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.

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.

Relationship between the components of mare breast milk and foal gut microbiome: shaping gut microbiome development after birth.

The gut microbiota (GM) is essential for mammalian health. Although the association between infant GM and breast milk (BM) composition has been well established in humans, such a relationship has not been investigated in horses. Hence, this study was conducted to analyze the GM formation of foals during lactation and determine the presence of low-molecular-weight metabolites in mares' BM and their role in shaping foals' GM. The fecal and BM samples from six pairs of foals and mares were subjected to 16S ribosomal RNA metagenomic and metabolomic analyses, respectively. The composition of foal GM changed during lactation time; hierarchical cluster analysis divided the fetal GM into three groups corresponding to different time points in foal development. The level of most metabolites in milk decreased over time with increasing milk yield, while threonic acid and ascorbic acid increased. Further analyses revealed gut bacteria that correlated with changes in milk metabolites; for instance, there was a positive correlation between Bacteroidaceae in the foal's gut microbiota and serine/glycine in the mother's milk. These findings help improve the rearing environment of lactating horses and establish artificial feeding methods for foals.

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.

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.

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.

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.

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.

Comparison of Bovine- and Porcine-Derived Decellularized Biomaterials: Promising Platforms for Tissue Engineering Applications.

Animal-derived xenogeneic biomaterials utilized in different surgeries are promising for various applications in tissue engineering. However, tissue decellularization is necessary to attain a bioactive extracellular matrix (ECM) that can be safely transplanted. The main objective of the present study is to assess the structural integrity, biocompatibility, and potential use of various acellular biomaterials for tissue engineering applications. Hence, a bovine pericardium (BP), porcine pericardium (PP), and porcine tunica vaginalis (PTV) were decellularized using a Trypsin, Triton X (TX), and sodium dodecyl sulfate (SDS) (Trypsin + TX + SDS) protocol. The results reveal effective elimination of the cellular antigens with preservation of the ECM integrity confirmed via staining and electron microscopy. The elasticity of the decellularized PP (DPP) was markedly (p < 0.0001) increased. The tensile strength of DBP, and DPP was not affected after decellularization. All decellularized tissues were biocompatible with persistent growth of the adipose stem cells over 30 days. The staining confirmed cell adherence either to the peripheries of the materials or within their matrices. Moreover, the in vivo investigation confirmed the biocompatibility and degradability of the decellularized scaffolds. Conclusively, Trypsin + TX + SDS is a successful new protocol for tissue decellularization. Moreover, decellularized pericardia and tunica vaginalis are promising scaffolds for the engineering of different tissues with higher potential for the use of DPP in cardiovascular applications and DBP and DPTV in the reconstruction of higher-stress-bearing abdominal walls.

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.

Impact of the mother's gut microbiota on infant microbiome and brain development.

The link between the gut microbiome and health has recently garnered considerable interest in its employment for medicinal purposes. Since the early microbiota exhibits more flexibility compared to that of adults, there is a considerable possibility that altering it will have significant consequences on human development. Like genetics, the human microbiota can be passed from mother to child. This provides information on early microbiota acquisition, future development, and prospective chances for intervention. The succession and acquisition of early-life microbiota, modifications of the maternal microbiota during pregnancy, delivery, and infancy, and new efforts to understand maternal-infant microbiota transmission are discussed in this article. We also examine the shaping of mother-to-infant microbial transmission, and we then explore possible paths for future research to advance our knowledge in this area.

Adipose Stem Cell-Seeded Decellularized Porcine Pericardium: A Promising Functional Biomaterial to Synergistically Restore the Cardiac Functions Post-Myocardial Infarction.

Myocardial infarction (MI) is a serious cardiovascular disease as the leading cause of death globally. Hence, reconstruction of the cardiac tissue comes at the forefront of strategies adopted to restore heart functions following MI. In this investigation, we studied the capacity of rat adipose-derived mesenchymal stem cells (r-AdMSCs) and decellularized porcine pericardium (DPP) to restore heart functions in MI animals. MI was induced in four different groups, three of which were treated either using DPP (MI-DPP group), stem cells (MI-SC group), or both (MI-SC/DPP group). Cardiac functions of these groups and the Sham group were evaluated using echocardiography, the intraventricular pressure gradient (IVPG) on weeks 2 and 4, and intraventricular hemodynamics on week 4. On day 31, the animals were euthanized for histological analysis. Echocardiographic, IVPG and hemodynamic findings indicated that the three treatment strategies shared effectively in the regeneration process. However, the MI-SC/DPP group had a unique synergistic ability to restore heart functions superior to the other treatment protocols. Histology showed that the MI-SC/DPP group presented the lowest (p < 0.05) degeneration score and fibrosis % compared to the other groups. Conclusively, stem cell-seeded DPP is a promising platform for the delivery of stem cells and restoration of heart functions post-MI.

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.

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.

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.

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.

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.

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.

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.

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.