Unlocking vinpocetine's oncostatic potential in early-stage hepatocellular carcinoma: A new approach to oncogenic modulation by a nootropic drug.

The development of new drugs for the inhibition of hepatocellular carcinoma (HCC) development and progression is a critical and urgent need. The median survival rate for HCC patients remains disappointingly low. Vinpocetine is a safe nootropic agent that is often used to enhance cognitive function. The impact of vinpocetine on HCC development and progression has not been fully explored. Our main objective was to investigate the possible inhibitory role of vinpocetine in rats exposed to diethylnitrosamine. We observed that vinpocetine increased the survival rate of these rats and improved the ultrastructure of their livers. Additionally, vinpocetine reduced the liver weight index, mitigated liver oxidative stress, and improved liver function. In both in vitro and in vivo settings, vinpocetine demonstrated antiproliferative and apoptotic properties. It downregulated the expression of CCND1 and Ki-67 while exhibiting anti-BCL-2 effects and enhancing the levels of Bax and cleaved caspase-3. Vinpocetine also successfully deactivated NF-κB, STAT3, and HIF-1α, along with their associated transcription proteins, thereby exerting anti-inflammatory and anti-angiogenic role. Furthermore, vinpocetine showed promise in reducing the levels of ICAM-1 and TGF-ß1 indicating its potential role in tissue remodeling. These findings strongly suggest that vinpocetine holds promise as a hepatoprotective agent by targeting a range of oncogenic proteins simultaneously. However, further approaches are needed to validate and establish causal links between our observed effects allowing for a more in-depth exploration of the mechanisms underlying vinpocetine's effects and identifying pivotal determinants of outcomes.

Tracking the therapeutic efficacy of a ketone mono ester and ß-hydroxybutyrate for ulcerative colitis in rats: New perspectives.

Ulcerative colitis (UC) is an inflammatory condition that affects the colon's lining and increases the risk of colon cancer. Despite ongoing research, there is no identified cure for UC. The recognition of NLRP3 inflammasome activation in the pathogenesis of UC has gained widespread acceptance. Notably, the ketone body ß-hydroxybutyrate inhibits NLRP3 demonstrating its anti-inflammatory properties. Additionally, BD-AcAc 2 is ketone mono ester that increases ß-hydroxybutyrate blood levels. It has the potential to address the constraints associated with exogenous ß-hydroxybutyrate as a therapeutic agent, including issues related to stability and short duration of action. However, the effects of ß-hydroxybutyrate and BD-AcAc 2 on colitis have not been fully investigated. This study found that while both exogenous ß-hydroxybutyrate and BD-AcAc 2 produced the same levels of plasma ß-hydroxybutyrate, BD-AcAc 2 demonstrated superior effectiveness in mitigating dextran sodium sulfate-induced UC in rats. The mechanism of action involves modulating the NF-κB signaling, inhibiting the NLRP3 inflammasome, regulating antioxidant capacity, controlling tight junction protein expression and a potential to inhibit apoptosis and pyroptosis. Certainly, BD-AcAc 2's anti-inflammatory effects require more than just increasing plasma ß-hydroxybutyrate levels and other factors contribute to its efficacy. Local ketone concentrations in the gastrointestinal tract, as well as the combined effect of specific ketone bodies, are likely to have contributed to the stronger protective effect observed with ketone mono ester ingestion in our experiment. As a result, further investigations are necessary to fully understand the mechanisms of BD-AcAc 2 and optimize its use.

Unraveling the role of miRNAs in the diagnosis, progression, and drug resistance of oral cancer.

Oral cancer (OC) is a widely observed neoplasm on a global scale. Over time, there has been an increase in both its fatality and incidence rates. Oral cancer metastasis is a complex process that involves a number of cellular mechanisms, including invasion, migration, proliferation, and escaping from malignant tissue through either lymphatic or vascular channels. MicroRNAs (miRNAs) are a crucial class of short non-coding RNAs recognized as significant modulators of diverse cellular processes and exert a pivotal influence on the carcinogenesis pathway, functioning either as tumor suppressors or as oncogenes. It has been shown that microRNAs (miRNAs) have a role in metastasis at several stages, including epithelial-mesenchymal transition, migration, invasion, and colonization. This regulation is achieved by targeting key genes involved in these pathways by miRNAs. This paper aims to give a contemporary analysis of OC, focusing on its molecular genetics. The current literature and emerging advancements in miRNA dysregulation in OC are thoroughly examined. This project would advance OC diagnosis, prognosis, therapy, and therapeutic implications.

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

microRNAs (also known as miRNAs or miRs) are a class of small non-coding RNAs that play a critical role in post-transcriptional gene regulation as negative gene regulators by binding complementary sequences in the 3'-UTR of target messenger RNAs (mRNAs) leading to translational repression and/or target degradation a wide range of genes and biological processes, including cell proliferation, invasion, migration, and apoptosis. The development and progression of cancer have been linked to the anomalous expression of miRNAs. According to recent studies, miRNAs have been found to regulate the expression of cancer-related genes through multiple signaling pathways in gallbladder cancer (GBC). Besides, miRNAs are implicated in several modulatory signaling pathways of GBC, including the Notch signaling pathway, JAK/STAT signaling pathway, protein kinase B (AKT), and Hedgehog signaling pathway. This review summarizes our current knowledge of the functions of miRNAs in the mechanisms underlying the pathogenic symptoms of GBC and illustrates their potential significance as treatment targets.

Decoding the role of miRNAs in multiple myeloma pathogenesis: A focus on signaling pathways.

Multiple myeloma (MM) is a cancer of plasma cells that has been extensively studied in recent years, with researchers increasingly focusing on the role of microRNAs (miRNAs) in regulating gene expression in MM. Several non-coding RNAs have been demonstrated to regulate MM pathogenesis signaling pathways. These pathways might regulate MM development, apoptosis, progression, and therapeutic outcomes. They are Wnt/ß-catenin, PI3K/Akt/mTOR, P53 and KRAS. This review highlights the impending role of miRNAs in MM signaling and their relationship with MM therapeutic interventions.

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.

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

Cancer of the salivary glands is one of the five major types of head and neck cancer. Due to radioresistance and a strong propensity for metastasis, the survival rate for nonresectable malignant tumors is dismal. Hence, more research is needed on salivary cancer's pathophysiology, particularly at the molecular level. The microRNAs (miRNAs) are a type of noncoding RNA that controls as many as 30% of all genes that code for proteins at the posttranscriptional level. Signature miRNA expression profiles have been established in several cancer types, suggesting a role for miRNAs in the incidence and progression of human malignancies. Salivary cancer tissues were shown to have significantly aberrant levels of miRNAs compared to normal salivary gland tissues, supporting the hypothesis that miRNAs play a crucial role in the carcinogenesis of salivary gland cancer (SGC). Besides, several SGC research articles reported potential biomarkers and therapeutic targets for the miRNA-based treatment of this malignancy. In this review, we will explore the regulatory impact of miRNAs on the processes underlying the molecular pathology of SGC and provide an up-to-date summary of the literature on miRNAs that impacted this malignancy. We will eventually share information about their possible use as diagnostic, prognostic, and therapeutic biomarkers in SGC.

The potential role of miRNAs in the pathogenesis of salivary gland cancer - A Focus on signaling pathways interplay.

Salivary gland cancer (SGC) is immensely heterogeneous, both in terms of its physical manifestation and its aggressiveness. Developing a novel diagnostic and prognostic detection method based on the noninvasive profiling of microribonucleic acids (miRs) could be a goal for the clinical management of these specific malignancies, sparing the patients' valuable time. miRs are promising candidates as prognostic biomarkers and therapeutic targets or factors that can advance the therapy of SGC due to their ability to posttranscriptionally regulate the expression of various genes involved in cell proliferation, differentiation, cell cycle, apoptosis, invasion, and angiogenesis. Depending on their biological function, many miRs may contribute to the development of SGC. Therefore, this article serves as an accelerated study guide for SGC and the biogenesis of miRs. Here, we shall list the miRs whose function in SGC pathogenesis has recently been determined with an emphasis on their potential applications as therapeutic targets. We will also offer a synopsis of the current state of knowledge about oncogenic and tumor suppressor miRs in relation to SGC.

The interplay of signaling pathways and miRNAs in the pathogenesis and targeted therapy of esophageal cancer.

Globally, esophageal cancer (EC) is the 6th leading cause of cancer-related deaths and the second deadliest gastrointestinal cancer. Multiple genetic and epigenetic factors, such as microRNAs (miRNAs), influence its onset and progression. miRNAs are short nucleic acid molecules that can regulate multiple cellular processes by regulating gene expression. Therefore, EC initiation, progression, apoptosis evasions, invasion capacity, promotion, angiogenesis, and epithelial-mesenchymal transition (EMT) enhancement are associated with miRNA expression dysregulation. Wnt/-catenin signaling, Mammalian target of rapamycin (mTOR)/P-gp, phosphoinositide-3-kinase (PI3K)/AKT/c-Myc, epidermal growth factor receptor (EGFR), and transforming growth factor (TGF)-ß signaling are crucial pathways in EC that are controlled by miRNAs. This review was conducted to provide an up-to-date assessment of the role of microRNAs in EC pathogenesis and their modulatory effects on responses to various EC treatment modalities.

Impact of Adipose Tissue Depot Harvesting Site on the Multilineage Induction Capacity of Male Rat Adipose-Derived Mesenchymal Stem Cells: An In Vitro Study.

Recently, substantial attention has been paid toward adipose-derived mesenchymal stem cells (AdMSCs) as a potential therapy in tissue engineering and regenerative medicine applications. Rat AdMSCs (r-AdMSCs) are frequently utilized. However, the influence of the adipose depot site on the multilineage differentiation potential of the r-AdMSCs is still ambiguous. Hence, the main objective of this study was to explore the influence of the adipose tissue harvesting location on the ability of r-AdMSCs to express the stem-cell-related markers and pluripotency genes, as well as their differentiation capacity, for the first time. Herein, we have isolated r-AdMSCs from the inguinal, epididymal, peri-renal, and back subcutaneous fats. Cells were compared in terms of their phenotype, immunophenotype, and expression of pluripotency genes using RT-PCR. Additionally, we investigated their potential for multilineage (adipogenic, osteogenic, and chondrogenic) induction using special stains confirmed by the expression of the related genes using RT-qPCR. All cells could positively express stem cell marker CD 90 and CD 105 with no significant in-between differences. However, they did not express the hematopoietic markers as CD 34 and CD 45. All cells could be induced successfully. However, epididymal and inguinal cells presented the highest capacity for adipogenic and osteogenic differentiation (21.36-fold and 11.63-fold for OPN, 29.69-fold and 26.68-fold for BMP2, and 37.67-fold and 22.35-fold for BSP, respectively, in epididymal and inguinal cells (p < 0.0001)). On the contrary, the subcutaneous cells exhibited a superior potential for chondrogenesis over the other sites (8.9-fold for CHM1 and 5.93-fold for ACAN, (p < 0.0001)). In conclusion, the adipose tissue harvesting site could influence the differentiation capacity of the isolated AdMSCs. To enhance the results of their employment in various regenerative cell-based therapies, it is thus vital to take the collection site selection into consideration.

miRNAs as potential game-changers in head and neck cancer: Future clinical and medicinal uses.

Head and neck cancers (HNCs) are a group of heterogeneous tumors formed most frequently from epithelial cells of the larynx, lips, oropharynx, nasopharynx, and mouth. Numerous epigenetic components, including miRNAs, have been demonstrated to have an impact on HNCs characteristics like progression, angiogenesis, initiation, and resistance to therapeutic interventions. The miRNAs may control the production of numerous genes linked to HNCs pathogenesis. The roles that miRNAs play in angiogenesis, invasion, metastasis, cell cycle, proliferation, and apoptosis are responsible for this impact. The miRNAs also have an impact on crucial HNCs-related mechanistic networks like the WNT/ß-catenin signaling, PTEN/Akt/mTOR pathway, TGFß, and KRAS mutations. miRNAs may affect how the HNCs respond to treatments like radiation and chemotherapy in addition to pathophysiology. This review aims to demonstrate the relationship between miRNAs and HNCs with a particular emphasis on how miRNAs impact HNCs signaling networks.

Advances and prospects of platelet-rich plasma therapy in veterinary ophthalmology.

In the recent decades, there has been a significant uptick on the use of platelet-rich plasma (PRP) as a better alternative for ophthalmologic therapies in pathologies, primarily of the ocular surface. PRP is a class of liquid platelet concentrate containing a supra-physiological concentration of platelets in a relatively small amount of plasma. Its potential to heal various tissues has piqued interest in its therapeutic application as a biomaterial in regenerative medicine. It is currently a popular therapeutic agent in plastic surgery, cardiothoracic surgery, reconstructive surgery, and even oral and maxillofacial surgery. Based on the data from in vitro and in vivo studies, it can be concluded that PRP possesses adequate therapeutic potential in ocular pathologies, especially those involving cornea. In addition, the high concentrations of growth factors (TGF-ß, VEGF, EGF) present in the PRP accelerate the healing of the corneal epithelium. PRP has great therapeutic prospects in veterinary ophthalmology as a regenerative therapeutic modality. However, several variables are yet to be defined and standardized that can directly affect the efficacy of PRP application in different ophthalmic conditions. There is a shortage of research on the use of PRP in ocular surface defects compared to the number of studies and reports on the use of autologous and allogeneic serum eye drops. Therefore, a data-driven approach is required to generate consensus/guidelines for the preparation, characterization, and therapeutic use of PRP in veterinary ophthalmology. This review aims to inform readers of the latest research on PRP, including its preparation methods, physiological and biochemical properties, clinical applications in veterinary ophthalmology, and their safety and efficacy.

miRNAs insights into rheumatoid arthritis: Favorable and detrimental aspects of key performers.

Rheumatoid arthritis (RA) is a severe autoimmune inflammation that mostly affects the joints. It's a multifactorial disease. Its clinical picture depends on genetic and epigenetic factors such as miRNAs. The miRNAs are small noncoding molecules that are able to negatively or positively modulate their target gene expression. In RA, miRNAs are linked to its pathogenesis. They disrupt immunity balance by controlling granulocytes, triggering the release of several proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-α, finally leading to synovium hyperplasia and inflammation. Besides, they also may trigger activation of some pathways as nuclear factor kappa-ß disrupts the balance between osteoclast and osteoblast activity, leading to increased bone destruction. Moreover, miRNAs are also applied with efficiency in RA diagnosis and prognosis. Besides the significant association between miRNAs and RA response to treatment, they are also applied as a choice for treatment based on their effects on the immune system and inflammatory cytokines. Hence, the review aims to present an updated overview of miRNAs, their biogenesis, implications in RA pathogenesis, and finally, the role of miRNAs in RA treatment.

Mutations in SARS-CoV-2: Insights on structure, variants, vaccines, and biomedical interventions.

COVID-19 is a worldwide pandemic caused by SARS-coronavirus-2 (SARS-CoV-2). Less than a year after the emergence of the Covid-19 pandemic, many vaccines have arrived on the market with innovative technologies in the field of vaccinology. Based on the use of messenger RNA (mRNA) encoding the Spike SARS-Cov-2 protein or on the use of recombinant adenovirus vectors enabling the gene encoding the Spike protein to be introduced into our cells, these strategies make it possible to envisage the vaccination in a new light with tools that are more scalable than the vaccine strategies used so far. Faced with the appearance of new variants, which will gradually take precedence over the strain at the origin of the pandemic, these new strategies will allow a much faster update of vaccines to fight against these new variants, some of which may escape neutralization by vaccine antibodies. However, only a vaccination policy based on rapid and massive vaccination of the population but requiring a supply of sufficient doses could make it possible to combat the emergence of these variants. Indeed, the greater the number of infected individuals, the faster the virus multiplies, with an increased risk of the emergence of variants in these RNA viruses. This review will discuss SARS-CoV-2 pathophysiology and evolution approaches in altered transmission platforms and emphasize the different mutations and how they influence the virus characteristics. Also, this article summarizes the common vaccines and the implication of the mutations and genetic variety of SARS-CoV-2 on the COVID-19 biomedical arbitrations.

Intraventricular pressure gradient: A novel tool to assess the post-infarction chronic congestive heart failure.

Congestive heart failure (CHF), the leading cause of death, is deemed a grave sequel of myocardial infarction (MI). The employment of left ventricular end-diastolic pressure (LVEDP), as a primary indication of CHF, becomes restricted owing to the potential impairment of heart function and caused injury to the aortic valve during its measurement. Echocardiography is the standard technique to detect cardiac dysfunction. However, it exhibits a low capacity to predict the progression of CHF post chronic MI. Being extremely sensitive, noninvasive, and preload-independent, intraventricular pressure gradient (IVPG) was lately introduced to evaluate cardiac function, specifically during cardiomyopathy. Yet, the utility of its use to assess the CHF progression after chronic MI was not investigated. Herein, in the current research, we aimed to study the efficacy of a novel echocardiographic-derived index as IVPG in the assessment of cardiac function in a chronic MI rat model with CHF. Fifty healthy male rats were involved, and MI was surgically induced in 35 of them. Six months post-surgery, all animals were examined using transthoracic conventional and color M-mode echocardiography (CMME) for IVPG. Animals were euthanized the following day after hemodynamics recording. Gross pathological and histological evaluations were performed. J-tree cluster analysis was conducted relying on ten echocardiographic parameters suggestive of CHF. Animals were merged into two main clusters: CHF+ (MI/HF + group, n = 22) and CHF- (n = 28) that was joined from Sham (n = 15), and MI/HF- (n = 13) groups. MI/HF+ group showed the most severe echocardiographic, hemodynamic, anatomic, and histologic alterations. There was no significant change in the total IVPG among various groups. However, the basal IVPG was significantly increased in MI/HF+ group compared to the other groups. The remaining IVPG measures were considerably increased in the MI/HF+ group than in the Sham one. The segmental IVPG measures were significantly correlated with the anatomical, histological, echocardiographic, and hemodynamic findings except for the heart rate. Moreover, they were significant predictors of CHF following a long-standing MI. Conclusively, IVPG obtained from CMME is a substantially promising noninvasive tool with a high ability to detect and predict the progression of CHF following chronic MI compared to conventional echocardiography.

Surgical treatment for left atrial rupture due to myxomatous mitral valve disease in three dogs: A case report.

INTRODUCTION: Myxomatous mitral valve degeneration (MMVD) is an acquired heart disease which sometimes result in pulmonary oedema and left atrial rupture. In previous reports, left atrial rupture has been non-surgically controlled and its prognosis investigated. There is, however, no report concerning surgically treated left atrial rupture with mitral valvuloplasty and follow-up results. OBJECTIVES: This report aimed to develop a surgical strategy for a case of left atrial rupture caused by MMVD. MATERIALS AND METHODS: Three dogs were presented at a private hospital for surgical treatment of MMVD. All three dogs had a previous history of left atrial rupture due to MMVD. The left atrium rapture was diagnosed from indicating that characteristics of the drained pericardial effusion consistent with blood. Mitral valvuloplasty was performed in all dogs using an extracorporeal circulation machine, and the surgical procedure was modified according to each case. In cases with severe adhesion between the pericardial and left atrial appendage, suturing of the left atrial appendage was performed strategically. Additionally, in cases with severe hypotension caused by left atrial rupture, cardiopulmonary bypass was started as soon as possible during the surgical procedure. DISCUSSION AND CONCLUSION: Since the haemodynamics of all dogs had improved, and the owner reported no cardiac-related clinical signs, all drugs were withdrawn 3 months after surgery. Since left atrial rupture due to MMVD can cause hypotension, cardiopulmonary bypass should be started as soon as possible during the surgical procedure to maintain the blood pressure and suturing of the left atrial appendage should be performed strategically.

Role of multidrug resistance-associated proteins in cancer therapeutics: past, present, and future perspectives.

Cancer, a major public health problem, is one of the world's top leading causes of death. Common treatments for cancer include cytotoxic chemotherapy, surgery, targeted drugs, endocrine therapy, and immunotherapy. However, despite the outstanding achievements in cancer therapies during the last years, resistance to conventional chemotherapeutic agents and new targeted drugs is still the major challenge. In the present review, we explain the different mechanisms involved in cancer therapy and the detailed outlines of cancer drug resistance regarding multidrug resistance-associated proteins (MRPs) and their role in treatment failures by common chemotherapeutic agents. Further, different modulators of MRPs are presented. Finally, we outlined the models used to analyze MRP transporters and proposed a future impact that may set up a base or pave the way for many researchers to investigate the cancer MRP further.

Evaluation of Changes in the Cardiac Function before and after Transcatheter Edge-to-Edge Mitral Valve Repair in Healthy Dogs: Conventional and Novel Echocardiography.

Mitral valve regurgitation is a common canine heart disease. Transcatheter Edge-to-Edge Repair (TEER) is a transcatheter, edge-to-edge mitral repair device that uses a hybrid approach. No detailed information has been published on the hemodynamic effect of TEER on cardiac function. The aim of this report is to provide a longitudinal observation of the cardiac functional changes observed after TEER implantation in normal dogs using traditional, two-dimensional speckle tracking, and color M-mode echocardiographic methods. In the current report, TEER was implanted into two healthy dogs under general anesthesia. An echocardiographic examination was performed at baseline and weekly postoperative follow-ups were conducted until the fourth week. Successful TEER implantation was achieved with a short operation time (98 and 63 min) in the two dogs. Functional mitral valve regurgitation, elevated E/e' ratio, elevated radial strain, and stable intraventricular pressure gradients (IVPG) were observed after the operation in the dogs. Mild non progressive mitral valve stenosis was observed in both dogs. TEER is a minimally invasive method for mitral valve surgery that necessitates more clinical trials. With longitudinal observation of heart function using novel approaches, better outcomes will be expected.