children with cerebral palsy (CP) to assess the safety and efficacy of umbilical cord blood mononuclear cell (UCB-MNC). We performed the diffusion tensor imaging to assess the changes in the white matter structure. METHODS: Males and females aged 4 to 14 years old with spastic CP were included. Eligible participants were allocated in 4:1 ratio to be in the experimental or control groups; respectively. Individuals who were assigned in UCB-MNC group were tested for human leukocyte antigen (HLA) and fully-matched individuals were treated with UCB-MNCs. A single dose (5 × 106 /kg) UCB-MNCs were administered via intrathecal route in experimental group. The changes in gross motor function measure (GMFM)-66 from baseline to one year after treatment were the primary endpoints. The mean changes in modified Ashworth scale (MAS), pediatric evaluation of disability inventory (PEDI), and CP quality of life (CP-QoL) were also evaluated and compared between groups. The mean changes in fractional anisotropy (FA) and mean diffusivity (MD) of corticospinal tract (CST) and posterior thalamic radiation (PTR) were the secondary endpoints. Adverse events were safety endpoint. RESULTS: There were 72 included individuals (36 cases in each group). The mean GMFM-66 scores increased in experimental group; compared to baseline (+ 9.62; 95%CI: 6.75, 12.49) and control arm (ß: 7.10; 95%CI: 2.08, 12.76; Cohen's d: 0.62) and mean MAS reduced in individuals treated with UCB-MNCs compared to the baseline (-0.87; 95%CI: -1.2, -0.54) and control group (ß: -0.58; 95%CI: -1.18, -0.11; Cohen's d: 0.36). The mean PEDI scores and mean CP-QoL scores in two domains were higher in the experimental group compared to the control. The imaging data indicated that mean FA increased and MD decreased in participants of UCB-MNC group indicating improvements in white matter structure. Lower back pain, headaches, and irritability were the most common adverse events within 24 h of treatment that were related to lumbar puncture. No side effects were observed during follow-up. CONCLUSIONS: This trial showed that intrathecal injection of UCB-MNCs were safe and effective in children with CP. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov ( NCT03795974 ).

Disease-modifying therapies and T1 hypointense lesions in patients with multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: Previous research has shown that cerebral T1 hypointense lesions are positively correlated with the disability of multiple sclerosis (MS) patients. Hence, they could be used as an objective marker for evaluating the progression of the disease. Up to this date, there has not been a systematic evaluation of the effects of disease-modifying therapies (DMTs) on this prognostic marker. OBJECTIVES: To evaluate the effects of FDA-approved DMTs on the numbers and volume of T1 hypointense lesions in adult patients with MS. METHODS: We included studies with the mentioned desired outcomes. In March 2021, we searched MEDLINE (Ovid), Embase, and CENTRAL to find relevant studies. All included studies were assessed for the risk of bias using the RoB-2 tool. Extracted data were analyzed using a random-effects model. Certainty of evidence was assessed using GRADE. RESULTS: Thirteen studies with 7484 participants were included. Meta-analysis revealed the mean difference between the intervention and comparator groups for the number of lesions was -1.3 (95% CI: -2.1, -0.5) and for the mean volume of lesions was -363.1 (95% CI: -611.6, -114.6). Certainty of evidence was judged to be moderate. Heterogeneity was considerable. DISCUSSION: DMTs reduce the number and volume of T1 hypointense lesions. Although, these findings must be interpreted cautiously due to the high values of heterogeneity.

The Roles of Signaling Pathways in Cardiac Regeneration.

In recent years, knowledge of cardiac regeneration mechanisms has dramatically expanded. Regeneration can replace lost parts of organs, common among animal species. The heart is commonly considered an organ with terminal development, which has no reparability potential during post-natal life. However, some intrinsic regeneration capacity has been reported for cardiac muscle, which opens novel avenues in cardiovascular disease treatment. Different endogenous mechanisms have been studied for cardiac repairing and regeneration in recent decades. Survival, proliferation, inflammation, angiogenesis, cell-cell communication, cardiomyogenesis, and anti-aging pathways are the most important mechanisms that have been studied in this regard. Several in vitro and animal model studies focused on proliferation induction for cardiac regeneration reported promising results. These studies have mainly focused on promoting proliferation signaling pathways and demonstrated various signaling pathways such as Wnt, PI3K/Akt, IGF- 1, TGF-ß, Hippo, and VEGF signaling cardiac regeneration. Therefore, in this review, we intend to discuss the connection between different critical signaling pathways in cardiac repair and regeneration.

Correlation between the clinical disability and T1 hypointense lesions' volume in cerebral magnetic resonance imaging of multiple sclerosis patients: A systematic review and meta-analysis.

BACKGROUND: To evaluate the correlation between T1 hypointense lesions' mean volume on cerebral MRI with disability level of patients with multiple sclerosis. METHODS: We included studies testing the desired outcome in adult patients diagnosed with RRMS or SPMS. In Feb 2021, we searched PubMed, Embase, CENTRAL, and Web of Science to find relevant studies. All included studies were assessed for the risk of bias using a tailored version of the Quality in Prognosis Studies (QUIPS) tool. Extracted correlation coefficients were converted to the Fisher's z scale, and a meta-analysis using a random-effects model was performed on the results. RESULTS: We included 27 studies (1919 participants). Meta-analysis revealed a correlation coefficient of 0.32 (95% CI 0.26-0.37) between T1 hypointense lesions' mean volume and EDSS score. DISCUSSION: The correlation between T1 hypointense lesions' mean volume and EDSS was interpreted as low to slightly moderate. The certainty of the evidence was judged to be high.

The serum levels of testosterone in coronary artery disease patients; relation to NO, eNOS, endothelin-1, and disease severity.

OBJECTIVES: The changes in testosterone level and its correlation with the endothelial nitric oxide systems balance in patients with coronary artery disease (CAD) remains uncertain. Therefore, in our study, we aimed to evaluate the levels of testosterone, endothelin-1 (ET-1), nitric oxide (NO), and endothelial NOS (eNOS) in CAD patients, and control group to find the relationship between these parameters and disease severity. METHODS: Forty-four patients as CAD group with significant (≥50%) stenosis confirmed by angiography was included in the study, and 40 healthy men were included as the control group. According to the number of vessels obstruction, CAD severity was determined. The serum indicated parameters were assessed to discriminate between patients and controls. RESULTS: It was found that testosterone levels in the CDA group were significantly lower than those of the control group (p<0.05). In addition, the level of ET-1 in the CAD group was higher than that in the control group, but levels of NO and eNOS in observation were significantly lower than those in the control group (p<0.05). The correlation analysis revealed that testosterone was passivity correlated with serum NO levels (r=0.550, p=0.001). CONCLUSIONS: The current study reports that serum levels of testosterone are closely related to endothelial NO levels and might be of relevance to the pathogenesis of endothelial dysfunction and disease severity in CAD patients.

MiR-622 acts as a tumor suppressor to induce cell apoptosis and inhibit metastasis in human prostate cancer.

Growing evidence indicating the critical modulator roles of microRNAs (miRNAs) involved in prostate cancer (PCa) metastasis that holds great promise as therapeutic targets. Herein, we transfected the miR-622 mimic into PC3 cells and evaluated the effects of this interference on these tumour cells' growth and the expression of specific metastatic genes. Transfecting of miR-622 mimic and inhibitor, negative control (NC) inhibitor and NC was established using Lipofectamine 2000. The mRNA levels of miR-622 and metastatic genes were evaluated using the qRT-PCR and Western blot. Cytotoxic effects of miR-622 were assessed by MTT. Apoptosis was detected using an ELISA cell death assay kit. miR-622 is down-regulated in PC3 cells. As expected, cell viability effects after transfection were described as miR-622 inhibitor >NC and NC inhibitor >miR-622 mimic (p < .01). Importantly, we showed that transfected miR-622 mimic could enhance the apoptosis of PC3 cells, while transfected miR-622 inhibitor could decrease cell apoptosis (p < .01). Furthermore, miR-622 overexpression could increase significantly down-regulated the MMP2, MMP9, CXCR-4, c-Myc and K-Ras expression levels. Findings demonstrate a novel mechanism by which miR-622 modulates PCa cells' metastasis by targeting metastatic genes. These data confirm the tumour-suppressive function of miR-622 in PCa cells by enhancing apoptosis and reducing metastasis.

Regulatory Roles of the Notch Signaling Pathway in Liver Repair and Regeneration: A Novel Therapeutic Target.

The liver is one of the significant regenerative organs in the body. Nevertheless, underlying molecular mechanisms regulating liver repair and regeneration following resection or damage remain largely unknown. The Notch signaling pathway is a profoundly evolutionarily well-conserved cell signaling system that mostly involves developing multicellular organisms. Malfunctions in this pathway lead to the progression of several liver disorders, including hepatoblastoma (HB), cholangiocarcinoma (CCA) and hepatocellular carcinoma (HCC). The Notch pathway plays a fundamental role in cell fate during the embryonic stage's progression to the adult stage in liver tissue. Modulation of Notch signaling may be used in many patients who succumb to cirrhosis due to chronic hepatitis by virus infection. This review describes the underlying mechanisms of the Notch signaling pathway in liver development and regeneration briefly and discusses how this pathway leads to the betterment of liver disorders in the clinic.