Linagliptin, a DPP-4 inhibitor, activates AMPK/FOXO3a and suppresses NFκB to mitigate the debilitating effects of diethylnitrosamine exposure in rat liver: Novel mechanistic insights.

Accumulating evidence suggests that dysregulation of FOXO3a plays a significant role in the progression of various malignancies, including hepatocellular carcinoma (HCC). FOXO3a inactivation, driven by oncogenic stimuli, can lead to abnormal cell growth, suppression of apoptosis, and resistance to anticancer drugs. Therefore, FOXO3a emerges as a potential molecular target for the development of innovative treatments in the era of oncology. Linagliptin (LNGTN), a DPP-4 inhibitor known for its safe profile, has exhibited noteworthy anti-inflammatory and anti-oxidative properties in previous in vivo studies. Several potential molecular mechanisms have been proposed to explain these effects. However, the capacity of LNGTN to activate FOXO3a through AMPK activation has not been investigated. In our investigation, we examined the potential repurposing of LNGTN as a hepatoprotective agent against diethylnitrosamine (DENA) intoxication. Additionally, we assessed LNGTN's impact on apoptosis and autophagy. Following a 10-week administration of DENA, the liver underwent damage marked by inflammation and early neoplastic alterations. Our study presents the first experimental evidence demonstrating that LNGTN can reinstate the aberrantly regulated FOXO3a activity by elevating the nuclear fraction of FOXO3a in comparison to the cytosolic fraction, subsequent to AMPK activation. Moreover, noteworthy inactivation of NFκB induced by LNGTN was observed. These effects culminated in the initiation of apoptosis, the activation of autophagy, and the manifestation of anti-inflammatory, antiproliferative, and antiangiogenic outcomes. These effects were concomitant with improved liver function and microstructure. In conclusion, our findings open new avenues for the development of novel therapeutic strategies targeting the AMPK/FOXO3a signaling pathway in the management of chronic liver damage.

Fexofenadine-loaded chitosan coated solid lipid nanoparticles (SLNs): A potential oral therapy for ulcerative colitis.

The targeting and mucoadhesive features of chitosan (CS)-linked solid lipid nanoparticles (SLNs) were exploited to efficiently deliver fexofenadine (FEX) into the colon, forming a novel and potential oral therapeutic option for ulcerative colitis (UC) treatment. Different FEX-CS-SLNs with varied molecular weights of CS were prepared and optimized. Optimized FEX-CS-SLNs exhibited 229 ± 6.08 nm nanometric size, 36.3 ± 3.18 mV zeta potential, 64.9 % EE, and a controlled release profile. FTIR, DSC, and TEM confirmed good drug entrapment and spherical particles. Mucoadhesive properties of FEX-CS-SLNs were investigated through mucin incubation and exhibited considerable mucoadhesion. The protective effect of FEX-pure, FEX-market, and FEX-CS-SLNs against acetic acid-induced ulcerative colitis in rats was examined. Oral administration of FEX-CS-SLNs for 14 days before ulcerative colitis induction reversed UC symptoms and almost restored the intestinal mucosa to normal integrity and inhibited Phosphatidylinositol-3 kinase (73.6 %), protein kinase B (73.28 %), and elevated nuclear factor erythroid 2-related factor 2 (185.9 %) in colonic tissue. Additionally, FEX-CS-SLNs inhibited tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) to (70.79 % & 72.99 %) in colonic tissue. The ameliorative potential of FEX-CS-SLNs outperformed that of FEX-pure and FEX-market. The exceptional protective effect of FEX-CS-SLNs makes it a potentially effective oral system for managing ulcerative colitis.

The potential role of miRNAs in the pathogenesis of schizophrenia - A focus on signaling pathways interplay.

microRNAs (miRNAs) play a crucial role in brain growth and function. Hence, research on miRNA has the potential to reveal much about the etiology of neuropsychiatric diseases. Among these, schizophrenia (SZ) is a highly intricate and destructive neuropsychiatric ailment that has been thoroughly researched in the field of miRNA. Despite being a relatively recent area of study about miRNAs and SZ, this discipline has advanced enough to justify numerous reviews that summarize the findings from the past to the present. However, most reviews cannot cover all research, thus it is necessary to synthesize the large range of publications on this topic systematically and understandably. Consequently, this review aimed to provide evidence that miRNAs play a role in the pathophysiology and progression of SZ. They have also been investigated for their potential use as biomarkers and therapeutic targets.

Tuning into miRNAs: A comprehensive analysis of their impact on diagnosis, and progression in asthma.

Asthma is a diverse inflammatory illness affecting the respiratory passages, leading to breathing challenges, bouts of coughing and wheezing, and, in severe instances, significant deterioration in quality of life. Epigenetic regulation, which involves the control of gene expression through processes such as post-transcriptional modulation of microRNAs (miRNAs), plays a role in the evolution of various asthma subtypes. In immune-mediated diseases, miRNAs play a regulatory role in the behavior of cells that form the airway structure and those responsible for defense mechanisms in the bronchi and lungs. They control various cellular processes such as survival, growth, proliferation, and the production of chemokines and immune mediators. miRNAs possess chemical and biological characteristics that qualify them as suitable biomarkers for diseases. They allow for the categorization of patients to optimize drug selection, thus streamlining clinical management and decreasing both the economic burden and the necessity for critical care related to the disease. This study provides a concise overview of the functions of miRNAs in asthma and elucidates their regulatory effects on the underlying processes of the disease. We provide a detailed account of the present status of miRNAs as biomarkers for categorizing asthma, identifying specific asthma subtypes, and selecting appropriate treatment options.

Smart/stimuli-responsive chitosan/gelatin and other polymeric macromolecules natural hydrogels vs. synthetic hydrogels systems for brain tissue engineering: A state-of-the-art review.

Currently, there are no viable curative treatments that can enhance the central nervous system's (CNS) recovery from trauma or illness. Bioengineered injectable smart/stimuli-responsive hydrogels (SSRHs) that mirror the intricacy of the CNS milieu and architecture have been suggested as a way to get around these restrictions in combination with medication and cell therapy. Additionally, the right biophysical and pharmacological stimuli are required to boost meaningful CNS regeneration. Recent research has focused heavily on developing SSRHs as cutting-edge delivery systems that can direct the regeneration of brain tissue. In the present article, we have discussed the pathology of brain injuries, and the applicable strategies employed to regenerate the brain tissues. Moreover, the most promising SSRHs for neural tissue engineering (TE) including alginate (Alg.), hyaluronic acid (HA), chitosan (CH), gelatin, and collagen are used in natural polymer-based hydrogels and thoroughly discussed in this review. The ability of these hydrogels to distribute bioactive substances or cells in response to internal and external stimuli is highlighted with particular attention. In addition, this article provides a summary of the most cutting-edge techniques for CNS recovery employing SSRHs for several neurodegenerative diseases.

The emerging role of miRNAs in epilepsy: From molecular signatures to diagnostic potential.

Epilepsy is a medical condition characterized by intermittent seizures accompanied by changes in consciousness. Epilepsy significantly impairs the daily functioning and overall well-being of affected individuals. Epilepsy is a chronic neurological disorder characterized by recurrent seizures resulting from various dysfunctions in brain activity. The molecular processes underlying changes in neuronal structure, impaired apoptotic responses in neurons, and disruption of regenerative pathways in glial cells in epilepsy remain unknown. MicroRNAs (miRNAs) play a crucial role in regulating apoptosis, autophagy, oxidative stress, neuroinflammation, and the body's regenerative and immune responses. miRNAs have been shown to influence many pathogenic processes in epilepsy including inflammatory responses, neuronal necrosis and apoptosis, dendritic growth, synaptic remodeling, and other processes related to the development of epilepsy. Therefore, the purpose of our current analysis was to determine the role of miRNAs in the etiology and progression of epilepsy. Furthermore, they have been examined for their potential application as biomarkers and therapeutic targets.

Unveiling the regulatory role of miRNAs in stroke pathophysiology and diagnosis.

Stroke, a major global cause of mortality, leads to a range of problems for those who survive. Besides its brutal events, stroke also tends to have a characteristic of recurrence, making it a complex disease involving intricate regulatory networks. One of the major cellular regulators is the non-coding RNAs (ncRNA), specifically microRNAs (miRNAs), thus the possible functions of miRNAs in the pathogenesis of stroke are discussed as well as the possibility of using miRNA-based therapeutic approaches. Firstly, the molecular mechanisms by which miRNAs regulate vital physiological processes, including synaptic plasticity, oxidative stress, apoptosis, and the integrity of the blood-brain barrier (BBB) are reviewed. The miRNA indirectly impacts stroke outcomes by regulating BBB function and angiogenesis through the targeting of transcription factors and angiogenic factors. In addition, the tendency for some miRNAs to be upregulated in response to hypoxia, which is a prevalent phenomenon in stroke and various neurological disorders, highlights the possibility that it controls hypoxia-inducible factor (HIF) signaling and angiogenesis, thereby influencing the integrity of the BBB as examples of the discussed mechanisms. Furthermore, this review explores the potential therapeutic targets that miRNAs may offer for stroke recovery and highlights their promising capacity to alleviate post-stroke complications. This review provides researchers and clinicians with valuable resources since it attempts to decipher the complex network of miRNA-mediated mechanisms in stroke. Additionally, the review addresses the interplay between miRNAs and stroke risk factors as well as clinical applications of miRNAs as diagnostic and prognostic markers.

miRNAs as modulators of neuroinflammation and excitotoxicity: Implications for stroke therapeutics.

Stroke is a widespread neurological disorder associated with physical disabilities, mortality, and economic burden. In recent decades, substantial progress has been achieved in reducing the impact of this public health problem. However, further understanding of the pathophysiology of stroke and the underlying genetic pathways is required. The pathological mechanisms of stroke comprise multifaceted molecular cascades regulated by various microRNAs (miRNAs). An increasing number of studies have highlighted the role of miRNAs, which have received much attention during the last decades as an important class of post-transcriptional regulators. It was shown that miRNAs exert their role in the etiology of stroke via mediating excitotoxicity and neuroinflammation. Additionally, miRNAs could be helpful as non-invasive or minimally invasive biomarkers and therapeutic agents. Thus, the current review focused on the interplay of these miRNAs in stroke pathology to upgrade the existing therapeutic strategies.

Unraveling the role of miRNAs in the diagnosis, progression, and therapeutic intervention of Alzheimer's disease.

Alzheimer's disease (AD) is a multifaceted, advancing neurodegenerative illness that is responsible for most cases of neurological impairment and dementia in the aged population. As the disease progresses, affected individuals may experience cognitive decline, linguistic problems, affective instability, and behavioral changes. The intricate nature of AD reflects the altered molecular mechanisms participating in the affected human brain. MicroRNAs (miRNAs, miR) are essential for the intricate control of gene expression in neurobiology. miRNAs exert their influence by modulating the transcriptome of brain cells, which typically exhibit substantial genetic activity, encompassing gene transcription and mRNA production. Presently, comprehensive studies are being conducted on AD to identify miRNA-based signatures that are indicative of the disease pathophysiology. These findings can contribute to the advancement of our understanding of the mechanisms underlying this disorder and can inform the development of therapeutic interventions based on miRNA and related RNA molecules. Therefore, this comprehensive review provides a detailed holistic analysis of the latest advances discussing the emerging role of miRNAs in the progression of AD and their possible application as potential biomarkers and targets for therapeutic interventions in future studies.

Unraveling the role of miRNAs in the diagnosis, progression, and therapeutic intervention of Parkinson's disease.

Parkinson's disease (PD) is a debilitating neurological disorder characterized by the impairment of the motor system, resulting in symptoms such as resting tremor, cogwheel rigidity, bradykinesia, difficulty with gait, and postural instability. The occurrence of striatal dopamine insufficiency can be attributed to a notable decline in dopaminergic neurons inside the substantia nigra pars compacta. Additionally, the development of Lewy bodies serves as a pathological hallmark of PD. While current therapy approaches for PD aim to preserve dopaminergic neurons or replenish dopamine levels in the brain, it is important to acknowledge that achieving complete remission of the condition remains elusive. MicroRNAs (miRNAs, miR) are a class of small, non-coding ribonucleic acids involved in regulating gene expression at the post-transcriptional level. The miRNAs play a crucial part in the underlying pathogenic mechanisms of several neurodegenerative illnesses, including PD. The aim of this review is to explore the role of miRNAs in regulating genes associated with the onset and progression of PD, investigate the potential of miRNAs as a diagnostic tool, assess the effectiveness of targeting specific miRNAs as an alternative therapeutic strategy to impede disease advancement, and discuss the utilization of newly developed nanoparticles for delivering miRNAs as neurodegenerative therapies.

Decoding the role of miRNAs in oral cancer pathogenesis: A focus on signaling pathways.

Oral cancer (OC) is the predominant type originating in the head and neck region. The incidence of OC is mostly associated with behavioral risk factors, including tobacco smoking and excessive alcohol intake. Additionally, there is a lower but still significant association with viral infections such as human papillomaviruses and Epstein-Barr viruses. Furthermore, it has been observed that heritable genetic variables are linked to the risk of OC, in addition to the previously mentioned acquired risk factors. The current absence of biomarkers for OC diagnosis contributes to the frequent occurrence of advanced-stage diagnoses among patients. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs, and circular RNAs, have been observed to exert a significant effect on the transcriptional control of target genes involved in cancer, either through direct or indirect mechanisms. miRNAs are a class of short ncRNAs that play a role in regulating gene expression by enabling mRNA degradation or translational repression at the post-transcriptional phase. miRNAs are known to play a fundamental role in the development of cancer and the regulation of oncogenic cell processes. Notch signaling, PTEN/Akt/mTOR axis, KRAS mutation, JAK/STAT signaling, P53, EGFR, and the VEGFs have all been linked to OC, and miRNAs have been shown to have a role in all of these. The dysregulation of miRNA has been identified in cases of OC and is linked with prognosis.

Deciphering signaling pathway interplay via miRNAs in malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a highly invasive form of lung cancer that adversely affects the pleural and other linings of the lungs. MPM is a very aggressive tumor that often has an advanced stage at diagnosis and a bad prognosis (between 7 and 12 months). When people who have been exposed to asbestos experience pleural effusion and pain that is not explained, MPM should be suspected. After being diagnosed, most MPM patients have a one- to four-year life expectancy. The life expectancy is approximately six months without treatment. Despite the plethora of current molecular investigations, a definitive universal molecular signature has yet to be discovered as the causative factor for the pathogenesis of MPM. MicroRNAs (miRNAs) are known to play a crucial role in the regulation of gene expression at the posttranscriptional level. The association between the expression of these short, non-coding RNAs and several neoplasms, including MPM, has been observed. Although the incidence of MPM is very low, there has been a significant increase in research focused on miRNAs in the past few years. In addition, miRNAs have been found to have a role in various regulatory signaling pathways associated with MPM, such as the Notch signaling network, Wnt/ß-catenin, mutation of KRAS, JAK/STAT signaling circuit, protein kinase B (AKT), and Hedgehog signaling pathway. This study provides a comprehensive overview of the existing understanding of the roles of miRNAs in the underlying mechanisms of pathogenic symptoms in MPM, highlighting their potential as viable targets for therapeutic interventions.

Possible role of miRNAs in pheochromocytoma pathology - Signaling pathways interaction.

Pheochromocytoma (PCC) is a type of neuroendocrine tumor that originates from adrenal medulla or extra-adrenal chromaffin cells and results in the production of catecholamine. Paroxysmal hypertension and cardiovascular crises were among the clinical signs experienced by people with PCC. Five-year survival of advanced-stage PCC is just around 40% despite the identification of various molecular-level fundamentals implicated in these pathogenic pathways. MicroRNAs (miRNAs, miRs) are a type of short, non-coding RNA (ncRNA) that attach to the 3'-UTR of a target mRNA, causing translational inhibition or mRNA degradation. Evidence is mounting that miRNA dysregulation plays a role in the development, progression, and treatment of cancers like PCC. Hence, this study employs a comprehensive and expedited survey to elucidate the potential role of miRNAs in the development of PCC, surpassing their association with survival rates and treatment options in this particular malignancy.

From diagnosis to resistance: a symphony of miRNAs in pheochromocytoma progression and treatment response.

Pheochromocytoma (PCC) is a neuroendocrine tumor that produces and secretes catecholamine from either the adrenal medulla or extra-adrenal locations. MicroRNAs (miRNAs, miR) can be used as biomarkers to detect cancer or the return of a previously treated disease. Blood-borne miRNAs might be envisioned as noninvasive markers of malignancy or prognosis, and new studies demonstrate that microRNAs are released in body fluids as well as tissues. MiRNAs have the potential to be therapeutic targets, which would greatly increase the restricted therapy options for adrenal tumors. This article aims to consolidate and synthesize the most recent studies on miRNAs in PCC, discussing their potential clinical utility as diagnostic and prognostic biomarkers while also addressing their limitations.

Melodic maestros: Unraveling the role of miRNAs in the diagnosis, progression, and drug resistance of malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is a highly lethal form of pleural cancer characterized by a scarcity of effective therapeutic interventions, resulting in unfavorable prognoses for afflicted individuals. Besides, many patients experience substantial consequences from being diagnosed in advanced stages. The available diagnostic, prognostic, and therapeutic options for MPM are restricted in scope. MicroRNAs (miRNAs) are a subset of small, noncoding RNA molecules that exert significant regulatory influence over several cellular processes within cell biology. A wide range of miRNAs have atypical expression patterns in cancer, serving specific functions as either tumor suppressors or oncomiRs. This review aims to collate, epitomize, and analyze the latest scholarly investigations on miRNAs that are believed to be implicated in the dysregulation leading to MPM. miRNAs are also discussed concerning their potential clinical usefulness as diagnostic and prognostic biomarkers for MPM. The future holds promising prospects for enhancing diagnostic, prognostic, and therapeutic modalities for MPM, with miRNAs emerging as a potential trigger for such advancements.

Antimicrobial, Antibiofilm, and Anticancer Activities of Syzygium aromaticum Essential Oil Nanoemulsion.

In the current study, clove oil nanoemulsion (CL-nanoemulsion) and emulsion (CL-emulsion) were prepared through an ecofriendly method. The prepared CL-nanoemulsion and CL-emulsion were characterized using dynamic light scattering (DLS) and a transmission electron microscope (TEM), where results illustrated that CL-nanoemulsion droplets were approximately 32.67 nm in size and spherical in shape, while CL-nanoemulsion droplets were approximately 225.8 nm with a spherical shape. The antibacterial activity of CL-nanoemulsion and CL-emulsion was carried out using a microbroth dilution method. Results revealed that the preferred CL-nanoemulsion had minimal MIC values between 0.31 and 5 mg/mL. The antibiofilm efficacy of CL-nanoemulsion against S. aureus significantly decreased the development of biofilm compared with CL-emulsion. Furthermore, results illustrated that CL-nanoemulsion showed antifungal activity significantly higher than CL-emulsion. Moreover, the prepared CL-nanoemulsion exhibited outstanding antifungal efficiency toward Candida albicans, Cryptococcus neoformans, Aspergillus brasiliensis, A. flavus, and A. fumigatus where MICs were 12.5, 3.12, 0.78, 1.56, and 1.56 mg/mL, respectively. Additionally, the prepared CL-nanoemulsion was analyzed for its antineoplastic effects through a modified MTT assay for evaluating apoptotic and cytotoxic effects using HepG2 and MCF-7 cell lines. MCF-7 breast cancer cells showed the lowest IC50 values (3.4-fold) in CL-nanoemulsion relative to that of CL-emulsion. Thus, CL-nanoemulsion induces apoptosis in breast cancer cells by inducing caspase-8 and -9 activity and suppressing VEGFR-2. In conclusion, the prepared CL-nanoemulsion had antibacterial, antifungal, and antibiofilm as well as anticancer properties, which can be used in different biomedical applications after extensive studies in vivo.

The emerging role of miRNAs in Merkel cell carcinoma pathogenesis: Signaling pathway crosstalk.

Merkel cell carcinoma (MCC) is an uncommon invasive form of skin cancer that typically manifests as a nodule on the face, head, or neck that is flesh-colored or bluish-red in appearance. Rapid growth and metastasis are hallmarks of MCC. MCC has the second-greatest mortality rate among skin cancers after melanoma. Despite the recent cascade of molecular investigations, no universal molecular signature has been identified as responsible for MCC's pathogenesis. The microRNAs (miRNAs) play a critical role in the post-transcriptional regulation of gene expression. Variations in the expression of these short, non-coding RNAs have been associated with various malignancies, including MCC. Although the incidence of MCC is very low, a significant amount of study has focused on the interaction of miRNAs in MCC. As such, the current survey is a speedy intensive route revealing the potential involvement of miRNAs in the pathogenesis of MCC beyond their association with survival in MCC.

miRNAs driving diagnosis, progression, and drug resistance in multiple myeloma.

Multiple myeloma (MM) is a tumor of transformed plasma cells. It's the second most common hematologic cancer after non-Hodgkin lymphoma. MM is a complex disease with many different risk factors, including ethnicity, race, and epigenetics. The microRNAs (miRNAs) are a critical epigenetic factor in multiple myeloma, influencing key aspects such as pathogenesis, prognosis, and resistance to treatment. They have the potential to assist in disease diagnosis and modulate the resistance behavior of MM towards therapeutic regimens. These characteristics could be attributed to the modulatory effects of miRNAs on some vital pathways such as NF-KB, PI3k/AKT, and P53. This review discusses the role of miRNAs in MM with a focus on their role in disease progression, diagnosis, and therapeutic resistance.

Stimuli-responsive hydrogels: smart state of-the-art platforms for cardiac tissue engineering.

Biomedicine and tissue regeneration have made significant advancements recently, positively affecting the whole healthcare spectrum. This opened the way for them to develop their applications for revitalizing damaged tissues. Thus, their functionality will be restored. Cardiac tissue engineering (CTE) using curative procedures that combine biomolecules, biomimetic scaffolds, and cells plays a critical part in this path. Stimuli-responsive hydrogels (SRHs) are excellent three-dimensional (3D) biomaterials for tissue engineering (TE) and various biomedical applications. They can mimic the intrinsic tissues' physicochemical, mechanical, and biological characteristics in a variety of ways. They also provide for 3D setup, adequate aqueous conditions, and the mechanical consistency required for cell development. Furthermore, they function as competent delivery platforms for various biomolecules. Many natural and synthetic polymers were used to fabricate these intelligent platforms with innovative enhanced features and specialized capabilities that are appropriate for CTE applications. In the present review, different strategies employed for CTE were outlined. The light was shed on the limitations of the use of conventional hydrogels in CTE. Moreover, diverse types of SRHs, their characteristics, assembly and exploitation for CTE were discussed. To summarize, recent development in the construction of SRHs increases their potential to operate as intelligent, sophisticated systems in the reconstruction of degenerated cardiac tissues.

miRNAs orchestration of gallbladder cancer - Particular emphasis on diagnosis, progression and drug resistance.

Gallbladder cancer (GBC) is characterized by a highly invasive nature and a poor prognosis, with adenocarcinoma being the main histological subtype. According to statistical data, patients diagnosed with advanced GBC have a survival rate of less than 5% for 5 years. Despite the novel therapeutic techniques, the unsatisfactory results could be related to the underlying biology of tumor cells and resistance to chemotherapy. Early diagnosis is more important than clinical therapy as it assists in determining the pathological stage of cancer and facilitates the selection of appropriate medication. Hence, it is very important to understand the precise pathogenesis of GBC and to discover potential novel biomarkers for early diagnosis of GBC. Non-coding RNAs, such as microRNAs, long non-coding RNAs, and circular RNAs, have been found to influence the transcriptional regulation of target genes associated with cancer, either directly or indirectly. microRNAs are a group of small, non-coding, single-stranded RNAs that are expressed endogenously. miRNAs play significant roles in various fundamental cellular processes. Therefore, miRNAs have the potential to serve as valuable biomarkers and therapeutic targets for GBC.